Next Article in Journal
Different Extracellular β-Amyloid (1-42) Aggregates Differentially Impair Neural Cell Adhesion and Neurite Outgrowth through Differential Induction of Scaffold Palladin
Previous Article in Journal
Identification of Bioactive Peptides from Nannochloropsis oculata Using a Combination of Enzymatic Treatment, in Silico Analysis and Chemical Synthesis
 
 
Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
Journals
Biomolecules
Volume 12
Issue 12
10.3390/biom12121807
biomolecules-logo
Submit to this Journal Review for this Journal Propose a Special Issue
► Article Menu

Article Menu

share Share announcement Help format_quote Cite question_answer Discuss in SciProfiles thumb_up
...
Endorse textsms
...
Comment
first_page
settings
Order Article Reprints
Font Type:
Arial Georgia Verdana
Font Size:
Aa Aa Aa
Line Spacing:
Column Width:
Background:
Review

Leucosceptosides A and B: Two Phenyl-Ethanoid Glycosides with Important Occurrence and Biological Activities

by
Claudio Frezza
1,*,
Daniela De Vita
1,
Chiara Toniolo
1,
Fabio Sciubba
1,2,
Lamberto Tomassini
1,
Alessandro Venditti
3,
Armandodoriano Bianco
3,
Mauro Serafini
1 and
Sebastiano Foddai
1
1
Dipartimento di Biologia Ambientale, Università di Roma “La Sapienza”, Piazzale Aldo Moro 5, 00185 Rome, Italy
2
NMR Lab, Università di Roma “La Sapienza”, Piazzale Aldo Moro 5, 00185 Rome, Italy
3
Dipartimento di Chimica, Università di Roma “La Sapienza”, Piazzale Aldo Moro 5, 00185 Rome, Italy
*
Author to whom correspondence should be addressed.
Biomolecules 2022, 12(12), 1807; https://doi.org/10.3390/biom12121807
Submission received: 19 September 2022 / Revised: 24 November 2022 / Accepted: 28 November 2022 / Published: 2 December 2022
Browse Figure
Versions Notes

Abstract

:
In this review paper, the occurrence in the plant kingdom, the chemophenetic value and the biological activities associated with two specific phenyl-ethanoid glycosides, i.e., leucosceptoside A and leucosceptoside B, were reported. This is the first work ever conducted on such a subject. Analysis of the literature data clearly led to three important conclusions: leucosceptoside A is much more common in plants than leucosceptoside B; leucosceptoside A exerts more biological activities than leucosceptoside B even if nothing can be generally concluded about which one is actually the most potent; neither of these compounds can be used as a chemophenetic marker. These three aspects and more are discussed in more depth in this work.

1. Introduction

Leucosceptoside A and leucosceptoside B are two natural compounds belonging to the class of phenyl-ethanoid glycosides which have gained increasing attention in recent years due to their important and effective biological activities [1].
Phenyl-ethanoid glycosides are biosynthetically generated merging two different processes, the shikimic acid pathway, which produces the β-hydroxy-tyrosol part of phenyl-ethanoid glycosides, and the cinnamate pathway, which produces its caffeic acid part after a series of intermediate steps [2].
The base compound of phenyl-ethanoid glycosides is called verbascoside, acetoside or acteoside, which is structurally characterized by a central glucose residue linked to one β-hydroxy-tyrosol and one rhamnose residue through ether bonds, and to one caffeic acid through an ester bond. Leucosceptoside A differs from verbascoside for the substitution with a methyl group in the caffeic acid moiety. Indeed, leucosceptoside B differs from verbascoside for the substitution with one methyl group each in the caffeic acid and β-hydroxy-tyrosol moieties as well as for the substitution with one β-D-apiose residue in the position 6 of the glucose moiety [3] (Figure 1).
In the literature, there are some review papers on phenyl-ethanoid glycosides in general, exploring mainly their occurrence, structure and biological activities [1,2,4]; however, no review paper has ever focused its complete attention on leucosceptoside A and leucosceptoside B, which have often been actually neglected regarding several of their aspects in the past reviews. In addition, some of these reviews are now outdated and do not cover the chemophenetics of these compounds or even of the phenyl-ethanoid glycosides in general. These represent the main reasons why this review paper was written. In this, the specific occurrence of leucosceptoside A and leucosceptoside B in the plant kingdom as well as their relative biological activities were reported with major details. In addition, chemophenetic conclusions on these compounds were drawn and a strict comparison on the biological activities of these two compounds in more senses was also performed, both for the first time. This review paper is based on all the published papers until now, as recovered from Scopus, Reaxys, Google Scholar and PubMed. Only works regarding plants were considered, thus, excluding cell cultures. In addition, only works without any kind of procedure possibly producing alterations and artifacts in the phytochemical pattern were cited. Lastly, papers not written in English were not considered.

2. Occurrence in the Plant Kingdom

In the following Tables, the occurrences of leucosceptoside A (Table 1) and leucosceptoside B (Table 2) in the plant kingdom are reported and divided according to the family of the plant they have been isolated from. These tables are sub-divided according to the plant species and report data on the collection area of the plant cited, the studied organs and the methodologies of isolation and identification for these compounds. In the collection area columns, if not differently specified, the studied population or populations are intended to be collected from the wild.
Leucosceptoside A proved to be quite common in the plant kingdom. In fact, it has been evidenced in eleven families. In particular, its lowest occurrence was observed in Asteraceae, Malvaceae and Oleaceae with one report each. In contrast, the highest occurrence has been noticed in the Lamiaceae family with 69 reports even though these were singular reports in most cases. Nevertheless, it is important to underline that not all the genera in the Lamiaceae family have shown the presence of this compound. Within the Lamiaceae family, this compound has been found particularly in the Phlomis L. genus with 15 reports whereas it is quite rare in Betonica L., Schnabelia Hand.-Mazz. and Volkameria L. genera with only one report of its presence each. Henceforth, further phytochemical studies on species belonging to these genera are necessary in order to verify if this compound is really part of their phytochemical components or if its presence was only accidental. All the other seven families see a moderate occurrence of leucosceptoside A. For what concerns the collection areas of the studied species, no significatively restricted zone for the occurrence of this compound has been observed since its presence has been found in species collected from four continents, i.e., America, Europe, Africa and Asia. Nothing can be stated at the moment about the Oceanian situation since no work on it has been found. As for the studied organs, leucosceptoside A has shown no particular preference for a specific accumulation site having been individuated in leaves, aerial parts, tubers, roots and the whole plant even if it seems this compound prefers aerial organs. A few procedures have been used to extract this compound mainly associated with maceration processes in their different forms. Indeed, several techniques have been used for its isolation and identification, including high performing liquid chromatography relative techniques, liquid chromatography relative techniques, thin-layer chromatography relative techniques, infrared, ultraviolet and nuclear magnetic resonance spectroscopies and mass spectrometry.
In the end, it is extremely relevant to highlight that Table 1 clearly indicates how leucosceptoside A cannot be used as a chemophenetic marker at any level since it has shown no specificity and also because the families where it was found are taxonomically very distant from each other.
With respect to leucosceptoside A, leucosceptoside B proved to be less common in the plant kingdom. In fact, it has been evidenced only in six families. Its lowest occurrence was observed in the Bignoniaceae, Orobanchaceae, Plantaginaceae and Verbenaceae families with one report each, whereas the highest occurrence has been noticed in the Lamiaceae family again with seventeen reports. There is a certain parallelism between the results found for leucosceptoside A and those found for leucosceptoside B for what concerns the collection areas of the studied species, the studied organs and the methodologies adopted for their isolation and identification. Indeed, there are some important differences for what concerns the families, genera and species where their presence has been reported. In particular, leucosceptoside B has not been reported in the Acanthaceae, Compositae, Linderniaceae, Malvaceae and Oleaceae families. In addition, for what concerns the Bignoniaceae, Scrophulariaceae and Verbenaceae families, leucosceptoside B has been found in completely different species, if not genera themselves, than leucosceptoside A. For what concerns the Lamiaceae family, the reported genera and species are not generally the same as for leucosceptoside A. In particular, leucosceptoside B has not been found in the Betonica L., Caryopteris Bunge, Clerodendrum L., Galeopsis L., Lagopsis Bunge, Leonurus L., Salvia L., Scutellaria L., Sideritis L. and Volkameria L. genera. This situation prompts the need to perform more phytochemical analyses on the species for its further research, also because several singular reports have been found in the literature with the same conclusions as drawn before.
Leucosceptoside B cannot also be used as a chemophenetic marker at any level for the same reasons as presented before, even if it presents a lower occurrence than leucosceptoside A.

3. Biological Activities

3.1. Leucosceptoside A

Leucosceptoside A has shown several interesting pharmacological activities. In the following lines, these activities are explored and detailed one-by-one.

3.1.1. Antioxidant and Radical Scavenging Activity

Leucosceptoside A proved to be a good antioxidant compound. Several studies against DPPH.+ confirm this with quite similar efficacy values. In particular, Ersöz et al. [58] obtained an IC50 value of 76.0 µM, which is lower than ascorbic acid used as a positive control (IC50 = 112 µM). Harput et al. [7] observed an IC50 value of 18.43 μg/mL, which is higher than quercetin but comparable (IC50 = 4.3 µg/mL), whereas Ono et al. [154] obtained an EC50 value of 25.7 µM, which is very similar to that for α-tocopherol (EC50 = 25.9 µM). Huang et al. [150] obtained an IC50 value of 72.14 μM, which is lower than vitamin C (IC50 = 81.83 µM). Lan et al. [117] obtained an EC50 value of 11.26 μM, which is slightly better than the positive control, ascorbic acid (EC50 value of 12.29 μM). Indeed, Calis et al. [60] obtained an IC50 value of 125.4 µM, which is quite higher than that of dl-α-tocopherol, used as a positive control (IC50 = 75.5 µM). Delazar et al. [61] obtained an RC50 of 0.0148 mg/mL, which is higher than trolox and quercetin, used as positive controls (RC50 values of 0.00307 and 0.0000278 mg/mL), instead. Lastly, Shen et al. [13] obtained an IC50 value of 53.32 µM, which was found to be higher than that of BHT, but no value of this latter was given.
On the other hand, Charami et al. [86] expressed the results as percentages of inhibition, which were 88.3% and 89.0% after 20 and 60 min, respectively, at the concentration of 0.1 mM, whereas the positive control acetyl salicylic, at the same concentration and times, showed a percentage of inhibition of 80.6%. Additionally, Harput et al. [54] expressed their results as percentages of inhibition and compared their results with three positive controls. In particular, the value for leucosceptoside A was 41.8% at the concentration of 200 µM, which is near to ascorbic acid and BHA (percentages of inhibition equal to 39.9 and 35.6%, respectively) but worse than chlorogenic acid (percentage of inhibition equal to 68.6%).

3.1.2. Radical Scavenging

Leucosceptoside A was observed to be a modest radical scavenging compound. In particular, Wang et al. [112] studied the scavenging properties of this compound with respect to superoxide anion and obtained a SC50 of 0.294 mM, which is higher than all the other phenyl-ethanoid glycosides studied in this work. The best one was verbascoside, which presents an SC50 value of 0.063 mM. In addition, Wang et al. [112] also studied the antioxidant potential of this compound through a luminol-enhanced chemiluminescence assay against N-formyl-methionyl-leucyl-phenylalanine in stimulated human polymorphonuclear neutrophils. The results showed that this compound is a weak inhibitor of hydroxyl radicals with a percentage of inhibition of 27.8% at the concentration of 0.55 mM and a modest iron reductor with a percentage of 17.86% at the concentration of 1.57 mM. The former value represents the lowest percentage of inhibition among all the phenyl-ethanoid glycosides considered in this study, whereas the latter value is the second worst. Verbascoside was the most active as an inhibitor of the hydroxyl radical with a percentage of 55.7% at the concentration of 0.55 mM, whereas pedicularioside M was the most active as an iron reductor with a percentage of 23.57% at the concentration of 1.73 mM. Heilmann et al. [185] also studied the radical scavenging effects of this compound in N-formyl-methionyl-leucyl-phenylalanine-stimulated human polymorphonuclear neutrophils through a luminol-enhanced chemiluminescence assay. The obtained IC50 value was 0.18 µM, which is higher but not too far from that of quercetin used as a positive control (IC50 value = 0.5 µM). Nevertheless, most of the other phenyl-ethanoid glycosides studied in this work showed better results than leucosceptoside A and, in particular, echinacoside was the best one with an IC50 value of 0.03 µM.

3.1.3. Anti-Inflammatory Activity

Leucosceptoside A shows moderate anti-inflammatory activities with respect to NO production. In particular, Han et al. [151] obtained an IC50 value of 9.0 µM in the Raw 264.7 cell line, whereas the positive control aminoguanidine had an IC50 value of 10.7 µM. Vien et al. [14] obtained a different result in LPS-stimulated BV2 microglial cells using the Griess assay, with an IC50 value of 61.1 µM, which is much higher than the positive control butein (IC50 = 4.5 µM). In contrast, Ochi et al. [147] obtained a moderate percentage of inhibition of 40% in cell culture supernatants of LPS-stimulated RAW264.7 macrophages at the concentration of 100 µM, whereas the positive control L-NMMA presents an inhibition value of 55% at the same concentration.

3.1.4. Enzyme Inhibitory Activity

Leucosceptoside A has been also studied for its potential inhibitory effects on some enzymes, i.e., α-glucosidase, acetylcholinesterase, protein kinase C alpha and tyrosinase.
Concerning α-glucosidase, this compound has shown contrasting results. In fact, Liu et al. [27] obtained an IC50 value of 0.7 mM, which is much lower than acarbose used as a positive control (IC50 = 14.4 mM). Indeed, Thu et al. [146] obtained an IC50 value of 273.0 µM, which is a little higher than that of acarbose (IC50 = 204.2 µM).
Leucosceptoside A also possesses between moderate and modest acetylcholinesterase inhibitory effects. In fact, Kang et al. [33] obtained an IC50 value of 423.7 µg/mL, which is much higher than Captopril® used as a positive control (IC50 value of 20 nM). In addition, Saidi et al. [186] obtained an IC50 value of 72.85 µM, which is also much higher than that of the positive control used in this study, i.e., galantamine (IC50 value of 4.14 µM). Indeed, Li et al. [187], using the Scheffe’s test, obtained an IC50 value of 3.86 mM, which is comparable to that of Captopril® used again as a positive control (IC50 value of 2.11 nM).
This compound is also a modest protein kinase C alpha inhibitor with an IC50 value of 19.0 µM. This value is good in number but, in the same study, other phenyl-ethanoid glycosides were found to be more active, such as forsythoside and verbascoside, showing IC50 values of 4.6 and 9.3 µM, respectively [131].
In addition, this compound shows only modest tyrosinase inhibitory activities, with a percentage of inhibition of 21.65% at the concentration of 0.051 mM. Kojic acid, used as a positive control, has a percentage of inhibition of 53.87% at the concentration of 0.047 mM [188]. A similar result was obtained by Saidi et al. [186], who observed a percentage of inhibition of 39.5% at the concentration of 100 µM, whereas the positive control hydroquinone has a percentage of inhibition of 72.0% at the same concentration.
Lastly, this compound has shown no effect on the hyaluronidase enzyme inhibition test and collagenase enzyme inhibition test at the concentration of 100 µg/mL [138].

3.1.5. Hepatoprotective Activity

At 100 µM, leucosceptoside A exerts strong hepatoprotective properties in pretreatment as obtained by studying the viability of HepG2 cells after CCl4 intoxication, by means of an MTT assay and flow cytometry, with values of cell number and cell viability both above 80%, thus, implying a restoration of cell survival. These values are extremely good in numbers, but no standard compound was tested for comparison. The mechanism of action occurs through the inhibition of NF-kB activation since it was observed that pretreatment with this compound can inhibit CCl4-induced lipid peroxidation in HepG2 cells by 177.73% and attenuate the decrease in SOD by 76.58%; furthermore, pre-incubation of the same cells with this compound can prevent ROS production by 183.56% [13].

3.1.6. Neuroprotective Activity

Leucosceptoside A, in pretreatment, exerts good neuroprotective effects against the 1-methyl-4-phenylpyridinium ion (MPP+)-induced cell death in mesencephalic neurons of rats. MPP+ is the ion produced after the biotransformation of the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine by the monoamine oxidase B, and it is well known to cause Parkinson’s disease in rats and non-human primates. By means of an MTT assay, it was observed that leucosceptoside A, at the concentration of 4 µM, reduces cell death by 7%, whereas at the concentration of 16 µM, it increases cell growth by 3.7%. These values are extraordinary, however, in the same study, a more efficient compound was found, i.e., pedicularioside A. In fact, at the concentration of 4 µM, this latter compound shows a reduction value of cell death by 3.4% and, at the concentration of 16 µM, it increases cell growth by 21.4% [189].

3.1.7. Cytoprotective Activity

Leucosceptoside A exhibits promising cytoprotective effects against t-BHP-induced toxicity in HepG2 cells with an IC50 value of 21.1 µM. This value is lower than silymarin used as a positive control (IC50 = 37.1 µM) [23].

3.1.8. Anticomplementary Activity

Leucosceptoside A exerts good anticomplementary effects with a CH50 value of 0.23 mM, which is slightly higher than that of the standard compound heparin (CH50 = 0.06 mM) [119].

3.1.9. Anti-HIV Activity

Leucosceptoside A has shown strong HIV-1 integrase inhibitory effects with an IC50 value of 29.4 µM. This value is better than curcumin (IC50 = 54.3 µM) and comparable to L-chicoric acid (IC50 = 21.0 µM) used as positive controls [32].

3.1.10. Cytotoxic Activity

According to Argyropoulou et al. [46], leucosceptoside A exerts very modest cytotoxic effects on HeLa (human epithelial carcinoma), MCF7 (breast metastatic adenocarcinoma) and HC7-116 (colon cancer) cell lines with IC50 values of 200, 189.08 and 182.33 µg/mL, respectively. The standard compound doxorubicin presents IC50 values of 0.175, 0.235 and 0.096 µg/mL, respectively, whereas the other standard compound actinomycin D presents IC50 values of 0.013, 0.022 and 0.019µg/mL, respectively. On the contrary, it showed no effect against melanoma. Saidi et al. [186] also tested the cytotoxic effects of this compound on HeLa cell lines obtaining an IC50 = 80.87 µM as well as a positive result on the A549 (adenocarcinomic human alveolar basal epithelial cells) cancer cell line obtaining an IC50 = 99.00 µM. All these values are much higher than the standard compounds used, i.e., doxorubicin for the former cancer cell line (IC50 = 0.36 µM) and ellipticine for the latter cancer cell line (IC50 = 0.31 µM). Abe et al. [159] obtained promising results on Hela (GI50 = 42 µM) and also against the B16F10 (murine melanoma) cell line with a GI50 value equal to 28 µM and against the MK-1 (gastric carcinoma with liver metastasis) cell line with a GI50 value equal to 33 µM. All these values are good in numbers, but some other phenyl-ethanoid glycosides studied in this work present better results in full or in part. In particular, iso-verbascoside was the most potent against B16F10 and MK-1 with GI50 values of 10 and 32 µM, respectively, whereas arenarioside was the most potent against HeLa with a GI50 value of 34 µM. Unlike the previous works, Saracoglu et al. [49] did not observe any effect on HeLa cells for this compound and this contrast all depends on the methodology adopted. Saracoglu et al. [49] did not observe any effect against dRLh-88 (rat hepatoma), P-388-d1 (mouse lymphoid neoplasma) and S-180 (sarcoma) cancer cell lines, too.

3.1.11. Inhibitory Activities

Leucosceptoside A exhibits good inhibitory effects against ADP + NADPH-induced lipid peroxidation in rat liver microsomes with an IC50 value of 1.69 µM, which is very promising. Yet, other phenyl-ethanoid glycosides studied in this work showed better results. In particular, iso-verbascoside was the most potent with an IC50 value of 0.38 µM [132].
This compound also exhibits inhibitory effects on the protonation of thymine radical anion induced by pulse radiolysis, which causes severe damages in cells with a reaction rate constant of electronic transfer equal to 1.54 × 109 dm3 mol−1 s−1. This value is very good in number, but without a direct comparison with any compound [190].

3.1.12. Antimicrobial Activities

Leucosceptoside A exerts poor antimicrobial effects against Staphylococcus aureus ATCC29213 and Enterococcus faecalis ATCC29212 with MIC values of 1000 µg/mL [60]. These values are extremely high and are generally considered to be inactive.
Indeed, it has shown no activity against Escherichia coli ATCC25922 [60], Mycobacterium tuberculosis H37Rv [30], Pseudomonas aeruginosa ATCC27853 [60], Bacillus subtilis NBRC3134 and Klebsiella pneumoniae NBRC3512 [24].

3.1.13. Antifungal Activities

Leucosceptoside A has shown no activity against Candida albicans ATCC90028, Candida krusei ATCC6258 and Candida parapsilosis ATCC22019 [60].

3.2. Leucosceptoside B

Leucosceptoside B has also shown some interesting pharmacological activities, even if less numerous than leucosceptoside A. In the following lines, these activities are explored and detailed one-by-one.

3.2.1. Antioxidant Activity

Leucosceptoside B proved to be an antioxidant compound. Several studies, according to different assays, confirm this with opposite efficacy values.
According to the DPPH.+ assay, this compound exerts between moderate and modest effects. In fact, Niu et al. [166] obtained an IC50 value of 31.16 µM, which is higher than ascorbic acid used as a positive control (IC50 = 7.81 µM). In addition, Georgiev et al. [182] obtained an IC50 value of 96 µg/mL, which is high with respect to the other phenyl-ethanoid glycosides studied in this work. In particular, this compound was found to be the weakest, whereas the most potent was forsythoside B with an IC50 value of 21 µg/mL. Indeed, Lan et al. [117] obtained an EC50 value of 13.05 μM, which is comparable to that of ascorbic acid (EC50 value of 12.29 μM). Lastly, Calis et al. [60] obtained an IC50 value of 61.3 µM, which is lower than that of dl-α-tocopherol used as a positive control (IC50 = 75.5 µM); yet there was one phenyl-ethanoid glycosides (myricoside) that is even more potent than this (IC50 = 46.8 µM).

3.2.2. Radical Scavenging Activity

Through a luminol-enhanced chemiluminescence assay with formyl-methionyl-leucyl-phenylalanine in stimulated human polymorphonuclear neutrophils, Heilmann et al. [185] reported the radical scavenging activities of this compound with an IC50 value of 0.17 µM, which is higher but not too far from that of quercetin used as a positive control (IC50 value = 0.5 µM).
Indeed, Georgiev et al. [182] also studied the ORAC, HORAC, FRAP and superoxide anion activities of this compound obtaining different results. In particular, good effects were observed for the first one with a value of 16264.7 ORACFL/g, which is higher than chlorogenic acid used as a standard compound (9172.8 ORACFL/g), and for the second one with a value of 3885.1 HORACFL/g, which is higher than chlorogenic acid used as a standard compound (3584.5 ORACFL/g). Conversely, poor effects were observed for the third assay with a value of absorbance of 0.602 at 700 nm, which is much lower than chlorogenic acid used as a reference compound (3.547), whereas moderate effects were observed for the last assay with an IC50 value of approximately 45 µg/mL, which is much higher with respect to the other phenyl-ethanoid glycosides studied in this work, and in particular, of verbascoside, which was the best one (IC50 = 4.2 µg/mL).

3.2.3. Anti-Inflammatory Activity

Leucosceptoside B exerts good inhibitory effects on cobra venom factor-induced alternative pathway activation in mouse sera with a percentage of inhibition of 40% and on COX-2 production with a percentage of inhibition near 30%. The positive control, indomethacin, presents a percentage of inhibition near 70%. In addition, it shows moderate inhibitory effects on NO production and IL-10 production as well as good inhibitory effects on COX-1, even if in the study, the values were not clearly expressed. Furthermore, all these values are higher than indomethacin [183].

3.2.4. Enzyme Inhibitory Activity

Georgiev et al. [182] studied the acetylcholinesterase and butyrylcholinesterase inhibitory activities of leucosceptoside B. In both cases, the activity is dose-dependent; however, in the former, the percentage of inhibition is almost 50% at the concentration of 100 µg/mL, whereas in the latter, the percentage of inhibition is a little above 10% at the concentration of 100 µg/mL. These values are much lower than the positive control galanthamine, which presents percentages of inhibition of 98.97 and 89.95%, respectively, at the same concentrations.
Indeed, Cespedes et al. [191] obtained a different result for the acetylcholinesterase inhibitory effects of this compound with an IC50 value of 20.1 µg/mL, whereas galanthamine has an IC50 value of 13.2 µg/mL.
Cespedes et al. [191] did not observe any butyrylcholinesterase inhibitory activity for leucosceptoside B.

3.2.5. Neuroprotective Activity

Leucosceptoside B, in pretreatment, is also able to exert strong neuroprotective effects against the 1-methyl-4-phenylpyridinium ion (MPP+)-induced cell death in mesencephalic neurons at the concentration of 40 µg/mL. The potency was measured as optical density with a value of 1.06. However, buddleoside A, another phenyl-ethanoid glycoside, was found to be much more potent with a value of 1.62 [149].

3.2.6. Inhibitory Activities

Leucosceptoside B has shown no human lactate dehydrogenase inhibitory activity [172].

3.2.7. Antimicrobial Activity

Leucosceptoside B has shown very poor antimicrobial effects against Staphylococcus aureus ATCC29213 and Enterococcus faecalis ATCC29212 with MIC values of 1000 µg/mL [60]. Again, these values are extremely high and are generally considered to be inactive.
In addition, it has proven to be inactive against Escherichia coli ATCC25922 and Pseudomonas aeruginosa ATCC27853 [60].

3.2.8. Antimicrobial Activity

Leucosceptoside B has shown no antifungal activity against Candida albicans ATCC90028, Candida krusei ATCC6258 and Candida parapsilosis ATCC22019 [60].

3.3. Comparing the Biological Results of Leucosceptosides A and B

Table 3 and Table 4 below summarize the biological activities and efficacy values of leucosceptoside A and leucosceptoside B, respectively.
According to the data as reported in Section 3.1 and Section 3.2 and Table 3 and Table 4, leucosceptoside A proved to be a more important biological compound than leucosceptoside B based on the number of biological assays performed on them. In fact, leucosceptoside A has been tested for more numerous biological assays than leucosceptoside B (10 vs. 5). In particular, leucosceptoside A was also tested for its hepatoprotective, cytoprotective, cytotoxic, anticomplementary and anti-HIV activities with respect to leucosceptoside B. This minor number of assays performed on leucosceptoside B may be explained not only by its minor occurrence in the plant kingdom but also for the fact that this compound is much more difficult to isolate in pure form since its co-elution with more polar compounds than phenyl-ethanoid glycosides is extremely common. On the contrary, given the literature data results, it is not so easy to ascertain which compound is generally the most efficient. This is due to the fact that leucosceptoside A and leucosceptoside B were directly compared only in two cases. The first case regards the radical scavenging effects of these compounds in formyl-methionyl-leucyl-phenylalanine-stimulated human polymorphonuclear neutrophils through a luminol-enhanced chemiluminescence assay and showed that leucosceptoside A and leucosceptoside B basically have the same efficacy (IC50 values of 0.18 µM vs. 0.17 µM) [185]. The second case regards the DPPH.+ radical scavenging assay and showed that leucosceptoside A is slightly better than leucosceptoside B (EC50 values of 11.26 µM vs. 13.05 µM) [117]. One further indirect comparison of the efficacy values of these two compounds can be made also according to the DPPH.+ radical scavenging assay; however, the relative studies led to extremely contrasting results. In fact, the IC50 values found for leucosceptoside A were 76.0 µM [58], 18.43 µM [7], 72.14 µM [150], 125.4 µM [60] and 53.32 µM [13], whereas the IC50 values found for leucosceptoside B were 31.16 µM [166], 96.0 µM [182] and 61.3 µM [60]. These discrepancies are due to several intrinsic methodological factors and are also dependent on the fact that leucosceptosides A and B were not studied together in these works. In this context, these results do not really allow to make any general conclusion on which of these compounds is the most potent. Indeed, for what concerns the rest of the biological activities, no comparison can be made since the two compounds were not studied together, different protocols were used, and the values were expressed in different unities of efficacy. These last aspects are certainly something to keep in consideration for future research in order to improve this situation.

4. Conclusions

This review article clearly shows how leucosceptoside A and leucosceptoside B are important compounds with regards to some aspects. In fact, they have been found in different species belonging to several families and, even though they do not possess chemophenetic significance on their own, they are also endowed with several interesting pharmacological activities including antioxidant, anti-inflammatory, enzyme inhibitory and neuroprotective. However, searching for these phytochemical components of plants is still quite limited due to the several factors. This review article also aimed to be a stimulus to amplify studies on both phytochemistry and pharmacology since there is still a lot to be discovered.

Author Contributions

Conceptualization, C.F.; Research, All the authors; Data curation, All the authors; Writing—original draft preparation, review and editing, All the authors. All authors have read and agreed to the published version of the manuscript.

Funding

This research received no external funding.

Institutional Review Board Statement

Not applicable.

Informed Consent Statement

Not applicable.

Data Availability Statement

Not applicable.

Conflicts of Interest

The authors declare no conflict of interest.

References

  1. Wu, L.; Georgiev, M.I.; Cao, H.; Nahar, L.; El-Seedi, H.-R.; Sarker, S.D.; Xiao, J.; Lu, B. Therapeutic potential of phenylethanoid glycosides: A systematic review. Med. Res. Rev. 2020, 40, 2605–2649. [Google Scholar] [CrossRef] [PubMed]
  2. Heldt, H.W.; Heldt, F. Phenylpropanoids comprise a multitude of plant secondary metabolites and cell wall components. In Plant Biochemistry, 3rd ed.; Elsevier Academic Press: San Diego, CA, USA, 2005; pp. 435–454. [Google Scholar]
  3. Tian, X.-Y.; Li, M.-X.; Lin, T.; Qiu, Y.; Zhu, Y.-T.; Li, X.-L.; Tao, W.-D.; Wang, P.; Ren, X.-X.; Chen, L.-P. A review on the structure and pharmacological activity of phenylethanoid glycosides. Eur. J. Med. Chem. 2021, 209, 112563. [Google Scholar] [CrossRef]
  4. Jiménez, C.; Riguera, R. Phenylethanoid glycosides in plants: Structure and biological activity. Nat. Prod. Rep. 1994, 11, 591–606. [Google Scholar] [CrossRef]
  5. Kanchanapoom, T.; Kasai, R.; Picheansoonthon, C.; Yamasaki, K. Megastigmane, aliphatic alcohol and benzoxazinoid glycosides from Acanthus ebracteatus. Phytochemistry 2001, 58, 811–817. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  6. Prasansuklab, A.; Tencomnao, T. Acanthus ebracteatus leaf extract provides neuronal cell protection against oxidative stress injury induced by glutamate. BMC Complement. Altern. Med. 2018, 18, 278. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  7. Harput, U.S.; Arihan, O.; Iskit, A.B.; Nagatsu, A.; Saracoglu, I. Antinociceptive, free radical-scavenging, and cytotoxic activities of Acanthus hirsutus Boiss. J. Med. Food 2011, 14, 767–774. [Google Scholar] [CrossRef] [PubMed]
  8. Noiarsa, P.; Ruchirawat, S.; Kanchanapoom, T. Acanmontanoside, a new phenylethanoid diglycoside from Acanthus montanus. Molecules 2010, 15, 8967–8972. [Google Scholar] [CrossRef] [Green Version]
  9. Ashour, M.A.-G. Isolation, HPLC/UV characterization and antioxidant activity of phenylethanoids from Blepharis edulis (Forssk.) Pers. growing in Egypt. Bull. Fac. Pharm. Cairo Univ. 2012, 50, 67–72. [Google Scholar] [CrossRef] [Green Version]
  10. Vo, T.N.; Nguyen, P.L.; Tran, T.T.N.; Nguyen, K.P.P.; Nguyen, N.S. Some phenylethanoids from roots of Pseuderanthemum carruthersii (Seem.) Guill var. atropurpureum (Bull.) Fosb. Vietnam J. Chem. 2010, 48, 325–331. [Google Scholar]
  11. Piccinelli, A.L.; De Simone, F.; Passi, S.; Rastrelli, L. Phenolic constituents and antioxidant activity of Wendita calysina leaves (Burrito), a folk Paraguayan tea. J. Agric. Food Chem. 2004, 52, 5863–5868. [Google Scholar] [CrossRef] [PubMed]
  12. Kanchanapoom, T.; Kasai, R.; Yamasaki, K. Lignan and phenylpropanoid glycosides from Fernandoa adenophylla. Phytochemistry 2001, 57, 1245–1248. [Google Scholar] [CrossRef] [PubMed]
  13. Shen, T.; Li, X.; Hu, W.; Zhang, L.; Xu, X.; Wu, H.; Ji, L. Hepatoprotective effect of phenylethanoid glycosides from Incarvillea compacta against CCl4-induced cytotoxicity in HepG2 cells. J. Korean Soc. Appl. Biol. Chem. 2015, 58, 617–625. [Google Scholar] [CrossRef]
  14. Ihtesham, Y.; Khan, U.; Dogan, Z.; Kutluay, V.M.; Saracoğlu, I. Evaluation of some biological effects of Incarvillea emodi (Royle ex Lindl.) Chatterjee and determination of its active constituents. Kafkas Univ. Vet. Fak. Derg. 2019, 25, 171–178. [Google Scholar]
  15. Arevalo, C.; Ruiz, I.; Piccinelli, A.L.; Campone, L.; Rastrelli, L. Phenolic derivatives from the leaves of Martinella obovata (Bignoniaceae). Nat. Prod. Commun. 2011, 6, 957–960. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  16. Vien, L.T.; Hanh, T.T.H.; Quang, T.H.; Cuong, N.T.; Cuong, N.X.; Oh, H.; Sinh, N.V.; Nam, N.H.; Minh, C.V. Phenolic glycosides from Oroxylum indicum. Nat. Prod. Res. 2022, 36, 2336–2340. [Google Scholar] [CrossRef]
  17. Kanchanapoom, T.; Kasai, R.; Yamasaki, K. Phenolic glycosides from Barnettia kerrii. Phytochemistry 2002, 59, 565–570. [Google Scholar] [CrossRef] [Green Version]
  18. Plaza, A.; Montoro, P.; Benavides, A.; Pizza, C.; Piacente, S. Phenylpropanoid glycosides from Tynanthus panurensis: Characterization and LC-MS quantitative analysis. J. Agric. Food Chem. 2005, 53, 2853–2858. [Google Scholar] [CrossRef]
  19. Çalis, I.; Başaran, A.; Saracoğlu, I.; Sticher, O. Iridoid and phenylpropanoid glycosides from Stachys macrantha. Phytochemistry 1992, 31, 167–169. [Google Scholar] [CrossRef]
  20. Yuan, J.-Q.; Qiu, L.; Zouc, L.-H.; Wei, Q.; Miao, J.-H.; Yao, X.-S. Two new phenylethanoid glycosides from Callicarpa longissima. Helv. Chim. Acta 2015, 98, 482–489. [Google Scholar] [CrossRef]
  21. Wang, J. N-butanol-soluble chemical constituents from Callicarpa nudiflora. Chin. Pharm. J. 2017, 24, 1983–1987. [Google Scholar]
  22. Zhao, D.P.; Matsunami, K.; Otsuka, H. Iridoid glucoside, (3R)-oct-1-en-3-ol glycosides, and phenylethanoid from the aerial parts of Caryopteris incana. J. Nat. Med. 2009, 63, 241–247. [Google Scholar] [CrossRef] [PubMed]
  23. Park, S.; Son, M.J.; Yook, C.-S.; Jin, C.; Lee, Y.S.; Kim, H.J. Chemical constituents from aerial parts of Caryopteris incana and cytoprotective effects in human HepG2 cells. Phytochemistry 2014, 101, 83–90. [Google Scholar] [CrossRef]
  24. Yoshikawa, K.; Harada, A.; Iseki, K.; Hashimoto, T. Constituents of Caryopteris incana and their antibacterial activity. J. Nat. Med. 2014, 68, 231–235. [Google Scholar] [CrossRef]
  25. Nugroho, A.; Lee, S.K.; Kim, D.; Choi, J.S.; Park, K.-S.; Song, B.-M.; Park, H.-J. Analysis of essential oil, quantification of six glycosides, and nitric oxide synthase inhibition activity in Caryopteris incana. Nat. Prod. Sci. 2018, 24, 181–188. [Google Scholar] [CrossRef]
  26. Li, Y.B.; Li, J.; Li, P.; Tu, P.F. Isolation and characterization of phenylethanoid glycosides from Clerodendron bungei. Acta Pharm. Sin. 2005, 40, 722–727. [Google Scholar]
  27. Liu, Q.; Hu, H.-J.; Li, P.-F.; Yang, Y.-B.; Wu, L.-H.; Chou, G.-X.; Wang, Z.-T. Diterpenoids and phenylethanoid glycosides from the roots of Clerodendrum bungei and their inhibitory effects against angiotensin converting enzyme and α-glucosidase. Phytochemistry 2014, 103, 196–202. [Google Scholar] [CrossRef] [PubMed]
  28. Gao, L.M.; Wei, X.M.; He, Y.Q. Studies on chemical constituents in leaves of Clerodendron fragrans. China J. Chin. Mat. Med. 2003, 28, 948–951. [Google Scholar]
  29. Uddin, J.; Çiçek, S.S.; Willer, J.; Shulha, O.; Abdalla, M.A.; Sönnichsen, F.; Girreser, U.; Zidorn, C. Phenylpropanoid and flavonoid glycosides from the leaves of Clerodendrum infortunatum (Lamiaceae). Biochem. Syst. Ecol. 2020, 92, 104131. [Google Scholar] [CrossRef]
  30. Yadav, A.K.; Gupta, M.M. Quantitative determination of bioactive phenylethanoid glycosides in Clerodendrum phlomidis using HPTLC. Med. Chem. Res. 2014, 23, 1654–1660. [Google Scholar] [CrossRef]
  31. Yadav, A.K.; Thakur, J.K.; Agrawal, J.; Saikia, D.; Pal, A.; Gupta, M.M. Bioactive chemical constituents from the root of Clerodendrum phlomidis. Med. Chem. Res. 2015, 24, 1112–1118. [Google Scholar] [CrossRef]
  32. Kim, H.J.; Woo, E.-R.; Shin, C.-G.; Hwang, D.J.; Park, H.; Lee, Y.S. HIV-1 integrase inhibitory phenylpropanoid glycosides from Clerodendron trichotomum. Arch. Pharm. Res. 2001, 24, 286–291. [Google Scholar] [CrossRef] [PubMed]
  33. Kang, D.G.; Lee, Y.S.; Kim, H.J.; Lee, Y.M.; Lee, H.S. Angiotensin converting enzyme inhibitory phenylpropanoid glycosides from Clerodendron trichotomum. J. Ethnopharmacol. 2003, 89, 151–154. [Google Scholar] [CrossRef] [PubMed]
  34. Lee, J.-W.; Bae, J.J.; Kwak, J.H. Glycosides from the flower of Clerodendrum trichotomum. Korean J. Pharmacogn. 2016, 47, 301–306. [Google Scholar]
  35. Miyase, T.; Koizumi, A.; Ueno, A.; Noro, T.; Kuroyanagi, M.; Fukushima, S.; Akiyama, Y.; Takemoto, T. Studies on the acyl glycosides from Leucosceptrum japonicum (Miq.) Kitamura et Murata. Chem. Pharm. Bull. 1982, 30, 2732–2737. [Google Scholar] [CrossRef] [Green Version]
  36. Murata, T.; Arai, Y.; Miyase, T.; Yoshizaki, F. An alkaloidal glycoside and other constituents from Leucosceptrum japonicum. J. Nat. Med. 2009, 63, 402–407. [Google Scholar] [CrossRef]
  37. Olennikov, D.N. Synanthropic plants as an underestimated source of bioactive phytochemicals: A case of Galeopsis bifida (Lamiaceae). Plants 2020, 9, 1555. [Google Scholar] [CrossRef]
  38. Zhang, J.; Huang, Z.; Huo, H.-X.; Li, Y.-T.; Pang, D.-R.; Zheng, J.; Zhang, Q.; Zhao, Y.-F.; Tu, P.-F.; Li, J. Chemical constituents from Lagopsis supina (Steph.) Ik.-Gal. ex Knorr. Biochem. Syst. Ecol. 2015, 61, 424–428. [Google Scholar] [CrossRef]
  39. Yang, L.; He, J. Lagopsis supina extract and its fractions exert prophylactic effects against blood stasis in rats via anti-coagulation, anti-platelet activation and anti-fibrinolysis and chemical characterization by UHPLC-qTOF-MS/MS. Biomed. Pharmacother. 2020, 132, 110899. [Google Scholar] [CrossRef]
  40. He, J.; Yang, L. Diuretic effect of Lagopsis supina fraction in saline-loaded rats is mediated through inhibition of aquaporin and renin-angiotensin-aldosterone systems and up-regulation of atriopeptin. Biomed. Pharmacother. 2021, 139, 111554. [Google Scholar] [CrossRef]
  41. Olennikov, D.N.; Chirikova, N.K. Caffeoylglucaric acids and other phenylpropanoids from Siberian Leonurus species. Chem. Nat. Compd. 2016, 52, 915–917. [Google Scholar] [CrossRef]
  42. Tasdemir, D.; Scapozza, L.; Zerbe, O.; Linden, A.; Calis, I.; Sticher, O. Iridoid glycosides of Leonurus persicus. J. Nat. Prod. 1999, 62, 811–816. [Google Scholar] [CrossRef] [PubMed]
  43. Schmidt, S.; Jakab, M.; Jav, S.; Streif, D.; Pitschmann, A.; Zehl, M.; Purevsuren, M.; Glasl, S.; Ritter, M. Extracts from Leonurus sibiricus L. increase insulin secretion and proliferation of rat INS-1E insulinoma cells. J. Ethnopharmacol. 2013, 150, 85–94. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  44. Pitschmann, A.; Zehl, M.; Heiss, E.; Purevsuren, S.; Urban, E.; Dirsch, M.V.; Glasl, S. Quantitation of phenylpropanoids and iridoids in insulin-sensitising extracts of Leonurus sibiricus L. (Lamiaceae). Phytochem. Anal. 2015, 27, 23–31. [Google Scholar] [CrossRef] [PubMed]
  45. Çaliş, I.; Hosny, M.; Khalifa, T.; Rüedi, P. Phenylpropanoid glycosides from Marrubium alysson. Phytochemistry 1992, 31, 3624–3626. [Google Scholar]
  46. Argyropoulou, A.; Samara, P.; Tsitsilonis, O.; Skaltsa, H. Polar constituents of Marrubium thessalum Boiss. & Heldr. (Lamiaceae) and their cytotoxic/cytostatic activity. Phytother. Res. 2012, 26, 1800–1806. [Google Scholar]
  47. Karioti, A.; Skaltsa, H.; Heilmann, J.; Sticher, O. Acylated flavonoid and phenylethanoid glycosides from Marrubium velutinum. Phytochemistry 2003, 64, 655–660. [Google Scholar] [CrossRef]
  48. Masoodi, M.; Ali, Z.; Liang, S.; Yin, H.; Wang, W.; Khan, I.A. Labdane diterpenoids from Marrubium vulgare. Phytochem. Lett. 2015, 13, 275–279. [Google Scholar] [CrossRef]
  49. Saracoglu, I.; Inoue, M.; Çalis, I.; Ogihara, Y. Studies on constituents with cytotoxic and cytostatic activity of two Turkish medicinal plants Plomis armeniaca and Scutellaria salviifolia. Biol. Pharm. Bull. 1995, 18, 1396–1400. [Google Scholar] [CrossRef]
  50. Kırmızıbekmez, H.; Montoro, P.; Piacente, S.; Pizza, C.; Dönmez, A.; Çalıs, I. Identification by HPLC-PAD-MS and quantification by HPLC-PAD of phenylethanoid glycosides of five Phlomis species. Phytochem. Anal. 2005, 16, 1–6. [Google Scholar] [CrossRef]
  51. Ersöz, T.; Saracoğlu, I.; Kırmızıbekmez, H.; Yalçın, F.N.; Harput, Ü.S.; Dönmez, A.A.; Çalıs, I. Iridoid, phenylethanoid and phenol glycosides from Phlomis chimerae. Hacet. Univ. J. Fac. Pharm. 2001, 21, 23–33. [Google Scholar]
  52. Stojković, D.; Gašić, U.; Drakulić, D.; Zengin, G.; Stevanović, M.; Rajčević, N.; Soković, M. Chemical profiling, antimicrobial, anti-enzymatic, and cytotoxic properties of Phlomis fruticosa L. J. Pharm. Biomed. Anal. 2021, 195, 113884. [Google Scholar] [CrossRef] [PubMed]
  53. Saracoglu, I.; Varel, M.; Çalıs, I.; Dönmez, A.A. Neolignan, flavonoid, phenylethanoid and iridoid glycosides from Phlomis integrifolia. Turk. J. Chem. 2003, 27, 739–747. [Google Scholar]
  54. Harput, U.S.; Çalıs, I.; Saracoglu, I.; Dönmez, A.A.; Nagatsu, A. Secondary metabolites from Phlomis syriaca and their antioxidant activities. Turk. J. Chem. 2006, 30, 383–390. [Google Scholar]
  55. Ersöz, T.; Schühly, W.; Popov, S.; Handjieva, N.; Sticher, O.; Çalıs, I. Iridoid and phenylethanoid glycosides from Phlomis longifolia var. longifolia. Nat. Prod. Lett. 2001, 15, 345–351. [Google Scholar] [CrossRef]
  56. Kırmızıbekmez, H.; Piacente, S.; Pizza, C.; Dönmez, A.A.; Çalıs, I. Iridoid and phenylethanoid glycosides from Phlomis nissolii and P. capitata. Z. Naturforsch. B 2004, 59, 609–613. [Google Scholar] [CrossRef]
  57. Çaliş, I.; Bedir, E.; Kirmizibekmez, H.; Ersöz, T.; Dönmez, A.A.; Khan, I.A. Secondary metabolites from Phlomis oppositiflora. Nat. Prod. Res. 2005, 19, 493–501. [Google Scholar] [CrossRef]
  58. Ersöz, T.; Alipieva, K.I.; Yalçın, F.N.; Akbay, P.; Handjieva, N.; Dönmez, A.A.; Popov, S.; Çaliş, I. Physocalycoside, a new phenylethanoid glycoside from Phlomis physocalyx Hub.-Mor. Z. Naturforsch. C 2003, 58, 471–476. [Google Scholar] [CrossRef]
  59. Ersöz, T.; Harput, U.S.; Çaliş, I.; Dönmez, A.A. Iridoid, phenylethanoid and monoterpene glycosides from Phlomis sieheana. Turk. J. Chem. 2002, 26, 1–8. [Google Scholar]
  60. Çaliş, I.; Kırmızıbekmez, H.; Beutler, J.A.; Dönmez, A.A.; Yalçın, F.N.; Kilic, E.; Özalp, M.; Rüedi, P.; Tasdemir, D. Secondary metabolites of Phlomis viscosa and their biological activities. Turk. J. Chem. 2005, 29, 71–81. [Google Scholar]
  61. Delazar, A.; Shoeb, M.; Kumarasamy, Y.; Byres, M.; Nahar, L.; Modarresi, M.; Sarker, S.D. Two bioactive ferulic acid derivatives from Eremostachys glabra. DARU J. Pharm. Sci. 2004, 12, 49–53. [Google Scholar]
  62. Çaliş, I.; Guevenc, A.; Armagan, M.; Koyuncu, M.; Gotfredsen, C.H.; Jensen, S.R. Secondary metabolites from Eremostachys laciniata. Nat. Prod. Commun. 2008, 3, 117–124. [Google Scholar] [CrossRef] [Green Version]
  63. Wang, J.; Gao, Y.-L.; Chen, Y.-L.; Chen, Y.-W.; Zhang, Y.; Xiang, L.; Pan, Z. Lamiophlomis rotata identification via ITS2 barcode and quality evaluation by UPLC-QTOF-MS coupled with multivariate analyses. Molecules 2018, 23, 3289. [Google Scholar] [PubMed] [Green Version]
  64. Li, T.; Jia, L.; Du, R.; Liu, C.; Huang, S.; Lu, H.; Han, L.; Chen, X.; Wang, Y.; Jiang, M. Comparative investigation of aerial part and root in Lamiophlomis rotata using UPLC-Q-Orbitrap-MS coupled with chemometrics. Arab. J. Chem. 2022, 15, 103740. [Google Scholar] [CrossRef]
  65. Çaliş, I.; Kırmızıbekmez, H.; Ersöz, T.; Dönmez, A.A.; Gotfredsen, C.H.; Jensen, S.R. Iridoid glucosides from Turkish Phlomis tuberosa. Z. Naturforsch. B 2005, 60, 1295–1298. [Google Scholar] [CrossRef]
  66. Wu, S.-J.; Chan, Y.-Y. Five new iridoids from roots of Salvia digitaloides. Molecules 2014, 19, 15521–15534. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  67. Rungsimakan, S.; Rowan, M.G. Terpenoids, flavonoids and caffeic acid derivatives from Salvia viridis L. cvar. Blue Jeans. Phytochemistry 2014, 108, 177–188. [Google Scholar] [CrossRef]
  68. Grzegorczyk-Karolak, I.; Kiss, A.K. Determination of the phenolic profile and antioxidant properties of Salvia viridis L. shoots: A comparison of aqueous and hydroethanolic extracts. Molecules 2018, 23, 1468. [Google Scholar] [CrossRef] [Green Version]
  69. Zengin, G.; Mahomoodally, F.; Picot-Allain, C.; Diuzheva, A.; Jekőd, J.; Cziáky, Z.; Cvetanović, A.; Aktumsek, A.; Zeković, Z.; Rengasamy, K.R.R. Metabolomic profile of Salvia viridis L. root extracts using HPLC–MS/MS technique and their pharmacological properties: A comparative study. Ind. Crops Prod. 2019, 131, 266–280. [Google Scholar] [CrossRef]
  70. Xu, H.-T.; Zhang, C.-G.; He, Y.-Q.; Shi, S.-S.; Wang, Y.-L.; Chou, G.-X. Phenylethanoid glycosides from the Schnabelia nepetifolia (Benth.) P.D.Cantino promote the proliferation of osteoblasts. Phytochemistry 2019, 164, 111–121. [Google Scholar] [CrossRef]
  71. Matsa, M.; Bardakci, H.; Gousiadou, C.; Kirmizibekmez, H.; Skaltsa, H. Secondary metabolites from Scutellaria albida L. ssp. velenovskyi (Rech. f.) Greuter & Burdet. Biochem. Syst. Ecol. 2019, 83, 71–76. [Google Scholar]
  72. Olennikov, D.N.; Chirikova, N.K.; Tankhaeva, L.M. Phenolic compounds of Scutellaria baicalensis Georgi. Russ. J. Bioorg. Chem. 2010, 36, 816–824. [Google Scholar] [CrossRef]
  73. Qiao, X.; Li, R.; Song, W.; Miao, W.-J.; Liu, J.; Chen, H.-B.; Guo, D.; Ye, M. A targeted strategy to analyze untargeted mass spectral data: Rapid chemical profiling of Scutellaria baicalensis using ultra-highperformance liquid chromatography coupled with hybrid quadrupole orbitrap mass spectrometry and key ion filtering. J. Chromatogr. A 2016, 1441, 83–95. [Google Scholar] [CrossRef] [PubMed]
  74. Yang, Z.-W.; Xu, F.; Liu, X.; Cao, Y.; Tang, Q.; Chen, Q.-Y.; Shang, M.-Y.; Liu, G.-X.; Wang, X.; Cai, S.-Q. An untargeted metabolomics approach to determine component differences and variation in their in vivo distribution between Kuqin and Ziqin, two commercial specifications of Scutellaria Radix. RSC Adv. 2017, 7, 54682–54695. [Google Scholar] [CrossRef] [Green Version]
  75. Zhang, F.; Li, Z.; Li, M.; Yuan, Y.; Cui, S.; Chen, J.; Li, R. An integrated strategy for profiling the chemical components of Scutellariae Radix and their exogenous substances in rats by ultra-high-performance liquid chromatography/quadrupole time-of-flight mass spectrometry. Rapid Commun. Mass Spectrom. 2020, 34, e8823. [Google Scholar] [CrossRef]
  76. Shah, M.; Rahman, H.; Khan, A.; Bibi, S.; Ullah, O.; Ullah, S.; Ur Rehman, N.; Murad, W.; Al-Harrasi, A. Identification of α-glucosidase inhibitors from Scutellaria edelbergii: ESI-LC-MS and computational approach. Molecules 2022, 27, 1322. [Google Scholar] [CrossRef]
  77. Kuroda, M.; Iwabuchi, K.; Mimaki, Y. Chemical constituents of the aerial parts of Scutellaria lateriflora and their α-glucosidase inhibitory activities. Nat. Prod. Commun. 2012, 7, 471–474. [Google Scholar] [CrossRef] [Green Version]
  78. Çaliş, I.; Saracoğlu, I.; Başaran, A.A.; Sticher, O. Two phenethyl alcohol glycosides from Scutellaria orientalis subsp. pinnatifida. Phytochemistry 1993, 32, 1621–1623. [Google Scholar] [CrossRef]
  79. Kikuchi, Y.; Miyaichi, Y.; Yamaguchi, Y.; Kizu, H.; Tomimori, T. Studies on the Nepalese crude drugs. XII. On the phenolic compounds from the root of Scutellaria prostrata Jacq. ex Benth. Chem. Pharm. Bull. 1991, 39, 1047–1050. [Google Scholar] [CrossRef] [Green Version]
  80. Lytra, K.; Tomou, E.-M.; Chrysargyris, A.; Drouza, C.; Skaltsa, H.; Tzortzakis, N. Traditionally used Sideritis cypria Post.: Phytochemistry, nutritional content, bioactive compounds of cultivated populations. Front. Pharmacol. 2020, 11, 650. [Google Scholar] [CrossRef]
  81. Lytra, K.; Tomou, E.-M.; Chrysargyris, A.; Christofi, M.-D.; Miltiadous, P.; Tzortzakis, N.; Skaltsa, H. Bio-guided investigation of Sideritis cypria methanol extract driven by in vitro antioxidant and cytotoxic assays. Chem. Biodivers. 2021, 18, e2000966. [Google Scholar] [CrossRef]
  82. Tomou, E.-M.; Chatzopoulou, P.; Skaltsa, H. NMR analysis of cultivated Sideritis euboea Heldr. Phytochem. Anal. 2020, 31, 147–153. [Google Scholar] [CrossRef] [PubMed]
  83. Tomou, E.-M.; Papaemmanouil, C.D.; Diamantis, D.A.; Kostagianni, A.D.; Chatzopoulou, P.; Mavromoustakos, T.; Tzakos, A.G.; Skaltsa, H. Anti-ageing potential of S. euboea Heldr. phenolics. Molecules 2021, 26, 3151. [Google Scholar] [CrossRef] [PubMed]
  84. Akcos, Y.; Ezer, N.; Çalis, I.; Demirdamar, R.; Tel, B.C. Polyphenolic Compounds of Sideritis lycia and their anti-inflammatory activity. Pharm. Biol. 1999, 37, 118–122. [Google Scholar] [CrossRef]
  85. Şahin, F.P.; Ezer, N.; Çalış, I. Three acylated flavone glycosides from Sideritis ozturkii Aytac & Aksoy. Phytochemistry 2004, 65, 2095–2099. [Google Scholar] [PubMed] [Green Version]
  86. Charami, M.-T.; Lazari, D.; Karioti, A.; Skaltsa, H.; Hadjipavlou-Litina, D.; Souleles, C. Antioxidant and antiinflammatory activities of Sideritis perfoliata subsp. perfoliata (Lamiaceae). Phytother. Res. 2008, 22, 450–454. [Google Scholar] [CrossRef]
  87. Petreska, J.; Stefkov, G.; Kulevanova, S.; Alipieva, K.; Bankova, V.; Stefova, M. Phenolic compounds of mountain tea from the Balkans: LC/DAD/ESI/MSn profile and content. Nat. Prod. Commun. 2011, 6, 21–30. [Google Scholar] [CrossRef] [Green Version]
  88. Pljevljakušić, D.; Šavikin, K.; Janković, K.; Zdunić, G.; Ristić, M.; Godjevac, D.; Konić-Ristić, A. Chemical properties of the cultivated Sideritis raeseri Boiss. & Heldr. subsp. raeseri. Food Chem. 2011, 124, 226–233. [Google Scholar]
  89. Menković, N.; Gođevac, D.; Šavikin, K.; Zdunić, G.; Milosavljević, S.; Bojadži, A.; Avramoski, O. Bioactive compounds of endemic species Sideritis raeseri subsp. raeseri grown in National Park Galičica. Rec. Nat. Prod. 2013, 7, 161–168. [Google Scholar]
  90. Kokras, N.; Poulogiannopoulou, E.; Sotiropoulos, M.G.; Paravatou, R.; Goudani, E.; Dimitriadou, M.; Papakonstantinou, E.; Doxastakis, G.; Perrea, D.N.; Hloupis, G.; et al. Behavioral and neurochemical effects of extra virgin olive oil total phenolic content and Sideritis extract in female mice. Molecules 2020, 25, 5000. [Google Scholar] [CrossRef]
  91. Tomou, E.-M.; Lytra, K.; Chrysargyris, A.; Christofi, M.-D.; Miltiadous, P.; Corongiu, G.L.; Tziouvelis, M.; Tzortzakis, N.; Skaltsa, H. Polar constituents, biological effects and nutritional value of Sideritis sipylea Boiss. Nat. Prod. Res. 2022, 36, 4200–4204. [Google Scholar] [CrossRef]
  92. Miyase, T.; Ueno, A.; Kitani, T.; Kobayashi, H.; Kawahara, Y.; Yamahara, J. Studies on Stachys sieboldii Miq. I. Isolation and structures of new glycosides. J. Pharm. Soc. Jpn. 1990, 110, 652–657. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  93. Nishimura, H.; Sasaki, H.; Inagaki, N.; Chin, M.; Mitsuhashi, H. Nine phenylethyl alcohol glycosides from Stachys sieboldii. Phytochemistry 1991, 30, 965–969. [Google Scholar] [CrossRef]
  94. Venditti, A.; Frezza, C.; Celona, D.; Bianco, A.; Serafini, M.; Cianfaglione, K.; Fiorini, D.; Ferraro, S.; Maggi, F.; Lizzi, A.R.; et al. Polar constituents, protection against reactive oxygen species, and nutritional value of Chinese artichoke (Stachys affinis Bunge). Food Chem. 2017, 221, 473–481. [Google Scholar] [CrossRef]
  95. Pritsas, A.; Tomou, E.-M.; Tsitsigianni, E.; Papaemmanouil, C.D.; Diamantis, D.A.; Chatzopoulou, P.; Tzakos, A.G.; Skaltsa, H. Valorisation of stachysetin from cultivated Stachys iva Griseb. as anti-diabetic agent: A multi-spectroscopic and molecular docking approach. J. Biomol. Struct. Dyn. 2020, 39, 6452–6466. [Google Scholar] [CrossRef] [PubMed]
  96. Delazar, A.; Delnavazi, M.R.; Nahar, L.; Moghadam, S.B.; Mojara, M.; Gupta, A.; Williams, A.S.; Rahman, M.M.; Sarker, S.D. Lavandulifolioside B: A new phenylethanoid glycoside from the aerial parts of Stachys lavandulifolia Vahl. Nat. Prod. Res. 2011, 25, 8–16. [Google Scholar] [CrossRef]
  97. Ergun, B.; Goger, F.; Kose, Y.B.; Iscan, G. Determination of phenolic compounds of Stachys rupestris Montbret et Aucher ex Bentham by LC-MS/MS and its biological activities. Fresenius Environ. Bull. 2018, 27, 1176–1182. [Google Scholar]
  98. Afouxenidi, A.; Milošević-Ifantis, T.; Skaltsa, H. Secondary metabolites from Stachys tetragona Boiss. & Heldr. ex Boiss. and their chemotaxonomic significance. Biochem. Syst. Ecol. 2018, 81, 83–85. [Google Scholar]
  99. Kanchanapoom, T.; Kasai, R.; Chumsri, P.; Hiraga, Y.; Yamasaki, K. Megastigmane and iridoid glucosides from Clerodendrum inerme. Phytochemistry 2001, 58, 333–336. [Google Scholar] [CrossRef]
  100. Passon, M.; Weber, F.; Jung, N.U.; Bartels, D. Profiling of phenolic compounds in desiccation-tolerant and non-desiccation-tolerant Linderniaceae. Phytochem. Anal. 2021, 32, 521–529. [Google Scholar] [CrossRef] [PubMed]
  101. Bai, H.; Li, S.; Yin, F.; Hu, L. Isoprenylated naphthoquinone dimers firmianones A, B, and C from Firmiana platanifolia. J. Nat. Prod. 2005, 68, 1159–1163. [Google Scholar] [CrossRef]
  102. Wu, L.; Liu, J.; Huang, W.; Wang, Y.; Chen, Q.; Lu, B. Exploration of Osmanthus fragrans Lour.’s composition, nutraceutical functions and applications. Food Chem. 2022, 377, 131853. [Google Scholar] [CrossRef]
  103. Shi, R.; Zhang, C.; Gong, X.; Yang, M.; Ji, M.; Jiang, L.; Leonti, M.; Yao, R.; Li, M. The genus Orobanche as food and medicine: An ethnopharmacological review. J. Ethnopharmacol. 2020, 263, 113154. [Google Scholar] [CrossRef]
  104. Jedrejek, D.; Pawelec, S.; Piwowarczyk, R.; Pecio, Ł.; Stochmal, A. Identification and occurrence of phenylethanoid and iridoid glycosides in six Polish broomrapes (Orobanche spp. and Phelipanche spp., Orobanchaceae). Phytochemistry 2020, 170, 112189. [Google Scholar] [CrossRef]
  105. Yang, M.-Z.; Wang, X.-Q.; Li, C. Chemical constituents from Orobanche cernua. Chin. Tradit. Herb. Drugs 2014, 45, 2447–2452. [Google Scholar]
  106. Qu, Z.-Y.; Zhang, Y.-W.; Yao, C.-L.; Jin, Y.-P.; Zheng, P.-H.; Sun, C.-H.; Liu, J.-X.; Wang, Y.-S.; Wang, Y.-P. Chemical constituents from Orobanche cernua Loefling. Biochem. Syst. Ecol. 2015, 60, 199–203. [Google Scholar] [CrossRef]
  107. Wang, X.; Li, C.; Jiang, L.; Huang, H.; Li, M. Phenylethaniod glycosides from Orobanche pycnostachya Hance and their chemotaxonomic significance. Biochem. Syst. Ecol. 2020, 93, 104168. [Google Scholar] [CrossRef]
  108. Ersöz, T.; Berkman, M.Z.; Taşdemir, D.; Çaliş, I.; Ireland, C.M. Iridoid and phenylethanoid glycosides from Euphrasia pectinata. Turk. J. Chem. 2002, 26, 179–188. [Google Scholar]
  109. Ersöz, T.; Berkman, M.Z.; Taşdemir, D.; Ireland, C.M.; Çaliş, I. An iridoid glucoside from Euphrasia pectinata. J. Nat. Prod. 2000, 63, 1449–1450. [Google Scholar] [CrossRef]
  110. Akdemir, Z.; Çaliş, I. Iridoid and phenylpropanoid glycosides from Pedicularis comosa var. acmodonta Boiss. Doga Turk. J. Pharm. 1992, 2, 63–70. [Google Scholar]
  111. Gao, J.J.; Jia, Z.J. Lignan: Iridoid and phenylpropanoid glycosides from Pedicularis alaschanica. Ind. J. Chem. Sect. B-Org. Chem. Incl. Med. Chem. 1995, 34, 466–468. [Google Scholar]
  112. Wang, P.; Kung, J.; Zheng, R.; Yung, Z.; Lu, J.; Guo, J.; Jiu, Z. Scavenging effects of phenylpropanoid glycosides from Pedicularis on superoxide anion and hydroxyl radical by the spin trapping method (95)02255-4. Biochem. Pharmacol. 1996, 51, 687–691. [Google Scholar] [CrossRef] [PubMed]
  113. Yin, J.-G.; Yuan, C.-S.; Jia, Z.-J. A new iridoid and other chemical constituents from Pedicularis kansuensis forma albiflora Li. Arch. Pharm. Res. 2007, 30, 431–435. [Google Scholar] [CrossRef] [PubMed]
  114. Chu, H.B.; Tan, N.H.; Xiong, J.; Zhang, Y.M.; Ji, C.J. Chemical constituents of Pedicularis dolichocymba Hand.-Mazz. Nat. Prod. Res. Dev. 2007, 19, 584–587. [Google Scholar]
  115. Ma, S.; Yang, A.; Yang, L.; Guo, W.; Li, C.; Shang, Q. Chemical constituents of Pedicularis kansuensis. Chem. Nat. Compd. 2017, 53, 586–588. [Google Scholar] [CrossRef]
  116. Venditti, A.; Frezza, C.; Serafini, M.; Bianco, A. Iridoids and phenylethanoid from Pedicularis kerneri Dalla Torre growing in Dolomites, Italy. Nat. Prod. Res. 2016, 30, 327–331. [Google Scholar] [CrossRef] [PubMed]
  117. Lan, Y.; Chi, X.; Zhou, G.; Zhao, X. Antioxidants from Pedicularis longiflora var. tubiformis (Klotzsch) P. C. Tsoong. Rec. Nat. Prod. 2018, 12, 332–339. [Google Scholar] [CrossRef]
  118. Akdemir, Z.; Çaliş, I.; Junior, P. Iridoids and phenyipropanoid glycosides from Pedicularis nordmanniana. Planta Med. 1991, 57, 584–585. [Google Scholar] [CrossRef]
  119. Wang, Y.; Shao, M.-H.; Yuan, S.-W.; Lu, Y.; Wang, Q. A new monoterpene glycoside from Pedicularis verticillata and anticomplementary activity of its compounds. Nat. Prod. Res. 2021, 35, 1–8. [Google Scholar] [CrossRef]
  120. Takeda, Y. A new phenolic glycoside from Phtheirospermum japonicum. J. Nat. Prod. 1988, 51, 180–183. [Google Scholar] [CrossRef]
  121. Friščić, M.; Bucar, F.; Hazler Pilepić, K. LC-PDA-ESI-MSn analysis of phenolic and iridoid compounds from Globularia spp. J. Mass Spectrom. 2016, 51, 1211–1236. [Google Scholar] [CrossRef]
  122. Friščić, M.; Petlevski, R.; Kosalec, I.; Madunić, J.; Matulić, M.; Bucar, F.; Hazler Pilepić, K.; Maleš, Ž. Globularia alypum L. and related species: LC-MS profiles and antidiabetic, antioxidant, anti-inflammatory, antibacterial and anticancer potential. Pharmaceuticals 2022, 15, 506. [Google Scholar] [CrossRef] [PubMed]
  123. Kirmizibekmez, H.; Çaliş, I.; Piacente, S.; Pizza, C. Phenolic compounds from Globularia cordifolia. Turk. J. Chem. 2004, 28, 455–460. [Google Scholar]
  124. Çaliş, I.; Kirmizibekmez, H.; Taşdemir, D.; Ireland, C.M. Iridoid glycosides from Globularia davisiana. Chem. Pharm. Bull. 2002, 50, 678–680. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  125. Çaliş, I.; Kirmizibekmez, H.; Taşdemir, D.; Sticher, O.; Ireland, C.M. Sugar esters from Globularia orientalis. Z. Naturforsch. C 2002, 57, 591–596. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  126. Kirmizibekmez, H.; Çaliş, I.; Piacente, S.; Pizza, C. Iridoid and phenylethyl glycosides from Globularia sintenisii. Helv. Chim. Acta 2004, 87, 1172–1179. [Google Scholar] [CrossRef]
  127. Li, C.; Liu, Y.; Abdulla, R.; Aisa, H.A.; Suo, Y. Determination of phenylethanoid glycosides in Lagotis brevituba Maxim. by high-performance liquid chromatography-electrospray ionization tandem mass spectrometry. Anal. Lett. 2014, 47, 1862–1873. [Google Scholar] [CrossRef]
  128. Yang, A.-M.; Lu, R.-H.; Shi, Y.-P. Phenylpropanoids from Lagotis ramalana. Nat. Prod. Res. Dev. 2007, 19, 263–265. [Google Scholar]
  129. Ye, M.; Zhao, Y.; Norman, V.L.; Starks, C.M.; Rice, S.M.; Goering, M.G.; O’Neil-Johnson, M.; Eldridge, G.R.; Hu, J.-F. Antibiofilm phenylethanoid glycosides from Penstemon centranthifolius. Phytother. Res. 2010, 24, 778–781. [Google Scholar] [CrossRef]
  130. Ismail, L.D.; El-Azizi, M.M.; Khalifa, T.I.; Stermitz, F.R. Verbascoside derivatives and iridoid glycosides from Penstemon crandallii. Phytochemistry 1995, 39, 1391–1393. [Google Scholar] [CrossRef]
  131. Zhou, B.-N.; Bahler, B.D.; Hofmann, G.A.; Mattern, M.R.; Johnson, R.K.; Kingston, D.G.I. Phenylethanoid glycosides from Digitalis purpurea and Penstemon linarioides with PKCr-inhibitory activity. J. Nat. Prod. 1998, 61, 1410–1412. [Google Scholar] [CrossRef]
  132. Miyase, T.; Ishino, M.; Akahori, C.; Ueno, A.; Ohkawa, Y.; Tanizawa, H. Phenylethanoid glycosides from Plantago asiatica. Phytochemistry 1991, 30, 2015–2018. [Google Scholar] [CrossRef]
  133. Qi, M.; Xiong, A.; Geng, F.; Yang, L.; Wang, Z. A novel strategy for target profiling analysis of bioactive phenylethanoid glycosides in Plantago medicinal plants using ultra-performance liquid chromatography coupled with tandem quadrupole mass spectrometry. J. Sep. Sci. 2012, 35, 1470–1478. [Google Scholar] [CrossRef] [PubMed]
  134. Wang, D.; Qi, M.; Yang, Q.; Tong, R.; Wang, R.; Annie Bligh, S.W.; Yang, L.; Wang, Z. Comprehensive metabolite profiling of Plantaginis Semen using ultra high-performance liquid chromatography with electrospray ionization quadrupole time-of-flight tandem mass spectrometry coupled with elevated energy technique. J. Sep. Sci. 2016, 39, 1842–1852. [Google Scholar] [CrossRef]
  135. Mazzutti, S.; Salvador Ferreira, S.R.; Herrero, M.; Ibãnez, E. Intensified aqueous-based processes to obtain bioactive extracts from Plantago major and Plantago lanceolata. J. Supercrit. Fluids 2017, 119, 64–71. [Google Scholar] [CrossRef]
  136. Afifi, M.S.A.; Amer, M.M.A.; ZaghIoul, A.M.; Ahmad, M.M.; Kinghorn, A.D.; Zaghloul, M.G. Chemical constituents of Plantago squarrosa. Mansoura J. Pharm. Sci. 2001, 17, 65–84. [Google Scholar]
  137. Genc, Y.; Sohretoglu, D.; Harput, U.S.; Ishiuchi, K.; Makino, T.; Saracoglu, I. Chemical constituents of Plantago holosteum and evaluation of their chemotaxonomic significance. Chem. Nat. Compd. 2020, 56, 566–568. [Google Scholar] [CrossRef]
  138. Dereli, F.T.G.; Genc, Y.; Saracoglu, I.; Akkol, E.K. Enzyme inhibitory assessment of the isolated constituents from Plantago holosteum Scop. Z. Naturforsch. C 2020, 75, 121–128. [Google Scholar] [CrossRef]
  139. Sasaki, H.; Nishimura, H.; Chin, M.; Mitsuhashi, H. Hydroxycinnamic acid esters of phenylalcohol glycosides from Rehmannia glutinosa var. purpurea. Phytochemistry 1989, 28, 875–879. [Google Scholar] [CrossRef]
  140. Nishimura, H.; Morota, T.; Yamaguchi, T.; Chin, M. Extraction of Phenethyl Alcohol Derivatives as Aldose Reductase Inhibitors for Treatment of Diabetes-Related Diseases. Japan Kokai Tokkyo Koho Patent JP 02036189, 1990. p. 13. [Google Scholar]
  141. Anh, N.T.H.; Sung, T.V.; Franke, K.; Wessjohann, L.A. Phytochemical studies of Rehmannia glutinosa rhizomes. Pharmazie 2003, 58, 593–595. [Google Scholar]
  142. Li, X.; Zhou, M.; Shen, P.; Zhang, J.; Chu, C.; Ge, Z.; Yan, J. Chemical constituents form Rehmannia glutinosa. China J. Chin. Mater. Med. 2011, 36, 3125–3129. [Google Scholar]
  143. Li, M.-N.; Dong, X.; Gao, W.; Liu, X.-G.; Wang, R.; Li, P.; Yang, H. Global identification and quantitative analysis of chemical constituents in traditional Chinese medicinal formula Qi-Fu-Yin by ultra-high performance liquid chromatography coupled with mass spectrometry. J. Pharm. Biomed. Anal. 2015, 114, 376–389. [Google Scholar] [CrossRef] [PubMed]
  144. Song, Q.-Q. Establishment of HPLC fingerprint of Rehmanniae Radix and its HPLC-ESI-MS analysis. Chin. Tradit. Herb. Drugs 2016, 24, 4247–4252. [Google Scholar]
  145. Zhang, B.; Weston, P.A.; Gu, L.; Zhang, B.; Li, M.; Wang, F.; Tu, W.; Wang, J.; Weston, L.A.; Zhang, Z. Identification of phytotoxic metabolites released from Rehmannia glutinosa suggest their importance in the formation of its replant problem. Plant Soil 2019, 441, 439–454. [Google Scholar] [CrossRef]
  146. Thu, V.K.; Thoa, N.T.; Hien, N.T.T.; Hang, D.T.T.; Kiem, P.V. Iridoid glycosides link with phenylpropanoids from Rehmannia glutinosa. Nat. Prod. Res. 2022, in press. [Google Scholar] [CrossRef] [PubMed]
  147. Ochi, M.; Matsunami, K.; Otsuka, H.; Takeda, Y. A new iridoid glycoside and NO production inhibitory activity of compounds isolated from Russelia equisetiformis. J. Nat. Med. 2012, 66, 227–232. [Google Scholar] [CrossRef]
  148. Yamamoto, A.; Nitta, S.; Miyase, T.; Ueno, A.; Wu, L.-J. Phenylethanoid and lignan-iridoid complex glycosides from roots of Buddleja davidii. Phytochemistry 1993, 32, 421–425. [Google Scholar] [CrossRef]
  149. Lu, J.-H.; Pu, X.-P.; Li, Y.-Y.; Zhao, Y.-Y.; Tu, G.Z. Bioactive phenylethanoid glycosides from Buddleia lindleyana. Z. Naturforsch. B 2005, 60, 211–214. [Google Scholar] [CrossRef]
  150. Huang, F.-B.; Liang, N.; Hussain, N.; Zhou, X.-D.; Ismail, M.; Xie, Q.-L.; Yu, H.-H.; Jian, Y.-Q.; Peng, C.-Y.; Li, B.; et al. Anti-inflammatory and antioxidant activities of chemical constituents from the flower buds of Buddleja officinalis. Nat. Prod. Res. 2022, 36, 3031–3042. [Google Scholar] [CrossRef]
  151. Han, M.-F.; Zhang, X.; Zhang, L.-Q.; Li, Y.-M. Iridoid and phenylethanol glycosides from Scrophularia umbrosa with inhibitory activity on nitric oxide production. Phytochem. Lett. 2018, 28, 37–41. [Google Scholar] [CrossRef]
  152. Frezza, C.; Bianco, A.; Serafini, M.; Foddai, S.; Salustri, M.; Reverberi, M.; Gelardi, L.; Bonina, A.; Bonina, F.P. HPLC and NMR analysis of the phenyl-ethanoid glycosides pattern of Verbascum thapsus L. cultivated in the Etnean area. Nat. Prod. Res. 2019, 33, 1310–1316. [Google Scholar] [CrossRef]
  153. de la Luz Cádiz-Gurrea, M.; Olivares-Vicente, M.; Herranz-López, M.; Arraez-Roman, D.; Fernández-Arroyo, S.; Micol, V.; Segura-Carretero, A. Bioassay-guided purification of Lippia citriodora polyphenols with AMPK modulatory activity. J. Funct. Foods 2018, 46, 514–520. [Google Scholar] [CrossRef]
  154. Ono, M.; Oda, E.; Tanaka, T.; Iida, Y.; Yamasaki, T.; Masuoka, C.; Ikeda, T.; Nohara, T. DPPH radical-scavenging effect on some constituents from the aerial parts of Lippia triphylla. J. Nat. Med. 2008, 62, 101–106. [Google Scholar] [CrossRef]
  155. Olivares-Vicente, M.; Sánchez-Marzo, N.; Encinar, J.A.; De la Luz Cádiz-Gurrea, M.; Lozano-Sánchez, J.; Segura-Carretero, A.; Arraez-Roman, D.; Riva, C.; Barrajón-Catalán, E.; Herranz-López, M.; et al. The potential synergistic modulation of AMPK by Lippia citriodora compounds as a target in metabolic disorders. Nutrients 2019, 11, 2961. [Google Scholar] [CrossRef] [Green Version]
  156. Sánchez-Marzo, N.; Lozano-Sánchez, J.; De la Luz Cádiz-Gurrea, M.; Herranz-López, M.; Micol, V.; Segura-Carretero, A. Relationships between chemical structure and antioxidant activity of isolated phytocompounds from Lemon Verbena. Antioxidants 2019, 8, 324. [Google Scholar] [CrossRef] [Green Version]
  157. Saidi, I.; Waffo-Teguo, P.; Ayeb-Zakhama, A.E.L.; Harzallah-Skhiri, F.; Marchal, A.; Jannet, H.B. Phytochemical study of the trunk bark of Citharexylum spinosum L. growing in Tunisia: Isolation and structure elucidation of iridoid glycosides. Phytochemistry 2018, 146, 47–55. [Google Scholar] [CrossRef]
  158. Timóteo, P.; Karioti, A.; Leitão, S.G.; Vincieri, F.F.; Bilia, A.R. A validated HPLC method for the analysis of herbal teas from three chemotypes of Brazilian Lippia alba. Food Chem. 2015, 175, 366–373. [Google Scholar] [CrossRef]
  159. Abe, F.; Nagao, T.; Okabe, H. Antiproliferative constituents in plants 9.1) Aerial parts of Lippia dulcis and Lippia canescens. Biol. Pharm. Bull. 2002, 25, 920–922. [Google Scholar] [CrossRef] [Green Version]
  160. Froelich, S.; Gupta, M.P.; Siems, K.; Jenett-Siems, K. Phenylethanoid glycosides from Stachytarpheta cayennensis (Rich.) Vahl, Verbenaceae, a traditional antimalarial medicinal plant. Braz. J. Pharmacogn. 2008, 18, 517–520. [Google Scholar] [CrossRef] [Green Version]
  161. Toledo de Silva, M.V.; Garrett, R.; Simas, D.L.R.; Ungaretti Paleo Konno, T.; Frazão Muzitano, M.; Corrêa Pinto, S.; Barth, T. Chemical profile of Stachytarpheta schottiana by LC-HRMS/MS dereplication and molecular networking. Rodriguésia 2021, 72, 1–11. [Google Scholar]
  162. Ono, M.; Oishi, K.; Abe, H.; Masuoka, C.; Okawa, M.; Ikeda, T.; Nohara, T. New iridoid glucosides from the aerial parts of Verbena brasiliensis. Chem. Pharm. Bull. 2006, 54, 1421–1424. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  163. Yokosuka, A.; Honda, M.; Kondo, H.; Mimaki, Y. Chemical constituents of the whole plant of Verbena hastata and their inhibitory activity against the production of AGEs. Nat. Prod. Commun. 2021, 16, 1–5. [Google Scholar] [CrossRef]
  164. Martin, F.; Hay, A.-E.; Corno, L.; Gupta, M.P.; Hostettmann, K. Iridoid glycosides from the stems of Pithecoctenium crucigerum (Bignoniaceae). Phytochemistry 2007, 68, 1307–1311. [Google Scholar] [CrossRef] [PubMed]
  165. Yang, Z.-Y.; Yuan, H.; Zhou, Y.; Lin, C.-Z.; Peng, G.-T.; Wu, A.-Z.; Zhu, C.-C. Phenylpropanoid compounds isolated from Callicarpa kwangtungensis and antibacterial activity research. Nat. Prod. Res. Dev. 2019, 31, 1928–1933. [Google Scholar]
  166. Niu, C.; Li, Q.; Yang, L.-P.; Zhang, Z.-Z.; Zhang, W.-K.; Liu, Z.-Q.; Wang, J.-H.; Wang, Z.-H.; Wang, H. Phenylethanoid glycosides from Callicarpa macrophylla Vahl. Phytochem. Lett. 2020, 38, 65–69. [Google Scholar] [CrossRef]
  167. Khitri, W.; Smati, D.; Mitaine-Offer, A.-C.; Paululat, T.; Lacaille-Dubois, M.-A. Chemical constituents from Phlomis bovei Noë and their chemotaxonomic significance. Biochem. Syst. Ecol. 2020, 91, 104054. [Google Scholar] [CrossRef]
  168. Saracoglu, I.; Harput, U.S.; Kojima, K.; Ogihara, Y. Iridoid and phenylpropanoid glycosides from Phlomis pungens var. pungens. Hacet. Univ. J. Fac. Pharm. 1997, 17, 63–72. [Google Scholar]
  169. Saracoglu, I.; Kojima, K.; Harput, U.S.; Ogihara, Y. Anew phenylethanoid glycoside from Phlomis pungens Willd. var. pungens. Chem. Pharm. Bull. 1998, 46, 726–727. [Google Scholar] [CrossRef] [Green Version]
  170. Saracoglu, I.; Suleimanov, T.; Shukurova, A.; Dogan, Z. Iridoids and phenylethanoid glycosides from Phlomis pungens of the flora of Azerbaijan. Chem. Nat. Compd. 2017, 53, 576–579. [Google Scholar] [CrossRef]
  171. Harput, U.S.; Saracoglu, I.; Çaliş, I.; Dönmez, A.A.; Nagatsu, A. Secondary Metabolites from Phlomis kotschyana. Turk. J. Chem. 2004, 28, 767–774. [Google Scholar]
  172. Bader, A.; Tuccinardi, T.; Granchi, C.; Martinelli, A.; Macchia, M.; Minutolo, F.; De Tommasi, N.; Braca, A. Phenylpropanoids and flavonoids from Phlomis kurdica as inhibitors of human lactate dehydrogenase. Phytochemistry 2015, 116, 262–268. [Google Scholar] [CrossRef] [Green Version]
  173. Saracoglu, I.; Harput, U.S.; Çaliş, I.; Ogihara, Y. Phenolic constituents from Phlomis lycia. Turk. J. Chem. 2002, 26, 133–142. [Google Scholar]
  174. Yue, H.-L.; Zhao, X.-H.; Mei, L.-J.; Shao, Y. Separation and purification of five phenylpropanoid glycosides from Lamiophlomis rotata (Benth.) Kudo by a macroporous resin column combined with high-speed counter-current chromatography. J. Sep. Sci. 2013, 36, 3123–3129. [Google Scholar] [CrossRef] [PubMed]
  175. Nguyen, D.H.; Le, D.D.; Zhao, B.T.; Ma, E.S.; Min, B.S.; Woo, M.H. Antioxidant compounds isolated from the roots of Phlomis umbrosa Turcz. Nat. Prod. Sci. 2018, 24, 119–124. [Google Scholar] [CrossRef] [Green Version]
  176. Dou, H.; Liao, X.; Peng, S.-L.; Pan, Y.-J.; Ding, L.S. Chemical constituents from the roots of Schnabelia tetradonta. Helv. Chim. Acta 2003, 86, 2797–2804. [Google Scholar] [CrossRef]
  177. Li, B.J.; Chen, C.-X.; Dou, H.; Li, R.; Ding, L.-S. Chemical constituents from the aerial parts of Schnabelia tetradonta. Nat. Prod. Res. Dev. 2006, 18, 61–64. [Google Scholar]
  178. Miyase, T.; Yamamoto, R.; Ueno, A. Phenylethanoid glycosides from Stachys officinalis. Phytochemistry 1996, 43, 475–479. [Google Scholar] [CrossRef] [PubMed]
  179. Georgiev, M.I.; Ali, K.; Alipieva, K.; Verpoorte, R.; Choi, Y.H. Metabolic differentiations and classification of Verbascum species by NMR-based metabolomics. Phytochemistry 2011, 72, 2045–2051. [Google Scholar] [CrossRef] [PubMed]
  180. Warashina, T.; Miyase, T.; Ueno, A. Phenylethanoid and lignan glycosides from Verbascum thapsus. Phytochemistry 1992, 31, 961–965. [Google Scholar] [CrossRef]
  181. Abou Gazar, H.; Bedir, E.; Khan, I.A.; Çaliş, I. Wiedemanniosides A-E: New phenylethanoid glycosides from the roots of Verbascum wiedemannianum. Planta Med. 2003, 69, 814–819. [Google Scholar]
  182. Georgiev, M.I.; Alipieva, K.; Orhna, I.; Abrashev, R.; Denev, P.; Angelova, M. Antioxidant and cholinesterase inhibitory activities of Verbascum xanthophoeniceum Griseb. and its phenylethanoid glycosides. Food Chem. 2011, 128, 100–105. [Google Scholar] [CrossRef]
  183. Dimitrova, P.; Kostadinova, E.; Milanova, V.; Alipieva, K.; Georgiev, M.I.; Ivanovska, N. Anti-inflammatory properties of extracts and compounds isolated from Verbascum xanthophoeniceum Griseb. Phytother. Res. 2012, 26, 1681–1687. [Google Scholar] [CrossRef] [PubMed]
  184. Abdel-Hady, H.; El-Sayed, M.M.; Abdel-Hady, A.A.; Hashash, M.M.; Abdel-Hady, A.M.; Aboushousha, T.; Abdel-Hameed, E.-S.S.; Abdel-Lateef, E.E.-S.; Morsi, E.A. Nephroprotective activity of methanolic extract of Lantana camara and squash (Cucurbita pepo) on cisplatin-induced nephrotoxicity in rats and identification of certain chemical constituents of Lantana camara by HPLC-ESI- MS. Pharmacogn. J. 2018, 10, 136–147. [Google Scholar] [CrossRef] [Green Version]
  185. Heilmann, J.; Çaliş, I.; Kirmizibekmez, H.; Schühly, W.; Harput, U.S.; Sticher, O. Radical scavenger activity of phenylethanoid glycosides in FMLP stimulated human polymorphonuclear leukocytes: Structure-activity relationships. Planta Med. 2000, 66, 746–748. [Google Scholar] [CrossRef] [PubMed]
  186. Saidi, I.; Nimbarte, V.D.; Schwalbe, H.; Waffo-Téguo, P.; Harrathe, A.H.; Mansoure, L.; Alwasele, S.; Jannet, H.B. Anti-tyrosinase, anti-cholinesterase and cytotoxic activities of extracts and phytochemicals from the Tunisian Citharexylum spinosum L.: Molecular docking and SAR analysis. Bioorg. Chem. 2020, 102, 104093. [Google Scholar] [CrossRef] [PubMed]
  187. Li, P.; Qi, M.; Hu, H.; Liu, Q.; Yang, Q.; Wang, D.; Guo, F.; Bligh, S.W.A.; Wang, Z.; Yang, L. Structure-inhibition relationship of phenylethanoid glycosides on angiotensin-converting enzyme using ultra-performance liquid chromatography-tandem quadrupole mass spectrometry. RSC Adv. 2015, 5, 51701–51707. [Google Scholar] [CrossRef]
  188. Karioti, A.; Protopappa, A.; Megoulas, N.; Skaltsa, H. Identification of tyrosinase inhibitors from Marrubium velutinum and Marrubium cylleneum. Bioorg. Med. Chem. 2007, 15, 2708–2714. [Google Scholar] [CrossRef]
  189. Li, Y.-Y.; Lu, J.-H.; Li, Q.; Zhao, Y.-Y.; Pu, X.-P. Pedicularioside A from Buddleia lindleyana inhibits cell death induced by 1-methyl-4-phenylpyridinium ions (MPP+) in primary cultures of rat mesencephalic neurons. Eur. J. Pharmacol. 2008, 579, 134–140. [Google Scholar] [CrossRef]
  190. Li, W.; Zheng, R.; Jia, Z.; Zou, Z.; Lin, N. Repair effect of phenylpropanoid glycosides on thymine radical anion induced by pulse radiolysis. Biophys. Chem. 1997, 67, 281–286. [Google Scholar] [CrossRef]
  191. Cespedes, C.L.; Muñoz, E.; Salazar, J.R.; Yamaguchi, L.; Werner, E.; Alarcon, J.; Kubo, I. Inhibition of cholinesterase activity by extracts, fractions and compounds from Calceolaria talcana and C. integrifolia (Calceolariaceae: Scrophulariaceae). Food Chem. Toxicol. 2013, 62, 919–926. [Google Scholar] [CrossRef]
Biomolecules 12 01807 g001 550
Figure 1. Structures of leucosceptoside A and leucosceptoside B.
Figure 1. Structures of leucosceptoside A and leucosceptoside B.
Biomolecules 12 01807 g001
Table
Table 1. Occurrence of leucosceptoside A in the plant kingdom.
Table 1. Occurrence of leucosceptoside A in the plant kingdom.
Leucosceptoside A
FamilyPlant SpeciesCollection AreaOrgansMethodology of Isolation and IdentificationReference
Acanthaceae
Juss.		Acanthus ebracteatus VahlThailandAerial partsSE, DP, CC, p-HPLC-UV, NMR [5]
Thailand (obtained from a botanical garden)LeavesSE, UHPLC-MS[6]
Acanthus hirsutus Boiss.Turkey (obtained from a botanical garden)Aerial partsSE, PP, CC, UV, IR, NMR, MS[7]
Acanthus montanus (Nees) T. Anderson Thailand (obtained from a botanical garden)Aerial partsSE, PP, CC, p-HPLC-RID, NMR[8]
Blepharis edulis (Forssk.) Pers.EgyptAerial partsSE, VLC, CC, TLC, HPLC-UV, NMR, MS[9]
Pseuderanthemum carruthersii (Seem.) Guillauminn.a.n.a.n.a.[10]
Asteraceae
Giseke		Balbisia calycina Hunz. and Ariza Esp.Paraguay (purchased from a company)LeavesSE, DP, CC, TLC, HPLC-UV, NMR, MS [11]
Bignoniaceae
Juss. 		Fernandoa adenophylla (Wall. ex G.Don) SteenisThailand (obtained from a botanical garden)Leaves and branchesSE, DP, CC, TLC, p-HPLC-UV, NMR[12]
Incarvillea compacta Maxim.ChinaRootsSE, PP, CC, rp-CC, sp-LC-UV, NMR, MS[13]
Incarvillea emodi (Royle ex Lindl.) ChatterjeePakistan (several populations)Whole plantSE, CC, HPLC-DAD[14]
Martinella obovata (Kunth) Bureau and K.Schum.HondurasLeavesSE, CC, TLC, HPLC-RID, NMR, MS[15]
Oroxylum indicum (L.) KurzVietnamStem barkUSE, PP, CC, rp-MPLC, NMR [16]
Santisukia kerrii (Barnett and Sandwith) BrummittThailand (obtained from a botanical garden)Leaves and branchesSE, DP, CC, TLC, p-HPLC-UV, NMR[17]
Tynanthus panurensis (Bureau ex Baill.) SandwithPeruBarkSE, CC, HPLC-DAD, NMR, MS[18]
Lamiaceae
Martinov		Betonica macrantha C. Koch.TurkeyAerial partsSE, DP, PP, CC, IR, IV, NMR[19]
Callicarpa longissima (Hemsl.) Merr.ChinaLeaves and stemsSER, CC, TLC, p-HPLC-UV, NMR[20]
Callicarpa nudiflora Hook. and Arn.n.a.n.a.n.a.[21]
Caryopteris incana (Thunb. ex Houtt.) Miq.JapanAerial partsSE, PP, CC, DCCC, NMR[22]
South Korea (obtained from a botanical garden)Aerial partsSE, PP, CC, TLC, NMR[23]
Japan (cultivated)Whole plantSE, PP, CC, p-HPLC-UV, TLC, NMR [24]
South KoreaLeavesSER, PP, CC, TLC, UV, IR, HPLC-UV, NMR [25]
Clerodendrum bungei Steud.n.a.n.a.n.a.[26]
ChinaRootsSER, PP, CC, sp-HPLC-UV, NMR[27]
Clerodendrum chinense (Osbeck) Mabb.n.a.n.a.n.a.[28]
Clerodendrum infortunatum L.BangladeshLeavesSE, PP, CC, TLC, sp-HPLC-UV, NMR[29]
Clerodendrum phlomidis L. f.India (obtained from a botanical garden)RootsSPE, PP, CC, HPTLC, NMR, MS[30]
India (obtained from a botanical garden)RootsSPE, PP, TLC, CC, p-TLC, NMR[31]
Clerodendrum trichotomum Thunb.South KoreaStemsSE, PP, CC, [α]D, UV, NMR, MS [32]
South KoreaStemsSE, PP, CC, NMR[33]
n.a.n.a.n.a.[34]
Comanthosphace japonica (Miq.) S.Moore JapanRootsHSE, PP, CC, [α]D, IR, UV, NMR [35]
JapanWhole plantHSE, PP, CC, rp-CC, p-LPLC-UV, p-HPLC-UV, NMR[36]
Galeopsis bifida Boenn.Siberia (several populations)LeavesUSE, SPE, HPLC-DAD-MS[37]
Siberia (several populations)FlowersUSE, SPE, HPLC-DAD-MS[37]
Siberia (several populations)StemsUSE, SPE, HPLC-DAD-MS[37]
Siberia (several populations)RootsUSE, SPE, HPLC-DAD-MS[37]
Lagopsis supina (Steph. ex Willd.) Ikonn.-Gal.ChinaWhole plantSE, PP, CC, LC-UV, rp-HPLC-UV, NMR [38]
Mongolia (obtained from a botanical garden)Whole plantSE, HPLC-DAD, UHPLC-MSn[39]
MongoliaWhole plantSE, PP, FP, TLC, UHPLC-MS[40]
Leonurus cardiaca L.SiberiaAerial partsHSE, PP, HPLC-UV[41]
Leonurus deminutus V.I.Krecz.SiberiaAerial partsHSE, PP, CC, HPLC-UV, NMR, MS[41]
Leonurus glaucescens BungeSiberiaAerial partsHSE, PP, HPLC-UV[41]
Leonurus mongolicus V.I.Krecz. and Kuprian.SiberiaAerial partsHSE, PP, HPLC-UV[41]
Leonurus persicus Boiss.TurkeyAerial partsSE, PP, VLC, TLC, NMR, MS[42]
Leonurus quinquelobatus Gilib.SiberiaAerial partsHSE, PP, HPLC-UV[41]
Leonurus sibiricus L.SiberiaAerial partsHSE, PP, HPLC-UV[41]
MongoliaAerial parts ASE, DP, PP, HPLC-MS[43]
Mongolia (several populations)Aerial partsASE, PP, CC, sp-HPLC-UV, HPLC-DAD-MS [44]
Leonurus tataricus L.SiberiaAerial partsHSE, PP, HPLC-UV[41]
Marrubium alysson L.EgyptAerial partsHSE, DP, CC, MPLC, NMR[45]
Marrubium thessalum Boiss. and Heldr.GreeceAerial partsSE, VLC, CC, TLC, NMR[46]
Marrubium velutinum SmGreeceAerial partsSE, VLC, CC, rp-HPLC-UV [47]
Marrubium vulgare L.IndiaWhole plantSE, PP, CC, TLC, p-TLC, NMR[48]
Phlomis armeniaca Willd.TurkeyAerial partsSE, PP, CC, TLC, NMR, MS [49]
Phlomis bruguieri Desf.TurkeyAerial partsHSE, PP, CC, HPLC-PAD, HPLC-PAD-MS [50]
Phlomis chimerae Boissieun.a.n.a.n.a.[51]
Phlomis fruticosa L.MontenegroAerial partsSE, UHPLC-MS[52]
Phlomis integrifolia Hub.-Mor.TurkeyAerial partsHSE, PP, CC, MPLC, TLC, IR, UV, NMR [53]
n.a.n.a.n.a.[54]
Phlomis kurdica Rech.f.TurkeyAerial partsHSE, PP, CC, HPLC-PAD, HPLC-PAD-MS [50]
Phlomis leucophracta P.H.Davis and Hub.-Mor.TurkeyAerial partsHSE, PP, CC, HPLC-PAD, HPLC-PAD-MS [50]
Phlomis longifolia Boiss. and BlancheTurkeyAerial partsSE, PP, VLC, MPLC, CC, TLC, rp-MPLC, NMR[55]
Phlomis nissolii L.TurkeyAerial partsSE, PP, CC, MPLC, HPLC, TLC, NMR, MS[56]
TurkeyAerial partsHSE, PP, CC, HPLC-PAD, HPLC-PAD-MS [50]
Phlomis oppositiflora Boiss. and Hausskn.TurkeyWhole plantSE, PP, CC, MPLC, TLC, NMR[57]
Phlomis physocalyx Hub.-Mor.TurkeyAerial partsSE, CC, LPLC-UV, NMR[58]
Phlomis russeliana (Sims) Lag. ex Benth.TurkeyAerial partsHSE, PP, CC, HPLC-PAD, HPLC-PAD-MS [50]
Phlomis sieheana Rech. F.TurkeyAerial partsHSE, PP, CC, MPLC, TLC, NMR [59]
Phlomis syriaca Boiss.TurkeyAerial partsHSE, PP, CC, MPLC, TLC, IR, UV, NMR, MS[54]
Phlomis viscosa Poir.TurkeyWhole plantSE, PP, CC, TLC, NMR, MS[60]
Phlomoides glabra (Boiss. ex Benth.) Kamelin and Makhm.IranRhizomesSXE, VLC, p-TLC, p-rp-HPLC-UV, NMR, UV, MS[61]
Phlomoides laciniata (L.) Kamelin and Makhm.TurkeyAerial partsHSE, DP, PP, rp-VLC, TLC, NMR[62]
Phlomoides rotata (Benth. ex Hook.f.) MathiesenChina (several populations)StemsUSE, UPLC-MS[63]
Tibet (several collections)Aerial partsUSE, UPLC-MS[64]
Tibet (several collections)RootsUSE, UPLC-MS[64]
Phlomoides tuberosa (L.) MoenchTurkeyAerial partsHSE, PP, CC, TLC, NMR, MS[65]
Salvia digitaloides DielsChinaRootsSE, PP, CC, TLC, NMR[66]
Salvia viridis L.England (cultivated)Aerial partsSE, PP, CC, TLC, HPLC-UV[67]
Poland (obtained from a botanical garden)Aerial partsHSE, UPLC-DAD, UPLC-DAD-MS [68]
TurkeyRootsSXE, UHPLC-MSn[69]
TurkeyRootsUSE, UHPLC-MSn[69]
TurkeyRootsMAE, UHPLC-MSn[69]
TurkeyRootsSE, UHPLC-MSn[69]
Schnabelia nepetifolia (Benth.) P.D.CantinoChinaWhole plantSE, PP, CC, MPLC, p-HPLC-UV, NMR[70]
Scutellaria albida subsp. velenovskyi (Rech.f.) Greuter and BurdetTurkeyWhole plantSE, MPLC, rp-HPLC-UV, NMR[71]
Scutellaria baicalensis Georgin.r.n.r.n.r.[72]
China (purchased from a company)RootsUSE, UHPLC-UV-MS[73]
China
(several commercial samples)		RootsUSE, UPLC-MS[74]
China (purchased from a company)RootsSER, UPLC-MS[75]
Scutellaria edelbergii Rech.f.PakistanWhole plantSE, PP, LC-MS[76]
Scutellaria lateriflora L.Japan (purchased from a company)Aerial partsSE, DP, PP, CC, TLC, NMR[77]
Scutellaria pinnatifida A.Ham.TurkeyAerial partsSE, PP, CC, TLC, IR, UV, NMR[78]
Scutellaria prostrata Jacquem. ex Benth.NepalRootsSE, TLC, GLC, NMR [79]
Scutellaria salviifolia Benth.TurkeyAerial partsSE, PP, CC, TLC, NMR, MS [49]
Sideritis cypria PostCyprus (cultivated)FlowersSE, CC, TLC, p-TLC, NMR[80]
Cyprus (cultivated)LeavesSE, CC, TLC, p-TLC, NMR[80]
Cyprus (cultivated)Aerial partsSE, CC, TLC, p-TLC, NMR[81]
Sideritis euboea Heldr.Greece (cultivated)Aerial partsSE, PP, VLC, CC, TLC, NMR[82]
Greece (cultivated)Aerial partsSE, CC, p-TLC, NMR [83]
Sideritis lycia Boiss. and Heldr.TurkeyAerial partsSE, PP, CC, MPLC, TLC, UV, IR, NMR[84]
Sideritis ozturkii Aytaç and AksoyTurkeyAerial partsSE, CC, VLC, MPLC, TLC, NMR[85]
Sideritis perfoliata L.GreeceAerial partsSXE, PP, VLC, CC, TLC, UV, NMR[86]
TurkeyAerial partsHP, SE, HPLC-DAD-MSn[87]
Sideritis raeseri Boiss. and Heldr.Albania (several populations)Aerial partsHP, SE, HPLC-DAD-MSn[87]
Macedonia (several populations)Aerial partsHP, SE, HPLC-DAD-MSn[87]
Serbia (cultivated)Aerial partsSXE, HPLC-DAD, HPLC-MS[88]
Serbia (several populations)Aerial partsSXE, DP, CC, HPLC-DAD-MS [89]
Sideritis scardica Griseb.Macedonia (several populations)Aerial partsHP, SE, HPLC-DAD-MSn[87]
BulgariaAerial partsHP, SE, HPLC-DAD-MSn[87]
Serbia (several populations)Aerial partsSXE, DP, CC, HPLC-MS[89]
Greece (purchased from a company)Aerial partsUSE, UPLC-MS, HPLC-DAD[90]
Sideritis sipylea Boiss.GreeceAerial partsHSE, CC, p-TLC, NMR[91]
Sideritis syriaca L.BulgariaAerial partsHP, SE, HPLC-DAD-MSn[87]
GreeceAerial partsHP, SE, HPLC-DAD-MSn[87]
Stachys affinis Bungen.a.n.a.n.a.[92]
Japan (cultivated)LeavesSE, CC, NMR[93]
Italy (cultivated)TubersSE, CC, NMR, MS[94]
Stachys iva Griseb.Greece (cultivated)Aerial partsHSE, CC, p-TLC, NMR[95]
Stachys lavandulifolia VahlAzerbaijanAerial partsSXE, SPE, p-rp-HPLC-UV, NMR, MS[96]
Stachys rupestris Montbret and Aucher ex Benth.Turkeyn.r.SE, HPLC-MS[97]
Stachys tetragona Boiss. and Heldr.GreeceAerial partsSE, VLC, CC, rp-HPLC, NMR [98]
Volkameria inermis L.Thailand (obtained from a botanical garden)Aerial partsSE, DP, CC, TLC, p-HPLC-UV, NMR[99]
Linderniaceae Borsch, Kai Müll. & Eb.Fisch.Craterostigma plantagineum Hochst.Rwanda (cultivated)LeavesUSE, HPLC-DAD-MS[100]
Lindernia brevidens SkanKenya (cultivated)LeavesUSE, HPLC-DAD-MS[100]
Lindernia subracemosa De Wild.Rwanda (cultivated)LeavesUSE, HPLC-DAD-MS[100]
Malvaceae
Juss.		Firmiana simplex (L.) W.WightChinaRootsSE, PP, CC, TLC, NMR[101]
Oleaceae
Hoffmanns. & Link		Osmanthus fragrans Lour.ChinaLeavesn.r.[102]
Orobanchaceae
Vent.		Orobanche aegyptiaca Pers.n.r.n.r.n.r.[103]
Orobanche arenaria Borkh.Poland Whole plantASE, SPE, rp-HPLC-UV, UHPLC-PDA-MS, sp-HPLC-PDA[104]
Orobanche artemisiae-campestris subsp. picridis (F. Schulz) O. Bolòs, Vigo, Masalles and NinotPoland Whole plantASE, SPE, rp-HPLC-UV, UHPLC-PDA-MS, sp-HPLC-PDA[104]
Orobanche caryophyllacea Sm.Poland Whole plantASE, SPE, rp-HPLC-UV, UHPLC-PDA-MS, sp-HPLC-PDA[104]
Orobanche caerulescens K.KochPoland Whole plantASE, SPE, rp-HPLC-UV, UHPLC-PDA-MS, sp-HPLC-PDA[104]
Orobanche cernua Loefl. ChinaWhole plantSER, HPLC-MS, NMR[105]
ChinaWhole plantSE, PP, CC, sp-HPLC-UV, NMR, MS [106]
Orobanche pycnostachya Hancen.r.n.r.n.r. [103]
ChinaWhole plantSE, PP, CC, TLC, UV, NMR, MS[107]
Euphrasia pectinata Ten.TurkeyAerial partsHSE, PP, VLC, CC, TLC, MPLC, NMR[108]
TurkeyAerial partsHSE, VLC, MPLC, IR, UV, NMR[109]
Pedicularis acmodonta Boiss.n.a.n.a.n.a.[110]
Pedicularis alaschanica Maxim.n.a.n.a.n.a.[111]
n.a.n.a.n.a.[112]
Pedicularis albiflora PrainChinaWhole plantSE, PP, CC, TLC, NMR, MS[113]
Pedicularis dolichocymba Hand.-Mazz.n.a.n.a.n.a.[114]
Pedicularis kansuensis Maxim.TibetWhole plantSER, PP, CC, TLC, ESP, NMR, MS[115]
Pedicularis kerneri Dalla TorreItalyAerial partsSE, CC, NMR, MS[116]
Pedicularis longiflora var. tubiformis (Klotzsch) TsoongChinaWhole plantSE, PP, CC, HSCCC, rp-HPLC-UV, NMR[117]
Pedicularis nordmanniana BungeTurkeyAerial partsSE, DP, CC, NMR[118]
Pedicularis verticillata L.ChinaWhole plantSE, PP, CC, TLC, NMR [119]
Phtheirospermum japonicum (Thunb.) KanitzJapanAerial partsSE, PP, CC, TLC, p-HPLC-UV, [α]D, NMR[120]
Plantaginaceae
Juss.		Globularia alypum L.CroatiaAerial partsHP, SER, HPLC-PDA-MS[121]
CroatiaAerial partsUSE, PP, HPLC-PDA-MS[122]
CroatiaAerial partsSXE, PP, HPLC-PDA-MS[122]
Globularia cordifolia L.TurkeyUnderground partsHSE, PP, VLC, MPLC, CC, NMR, MS[123]
CroatiaAerial partsHP, SER, HPLC-PDA-MS[121]
CroatiaAerial partsUSE, PP, HPLC-PDA-MS[122]
CroatiaAerial partsSXE, PP, HPLC-PDA-MS[122]
Globularia davisiana O.Schwarz TurkeyAerial partsHSE, PP, VLC, CC, TLC, rp-MPLC, NMR[124]
Globularia meridionalis (Podp.) O.SchwarzCroatiaAerial partsHP, SER, HPLC-PDA-MS[121]
CroatiaAerial partsUSE, PP, HPLC-PDA-MS[122]
CroatiaAerial partsSXE, PP, HPLC-PDA-MS[122]
Globularia orientalis L.
TurkeyAerial partsHSE, PP, VLC, MPLC, NMR[125]
Globularia punctata Lapeyr.CroatiaAerial partsHP, SER, HPLC-PDA-MS[121]
CroatiaAerial partsUSE, PP, HPLC-PDA-MS[122]
CroatiaAerial partsSXE, PP, HPLC-PDA-MS[122]
Globularia sintenisii Hausskn. and Wettst.TurkeyUnderground partsSE, CC, MPLC, TLC, NMR[126]
Lagotis brevituba Maxim.China (purchased from a company)Whole plantSE, PP, HPLC-UV-MS[127]
Lagotis ramalana Batalinn.a.n.a.n.a.[128]
Penstemon centranthifolius (Benth.) Benth.CaliforniaAerial partsSE, FCC, CC, TLC, NMR, MS[129]
Penstemon crandallii A. NelsonColoradoLeavesSE, PP, VLC, NMR[130]
Penstemon linarioides A. GrayNew MexicoWhole plantSE, PP, CC, TLC, [α]D, UV, NMR, MS[131]
Plantago asiatica L.JapanWhole plantHSE, CC, NMR[132]
China (several populations)SeedsHSE, UPLC-MSn[133]
China SeedsUSE, UHPLC-MS[134]
Plantago depressa Willd.China (several populations)SeedsHSE, UPLC-MSn[133]
ChinaSeeds USE, UHPLC-MS[134]
Plantago lanceolata L.Brazil (purchased from a company)Aerial partsSWE, HPLC-DAD-MS[135]
Plantago major L. ChinaSeedsUSE, UHPLC-MS[134]
Brazil (purchased from a company)Aerial partsSWE, HPLC-DAD-MS[135]
Plantago squarrosa MurrayEgyptWhole plantPE, PP, TLC, CC, UV, IR, NMR, MS[136]
Plantago subulata L.n.r.Aerial partsHSE, PP, CC, MPLC, UV, IR, NMR, MS[137]
TurkeyAerial partsHSE, PP, CC, MPLC, TLC, NMR [138]
TurkeyRootsHSE, PP, CC, MPLC, TLC, NMR [138]
Rehmannia glutinosa (Gaertn.) DC.Japan (purchased from a company)RootsSE, CC, HPLC-UV, TLC, NMR[139]
n.a.n.a.n.a.[140]
China (purchased from a local market)RhizomesSE, PP, CC, TLC, NMR[141]
n.a.n.a.n.a.[142]
ChinaRootsSER, UHPLC-MS [143]
ChinaTuber rootSE, HPLC-UV, UHPLC-MS[144]
China (cultivated)LeavesSE, UHPLC-MS[145]
China (cultivated)TubersSE, UHPLC-MS[145]
VietnamRootsHSE, PP, DP, CC, TLC, NMR[146]
Russelia equisetiformis Schltdl. and Cham.JapanAerial partsSE, PP, CC, TLC, DCCC, HPLC-UV, NMR[147]
Scrophulariaceae
Juss.		Buddleja davidii Franch.ChinaRootsSER, PP, CC, TLC, p-HPLC-UV, NMR [148]
Buddleja lindleyana FortuneChinaPowderSE, PP, CC, rp-CC, NMR[149]
Buddleja officinalis Maxim.ChinaFlower budsSE, PP, CC, TLC, NMR[150]
Scrophularia umbrosa L.ChinaWhole plantSER, PP, CC, sp-rp-HPLC-UV, NMR[151]
Verbascum thapsus L.Italy (cultivated)LeavesSE, HPLC-DAD-MS, NMR[152]
Verbenaceae
J.St.-Hil.		Aloysia citriodora PalauSpainCommercial extractHPLC-UV, HPLC-MS[153]
Peru (purchased from a company)Aerial partsSER, PP, CC, HPLC-UV, NMR[154]
Spain (commercial extract)Leaves SE, sp-HPLC-UV, rp-HPLC-DAD- MS[155]
Spain (commercial extract)Leaves SE, HPLC-UV, HPLC-MS, sp-HPLC-UV[156]
Citharexylum flexuosum (Ruiz and Pav.) D.DonTunisia (obtained from a botanical garden)Trunk barkSE, CC, p-HPLC-UV, NMR[157]
Lippia alba (Mill.) N.E.Br. ex Britton and P.WilsonBrazil (different chemotypes)LeavesHSE, HPLC-DAD-MS[158]
Phyla canescens (Kunth) GreeneJapan (obtained from a botanical garden)Aerial partsSE, PP, CC, HPLC-UV, NMR, MS[159]
Stachytarpheta cayennensis (Rich.) VahlPanamaWhole plantSE, PP, CC, p-TLC, NMR, MS[160]
Stachytarpheta schottiana SchauerBrazil (obtained from a botanical garden)Aerial partsSE, DP, LC-MS [161]
Verbena brasiliensis Vell.JapanAerial partsSE, PP, CC, HPLC, NMR[162]
Verbena hastata L.Canada (purchased from a company)Whole plantSE, DP, CC, TLC, pHPLC, NMR[163]
[α]D: optical rotation; ASE = accelerated solvent extraction; CC: column chromatography; DCCC: droplet counter current chromatograph; DP: defatting procedure; ESP: procedure to eliminate sugars; FCC: flash column chromatography; FP = fraction purification; GLC: gas liquid chromatography; HP = homogenization procedure; HPLC-DAD: high pressure liquid chromatography coupled to diode array detector; HPLC-DAD-MS: high pressure liquid chromatography coupled to diode array detector and mass spectrometry; HPLC-DAD-MSn: high pressure liquid chromatography coupled to tandem mass spectrometry; HPLC-MS: high pressure liquid chromatography coupled to mass spectrometry; HPLC-PAD: high pressure liquid chromatography coupled to pulsed amperometry detector; HPLC-PAD-MS: high pressure liquid chromatography coupled to pulsed amperometry detector and mass spectrometry; HPLC-UV: high pressure liquid chromatography coupled to ultraviolet detector; HPLC-UV-MS: high pressure liquid chromatography coupled to ultraviolet detector and mass spectrometry; HPTLC: high performance thin layer chromatography; HSE: hot solvent extraction; HSCCC = high-performance countercurrent chromatography; IR: infrared spectroscopy; LC-MS: liquid chromatography coupled to mass spectrometry; LC-UV: liquid chromatography coupled to ultraviolet detector; LPLC-UV: preparative low pressure liquid chromatography coupled to ultraviolet detector; MAE = microwave-assisted extraction; MPLC: medium pressure liquid chromatography; MS: mass spectrometry; NMR: nuclear magnetic resonance spectroscopy; n.a. = not accessible; n.r. = not reported; PE = percolation procedure; p-HPLC: preparative high pressure liquid chromatography; p-HPLC-RID: preparative high pressure liquid chromatography coupled to a refractive index detector; p-HPLC-UV: preparative high pressure liquid chromatography coupled to ultraviolet detector; p-LPLC-UV: preparative low pressure liquid chromatography coupled to ultraviolet detector; p-rp-HPLC-UV: preparative reversed-phase high pressure liquid chromatography coupled to ultraviolet detector; PP: partition procedure; p-TLC: preparative thin-layer chromatography; rp-CC: reversed-phase column chromatography; rp-HPLC-DAD-MS: reversed-phase high pressure liquid chromatography coupled to diode array detector and mass spectrometry; rp-HPLC-UV: reversed-phase high pressure liquid chromatography coupled to ultraviolet detector; rp-MPLC: reversed-phase medium pressure liquid chromatography; rp-VLC: reversed-phase vacuum liquid chromatography; SE: solvent extraction; SER: solvent extraction under reflux; SPE = solvent extraction via percolation; sp-HPLC-PDA: semipreparative high pressure liquid chromatography coupled to photodiode array detector; sp-HPLC-UV: semipreparative high pressure liquid chromatography coupled to ultraviolet detector; sp-LC-UV: semipreparative liquid chromatography coupled to ultraviolet detector; sp-rp-HPLC-UV: semipreparative reversed-phase high pressure liquid chromatography coupled to ultraviolet detector; SWE: subcritical water extraction; SXE: Soxhlet extraction; TLC: thin-layer chromatography; UHPLC-PDA-MS: ultra-high pressure liquid chromatography coupled to photodiode array detector and mass spectrometry; UHPLC-UV-MS: ultra-high pressure liquid chromatography coupled to ultraviolet detector and mass spectrometry; UHPLC-MS: ultra-high pressure liquid chromatography coupled to mass spectrometry; UHPLC-MSn: ultra-high pressure liquid chromatography coupled to tandem mass spectrometry; UPLC-DAD: ultra-pressure liquid chromatography coupled to diode array detector; UPLC-DAD-MS: ultra-pressure liquid chromatography coupled to diode array detector and mass spectrometry; UPLC-MS: ultra-pressure liquid chromatography coupled to mass spectrometry; UPLC-MSn: ultra-pressure liquid chromatography coupled to tandem mass spectrometry; USE = solvent extraction under ultrasonic action; UV: ultraviolet spectroscopy; VLC: vacuum liquid chromatography.
Table
Table 2. Occurrence of leucosceptoside B in the plant kingdom.
Table 2. Occurrence of leucosceptoside B in the plant kingdom.
Leucosceptoside B
FamilyPlant SpeciesCollection AreaOrgansMethodology of Isolation and IdentificationReference
Bignoniaceae
Juss.		Amphilophium crucigerum (L.) L.G.LohmannPanama StemsSE, PP, MPLC, LPLC-UV, NMR[164]
Lamiaceae
Martinov		Callicarpa kwangtungensis Chunn.a.n.a.n.a.[165]
Callicarpa macrophylla VahlChinaWhole plantSE, PP, CC, sp-rp-HPLC-UV, NMR [166]
Comanthosphace japonica (Miq.) S.Moore JapanRootsHSE, PP, CC, [α]D, IR, UV, NMR [35]
Marrubium alysson L.EgyptAerial partsHSE, DP, CC, MPLC, NMR, MS[45]
Phlomis bovei NoëAlgeriaRootsVLC, CC, MPLC, rp-MPLC, NMR, MS[167]
Phlomis herba-venti subsp. pungens (Willd.) Maire ex DeFilippsn.a.n.a.n.a.[168]
TurkeyAerial partsHSE, PP, CC, rp-MPLC, NMR[169]
AzerbaijanAerial partsSE, PP, CC, UV, IR, NMR, MS[170]
Phlomis kotschyana Hub.-Mor.TurkeyAerial partsHSE, PP, CC, rp-MPLC, UV, IR, NMR[171]
Phlomis kurdica Rech.f.JordanAerial partsSE, CC, rp-HPLC-UV, NMR[172]
TurkeyAerial partsHSE, PP, CC, HPLC-PAD, HPLC-PAD-MS [50]
Phlomis lycia D.Don TurkeyAerial partsHSE, PP, CC, MPLC, TLC, IR, UV, NMR, MS[173]
Phlomis nissolii L.TurkeyAerial partsSE, PP, CC, MPLC, HPLC-UV, TLC, NMR, MS[56]
TurkeyAerial partsHSE, PP, CC, HPLC-PAD, HPLC-PAD-MS [50]
Phlomis russeliana (Sims) Lag. ex Benth.TurkeyAerial partsHSE, PP, CC, HPLC-PAD, HPLC-PAD-MS [50]
Phlomis viscosa Poir.TurkeyWhole plantSE, PP, CC, MPLC, TLC, NMR, MS[60]
Phlomoides rotata (Benth. ex Hook.f.)ChinaWhole plantSER, PP, CC, HSCCC, HPLC-UV[174]
Phlomoides umbrosa (Turcz.) Kamelin and Makhm.South KoreaRootsSE, PP, CC, TLC, rp-HPLC-UV, sp-HPLC-UV, NMR[175]
Schnabelia nepetifolia (Benth.) P.D.CantinoChinaWhole plantSE, PP, CC, MPLC, HPLC-UV, LC-UV, NMR[70]
Schnabelia tetradonta (Y.Z.Sun) C.Y.Wu and C.ChenChinaRootsSE, PP, CC, NMR[176]
n.a.n.a.n.a.[177]
Stachys officinalis (L.) Trevis. Japan (cultivated)Aerial partsSE, CC, p-HPLC-UV, NMR[178]
Orobanchaceae
Vent.		Pedicularis longiflora var. tubiformis (Klotzsch) TsoongChinaWhole plantSE, PP, CC, HSCCC, rp-HPLC-UV, NMR[117]
Plantaginaceae
Juss.		Lagotis brevituba Maxim.China (purchased from a company)Whole plantSE, PP, HPLC-UV-MS[127]
Scrophulariaceae
Juss.		Buddleja davidii Franch.ChinaRootsSER, PP, CC, p-HPLC-UV, [148]
Buddleja lindleyana FortuneChinaPowderSE, PP, CC, rp-CC, NMR[149]
Verbascum densiflorum Bertol.Bulgaria (cultivated)Leaves SE, HPLC-DAD, NMR[179]
Verbascum nigrum L.Bulgaria (cultivated)Leaves SE, HPLC-DAD, NMR[179]
Verbascum phlomoides L.Bulgaria (cultivated)Leaves SE, HPLC-DAD, NMR[179]
Verbascum phoeniceum L.Bulgaria (cultivated)Leaves SE, HPLC-DAD, NMR[179]
Verbascum thapsus L.Japan (obtained from a botanical garden)Whole plantSE, CC, NMR[180]
Italy (cultivated)LeavesSE, HPLC-DAD-MS, NMR[152]
Verbascum wiedemannianum Fisch. and C.A.Mey.TurkeyRootsSER, VLC, MPLC, CC, TLC, [α]D, NMR, MS [181]
Verbascum xanthophoeniceum Griseb.Bulgaria (several populations) Aerial parts SE, PP, CC, rp-HPLC-UV, NMR[182]
Bulgaria (cultivated)Leaves SE, HPLC-DAD, NMR[179]
Bulgaria (several populations)Whole plantSE, PP, CC, LC-MS, NMR[183]
Verbenaceae
J.St.-Hil.		Lantana camara L.Egypt (obtained from a botanical garden)LeavesSE, DP, PP, HPLC-MS[184]
[α]D: optical rotation; CC: column chromatography; DP: defatting procedure; HPLC-DAD: high pressure liquid chromatography coupled to diode array detector; HPLC-DAD-MS: high pressure liquid chromatography coupled to diode array detector and mass spectrometry; HPLC-MS: high pressure liquid chromatography coupled to mass spectrometry; HPLC-PAD: high pressure liquid chromatography coupled to pulsed amperometry detector; HPLC-PAD-MS: high pressure liquid chromatography coupled to pulsed amperometry detector and mass spectrometry; HPLC-UV: high pressure liquid chromatography coupled to ultraviolet detector; HPLC-UV-MS: high pressure liquid chromatography coupled to ultraviolet detector and mass spectrometry; HSE: hot solvent extraction; HSCCC = high-performance countercurrent chromatography; IR: infrared spectroscopy; LC-MS: liquid chromatography coupled to mass spectrometry; LC-UV: liquid chromatography coupled to ultraviolet detector; LPLC-UV: preparative low pressure liquid chromatography coupled to ultraviolet detector; MPLC: medium pressure liquid chromatography; NMR: nuclear magnetic resonance spectroscopy; MS: mass spectrometry; p-HPLC-UV: preparative high pressure liquid chromatography coupled to ultraviolet detector; PP: partition procedure; rp-CC: reversed-phase column chromatography; rp-HPLC-UV: reversed-phase high pressure liquid chromatography coupled to ultraviolet detector; rp-MPLC: reversed-phase medium pressure liquid chromatography; SE: solvent extraction; SER: solvent extraction under reflux; sp-HPLC-UV: semipreparative high pressure liquid chromatography coupled to ultraviolet detector; sp-rp-HPLC-UV: semipreparative reversed-phase high pressure liquid chromatography coupled to ultraviolet detector; TLC: thin-layer chromatography; UV: ultraviolet spectroscopy; VLC: vacuum liquid chromatography.
Table
Table 3. Summary of the biological activities and efficacy values of leucosceptoside A.
Table 3. Summary of the biological activities and efficacy values of leucosceptoside A.
Leucosceptoside A
Biological ActivityStudied ElementSpecific Methodology and/or Studied Cells Efficacy ValueReference
Antioxidant DPPH.+ IC50 = 18.43 µg/mL[7]
IC50 = 53.32 µM[13]
IC50 = 76.0 µM[58]
IC50 = 125.4 µM[60]
IC50 = 72.14 µM[150]
EC50 = 11.26 µM[117]
EC50 = 25.7 µM[154]
RC50 = 0.0148 µg/mL[61]
Inhibition % = 41.8%
(at the concentration of 200 µM)		[54]
- Inhibition % = 88.3%
(after 20 min at the concentration of 0.1 mM)
- Inhibition % = 89.0%
(after 60 min at the concentration of 0.1 mM)		[86]
Radical scavengingSuperoxide anionLuminol-enhanced chemiluminescence assay in stimulated human polymorphonuclear neutrophilsSC50 = 0.294 mM[112]
Hydroxyl radicalLuminol-enhanced chemiluminescence assay in stimulated human polymorphonuclear neutrophilsInhibition % = 27.8%
(at the concentration of 0.55 mM)		[112]
Iron reductorLuminol-enhanced chemiluminescence assay in stimulated human polymorphonuclear neutrophilsInhibition % = 17.86%
(at the concentration of 1.57 mM)		[112]
N-formyl-methionyl-leucyl-phenylalanineLuminol-enhanced chemiluminescence assay in stimulated human polymorphonuclear neutrophilsIC50 = 0.18 µM[185]
Anti-inflammatoryNO productionGriess assay in LPS-stimulated BV2 microglial cellsIC50 = 61.1 µM[14]
Cell culture supernatants of LPS-stimulated RAW264.7 macrophagesInhibition % = 40.0%
(at the concentration of 100 µM)		[147]
Raw 264.7 cellsIC50 = 9.0 µM[151]
Enzyme inhibitory A-glucosidase IC50 = 0.7 mM[27]
IC50 = 273.0 µM[146]
Acetylcholinesterase IC50 = 423.7 µg/mL[33]
IC50 = 72.85 µM[186]
Scheffe’s testIC50 = 3.86 mM[187]
Protein kinase C alpha IC50 = 19.0 µM[131]
Tyrosinase - Inhibition % = 39.5%
(at the concentration of 100 µM)		[186]
- Inhibition % = 21.65%
(at the concentration of 0.051 mM)		[188]
Hyaluronidase No activity[138]
HepatoprotectiveCCl4 intoxicationMTT assay and flow cytometry in HepG2 cells- Cell number % > 80%
- Cell viability % > 80%
- Inhibition % of CCl4-induced lipid peroxidation = 177.73%
- SOD decrease attenuation % = 76.58%		[13]
Neuroprotective1-methyl-4-phenylpyridinium ion (MPP+)-induced cell death MTT assay in mesencephalic neurons of rats- Cell death reduction % = 7%
(at the concentration of 4 µM)
- Cell growth increase % = 3.7%
(at the concentration of 16 µM)		[189]
Cytoprotectivet-BHP-induced toxicity HepG2 cellsIC50 = 21.1 µM[23]
Anticomplementary CH50 = 0.23 mM[119]
Anti-HIV IC50 = 29.4 µM[32]
CytotoxicA549 IC50 = 99.00 µM[186]
B16F10 GI50 = 28 µM[159]
dRLh-88 No activity[49]
Hela IC50 = 200 µg/mL[46]
IC50 = 80.87 µM[186]
GI50 = 42 µM[159]
No activity[49]
HC7-116 IC50 = 182.33 µg/mL [46]
MCF7 IC50 = 189.08 µg/mL[46]
MK-1 GI50 = 33 µM[159]
Melanoma No activity[46]
P-388-d1 No activity[49]
S-180 No activity[49]
InhibitoryADP + NADPH-induced lipid peroxidationRat liver microsomeIC50 = 1.69 µM[132]
Protonation of thymine radical anion induced by pulse radiolysis Reaction rate constant = 1.54 × 109 dm3 mol−1 s−1[190]
AntimicrobialStaphylococcus aureus ATCC29213 MIC = 1000 µg/mL[60]
Enterococcus faecalis ATCC29212 MIC = 1000 µg/mL[60]
Bacillus subtilis NBRC3134 No activity[24]
Escherichia coli ATCC25922 No activity[60]
Klebsiella pneumoniae NBRC3512 No activity[24]
Mycobacterium tuberculosis H37Rv No activity[30]
Pseudomonas aeruginosa ATCC27853 No activity[60]
AntifungalCandida albicans ATCC90028 No activity[60]
Candida krusei ATCC6258 No activity[60]
Candida parapsilosis ATCC22019 No activity[60]
Table
Table 4. Summary of the biological activities and efficacy values of leucosceptoside B.
Table 4. Summary of the biological activities and efficacy values of leucosceptoside B.
Leucosceptoside B
Biological ActivityStudied Element Specific Methodology and/or Studied Cells Efficacy ValueReference
Antioxidant DPPH.+ IC50 = 61.3 µM[166]
IC50 = 31.16 µM[166]
IC50 = 96 µM[182]
EC50 = 13.05 µM[117]
EC50 = 25.7 µM[154]
Radical scavengingFRAP Absorbance value = 0.602
(at 700 nm)		[183]
HORAC 3885.1 HORACFL/g[182]
ORAC 16264.7 ORACFL/g[182]
Superoxide anion IC50 = about 45 µg/mL[182]
N-formyl-methionyl-leucyl-phenylalanineLuminol-enhanced chemiluminescence assay in stimulated human polymorphonuclear neutrophilsIC50 = 0.17 µM[185]
Anti-inflammatoryCobra venom factor induced alternative pathway activationMouse seraInhibition % = 40%[183]
COX-2 productionInhibition % = about 30%[183]
IL-10 productionValue not reported[183]
NO productionValue not reported[183]
Enzyme inhibitory Acetylcholinesterase inhibition % = about 50%
(at the concentration of 100 µg/mL)		[182]
IC50 = 20.1 µg/mL[191]
Butyrylcholinesterase Inhibition % = a little above 10%
(at the concentration of 100 µg/mL)		[182]
No activity[191]
Neuroprotective1-methyl-4-phenylpyridinium ion (MPP+)-induced cell death MTT assay in mesencephalic neurons of ratsOptical density value = 1.06
(at the concentration of 40 µg/mL)		[149]
InhibitoryHuman lactate dehydrogenase No activity[172]
AntimicrobialStaphylococcus aureus ATCC29213 MIC = 1000 µg/mL[60]
Enterococcus faecalis ATCC29212 MIC = 1000 µg/mL[60]
Bacillus subtilis NBRC3134 No activity[24]
Escherichia coli ATCC25922 No activity[60]
Pseudomonas aeruginosa ATCC27853 No activity[60]
AntifungalCandida albicans ATCC90028 No activity[60]
Candida krusei ATCC6258 No activity[60]
Candida parapsilosis ATCC22019 No activity[60]
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Share and Cite

MDPI and ACS Style

Frezza, C.; De Vita, D.; Toniolo, C.; Sciubba, F.; Tomassini, L.; Venditti, A.; Bianco, A.; Serafini, M.; Foddai, S. Leucosceptosides A and B: Two Phenyl-Ethanoid Glycosides with Important Occurrence and Biological Activities. Biomolecules 2022, 12, 1807. https://doi.org/10.3390/biom12121807

AMA Style

Frezza C, De Vita D, Toniolo C, Sciubba F, Tomassini L, Venditti A, Bianco A, Serafini M, Foddai S. Leucosceptosides A and B: Two Phenyl-Ethanoid Glycosides with Important Occurrence and Biological Activities. Biomolecules. 2022; 12(12):1807. https://doi.org/10.3390/biom12121807

Chicago/Turabian Style

Frezza, Claudio, Daniela De Vita, Chiara Toniolo, Fabio Sciubba, Lamberto Tomassini, Alessandro Venditti, Armandodoriano Bianco, Mauro Serafini, and Sebastiano Foddai. 2022. "Leucosceptosides A and B: Two Phenyl-Ethanoid Glycosides with Important Occurrence and Biological Activities" Biomolecules 12, no. 12: 1807. https://doi.org/10.3390/biom12121807

APA Style

Frezza, C., De Vita, D., Toniolo, C., Sciubba, F., Tomassini, L., Venditti, A., Bianco, A., Serafini, M., & Foddai, S. (2022). Leucosceptosides A and B: Two Phenyl-Ethanoid Glycosides with Important Occurrence and Biological Activities. Biomolecules, 12(12), 1807. https://doi.org/10.3390/biom12121807

Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.

Article Metrics

Back to TopTop