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Article

Chemical Constituents and α-Glucosidase Inhibitory Activities of the Leaves of Embelia parviflora—In Vitro and In Silico Studies

by
Sy Danh Thuong
1,*,
Mai Thi Hoang Anh
1,
Nguyen Van Phuong
2,
Chu Hoang Mau
1,
Nguyen Huu Quan
1,
Nguyen Thanh Cong
3 and
Le Nguyen Thanh
4,*
1
Faculty of Biology, Thai Nguyen University of Education, Thai Nguyen University, Thai Nguyen 250000, Vietnam
2
Department of Pharmacognosy, Faculty of Pharmacognosy and Traditional Medicine, Hanoi University of Pharmacy, Hanoi 10000, Vietnam
3
Department of Pharmacy, Dai Nam University, Hanoi 10000, Vietnam
4
National Institute of Medicinal Materials, Ministry of Health, Hanoi 10000, Vietnam
*
Authors to whom correspondence should be addressed.
Life 2025, 15(5), 680; https://doi.org/10.3390/life15050680
Submission received: 18 March 2025 / Revised: 17 April 2025 / Accepted: 17 April 2025 / Published: 22 April 2025
(This article belongs to the Section Pharmaceutical Science)
Browse Figures
Versions Notes

Abstract

:
Phytochemical investigation of the methanol extract of Embelia parviflora Wall. Ex A. DC. leaves (Primulaceae family) led to the isolation of sixteen compounds including three sterols (1–3), one triterpene (4), four flavonoids (5–8), four megastigmanes (9–12), three phenolic compounds (13–15), and one furan derivative (16). Their chemical structures were determined based on ESI-MS and NMR spectral data. This is the first chemical study of E. parviflora. Compounds 3, 8–13, and 16 were found in the Embelia genus for the first time. Compounds 9–11, 13, and 16 represent the first isolation from the Primulaceae family. In the α-glucosidase activity assay, MeOH extract, compounds 4 and 5 strongly inhibited enzyme α-glucosidase activity. A molecular docking study revealed that compounds 4 and 5 showed different interactions with enzyme α-glucosidase.

1. Introduction

Embelia Burm. f. belongs to a genus of tropical climber plants. It was previously placed in the Myrsinaceae family but is currently classified under the Primulaceae family [1]. This genus comprises around 100 species [1], many of which have been widely used in traditional medicine systems such as Ayurveda, Siddha, and Chinese medicine for centuries. Dried berries from this genus possess various biological activities, including antibacterial, antidiabetic, anthelmintic, and carminative properties [2]. Phytochemical investigations have identified diverse compounds in Embelia species, including triterpenoids, alkaloids, flavonoids, steroids, alkylresorcinols, and phenolics [3,4,5,6,7,8,9,10,11,12,13,14]. Pharmacological studies, which focused on Embelia ribes and embelin, the main compound in the fruits of E. ribes, further indicate that the E. ribes extract and isolated compounds exhibit many different biological effects, such as antidiabetic [15,16,17,18,19,20,21], anti-obesity [21,22], antipsychotic [23,24], neuroprotective [25,26,27], antioxidant, antimicrobial, and antiviral effects [28,29,30]. In addition, E. ruminata and E. schimperi extracts showed antioxidant, anticancer, and anthelmictic activities [31,32].
In Vietnam, fifteen Embelia species have been documented, but only Embelia ribes stems and leaves were investigated for the chemical constituents and α-glucosidase inhibitory activity [8,9]. Embelia parviflora Wall. Ex A. DC. is a climbing shrub sparsely distributed in the forests of Malaysia, India, China, and Vietnam. It has been traditionally used to promote circulation, alleviate pain, and treat gynecological disorders such as irregular menstruation and amenorrhea [33]. In the northern parts of Vietnam, E. parviflora is known as ‘Thien Ly Huong’ and has been used as a traditional medicine for the treatment of diabetes, inflammation, oral and throat troubles, and skin diseases [34]. To date, research on the phytochemical constituents and biological activities of E. parviflora remains limited. The essential oil composition of E. parviflora has been analyzed, revealing 11 constituents in the root (77.67% of total volatile oil), 36 in the stems (92.88%), and 74 in the leaves (85.11%) [35]. Notably, E. parviflora has exhibited antioxidant [36] and anti-inflammatory [36] activities, as well as potential hematopoietic effects [37]. In our screening results, the MeOH extract showed 84% inhibition of α-glucosidase enzyme activity at the concentration of 256 μg/mL. Further research is needed to fully elucidate its phytochemical profile and pharmacological properties. As part of our continuing search for bioactive compounds from Embelia species, we report here the isolation and structural elucidation of sixteen compounds from the leaves of E. parviflora collected in Bac Kan province, Vietnam. These include three sterols (1–3), one triterpene (4), four flavonoids (5–8), four megastigmane derivatives (9–12), three phenolic compounds (13–15), and one furan derivative (16). Their chemical structures were determined based on ESI-MS and NMR spectroscopic data. The MeOH extract and isolated compounds were evaluated for their α-glucosidase inhibitory activity. The interactions of active compounds with α-glucosidase enzyme were studied by molecular docking approach.

2. Materials and Methods

2.1. Plant Materials

The leaf samples were collected from the Bac Kan province, Vietnam, in 2021. The plant was taxonomically identified as Embelia parviflora Wall. Ex A. DC. by Assoc. Prof. Dr. Sy Danh Thuong, Thai Nguyen University of Education, Thai Nguyen University. A voucher specimen (Thuong18102021.01) has been deposited at the Herbarium of the Department of Biology, Thai Nguyen University of Education, Thai Nguyen University.

2.2. General Experimental Procedures

All chemical solvents (analytical grade) were obtained from a reputable chemical supplier and used as received without additional purification. Enzyme α-glucosidase from Saccharomyces cerevisiae (E.C. 232-604-7) and p-nitrophenyl-α-D-glucopyranoside were purchased from Sigma Aldrich (St. Louis, MO, USA). Dimethyl sulfoxide and acarbose were obtained from Merck (Darmstadt, Germany). For column chromatography (CC), the following materials were employed: silica gel (Merck, 230–400 mesh, Darmstadt, Germany), Sephadex® LH-20 (Sigma Aldrich), MCI, and Diaion HP-20 resins (Mitsubishi Chemical, Tokyo, Japan). Thin-layer chromatography (TLC) was performed using precoated aluminum silica gel plates (Merck 60 F254, Darmstadt, Germany), and spots were visualized by spraying with 10% aqueous sulfuric acid followed by heating. Nuclear magnetic resonance (NMR) spectra, including 1H, 13C, HSQC, and HMBC, were recorded on either a Bruker AVANCE 500 MHz or a Bruker AVANCE NEO 600 MHz spectrometer (Bruker, Billerica, MA, USA) at the Institute of Chemistry, the Vietnam Academy of Science and Technology, with tetramethylsilane (TMS) as the internal standard. Electrospray ionization mass spectrometry (ESI-MS) data were acquired using an Agilent 1260 series single quadrupole LC/MS system (Agilent Technologies, Palo Alto, CA, USA).

2.3. Extraction and Isolation

The dried leaves of E. parviflora (3.6 kg) were marcerated with MeOH (4 × 20 L for 24 h) at room temperature. The MeOH solvents were removed using a vacuum. The crude extract (280 g) was suspended with distilled water (1 L) and extracted consecutively with n-hexane and EtOAc to give n-hexane (46 g), EtOAc residue (96 g), and water layer, respectively. The water fraction (140 g) was applied to Diaion HP-20 CC and eluted with a solvent mixture of MeOH/water (0/100, 50/50, and 100/0, v/v) to yield a MeOH fraction (25 g).
The n-hexane residue (45 g) was subjected to silica gel CC (225 g, column 8 cm size) and eluted with a gradient of n-hexane/EtOAc (100/1–0/100, v/v) to yield 6 fractions (H1–H6). Compound 1 (β-sitosterol) was obtained from fraction H4 (230 mg) by crystallization.
The EtOAc extract (95 g) was chromatographed using silica gel CC (300 g, column 10 cm size) and eluted with a gradient of n-hexane/EtOAc (100/1–0/100, v/v) to yield 9 fractions (E1–E9). Fraction E4 (2.09 g) was subjected to silica gel CC (40 g, column 3 cm size) and eluted with n-hexane/EtOAc (9:1, v/v) to afford 7 fractions E4.1–E4.7. Fraction E4.2 (35 mg) was further purified by silica gel CC (7 g, column 1.5 cm size) and eluted with n-hexane/acetone (9:1, v/v) to give compound 4 (4.3 mg).
Fraction E6 (2.0 g) was fractionated by Sephadex® LH-20 CC (90 g, column 2.5 cm size) and eluted with MeOH/CH2Cl2 (9:1, v/v) to yield 10 fractions E6.1–E6.10. Fraction E6.5 (135 mg) was purified by silica gel CC (27 g, column 2.0 cm size) and eluted with n-hexane/acetone (8:2, v/v) to give compound 5 (5.4 mg). Fraction E6.2 (1.3 g) was purified by Sephadex® LH-20 CC (90 g, column 2.5 cm size) eluted with MeOH to yield 7 fractions E6.2.1–E6.2.7. Fraction E6.2.5 (116 mg) was purified by silica gel CC (25 g, column 2.0 cm size) and eluted with n-hexane/EtOAc (8:2, v/v) to give compound 3 (6.1 mg). Compound 14 (2.1 mg) was obtained from fraction E.6.2.2 (66 mg) by crystallization.
Fraction E9 (12.1 g) was chromatographed on silica gel CC (180 g, column 5 cm size) eluted with CH2Cl2/MeOH (10:1–0/1, v/v) to give 9 fractions E9.1–E9.9. Fraction E9.4 (22 mg) was further purified by silica gel CC (7 g, column 1.5 cm size) and eluted with n-hexane/EtOAc (7:3, v/v) to give compound 15 (2.2 mg). Compound 2 (5 mg) was obtained from fraction E9.7 (76 mg) by crystallization in CH2Cl2. Fraction E9.9 (1.7 g) was fractionated by MCI gel CC (120 g, column 3 cm size) and eluted with MeOH/H2O (1:1, v/v) to give compound 6 (10.2 mg) and seven fractions E.9.9.1–E.9.9.7. Fraction E9.7.5 (24 mg) was purified by Sephadex® LH-20 CC (20 g, column 1.5 cm size), using MeOH as the mobile phase to afford compound 7 (12.2 mg).
The MeOH fraction (25 g) was applied to silica gel CC (150 g, column 6 cm size) and eluted with CH2Cl2/MeOH (10:1–0/1, v/v) to give 14, fractions W1–W14. Fraction W3 (180 mg) was purified by MCI gel CC (40 g, column 2 cm size) and eluted with MeOH/H2O (1:1, v/v) to obtain compound 16 (15.1 mg) and 9 fractions, W3.1–W3.9. Fraction W3.7 (41.5 mg) was purified by preparative HPLC and eluted with MeOH/water (40%) to yield compound 9 (4.2 mg). Fraction W3.9 (6.5 mg) was purified by preparative HPLC and eluted with MeOH/water (40%) to give compound 13 (2.1 mg). Fraction W4 (280 mg) was purified by MCI gel CC (60 g, column 2 cm size) and eluted with MeOH/H2O (1:2–1:0, v/v) to yield 9 fractions, W4.1–W4.9. Fraction W4.3 (22 mg) was purified by silica gel CC (7 g, column 1.5 cm size) and eluted with n-hexane/acetone (4:1, v/v) to give compound 10 (2.5 mg). Fraction W4.9 (22 mg) was purified by silica gel CC (10 g, column 1.5 cm size) and eluted with n-hexane/acetone (2:1, v/v) to yield compound 12 (2.5 mg). Fraction W12 (180 mg) was purified by reversed-phase CC (70 g, column 2.5 cm size) and eluted with MeOH/H2O (1:2–2:1, v/v) to afford 5 fractions, W12.1–W12.5. Fraction W12.1 (41.5 mg) was purified by preparative HPLC and eluted with acetonitrile/water (1:4, v/v) to yield compound 11 (4.2 mg). Fraction W12.3 (200 mg) was fractionated by silica gel CC (40 g, column 2 cm size) and eluted with CH2Cl2/MeOH/water (5:1:0.05, v/v/v) and then Sephadex® LH-20 CC (50 g, column 2 cm size), using MeOH as the mobile phase to give compound 8 (10.2 mg).

2.4. Assay of α-Glucosidase Enzyme Inhibition

The in vitro assay of α-glucosidase enzyme inhibition of the E. parviflora MeOH extract and tested compounds was conducted following the methodology outlined in our earlier study [38]. Briefly, solutions of MeOH extract and isolated compounds at 256 μg/mL, 64 μg/mL, 16 μg/mL, 4 μg/mL, and 1 μg/mL concentrations were prepared using DMSO (Merck). The compound solution (2 μL) and 0.2 U/mL α-glucosidase enzyme solution (25 µL) in 120 µL phosphate buffer were mixed. After 5 min preincubation, a solution of 2.5 mM p-nitrophenyl α-D-glucopyranoside (25 µL) prepared in phosphate buffer was added. The reaction mixture was incubated at 37 °C for 30 min and was stopped by adding 0.2 M of Na2CO3 (100 µL). Enzymatic activity (the absorbance of the released p-nitrophenol) was quantified by measuring at 410 nm using a Biotek reader. The % inhibition was calculated using the following equation:
Inhibition (%) = [1 − (Asample/Acontrol)] × 100
The IC50 value was defined as the concentration of compound that inhibited 50% of α-glucosidase enzyme activity and was calculated by using the program Table Curve. Acarbose, a well-known α-glucosidase inhibitor, served as the positive control in this experiment.

2.5. Molecular Docking

In this study, molecular docking was performed to investigate the mechanisms of interaction between potential compounds identified from the in vitro assay and α-glucosidase, following a well-established protocol [39]. Since the crystal structure of α-glucosidase from Saccharomyces cerevisiae is unavailable, a homology model was obtained from isomaltase in the RCSB Protein Data Bank (https://www.rcsb.org, accessed on 15 February 2025) (PDB ID: 3AJ7) as a template. In the next step, water molecules were removed, followed by adding hydrogen atoms and assigning partial charges. Ligand structures were downloaded from PubChem and converted into pdbqt format using Autodock Tool 1.5.6. After that, molecular docking was conducted using Autodock Vina, with a grid box size of 25 × 25 × 25 Å3. The grid center was set at x = 20.226, y = −8.148, and z = 17.909 for 5–7, while for compound 4, it was adjusted to x = 20.315, y = −26.388, and z = 27.802. The positive control used in this study is acarbose, and docking results were analyzed using BIOVIA Discovery Studio Visualizer 4.5.

2.6. Statistical Analysis

The biological experiments were performed in triplicate. The IC50 values are presented as the mean ± standard deviation (S.D) using the program Statistica 10.

3. Results and Discussion

3.1. Chemical Constituents and Chemotaxonomy Significance

Combined chromatographic separation of the n-hexane, ethyl acetate, and water fractions from the MeOH extract of E. parviflora leaves afforded sixteen known compounds (1–16) (Figure 1) including three sterols (1–3), one triterpene (4), four flavonoids (5–8), four megastigmanes (9–12), three phenolic compounds (13–15), and one furano derivative (16). The chemical structures of the isolated compounds were identified as β-sistosterol (1) [40], daucosterol (2) [41], 3-O-(6′-O-palmitoyl)-β-D-glucopyranosyl stigmasterol (3) [42], ursolic acid (4) [43], kaempferol (5) [44], kaempferin (6) [45], quercitrin (7) [46], quercetin-3-rhamnoside-3′-glucoside (8) [47], (6R,9R)-9-hydroxy-4,7-megastigmadien-3-one (9) [48], grasshopper ketone (10) [49], (6R,7E,9R)-9-hydroxy-4,7-megastigmadien-3-one-9-O-β-D-apiofuranosyl(1->6)-β-D-glucopyranoside (11) [50], vomifoliol (12) [51], methyl trans-p-coumarate (13) [52], vanillic acid (14) [53], syringic acid (15) [54], and sotolone (16) [55,56] by the comparison of the NMR spectral data (Supplementary Materials) with those in the literature [40,41,42,43,44,45,46,47,48,49,50,51,52,53,54,55,56]. Interestingly, several pairs of an aglycone and its glycosides were found in our chemical study, such as compounds 1 and 2, compounds 5 and 6, and compounds 9 and 11. In addition, two flavonoid glycosides, 7 and 8, have the same quercetin skeleton.
To the best of our knowledge, this is the first phytochemical study of E. parviflora leaves. Sterols 1 and 2 are common compounds found in many plants, while compound 3 was isolated from a few plant families like Primulaceae [42,57] and Pontederiaceae [58] (Table 1 and Table 2). Sitosterol (1) and daucosterol (2) have been identified in leaf extracts of E. ribes and E. rowlandii, respectively [5]. In addition, ursolic acid (4), kaempferol (5), kaempferin (6), and quercitrin (7) have been isolated from E. ribes leaves [9]. Two phenolic acids, 14–15, have been reported in the leaves of E. laeta [11] (Table 1).
In our study, compounds 3, 8–13, and 16 represent the first isolation of these compounds from the Embelia genus. The partial distribution in plants of compounds 3, 8–13, and 16 is presented in Table 2. Compounds 3, 8, and 12 were previously isolated from the Primulaceae family [42,47,57,72]. Compounds 9–11, 13, and 16 were found in the Primulaceae family for the first time.
As shown in Table 2, compounds 12 and 13 were distributed in many plant families, such as Annonaceae, Bignoniaceae, Celastraceae, Caryophyllaceae, Euphorbiaceae, Myrtaceae, Onagraceae, Rhizophoraceae, Rutaceae, Rubiaceae, Solanaceae, etc. The occurrences of megastimanes 9–11 in plants are quite limited. They were identified from Apocynaceae, Caprifoliaceae, Commelinaceae, Cornaceae, Cannabaceae, Chenopodiaceae, Lamiaceae, Magnoliaceae, Nelumbonaceae, Rosaceae, and Piperaceae families. As mentioned earlier, sterol 3 was isolated from the Primulaceae and Pontederiaceae families. Notably, compounds 8 and 16 were only discovered from Myrsine seguinii (Primulaceae) and Quararibea funebris (Bombacaceae), respectively. Our phytochemical study enriches our understanding of the chemical constituents of Embelia species and further provides a basis for the chemical taxonomic research of E. parviflora. Compounds 3, 8–13, and 16 might be regarded as potential fingerprint markers for E. parviflora plant.

3.2. α-Glucosidase Inhibitory Activity

The antidiabetic activity of Embelia species, especially E. ribes, has been extensively studied. In Vietnam, the α-glucosidase inhibitory activity of E. ribes stems and leaves have been reported [8,9]. Therefore, in our investigation, the α-glucosidase inhibitory activity of the methanol (MeOH) extract of E. parviflora and its isolated compounds was assessed. Acarbose, a widely recognized α-glucosidase inhibitor, served as the positive control, demonstrating an IC50 value of 198.5 ± 6.25 μg/mL. The MeOH extract showed strong inhibition of α-glucosidase activity with an IC50 of 12.80 ± 0.62 μg/mL. Compounds 4 and 5 showed strong inhibition with IC50 values of 1.40 ± 0.06 μg/mL and 1.75 ± 0.08 μg/mL, respectively, whereas compounds 6 and 7 exhibited moderate activity, with IC50 values of 162.13 ± 3.28 μg/mL and 168.01 ± 4.15 μg/mL, respectively.
This is the first report of the α-glucosidase inhibitory activity of compounds 3, 8–11, and 16, but unfortunately, these isolated compounds were inactive (Table 3). Our biological results were quite similar to the results of previous reports. β-Sistosterol (1) and daucosterol (2) were documented to have weak anti-α-glucosidase activity, with IC50 values of 283.67 μg/mL and 247.35 μg/mL, which are close to our results [93]. Ding et al. have reported that ursolic acid (4) showed an enzyme inhibitory effect with an IC50 value of 16.9 μM (7.7 μg/mL) in a non-competitive manner [94]. In Peng’s study, kaempferol (5) showed strong activity against glucosidase with an IC50 value of 11.6 μM (3.32 μg/mL) [95]. Similar to our results, vomifoliol (12) was also found inactive in the biological assay [96].
However, different inhibitory effects have also been found in the literature. In the investigation of Dang’s group [9], compounds 5–7 showed moderate inhibitory activity, with IC50 values of 84.9, 94.7, and 26.5 μM, respectively. Compound 13 was reported to exhibit the inhibition of α-glucosidase, with an IC50 value of 54.15 μM [97]. Perhaps the different assay conditions have led to different results in terms of the activity.
Overall, our biological results suggest that the MeOH extract of E. parviflora and several isolated compounds, i.e., compounds 4–7, can be used as a source for the development of natural antidiabetic agents.

3.3. Molecular Docking

To further investigate their interactions with the protein, molecular docking was performed. Previous research indicated that flavonoids, such as kaempferol, inhibited α-glucosidase through a competitive mechanism by binding to the enzyme’s active site [95,98]. In contrast, triterpenoids like ursolic acid achieve their inhibitory effect via interactions with the allosteric site [94,99]. Therefore, in this study, compounds 5–7 were docked into the enzyme’s active site, while 4 was docked into the allosteric site. The results are summarized in Table 4.
The results showed that the positive control, acarbose, exhibited good affinity for the enzyme, with a binding energy of −6.7 kcal/mol, corresponding to an IC50 value of 198.5 ± 6.25 μg/mL. Notably, compound 4 demonstrated strong binding to the allosteric site of α-glucosidase, with a binding energy of −9.2 kcal/mol. This finding aligns well with the low IC50 value of ursolic acid (4) determined from the in vitro assay (1.40 μg/mL). Our results also indicated that ursolic acid (4) strongly interacts with α-glucosidase via hydrogen bonding and Van der Waals interactions with residues Arg175, Ser179, and Asn411 (Figure 2). Interestingly, these interactions are consistent with previous studies on the mode of binding of ursolic acid to enzymes. Ding et al. reported that ursolic acid exhibits potent α-glucosidase inhibitory activity through interactions with multiple enzyme residues, including Ser179 and Asn411, where hydrogen bonding plays a crucial role in its effect [94]. Similarly, a study by Elmira F. Khusnutdinova et al. on betulinic acid, a compound structurally similar to ursolic acid, found that hydrogen bonding with Arg175 and Ser179 is essential for the α-glucosidase inhibitory activities of this class of compounds [100].
Regarding compound 5, the results showed that this compound could strongly bind to α-glucosidase, with a binding affinity of −7.9 kcal/mol. This result was consistent with a study by Xi Peng et al., in which the binding energy between kaempferol and the α-glucosidase was determined as −7.12 kcal/mol [95]. Further analysis revealed that 5 interacted with the enzyme through hydrogen bonds formed between its C4′-OH, C3-OH, and C5-OH groups and the residues Arg312, Asp408, and Arg439 (Figure 3).
This observation aligned well with a previous study by Nana Li et al., which demonstrated that the C4′-OH, C5′-OH, and C3-OH groups played a crucial role in the interaction between flavonoids and α-glucosidase enzyme [101]. In contrast, while compounds 6 and 7 exhibited strong binding affinities of −9.3 and −9.1 kcal/mol, respectively, their in vitro inhibitory activity was not as potent as that of kaempferol. This may be due to their larger molecular size, which likely hinders their access to the enzyme’s active site compared to the aglycone form. As a result, their inhibitory effect is weaker [95]. Additionally, the glycosylation of the C3-OH group may prevent these compounds from forming critical hydrogen bonds with the enzyme. Accordingly, despite their high binding affinity, their interactions may be less significant for α-glucosidase inhibitory activities than those of kaempferol (5) [101].

4. Conclusions

Sixteen compounds including β-sistosterol (1), daucosterol (2), 3-O-(6′-O-palmitoyl)-β-D-glucopyranosyl stigmasterol (3), ursolic acid (4), kaempferol (5), kaempferin (6), quercitrin (7), quercetin-3-rhamnoside-3′-glucoside (8), (6R,9R)-9-hydroxy-4,7-megastigmadien-3-one (9), grasshopper ketone (10), (6R,7E,9R)-9-hydroxy-4,7-megastigmadien-3-one-9-O-β-D-apiofuranosyl(1->6)-β-D-glucopyranoside (11), vomifoliol (12), methyl p-coumarate (13), vanillic acid (14), syringic acid (15), and sotolone (16) were isolated from the leaves of E. parviflora. This is the first phytochemical investigation of E. parviflora. Compounds 3, 8–13, and 16 were first reported in the Embelia genus. Compounds 9–11, 13, and 16 have not been previously discovered in the Primulaceae family. In the biological assay, the MeOH extract of E. parviflora leaves and isolated compounds 4 and 5 showed strong inhibition of enzyme α-glucosidase activity with IC50 values of 12.80 ± 0.62 μg/mL, 1.40 ± 0.06 μg/mL, and 1.75 ± 0.08 μg/mL, respectively. Molecular docking studies revealed that compounds 4 and 5 had different binding modes to enzyme α-glucosidase. Triterpene (4) interacts with an allosteric site of the enzyme with a binding energy of −9.2 kcal/mol, whereas flavonoid (5) binds to an active site of α-glucosidase enzyme with a binding affinity of −7.9 kcal/mol. The strong α-glucosidase inhibitory activity of compounds 4 and 5 made the most significant contribution to the antidiabetic activity of E. parviflora leaves.

Supplementary Materials

The following supporting information can be downloaded at: https://www.mdpi.com/article/10.3390/life15050680/s1, Physical and Spectroscopic Data of Compounds 1–16; Figure S1. 1H-NMR spectrum of compound 1; Figure S2. 1H-NMR spectrum of compound 2; Figure S3. 13C-NMR spectrum of compound 2; Figure S4. 1H-NMR spectrum of compound 3; Figure S5. 13C-NMR spectrum of compound 3; Figure S6. 1H-NMR spectrum of compound 4; Figure S7. 13C-NMR spectrum of compound 4; Figure S8. 1H-NMR spectrum of compound 5; Figure S9. 13C-NMR spectrum of compound 5; Figure S10. 1H-NMR spectrum of compound 6; Figure S11. 13C-NMR spectrum of compound 6; Figure S12. 1H-NMR spectrum of compound 7; Figure S13. 13C-NMR spectrum of compound 7; Figure S14. 1H-NMR spectrum of compound 8; Figure S15. 13C-NMR spectrum of compound 8; Figure S16. HSQC spectrum of compound 8; Figure S17. HMBC spectrum of compound 8; Figure S18. 1H-NMR spectrum of compound 9; Figure S19. 13C-NMR spectrum of compound 9; Figure S20. 1H-NMR spectrum of compound 10; Figure S21. 13C-NMR spectrum of compound 10; Figure S22. 1H-NMR spectrum of compound 11; Figure S23. 13C-NMR spectrum of compound 11; Figure S24. HSQC spectrum of compound 11; Figure S25. HMBC spectrum of compound 11; Figure S26. 1H-NMR spectrum of compound 12; Figure S27. 1H-NMR spectrum of compound 13; Figure S28. 13C-NMR spectrum of compound 13; Figure S29. 1H-NMR spectrum of compound 14; Figure S30. 13C-NMR spectrum of compound 14; Figure S31. 1H-NMR spectrum of compound 15; Figure S32. 13C-NMR spectrum of compound 15; Figure S33. 1H-NMR spectrum of compound 16; Figure S34. 13C-NMR spectrum of compound 16; Figure S35. HSQC spectrum of compound 16; Figure S36. HMBC spectrum of compound 16.

Author Contributions

Conceptualization, S.D.T. and L.N.T.; Investigation, M.T.H.A., N.T.C., N.H.Q. and C.H.M.; Formal analysis, N.V.P. and N.T.C.; Funding acquisition, S.D.T.; Project administration, S.D.T.; Writing—Original Draft Preparation, S.D.T., N.V.P. and L.N.T.; Writing—Review and Editing, S.D.T., C.H.M. and L.N.T. All authors have read and agreed to the published version of the manuscript.

Funding

This research is funded by the Vietnam Ministry of Education and Training under grant number B2023-TNA-25.

Institutional Review Board Statement

Not applicable.

Informed Consent Statement

Not applicable.

Data Availability Statement

The data presented in this study are available upon request from the corresponding author.

Conflicts of Interest

The authors declare no conflicts of interest.

References

  1. Dubéarnès, A.; Julius, A.; Utteridge, T.M.A. A synopsis of the genus Embelia in peninsular Malaysia and Singapore. Studies in Malaysian Myrsinaceae III. Kew Bull. 2015, 70, 25. [Google Scholar] [CrossRef]
  2. Vijayan, K.R.; Raghu, A.V. Embelin: An HPTLC method for quantitative estimation in five species of genus Embelia Burm. f. Future J. Pharm. Sci. 2021, 7, 55. [Google Scholar] [CrossRef]
  3. Sharma, V.; Gautam, D.N.S.; Radu, A.F.; Behl, T.; Bungau, S.G.; Vesa, C.M. Reviewing the traditional/modern uses, phytochemistry, essential oils/extracts and pharmacology of Embelia ribes Burm. Antioxidants 2022, 11, 1359. [Google Scholar] [CrossRef] [PubMed]
  4. Manguro, L.O.A.; Okwiri, S.O.; Lemmen, P. Oleanane-type triterpenes of Embelia schimperi leaves. Phytochemistry 2006, 67, 2641–2650. [Google Scholar] [CrossRef]
  5. Bouzeko, I.L.T.; Ndontsa, B.L.; Nguekeu, Y.M.M.; Awouafack, M.D.; Wong, C.P.; Mpetga, J.D.S.; Mbouangouere, R.; Tane, P.; Morita, H. A new alkylbenzoquinone from Embelia rowlandii Gilg. (Myrsinaceae). Nat. Prod. Res. 2019, 33, 1909–1915. [Google Scholar] [CrossRef] [PubMed]
  6. Manguro, L.O.A.; Ugi, I.; Lemmen, P. Flavonol glycosides from the leaves of Embelia keniensis. J. Chin. Chem. Soc. 2005, 52, 201–208. [Google Scholar] [CrossRef]
  7. Qin, Y.; Chen, J.P.; Li, C.Y.; Zhu, L.J.; Zhang, X.; Wang, J.H.; Yao, X.S. Flavonoid glycosides from the fruits of Embelia ribes and their anti-oxidant and α-glucosidase inhibitory activities. J. Asian Nat. Prod. Res. 2021, 23, 724–730. [Google Scholar] [CrossRef] [PubMed]
  8. Dang, P.H.; Nguyen, H.X.; Nguyen, N.T.; Le, H.N.T.; Nguyen, M.T.T. α-Glucosidase inhibitors from the stems of Embelia ribes. Phytother. Res. 2014, 28, 1632–1636. [Google Scholar] [CrossRef]
  9. Dang, P.H.; Nguyen, N.T.; Nguyen, H.X.; Nguyen, L.B.; Le, T.H.; Van Do, T.N.; Can, M.V.; Nguyen, M.T.T. α-Glucosidase inhibitors from the leaves of Embelia ribes. Fitoterapia 2015, 100, 201–207. [Google Scholar] [CrossRef]
  10. Yang, L.J. Chemical constituents from the fruits of Embelia laeta. Chin. Pharm. J. 2016, 24, 1179–1182. [Google Scholar]
  11. Feng, X.; Li, Y.H.; Liang, C.Y.; Wang, H.; Zhang, X.W. Chemical constituents from Embelia laeta. Zhong Yao Cai (J. Chin. Med. Mater.) 2013, 36, 1947–1949. [Google Scholar]
  12. Chen, J.P.; Zhu, L.J.; Su, X.X.; Zhang, K.X.; Zhang, X.; Wang, J.H.; Yao, X.S. New alkylresorcinols from the fruits of Embelia ribes. Fitoterapia 2018, 128, 66–72. [Google Scholar] [CrossRef] [PubMed]
  13. Machocho, A.K.; Kiprono, P.C.; Grinberg, S.; Bittner, S. Pentacyclic triterpenoids from Embelia schimperi. Phytochemistry 2003, 62, 573–577. [Google Scholar] [CrossRef] [PubMed]
  14. Manguro, L.O.A.; Ugi, I.; Lemen, P. Further flavonol glycosides of Embelia schimperi leaves. Bull. Chem. Soc. Ethiop. 2004, 18, 51–57. [Google Scholar] [CrossRef]
  15. Mahendran, S.; Badami, S.; Maithili, V. Evaluation of antidiabetic effect of embelin from Embelia ribes in alloxan induced diabetes in rats. Biomed. Prev. Nutr. 2011, 1, 25–31. [Google Scholar] [CrossRef]
  16. Bhandari, U.; Kanojia, R.; Pillai, K.K. Effect of ethanolic extract of Embelia ribes on dyslipidemia in diabetic rats. J. Diabetes Res. 2002, 3, 159–162. [Google Scholar] [CrossRef]
  17. Bhandari, U.; Jain, N.; Pillai, K.K. Further studies on antioxidant potential and protection of pancreatic β-cells by Embelia ribes in experimental diabetes. J. Diabetes Res. 2007, 2007, 015803. [Google Scholar] [CrossRef] [PubMed]
  18. Durg, S.; Veerapur, V.P.; Neelima, S.; Dhadde, S.B. Antidiabetic activity of Embelia ribes, embelin and its derivatives: A systematic review and meta-analysis. Biomed. Pharmacother. 2017, 86, 195–204. [Google Scholar] [CrossRef]
  19. Bhandari, U.; Chaudhari, H.S.; Khanna, G.; Najmi, A.K. Antidiabetic effects of Embelia ribes extract in high fat diet and low dose streptozotocin-induced type 2 diabetic rats. Front. Life Sci. 2013, 7, 186–196. [Google Scholar] [CrossRef]
  20. Bhandari, U.; Jain, N.; Ansari, M.N.; Pillai, K.K. Beneficial effect of Embelia ribes ethanolic extract on blood pressure and glycosylated hemoglobin in streptozotocin-induced diabetes in rats. Fitoterapia 2008, 79, 351–355. [Google Scholar] [CrossRef]
  21. Chaudhari, H.S.; Bhandari, U.; Khanna, G. Preventive effect of embelin from Embelia ribes on lipid metabolism and oxidative stress in high-fat diet-induced obesity in rats. Planta Med. 2012, 78, 651–657. [Google Scholar] [CrossRef] [PubMed]
  22. Nazish, I.; Ansari, S.H.; Arora, P. Antiobesity actions of Embelia ribes. Pharmacogn. J. 2012, 4, 73–80. [Google Scholar] [CrossRef]
  23. Gupta, G.; Kazmi, I.; Afzal, M.; Upadhyay, G.; Singh, R.; Habtemariam, S. Antidepressant-like activity of embelin isolated from Embelia ribes. Phytopharmacology 2013, 4, 87–95. [Google Scholar]
  24. Thippeswamy, B.S.; Nagakannan, P.; Shivasharan, B.D.; Mahendran, S.; Veerapur, V.P.; Badami, S. Protective effect of embelin from Embelia ribes Burm. against transient global ischemia-induced brain damage in rats. Neurotox. Res. 2011, 20, 379–386. [Google Scholar] [CrossRef] [PubMed]
  25. Durg, S.; Kumar, N.; Vandal, R.; Dhadde, S.B.; Thippeswamy, B.S.; Veerapur, V.P.; Badami, S. Antipsychotic activity of embelin isolated from Embelia ribes: A preliminary study. Biomed. Pharmacother. 2017, 90, 328–331. [Google Scholar] [CrossRef] [PubMed]
  26. Dhayalan, M.; Denison, M.I.J.; L, J.A.; Krishnan, K.; N, G.N. In vitro antioxidant, antimicrobial, cytotoxic potential of gold and silver nanoparticles prepared using Embelia ribes. Nat. Prod. Res. 2017, 31, 465–468. [Google Scholar] [CrossRef]
  27. Afzal, M.; Gupta, G.; Kazmi, I.; Rahman, M.; Upadhyay, G.; Ahmad, K.; Imam, F.; Pravez, M.; Anwar, F. Evaluation of anxiolytic activity of embelin isolated from Embelia ribes. Biomed. Aging Pathol. 2012, 2, 45–47. [Google Scholar] [CrossRef]
  28. Ansari, M.N.; Bhandari, U.; Islam, F.; Tripathi, C.D. Evaluation of antioxidant and neuroprotective effect of ethanolic extract of Embelia ribes Burm in focal cerebral ischemia/reperfusion-induced oxidative stress in rats. Fundam. Clin. Pharmacol. 2008, 22, 305–314. [Google Scholar] [CrossRef]
  29. Swamy, H.K.; Krishna, V.; Shankarmurthy, K.; Rahiman, B.A.; Mankani, K.L.; Mahadevan, K.M.; Harish, B.G.; Naika, H.R. Wound healing activity of embelin isolated from the ethanol extract of leaves of Embelia ribes Burm. J. Ethnopharmacol. 2007, 109, 529–534. [Google Scholar] [CrossRef]
  30. Hossan, M.S.; Fatima, A.; Rahmatullah, M.; Khoo, T.J.; Nissapatorn, V.; Galochkina, A.V.; Slita, A.V.; Shtro, A.A.; Nikolaeva, Y.; Zarubaev, V.V.; et al. Antiviral activity of Embelia ribes Burm. f. against influenza virus in vitro. Arch. Virol. 2018, 163, 2121–2131. [Google Scholar] [CrossRef]
  31. Rambaran, N.; Naidoo, Y.; Dwarka, D.; Mellem, J.; Thimmegowda, S.C.; Baijnath, H. In vitro antioxidant and anticancer potential of the vegetative and reproductive organs of Embelia ruminata. J. Herbs Spices Med. Plants 2024, 30, 429–441. [Google Scholar] [CrossRef]
  32. Lemmich, J. Anthelmintic usage of extracts of Embelia schimperi from Tanzania. J. Ethnopharmacol. 1996, 50, 35–42. [Google Scholar] [CrossRef]
  33. Li, W.; Liu, X.; Liang, X.L.; Chen, Y.; Pang, D.; Huang, Z.; Han, Q.; Liu, W.; Chen, L. Optimization of extraction process and antioxidant activity of polysaccharide in Embelia parviflora Wall. by RSM. Med. Plant 2020, 11, 34–42. [Google Scholar] [CrossRef]
  34. Anh, M.T.H.; Mau, C.H.; Thuong, S.D. Morphological characteristics and sequence of trnE-trnT of Embelia parviflora Wall. ex A. DC.). TNU J. Sci. Technol. 2025, 230, 259–266. [Google Scholar] [CrossRef]
  35. Lu, S.H.; Li, Y.H.; Chen, Y.; Zeng, H.S.; Zhang, L.; Zheng, X.R. Study on the chemical constituents of volatile oil from different parts of Embelia parviflora Wall. ex A. DC by GC-MS. Med. Plant 2012, 3, 58–61. [Google Scholar]
  36. Wei, J.; Chen, Y.; Ma, X.; Qiu, M.; Qing, B.; Jiang, L.; Wen, Z.; Qin, Z. Anti-inflammatory effect of polysaccharide from Embelia parviflora Wall, on rheumatoid arthritis in rats. Med. Plant 2024, 15, 41. [Google Scholar] [CrossRef]
  37. Liu, W.; Que, Z.; Li, J.; Chen, Z.; Huang, Z.; Pang, D.; Chen, L.; Chen, Y. Study on sreening of effective components of Embelia parviflora for tonifying blood and its mechanism. China Pharm. 2020, 12, 293–297. [Google Scholar]
  38. Oanh, V.T.K.; Ha, N.T.T.; Duc, H.V.; Thuc, D.N.; Hang, N.T.M.; Thanh, L.N. New triterpene and nor-diterpene derivatives from the leaves of Adinandra poilanei. Phytochem. Lett. 2021, 46, 110–113. [Google Scholar] [CrossRef]
  39. Phuong, D.T.L.; Van Phuong, N.; Le Tuan, N.; Cong, N.T.; Hang, N.T.; Thanh, L.N.; Bankova, V. Antimicrobial, cytotoxic, and α-glucosidase inhibitory activities of ethanol extract and chemical constituents isolated from Homotrigona apicalis propolis—In vitro and molecular docking studies. Life 2023, 13, 1682. [Google Scholar] [CrossRef]
  40. Sosińska, E.; Przybylski, R.; Hazendonk, P.; Zhao, Y.Y.; Curtis, J.M. Characterisation of non-polar dimers formed during thermo-oxidative degradation of β-sitosterol. Food Chem. 2013, 139, 464–474. [Google Scholar] [CrossRef]
  41. Faizi, S.; Ali, M.; Saleem, R.; Irfanullah, B.S. Complete 1H and 13C NMR assignments of stigma-5-en-3-O-β-glucoside and its acetyl derivative. Magn. Reson. Chem. 2001, 39, 399–405. [Google Scholar] [CrossRef]
  42. Lavaud, C.; Massiot, G.; Moretti, C.; Le Men-Olivier, L. Triterpene saponins from Myrsine pellucida. Phytochemistry 1994, 37, 1671–1677. [Google Scholar] [CrossRef] [PubMed]
  43. Acebey-Castellon, I.L.; Voutquenne-Nazabadioko, L.; Doan Thi Mai, H.; Roseau, N.; Bouthagane, N.; Muhammad, D.; Lavaud, C. Triterpenoid saponins from Symplocos lancifolia. J. Nat. Prod. 2011, 74, 163–168. [Google Scholar] [CrossRef]
  44. Li, Y.L.; Li, J.; Wang, N.L.; Yao, X.S. Flavonoids and a new polyacetylene from Bidens parviflora Willd. Molecules 2008, 13, 1931–1941. [Google Scholar] [CrossRef] [PubMed]
  45. Ngoc, L.T.; Mai, N.T. Chemical constituents of Saraca dives. Vietnam J. Sci. Technol. 2014, 123, 107–111. [Google Scholar]
  46. Thanh, N.T.V.; Hien, D.T.T.; Minh, T.T.; Cuong, H.D.; Nhiem, N.X.; Yen, P.H.; Van Kiem, P. Quercetin glycosides and sesquiterpenes from Phoebe poilanei Kosterm. Vietnam J. Chem. 2019, 57, 401–405. [Google Scholar] [CrossRef]
  47. Zhong, X.N.; Otsuka, H.; Ide, T.; Hirata, E.; Takushi, A.; Takeda, Y. Three flavonol glycosides from leaves of Myrsine seguinii. Phytochemistry 1997, 46, 943–946. [Google Scholar] [CrossRef]
  48. Niu, C.; Yang, L.P.; Zhang, Z.Z.; Zhou, D.J.; Kong, J.C.; Liu, Z.Q.; Wang, Z.H. Chemical constituents of Ampelopsis japonica. Chem. Nat. Comp. 2022, 58, 545–547. [Google Scholar] [CrossRef]
  49. Wang, H.; Cong, W.L.; Fu, Z.L.; Chen, D.F.; Wang, Q. Anti-complementary constituents of Viola kunawarensis. Nat. Prod. Res. 2017, 31, 2312–2315. [Google Scholar] [CrossRef]
  50. Wu, Q.L.; Wang, M.; Simon, J.E.; Yu, S.C.; Xiao, P.G.; Ho, C.T. Studies on the chemical constituents of loquat leaves (Eriobotrya japonica). Orient. Food Herbs 2003, 22, 292–306. [Google Scholar]
  51. Ren, Y.; Anaya-Eugenio, G.D.; Czarnecki, A.A.; Ninh, T.N.; Yuan, C.; Chai, H.B.; Soejarto, D.D.; Burdette, J.E.; de Blanco, E.J.C.; Kinghorn, A.D. Cytotoxic and NF-κB and mitochondrial transmembrane potential inhibitory pentacyclic triterpenoids from Syzygium corticosum and their semi-synthetic derivatives. Bioorg. Med. Chem. 2018, 26, 4452–4460. [Google Scholar] [CrossRef] [PubMed]
  52. Huong, P.T.T.; Nguyen, V.T.; Diep, C.N.; Thao, N.P.; Cuong, N.X.; Nam, N.H.; Minh, C.V. Antimicrobial compounds from Rhizophora stylosa. Vietnam J. Sci. Technol. 2015, 53, 205–210. [Google Scholar] [CrossRef]
  53. Khallouki, F.; Hull, W.E.; Würtele, G.; Haubner, R.; Erben, G.; Owen, R.W. Isolation of the major phenolic compounds in the pits of brined green olive drupes: Structure elucidation by comprehensive 1H/13C-NMR spectroscopy. Nat. Prod. Comm. 2019, 14, 1–8. [Google Scholar] [CrossRef]
  54. Itoh, A.; Isoda, K.; Kondoh, M.; Kawase, M.; Watari, A.; Kobayashi, M.; Tamesada, M.; Yagi, K. Hepatoprotective effect of syringic acid and vanillic acid on CCl4-induced liver injury. Biol. Pharm. Bull. 2010, 33, 983–987. [Google Scholar] [CrossRef]
  55. Raffauf, R.F.; Zennie, T.M.; Onan, K.D.; Le Quesne, P.W. Funebrine, a structurally novel pyrrole alkaloid, and other. gamma.-hydroxyisoleucine-related metabolites of Quararibea funebris (Llave) Vischer (Bombacaceae). J. Org. Chem. 1984, 49, 2714–2718. [Google Scholar] [CrossRef]
  56. Trang, B.T.; Thuong, C.H.; Thao, P.X.; Mac, D.H.; Gree, R. A new approach for the synthesis of sotolon in racemic and enantioenriched forms. Vietnam J. Chem. 2021, 59, 42–46. [Google Scholar] [CrossRef]
  57. Ali, Z.; Khan, I.A. Alkyl phenols and saponins from the roots of Labisia pumila (Kacip Fatimah). Phytochemistry 2011, 72, 2075–2080. [Google Scholar] [CrossRef] [PubMed]
  58. Row, L.C.; Chen, C.M.; Ho, J.C. Two cerebrosides and one acylglycosyl sterol from Monochoria vaginalis. J. Chin. Chem. Soc. 2003, 50, 1103–1107. [Google Scholar] [CrossRef]
  59. Zhang, G.L.; Li, N.; Wang, Y.H.; Zheng, Y.T.; Zhang, Z.; Wang, M.W. Bioactive lignans from Peperomia heyneana. J. Nat. Prod. 2007, 70, 662–664. [Google Scholar] [CrossRef]
  60. Jiang, J.; Sun, C.; Wang, G.; Xu, Q.; Bian, Y.; Li, J.; Li, J.; Ding, R.; Lin, H.; Tian, W.; et al. C-13 Norisoprenoids and Eudesmanoids from Nelumbo nucifera Gaertn. Regulate the Lipid Metabolism via the AMPK/ACC/SREBP-1c Signaling Pathway. Chem. Biodiver. 2025, 22, e202401778. [Google Scholar] [CrossRef]
  61. Liu, J.J.; Hao, J.J.; Tan, M.; Liao, C.C.; Liu, D.; Li, H.M.; Li, R.T. Iridoids and other constituents from the leaves and stems of Valeriana officinalis var. latifolia. Phytochemistry 2024, 218, 113934. [Google Scholar] [CrossRef] [PubMed]
  62. Wang, L.J.; Xiong, J.; Zou, Y.; Mei, Q.B.; Wang, W.X.; Hu, J.F. Sesquiterpenoids from the Chinese endangered plant Manglietia aromatica. Phytochem. Lett. 2016, 18, 202–207. [Google Scholar] [CrossRef]
  63. Tu, P.C.; Tseng, H.C.; Liang, Y.C.; Huang, G.J.; Lu, T.L.; Kuo, T.F.; Kuo, Y.H. Phytochemical investigation of Tradescantia albiflora and anti-inflammatory butenolide derivatives. Molecules 2019, 24, 3336. [Google Scholar] [CrossRef]
  64. Pan, Y.B.; Song, X.Q.; Sun, P.; Zhang, H. Chemical constituents from the stems of Marsdenia tenacissima. Phytochem. Lett. 2023, 58, 24–28. [Google Scholar] [CrossRef]
  65. Liu, Q.W.; Chen, C.H.; Wang, X.F.; Jiang, K.; Qu, S.J.; Dai, Y.R.; Tan, C.H. Triterpenoids, megastigmanes and hydroxycinnamic acid derivatives from Anisomeles indica. Nat. Prod. Res. 2019, 33, 41–46. [Google Scholar] [CrossRef] [PubMed]
  66. Yang, H.H.; Oh, K.E.; Jo, Y.H.; Ahn, J.H.; Liu, Q.; Turk, A.; Jang, J.Y.; Hwang, B.Y.; Lee, M.K. Characterization of tyrosinase inhibitory constituents from the aerial parts of Humulus japonicus using LC-MS/MS coupled online assay. Bioorg. Med. Chem. 2018, 26, 509–515. [Google Scholar] [CrossRef] [PubMed]
  67. DellaGreca, M.; Di Marino, C.; Zarrelli, A.; D’Abrosca, B. Isolation and phytotoxicity of apocarotenoids from Chenopodium album. J. Nat. Prod. 2004, 67, 1492–1495. [Google Scholar] [CrossRef]
  68. Wang, H.L.; Ding, J. Extraction Method of Neoflavonoid Compound. Patent CN111732617, 1 October 2020. [Google Scholar]
  69. Otsuka, H.; Yao, M.; Kamada, K.; Takeda, Y. Alangionosides G-M: Glycosides of megastigmane derivatives from the leaves of Alangium premnifolium. Chem. Pharm. Bull. 1995, 43, 754–759. [Google Scholar] [CrossRef]
  70. De Tommasi, N.; Piacente, S.; De Simone, F.; Pizza, C. Constituents of Cydonia vulgaris: Isolation and structure elucidation of four new flavonol glycosides and nine new α-ionol-derived glycosides. J. Agric. Food Chem. 1996, 44, 1676–1681. [Google Scholar] [CrossRef]
  71. Srinroch, C.; Sahakitpichan, P.; Techasakul, S.; Chimnoi, N.; Ruchirawat, S.; Kanchanapoom, T. 2-Aminobenzoyl and megastigmane glycosides from Wrightia antidysenterica. Phytochem. Lett. 2019, 29, 61–64. [Google Scholar] [CrossRef]
  72. Michalska, K.; Galanty, A.; Le, T.N.; Malarz, J.; Vuong, N.Q.; Pham, V.C.; Stojakowska, A. New polyesterified ursane derivatives from leaves of Maesa membranacea and their cytotoxic activity. Molecules 2021, 26, 7013. [Google Scholar] [CrossRef] [PubMed]
  73. Manome, T.; Hara, Y.; Ishibashi, M. A new 1, 2-diketone physalin isolated from Physalis minima and TRAIL-resistance overcoming activity of physalins. J. Nat. Med. 2023, 77, 370–378. [Google Scholar] [CrossRef] [PubMed]
  74. Ninh, B.H.; Dung, D.T.; Tai, B.H.; Yen, P.H.; Nhiem, N.X.; Hien, T.T.T.; Kiem, P.V. New isopropyl chromone and flavanone glucoside compounds from the leaves of Syzygium cerasiforme (Blume) Merr. & LM Perry and their inhibition of nitric oxide production. Chem. Biodiver. 2023, 20, e202201048. [Google Scholar] [CrossRef]
  75. Thao, N.P.; Linh, K.T.P.; Quan, N.H.; Trung, V.T.; Binh, P.T.; Cuong, N.T.; Nam, N.H.; Thanh, N.V. Cytotoxic metabolites from the leaves of the mangrove Rhizophora apiculata. Phytochem. Lett. 2022, 47, 51–55. [Google Scholar] [CrossRef]
  76. Kornpointner, C.; Hochenegger, N.J.; Shi, B.B.; Berger, A.; Theiner, J.; Brecker, L.; Schinnerl, J. Phytochemistry meets geochemistry—Blumenol C sulfate: A new megastigmane sulfate from Palicourea luxurians (Rubiaceae: Palicoureeae). Molecules 2022, 27, 7284. [Google Scholar] [CrossRef]
  77. Thapsut, M.; Singha, S.; Seeka, C.; Sutthivaiyakit, S. Megastigmanes from the aerial part of Euphorbia heterophylla. Phytochem. Lett. 2021, 44, 42–47. [Google Scholar] [CrossRef]
  78. Uyen, N.H.; Widyowati, R.; Sulistyowaty, M.I.; Sugimoto, S.; Yamano, Y.; Kawakami, S.; Otsuka, H.; Matsunami, K. Firmosides A and B: Two new sucrose ferulates from the aerial parts of Silene firma and evaluation of radical scavenging activities. J. Nat. Med. 2020, 74, 796–803. [Google Scholar] [CrossRef]
  79. Deng, L.; Zong, W.; Tao, X.; Liu, S.; Feng, Z.; Lin, Y.; Liao, Z.; Chen, M. Evaluation of the therapeutic effect against benign prostatic hyperplasia and the active constituents from Epilobium angustifolium L. J. Ethnopharmacol. 2019, 232, 1–10. [Google Scholar] [CrossRef] [PubMed]
  80. Lin, Q.M.; Wang, Y.; Yu, J.H.; Liu, Y.L.; Wu, X.; He, X.R.; Zhou, Z.W. Tyrosinase inhibitors from the leaves of Eucalyptus globulus. Fitoterapia 2019, 139, 104418. [Google Scholar] [CrossRef]
  81. Yan, J.; Shi, X.; Donkor, P.O.; Zhu, H.; Gao, X.; Ding, L.; Qiu, F. Nine pairs of megastigmane enantiomers from the leaves of Eucommia ulmoides Oliver. J. Nat. Med. 2017, 71, 780–790. [Google Scholar] [CrossRef]
  82. Phetkul, U.; Hayiawae, N.; Khunthong, S.; Daus, M.; Voravuthikunchai, S.P.; Tamvapee, P.; Watanapokasin, R.; Chakthong, S. Zanthoisobutylamides A−C: Rare dimeric C-6 substituent dihydrobenzophenanthridine alkaloids from the roots of Zanthoxylum nitidum. Nat. Prod. Res. 2023, 37, 1249–1257. [Google Scholar] [CrossRef]
  83. Rahim, A.; Saito, Y.; Miyake, K.; Goto, M.; Nakagawa-Goto, K. Novel seco-phenanthroquinolizidine alkaloids from Indonesian Boehmeria virgata. Phytochem. Lett. 2021, 45, 132–136. [Google Scholar] [CrossRef]
  84. Shen, D.Y.; Kuo, P.C.; Huang, S.C.; Hwang, T.L.; Chan, Y.Y.; Shieh, P.C.; Ngan, N.T.; Thang, T.D.; Wu, T.S. Constituents from the leaves of Clausena lansium and their anti-inflammatory activity. J. Nat. Med. 2017, 71, 96–104. [Google Scholar] [CrossRef] [PubMed]
  85. Vitek, R.; de Novais, L.M.; Torquato, H.F.; Paredes-Gamero, E.J.; de Carvalho, M.G.; de Sousa, P.T., Jr.; Jacinto, M.J.; da Silva, V.C. Chemical constituents and antileukemic activity of Eugenia dysenterica. Nat. Prod. Res. 2017, 31, 1930–1934. [Google Scholar] [CrossRef]
  86. Lee, M.; Lee, H.H.; Lee, J.K.; Ye, S.K.; Kim, S.H.; Sung, S.H. Anti-adipogenic activity of compounds isolated from Idesia polycarpa on 3T3-L1 cells. Bioorg. Med. Chem. Lett. 2013, 23, 3170–3174. [Google Scholar] [CrossRef] [PubMed]
  87. Sob, S.V.T.; Wabo, H.K.; Tang, C.P.; Tane, P.; Ngadjui, B.T.; Ye, Y. Phenol esters and other constituents from the stem barks of Stereospermum acuminatissimum. J. Asian Nat. Prod. Res. 2011, 13, 1128–1134. [Google Scholar] [CrossRef] [PubMed]
  88. Tip-pyang, S.; Limpipatwattana, Y.; Khumkratok, S.; Siripong, P.; Sichaem, J. A new cytotoxic 1-azaanthraquinone from the stems of Goniothalamus laoticus. Fitoterapia 2010, 81, 894–896. [Google Scholar] [CrossRef] [PubMed]
  89. Chiang, Y.M.; Liu, H.K.; Lo, J.M.; Chien, S.C.; Chan, Y.F.; Lee, T.H.; Su, J.K.; Kuo, Y.H. Cytotoxic constituents of the leaves of Calocedrus formosana. J. Chin. Chem. Soc. 2003, 50, 161–166. [Google Scholar] [CrossRef]
  90. Pan, W.B.; Chang, F.R.; Wei, L.M.; Wu, Y.C. New flavans, spirostanol sapogenins, and a pregnane genin from Tupistra chinensis and their cytotoxicity. J. Nat. Prod. 2003, 66, 161–168. [Google Scholar] [CrossRef]
  91. Chen, C.Y.; Chang, F.R.; Teng, C.M.; Wu, Y.C. Cheritamine, A new N-fatty acyl tryptamine and other constituents from the stems of Annona cherimola. J. Chin. Chem. Soc. 1999, 46, 77–86. [Google Scholar] [CrossRef]
  92. Van Nguyen Thien, T.; Do, L.T.M.; Dang, P.H.; Huynh, N.V.; Dang, H.P.; Nguyen, T.T.; Tran, K.T.; Huu, N.D.M.; That, Q.T. A new lignan from the flowers of Hibiscus sabdariffa L. (Malvaceae). Nat. Prod. Res. 2021, 35, 2218–2223. [Google Scholar] [CrossRef]
  93. Sheng, Z.; Dai, H.; Pan, S.; Wang, H.; Hu, Y.; Ma, W. Isolation and characterization of an α-glucosidase inhibitor from Musa spp.(Baxijiao) flowers. Molecules 2014, 19, 10563–10573. [Google Scholar] [CrossRef] [PubMed]
  94. Ding, H.; Hu, X.; Xu, X.; Zhang, G.; Gong, D. Inhibitory mechanism of two allosteric inhibitors, oleanolic acid and ursolic acid on α-glucosidase. Inter. J. Biol. Macromol. 2018, 107, 1844–1855. [Google Scholar] [CrossRef] [PubMed]
  95. Peng, X.; Zhang, G.; Liao, Y.; Gong, D. Inhibitory kinetics and mechanism of kaempferol on α-glucosidase. Food Chem. 2016, 190, 207–215. [Google Scholar] [CrossRef] [PubMed]
  96. Van Do, T.N.; Nguyen, H.X.; Truong, T.Q.; Ly, D.T.; Dang, N.M.T.; Le, T.H.; Nguyen, M.T.T. Some terpenoid compounds from the ethyl acetate extract of Annona muricata L. leaves and their α-glucosidase inhibitory activity. Sci. Technol. Dev. J. Nat. Sci. 2024, 8, 1–7. (In Vietnamese) [Google Scholar] [CrossRef]
  97. Tabussum, A.; Riaz, N.; Saleem, M.; Ashraf, M.; Ahmad, M.; Alam, U.; Jabeen, B.; Malik, A.; Jabbar, A. α-Glucosidase inhibitory constituents from Chrozophora plicata. Phytochem. Lett. 2013, 6, 614–619. [Google Scholar] [CrossRef]
  98. Liu, Y.; Zhan, L.; Xu, C.; Jiang, H.; Zhu, C.; Sun, L.; Sun, C.; Li, X. α-Glucosidase inhibitors from Chinese bayberry (Morella rubra Sieb. et Zucc.) fruit: Molecular docking and interaction mechanism of flavonols with different B-ring hydroxylations. RSC Adv. 2020, 10, 29347–29361. [Google Scholar] [CrossRef]
  99. Wang, J.; Zhao, J.; Yan, Y.; Liu, D.; Wang, C.; Wang, H. Inhibition of glycosidase by ursolic acid: In vitro, in vivo and in silico study. J. Sci. Food Agric. 2020, 100, 986–994. [Google Scholar] [CrossRef]
  100. Khusnutdinova, E.F.; Petrova, A.V.; Thu, H.N.T.; Tu, A.L.T.; Thanh, T.N.; Thi, C.B.; Bavkov, D.; Kazakova, O.B. Structural modifications of 2,3-indolobetulinic acid: Design and synthesis of highly potent α-glucosidase inhibitors. Bioorg. Chem. 2019, 88, 102957. [Google Scholar] [CrossRef]
  101. Li, N.; Yang, J.; Wang, C.; Wu, L.; Liu, Y. Screening bifunctional flavonoids of anti-cholinesterase and anti-glucosidase by in vitro and in silico studies: Quercetin, kaempferol and myricetin. Food Biosci. 2023, 51, 102312. [Google Scholar] [CrossRef]
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Figure 1. The chemical structure of isolated compounds 1–16 from the leaves of E. parviflora.
Figure 1. The chemical structure of isolated compounds 1–16 from the leaves of E. parviflora.
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Figure 2. The binding mode of ursolic acid (4) with α-glucosidase enzyme.
Figure 2. The binding mode of ursolic acid (4) with α-glucosidase enzyme.
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Figure 3. The binding modes of compounds 5, 6, and 7 with α-glucosidase enzyme.
Figure 3. The binding modes of compounds 5, 6, and 7 with α-glucosidase enzyme.
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Table 1. The distribution of compounds 1–2, 4–7, and 14–15 in the Embelia plants.
Table 1. The distribution of compounds 1–2, 4–7, and 14–15 in the Embelia plants.
CompoundsNamePlantsPartsReferences
1β-SistosterolE. ribesleaves[3]
2DaucosterolE. rowlandiileaves[5]
E. ribesleaves[3]
4Ursolic acidE. ribesleaves[9]
5KaempferolE. ribesleaves[9]
6KaempferinE. ribesleaves[9]
7QuercitrinE. ribesleaves[9]
14Vanillic acidE. laetaleaves[11]
15Syringic acidE. laetaleaves[11]
Table 2. The partial distribution of compounds 3, 8–13, and 16.
Table 2. The partial distribution of compounds 3, 8–13, and 16.
CompoundsSpeciesFamilyReferences
3-O-(6′-O-Palmitoyl)-β-D-glucopyranosyl stigmasterol (3)Myrsine pellucidaPrimulaceae[42]
Labisia pumilaPrimulaceae[57]
Monochoria vaginalisPontederiaceae[58]
Quercetin-3-rhamnoside-3′-glucoside (8)Myrsine seguiniiPrimulaceae[47]
(6R,9R)-9-Hydroxy-4,7-megastigmadien-3-one (9)Peperomia heyneanaPiperaceae[59]
Nelumbo nuciferaNelumbonaceae[60]
Valeriana officinalis var. latifoliaCaprifoliaceae[61]
Manglietia aromaticaMagnoliaceae[62]
Tradescantia albifloraCommelinaceae[63]
Grasshopper ketone (10)Nelumbo nuciferaNelumbonaceae[60]
Marsdenia tenacissimaApocynaceae[64]
Anisomeles indicaLamiaceae[65]
Humulus japonicusCannabaceae[66]
Chenopodium albumChenopodiaceae[67]
(6R,7E,9R)-9-Hydroxy-4,7-megastigmadien-3-one, 9-O-β-D-Apiofuranosyl(1->6)-β-D-glucopyranoside (11)Eriobotrya japonicaRosaceae[68]
Alangium premnifoliumCornaceae[69]
Cydonia vulgarisRosaceae[70]
Wrightia antidysentericaApocynaceae[71]
Vomifoliol (12)Maesa membranaceaPrimulaceae[72]
Physalis minimaSolanaceae[73]
Syzygium cerasiformeMyrtaceae[74]
Rhizophora apiculataRhizophoraceae[75]
Palicourea adustaRubiaceae[76]
Euphorbia heterophyllaEuphorbiaceae[77]
Silene firmaCaryophyllaceae[78]
Epilobium angustifoliumOnagraceae[79]
Eucalyptus globulusMyrtaceae[80]
Eucommia ulmoidesEucommiaceae[81]
Methyl trans-p-coumarate (13)Zanthoxylum nitidumRutaceae[82]
Boehmeria virgataUrticaceae[83]
Clausena lansiumRutaceae[84]
Eugenia dysentericaMyrtaceae[85]
Idesia polycarpaSalicaceae[86]
Stereospermum acuminatissimumBignoniaceae[87]
Goniothalamus laoticusAnnonaceae[88]
Calocedrus formosanaCupressaceae[89]
Tupistra chinensisLiliaceae[90]
Annona cherimolaAnnonaceae[91]
Hibiscus sabdariffaMalvaceae[92]
Sotolone (16)Quararibea funebrisBombacaceae[55]
Table 3. α-Glucosidase inhibitory activity of the MeOH extract of E. parviflora and isolated compounds.
Table 3. α-Glucosidase inhibitory activity of the MeOH extract of E. parviflora and isolated compounds.
No.CompoundsIC50 (µg/mL)No.CompoundsIC50 (µg/mL)
11>25699>256
22>2561010>256
33>2561111>256
441.40 ± 0.061212>256
551.75 ± 0.081313>256
66162.13 ± 3.281416>256
77168.01 ± 4.1515MeOH extract12.80 ± 0.62
88>25616Acarbose198.5 ± 6.25
Table 4. Molecular docking results between potential compounds and α-glucosidase.
Table 4. Molecular docking results between potential compounds and α-glucosidase.
CompoundBinding Energy (kcal/mol)Interacted Residues
Active SiteAllosteric Site
4N.D *−9.2Arg175, Ser179, Asn411
5−7.9N.D *Glu304, Arg312, Arg439, Asp408, Phe157
6−9.3N.D *Lys155, Asp349, Phe157, Arg312, His239
7−9.1N.D *Arg312, Glu304,
Acarbose−6.7N.D *Glu304, His279, Pro309, Phe300, Arg312, Glu276, Gln350, Asp349, Tyr313, Asp408, Phe157
* N.D: not determined.
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Thuong, S.D.; Anh, M.T.H.; Phuong, N.V.; Mau, C.H.; Quan, N.H.; Cong, N.T.; Thanh, L.N. Chemical Constituents and α-Glucosidase Inhibitory Activities of the Leaves of Embelia parviflora—In Vitro and In Silico Studies. Life 2025, 15, 680. https://doi.org/10.3390/life15050680

AMA Style

Thuong SD, Anh MTH, Phuong NV, Mau CH, Quan NH, Cong NT, Thanh LN. Chemical Constituents and α-Glucosidase Inhibitory Activities of the Leaves of Embelia parviflora—In Vitro and In Silico Studies. Life. 2025; 15(5):680. https://doi.org/10.3390/life15050680

Chicago/Turabian Style

Thuong, Sy Danh, Mai Thi Hoang Anh, Nguyen Van Phuong, Chu Hoang Mau, Nguyen Huu Quan, Nguyen Thanh Cong, and Le Nguyen Thanh. 2025. "Chemical Constituents and α-Glucosidase Inhibitory Activities of the Leaves of Embelia parviflora—In Vitro and In Silico Studies" Life 15, no. 5: 680. https://doi.org/10.3390/life15050680

APA Style

Thuong, S. D., Anh, M. T. H., Phuong, N. V., Mau, C. H., Quan, N. H., Cong, N. T., & Thanh, L. N. (2025). Chemical Constituents and α-Glucosidase Inhibitory Activities of the Leaves of Embelia parviflora—In Vitro and In Silico Studies. Life, 15(5), 680. https://doi.org/10.3390/life15050680

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