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Review

The Chemical and Pharmacological Research Progress on a Kind of Chinese Herbal Medicine, Fructus Malvae

by
Xiaoyu Li
1,2,3,*,
Xianglei Wang
1,
Menglu Zhao
4,
He Zhang
5 and
Chao Liu
3,*
1
Nanjing University of Chinese Medicine, Nanjing 210023, Jiangsu, China
2
Department of Pharmaceutical Analysis, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210028, Jiangsu, China
3
Department of Endocrinology, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210028, Jiangsu, China
4
Pharmaceutical Sciences, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kanazawa 920-1192, Ishikawa, Japan
5
Department of Pharmacy, The Affiliated Dongnan Hospital of Xiamen University, Zhangzhou 363000, Fujian, China
*
Authors to whom correspondence should be addressed.
Molecules 2022, 27(17), 5678; https://doi.org/10.3390/molecules27175678
Submission received: 15 July 2022 / Revised: 10 August 2022 / Accepted: 16 August 2022 / Published: 2 September 2022
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Abstract

:
Since the outbreak of the COVID-19 pandemic, traditional Chinese medicine has played an important role in the treatment process. Furthermore, the discovery of artemisinin in Artemisia annua has reduced the incidence of malaria all over the world. Therefore, it is becoming urgent and important to establish a novel method of conducting systematic research on Chinese herbal medicine, improving the medicinal utilization value of traditional Chinese medicine and bringing great benefits to human health all over the world. Fructus Malvae, a kind of Chinese herbal medicine which has been recorded in the “Chinese Pharmacopoeia” (2020 edition), refers to the dry, ripe fruits of Malva verticillata L. Recently, some studies have shown that Fructus Malvae exhibits some special pharmacological activities; for example, it has diuretic, anti-diabetes, antioxidant and anti-tumor properties, and it alleviates hair loss. Furthermore, according to the reports, the active ingredients separated and identified from Fructus Malvae contain some very novel compounds such as nortangeretin-8-O-β-d-glucuronopyranoside and 1-O-(6-deoxy-6-sulfo)-glucopyranosyl-2-O-linolenoyl-3-O-palmitoyl glyceride, which could be screened as important candidate compounds for diabetes- or tumor-treatment drugs, respectively. Therefore, in this research, we take Fructus Malvae as an example and systematically summarize the chemical constituents and pharmacological activity research progress of it. This review will be helpful in promoting the development and application of Fructus Malvae and will also provide an example for other investigations of traditional Chinese medicine.

1. Introduction

Since the outbreak of the COVID-19 pandemic, the economic development and public health services in many countries and regions have been influenced and challenged [1]. Traditional Chinese medicine (TCM), with thousands of years of history of use and practice in China, has played an important role in the treatment of diseases and the maintenance of human health. In the fight against the COVID-19 pandemic in China, traditional Chinese medicine (TCM) is widely used and has achieved remarkable success [2]. Additionally, the discovery of artemisinin in Artemisia annua has reduced the incidence of malaria around the world [3]. Therefore, it is becoming urgent and important to establish a novel method of conducting systematic research on Chinese herbal medicine, improving the medicinal value of traditional Chinese medicine and bringing great benefits to human health all over the world.
Fructus Malvae, a kind of Mongolian medicinal material which has been included in “Chinese Pharmacopoeia” (2020 edition), refers to the dried and ripe fruit of Malva verticillata L. [4] (Figure 1). It is cold in nature, and sweet and astringent in taste, with the effects of clearing away heat, inducing diuresis and reducing swelling [4]. In a clinical setting, it is generally utilized for the treatment of urinary retention, edema, thirst, urinary tract infection, etc. The original production area of Fructus Malvae is Inner Mongolia [5]. Additionally, it also grows in Shandong, Hebei, Sichuan and many other provinces in China [6,7]. Fructus Malvae has been used for more than 2000 years in China. From “Shen Nong’s Materia Medica” to the “Compendium of Materia Medica” to the “Illustrated Catalogue of Plants” [8,9,10], there are plenty of related records and descriptions of it. Furthermore, Fructus Malvae is also included in four current editions of Chinese herbal medicine processing specifications, including the Chinese Herbal Medicine Processing Specifications of Jiangxi Province (2008 edition), the Chinese Herbal Medicine Processing Specifications of Hunan Province (2010 edition), the Chinese Herbal Medicine Processing Specifications of Guangxi Province (2007 edition) and the Chinese herbal medicine processing specification of Gansu Province (2009 edition). Fructus Malvae is included in the national medical insurance reimbursement list, as well. All of this indicates that it is very necessary and significant to further study the medicinal value of Fructus Malvae.
Recently, some studies have found that Fructus Malvae performs some very special pharmacological activities; for example, it has anti-diabetes, antioxidant and anti-tumor properties, it alleviates hair loss, etc. Furthermore, according to the reports, the active ingredients separated and identified from Fructus Malvae contain some very novel compounds, such as nortangeretin-8-O-β-d-glucuronopyranoside and 1-O-(6-deoxy-6-sulfo)-glucopyranosyl-2-O-linolenoyl-3-O-palmitoyl glyceride, which could be screened as important candidate compounds for diabetes- and tumor-treatment drugs, respectively. Myristoleic acid was isolated and identified from dichloromethane extract, and linolenic acid was isolated and identified from n-butanol extract, which are the two main active compounds of Fructus Malvae in the treatment of hair loss. Therefore, in this study, we take Fructus Malvae as an example and systematically summarize the chemical constituents and pharmacological activities of it. This review will be helpful in promoting the development and application of the medicinal value of Fructus Malvae and will also provide an example for the investigation of other traditional Chinese medicines.

2. Research Progress on Chemical Constituents

As a kind of Chinese herbal medicine with more than 2000 years of history of application, certain studies have been performed on the chemical constituents of Fructus Malvae. The medicinal parts studied include the fruit [7,11,12,13,14,15,16,17,18,19,20], the seed [21,22,23,24,25,26,27,28,29,30] and the stem, leaf and seed mixture [31,32,33,34,35] of Malva verticillata L. Common extraction methods include ultrasonic extraction [22,31], soaking in solution at room temperature [32,33,34], boiling in hot water [23] and refluxing extraction [4]. Solvents including 80% methanol [32,33,34], 90% ethanol [31], 95% ethanol [21], ethanol [22,24], distilled water [22,23], ethyl acetate [22], n-butanol [32], n-hexane [21] and methylene chloride [22] are often used for their extraction, elution and purification. The extraction, separation and purification process of the chemical components of Fructus Malvae is usually as follows: Fructus Malvae or the stem, leaf and seed mixture of Malva verticillata L. are extracted using a certain solvent through ultrasound, soaking at room temperature or heating under reflux. The extraction solution is filtered and concentrated under reduced pressure to obtain the corresponding extracts. Then, the extracts are dissolved and sequentially extracted using different solvents [32,33,34]. The compounds are separated and purified from different solvent fractions via column chromatography. Finally, the compounds are identified and characterized by using NMR, IR, FAB-MS, GC-MS, HPLC, UPLC-QTOF-MS or other instrumental analysis methods [32,33,34].
The chemical compounds identified from Fructus Malvae include 9 acid compounds (compounds 1–9), 21 flavonoids (compounds 10–30), 3 sterols (compounds 31–33), 17 glycerides (compounds 34–50), 24 volatile oils (compounds 51–74), 9 polysaccharides (compounds 75–83), 15 amino acids (compounds 84–98) and 5 other compounds (compounds 99–103). Among them, caffeic acid and ferulic acid are two phenolic acid compounds identified from Fructus Malvae [7,11,12,13,14,15,16,17]. The two compounds are often selected as indicator components for the qualitative or quantitative analysis of Fructus Malvae in the associated drug standards or literature. UPLC-QTOF-MS/MS semi-quantitative analysis shows that the contents of the flavonoids hypericin and kaempferol-3-O-rutinoside are the highest in the seeds of Malva verticillata L. [31]. In addition, Nortangeretin-8-O-β-d-glucuronide, isoscutellarein 8-O-glucuronopyranosid, hypolaetin 8-O-glucuronopyranoside, herbacetin 8-O-glucuronopyranoside, herbacetin 3-O-glucopyranosyl-8-O-glucuronopyranoside and isoscutellarein 7-O-glucopyranoside are six flavonoids identified from the stem, leaf and seed mixture of Malva verticillata L., and 8-O-glucuronide, attached to the flavonoid moiety, has rarely been reported in plant systems [32]. There are 13 glycosylglycerides included in 17 glycerides, according to the reports [33,34]. Among them, 1-O-galactopyranosyl-3-O-isostearoyl glyceride (compound 42) is a novel glycosylglyceride compound. 1-O-(6-deoxy-6-sulfo)-glucopyranosyl-2-O-linolenoyl-3-O-palmitoyl glyceride and 1-O-(6-deoxy-6-sulfo)-glucopyranosyl-2,3-di-O-linolenoyl glyceride (compounds 38, 39) are two sulfoquinovosyl glycerides, which contain a unique chemical structure “(6-deoxy-6-sulfo)-a-d-glucopyranose” rarely reported in plants [34].

2.1. Acid Compounds

For the acid compounds identified from Fructus Malvae, caffeic acid [7,11,12,13,14,15] and ferulic acid [7,15,16,17] are two phenolic acids and they are often screened as marker compounds of Fructus Malvae for qualitative or quantitative analysis in the associated drug standards or literature. In terms of extraction methods, in the Chinese Pharmacopoeia (2020 vision), Fructus Malvae was extracted using 70% ethanol under heating and refluxing, and then, caffeic acid was determined via thin-layer chromatography [4]. In addition, in some other studies, Fructus Malvae was also extracted via water decoction, ultrasonic extraction or Soxhlet extraction; then, the caffeic acid was determined via high-performance liquid chromatography [15]. The extraction, separation and identification methods of ferulic acid are similar to that of caffeic acid [15,16,17]. The stem, leaf and seed mixture of Malva verticillata L. was extracted using 90% ethanol under ultrasound; after that, four fatty-acid compounds (compounds 3–6) were identified from extracts based on UPLC-QTOF-MS/MS analysis [31]. In another study, Fructus Malvae was extracted using ethanol, and then, the extraction was successively extracted using dichloromethane, ethyl acetate, water, n-hexane and other solvents. Finally, linolenic acid and oleic acid were isolated and identified from n-butanol extract [21] and myristoleic acid (compound 8) was separated and identified from dichloromethane extract [22], which are three polyunsaturated fatty-acid compounds contained in Fructus Malvae. Additionally, palmitic acid, a kind of saturated fatty acid, was also identified using GC/MS from the water extract of Fructus Malvae [23]. The information and chemical structures of the acid compounds identified from Fructus Malvae are shown in Table 1 and Figure 2.

2.2. Flavonoids

For the flavonoids identified from Fructus Malvae, 21 flavonoids (compounds 10–30) have been determined so far. A total of 14 flavonoid compounds (compounds 10–23) were identified via UPLC-QTOF-MS/MS from a 90% ethanol extract of the stem, leaf and seed mixture of Fructus Malvae [31]. In another study, the stem, leaf and seed mixture was extracted using 80% methanol at room temperature for 24 h, and then, successively extracted using water, ethyl acetate and n-butanol. A total of six flavonoid compounds, including nortangeretin-8-O-β-d-glucuronopyranoside (compound 25), isoscutellarein 8-O-β-d-glucuronopyranoside (compound 26), hypolaetin8-O-β-d-glucuronopyranoside (compound 27), herbacetin-8-O-β-d-glucuronopyranoside (compound 29) and isoscutellarein 7-O-β-d-glucopyranoside (compound 30), were separated and identified from the water extract [32]. Among the six flavonoids, ortangeretin-8-O-β-d-glucuronopyranoside is a new compound. The 5,6,7,8-tetrahydroxy group and the 8-O-glucuronide attached to the A ring of the flavonoid moiety are rarely reported in plants [32]. Additionally, the study also proved that 8-O-glucuronide attached to the flavonoid moiety was crucial for the antioxidant activity of Fructus Malvae [32]. The flavonoid rutin was separated and identified from the EtOAc extract of Fructus Malvae using UV, IR, MS and some other technologies [18]. The chemical names, molecular formulas and chemical structures of all the identified flavonoids are shown in Table 2 and Figure 3.

2.3. Sterols

For sterols separated from Fructus Malvae, there are only three sterol compounds identified from Fructus Malvae. They are β-sitosterol, verticilloside and daucosterol. Fructus Malvae was ultrasonically extracted using ethanol for 6 h, and then, the extraction was successively extracted using dichloromethane, ethyl acetate and water. Sterols including β-sitosterol, verticilloside and daucosterol were identified from the dichloromethane extraction [22]. The above sterol compounds could also be separated using other extraction methods [18,23,24]. The information on and chemical structures of the sterol compounds identified from Fructus Malvae are shown in Table 3 and Figure 4.

2.4. Glycerides

For glycerides, so far, there have been 17 glyceride compounds separated and identified from Fructus Malvae [33,34]. The stem, leaf and seed mixture of Fructus Malvae was extracted using 80% methanol; after that, the extract was dissolved and extracted using water, ethyl acetate and n-butanol, in sequence. After column chromatography, 17 glyceride compounds, including 13 glycosylglycerides, were identified from the n-butanol extraction through NMR, IR, FAB-MS and GC-MS analysis [33,34]. 1-O-palmitoyl glyceride, 1-O-stearoyl glyceride and 1-O-linolenoyl glyceride were three monoacylglyceride compounds, while 1,2-di-O-linoleoyl glyceride was a diacylglyceride compound. The above four glyceride compounds all showed antitumor activity [33]. Regarding the structure–activity relationship, monoacylglycerides have stronger antitumor activity than diacylglycerides. Furthermore, for monoacylglycerides, the longer the carbon chain of fatty acids, the better the antitumor activity; unsaturated fatty acids show better activity than saturated fatty acids [33]. Among the 13 glycosylglycerides, 1-O-galactopyranosyl-3-O-isostearoyl glyceride (compound 42) is a novel glycosylglyceride compound. 1-O-(6-deoxy-6-sulfo)-glucopyranosyl-2-O-linolenoyl-3-O-palmitoyl glyceride and 1-O-(6-deoxy-6-sulfo)-glucopyranosyl-2,3-di-O-linolenoyl glyceride (compounds 38, 39) are two sulfoquinovosyl glycerides, and both of them contain a unique chemical structure “(6-deoxy-6-sulfo)-a-d-glucopyranose” which is rarely reported in plants [34]. The chemical names, molecular formulas and chemical structures of the 17 glycerides are shown in Table 4 and Figure 5.

2.5. Volatile Oils

For the volatile oils, there are 24 volatile oil compounds identified from Fructus Malvae in total. Volatile oils are often extracted via water-vapor distillation. An appropriate amount of Fructus Malvae powder is weighed and soaked in water for 12 h, and finally, a volatile oil extractor is used for steam distillation for 8 h. The effluent is collected and extracted using n-hexane; after that, it is dried using anhydrous sodium sulfate [19,20]. The information and chemical structures of the 24 volatile oil compounds, identified via GC-MS analysis, are shown in Table 5 and Figure 6.

2.6. Polysaccharides

For the polysaccharides, seven polysaccharides and two oligosaccharides have been identified from Fructus Malvae so far. The water extraction and alcohol precipitation methods were used for polysaccharides extraction. Then, the obtained crude polysaccharides were separated and purified via column chromatography [28]. After dealing with periodate oxidation, the smith degradation reaction, methylation analysis, partial acid hydrolysis and an enzymatic reaction, the monosaccharide composition and structural characteristics of the polysaccharides were determined via thin-layer chromatography (TLC), high-performance liquid chromatography (HPLC), GC-MS analysis, gel chromatography analysis, nuclear magnetic resonance (NMR) analysis and electrophoresis analysis [26,27,28]. At present, the polysaccharides identified from Fructus Malvae mainly include the neutral polysaccharides MVS-I, MVS-IIA, MVS-IIG, the acidic polysaccharides MVS-IIIA, MVS-IVA, MVS-VI and the peptidoglycan MVS-V [25,26,27,28,29,30]. The monosaccharide composition and molar ratio of the neutral polysaccharide MVS-Ⅰ were determined to be l-arabinose:d-galactose:d-glucose = 3:6:7 [26,28], and the monosaccharide composition and molar ratio of the acidic polysaccharide MVS-VI were l-arabinose:d-xylose:d-glucose:l-rhamnose:d-galacturonic acid = 30:15:20:3:2:10 [27]. In addition, the oligosaccharides sucrose and raffinose were also isolated and identified from the dichloromethane extract of Malva verticillata seeds [22]. The information and chemical structures are summarized in Table 6 and Figure 7.

2.7. Amino Acids

For amino acids, 15 amino acids have been detected from Fructus Malvae at present (Table 7 and Figure 8). The medicinal powder of Fructus Malvae was soaked in water for 12 h, and then, boiled in hot water for half an hour. It was filtered, the filtrates were combined and the supernatant was taken after centrifugation. After that, the supernatant was eluted using a 732 cation-exchange resin. Finally, a total of 14 amino acids were detected using the amino acid automatic analysis and test system [14,18]. Furthermore, tryptophan was the 15th amino acid detected from n-butanol or 90% ethanol extracts of the Malva verticillata stem, leaf and seed mixture [31,35]. Additionally, tryptophan showed a synergistic antidiabetic effect together with 3,5,6,9-tetrahydroxy-7-megastigmene in [35].

2.8. Other Substances

In addition to the above substances, oleamide, 1,3-dihydroxyacetone dimer, 5-hydroxymethyl furfural, 2-hydroxy-gamma-butyrolactone and other compounds were identified via GC-MS from the water extract of Fructus Malvae [23]. The compound 3,5,6,9-tetrahydroxy-7-megastigmene was identified from the n-butanol extract of the Malva verticillata stem, leaf and seed mixture [35]. Additionally, 15 trace elements including K, Na, Ca, Mg, Fe, Mn, Zn, Cu, Cr, Se, Pb, Al, Cd, Mo and Ni were also detected from Fructus Malvae using an atomic absorption spectrophotometer [36]. The chemical name, molecular formula, medicinal parts and chemical structures are summarized in Table 8 and Figure 9.

3. Research Progress on Pharmacological Activity

Shizhen Li recorded the following in the “Compendium of Materia Medica”: “Kui, the smell and taste both are light. The character of light and slippery belongs to yang. Therefore, it could promote lactation, reduce swelling and induce abortion. Its roots and leaves have the same function as the seeds”. In the Chinese Pharmacopoeia (2020 edition), it is described as follows: “Fructus Malvae has the effects of clearing heat, inducing diuresis and reducing swelling”. In addition, Fructus Malvae also shows some other pharmacological effects such as having anti-diabetes, antioxidant and anti-tumor properties, the alleviation hair loss, etc. As shown in Table 9.

3.1. Diuretic Effect

The diuretic effect is the typical pharmacological effect of Fructus Malvae, as reported in Chinese Pharmacopoeia (2020 edition) and in the literature. Additionally, it is usually used to treat urinary retention, edema and thirst in a clinical setting [4,31]. Furthermore, heart failure [37,38], liver cirrhosis ascites [39,40], urinary calculi [41,42], hypertensive nephropathy [41] and other diseases often need diuretic drugs for treatment in a clinical setting. With regard to animal experiments, the rat metabolic-cage experiment is often utilized to detect the diuretic effect of drugs [43,44,45]. Additionally, male SD rats [46] or Wistar rats [47] are generally selected. Usually, the rats are fasted for 12–18 h, after pressing the abdomen of the rats to drain the remaining urine in the bladder, 0.9% normal saline or deionized water is administered to form a water-loaded rat model [44,48,49]. Hydrochlorothiazide or furosemide are often selected as positive drugs [47,48], and the urine volume, concentration of electrolytes (sodium ion, chloride ion and potassium ion) and the urine pH are measured to help analyze the diuretic effects [50]. For the rat metabolic-cage diuretic experiment of Fructus Malvae, the medicinal powder was refluxed using 70% ethanol, and then, extracted usinf petroleum ether, ethyl acetate, n-butanol and water, respectively, to obtain different solvent extracts [18]. The medication administration groups were given different solvent extracts, and the positive control group was given hydrochlorothiazide [18]. Compared with the negative control group, the results showed that the petroleum ether extract and ethyl acetate extract of Fructus Malvae could significantly increase the urine volume of rats. Additionally, the petroleum ether extract also significantly increased the urinary potassium excretion of rats, showing a strong diuretic effect [18].

3.2. Anti-Diabetic Effect

At present, the ethyl acetate extract, n-butanol extract, water extract and n-hexane extracts of Fructus Malvae show an anti-diabetic effect [32,35]. Additionally, flavonoids including nortangeretin-8-O-β-d-glucuronide, hypolaetin 8-O-β-d-glucuronopyranoside, herbacetin 8-O-β-d-glucuronopyranoside, isoscutellarein 7-O-β-d-glucopyranoside and polysaccharides (including neutral polysaccharide MVS-Ⅰ, peptidoglycan MVS-V and peptidoglycan-enriched fraction MVS-V-C) also showed anti-diabetic activity [29,32]. l-tryptophan and 3,5,6,9-tetrahydroxy-7-megastigmene showed synergistic antidiabetic effect [35]. Most of them were experimentally validated at the whole animal level. Alloxan-induced islet-damage models in zebrafish larvae, type 2 diabetes db/db mice and L6 myotube cells are the common experimental models utilized in anti-diabetes activity studies [24,32,35]. The administration of the method includes soak absorption, oral administration, incubation and intraperitoneal injection [24,29,32,35]. Common detection indicators include fasting blood glucose; body weight; islet size; triglycerides; low-density lipoproteins; high-density lipoproteins; total cholesterol; liver and kidney weight and histopathology; the cytokines TNF-α, IL-1 and IL-6; aspartate aminotransferase; alanine aminotransferase, etc. [51,52].
For the anti-diabetic study of Fructus Malvae, zebrafish larvae were placed in a 24-well plate and exposed to 600 μM alloxan solution for 3 h to build the islet cell injury model [32,35]. After that, the zebrafish were treated with n-butanol, ethyl acetate water extractions (10 μg/mL) and the six flavonoids (0.1 μM) separated from Fructus Malvae for 12 h. Glimepiride was used as a positive drug in the control group [32]. As result, the nortangeretin-8-O-β-d-glucuronide (25), hypolaetin 8-O-β-d-glucuron opyranoside (27), herbacetin 8-O-β-d-glucuronopyranoside (28) and isoscutellarein 7-O-β-d-glucopyranoside (30) significantly increased the size of the damaged islets. Additionally, compounds 25 and 30 significantly increased the insulin secretion by regulating KATP channels compared with the model group [32]. 3,5,6,9-tetrahydroxy-7-megastigmene (103) and tryptophan (85) were isolated from the n-butanol extract of Fructus Malvae [35]. The zebrafish models were treated with n-butanol extract (10 μg/mL), the two compounds mentioned above and a mixture of them (1 μg/mL) for 12 h [35]. Compared with the model groups after treatment, compound 103 and compound 85 increased the size of the damaged islets by 22.3% and 18.9%, respectively, while the mixture of the two compounds increased the size of the damaged islets by 48.6%, indicating that 3,5,6,9-tetrahydroxy-7-megastigmene (103) and tryptophan (85) obviously exhibit synergistic antidiabetic activity [35]. In another study, the type 2 diabetic mice (db/db) were administrated the n-hexane extract of Fructus Malvae (40 mg/kg) for 4 weeks. The result showed that the non-fasting blood glucose and fasting blood glucose of the mice decreased by 17.1% and 23.3%, respectively [24]. Meanwhile, the phosphorylation levels of AMPK and ACC significantly increased. Furthermore, β-sitosterol (31) was the main active compound in this n-hexane extraction [24]. The neutral polysaccharide MVS-I (75) contained in Fructus Malvae also showed hypoglycemic activity, according to [29].
Clinically, diabetes is a kind of chronic metabolic disease [53,54], often accompanied by complications such as diabetic nephropathy, diabetic retinopathy, diabetic foot and cardiovascular disease [54,55,56], which are extremely harmful to human health. Exercise, dietary intervention and drug therapy are generally used for the treatment of diabetes [57,58]. In terms of drug treatment, insulin, metformin, glimepiride and other drugs are generally used clinically, but they would also lead to some adverse reactions such as hypotension, obesity, etc. [58]. The use of Fructus Malvae in the treatment of diabetes may produce synergistic effects with above western drugs, reducing the corresponding toxic and side-effects. Therefore, further research on the anti-diabetic effect of Fructus Malvae would be of great benefit. In addition, the above findings will also contribute to the discovery of new antidiabetic drugs.

3.3. Antioxidant Effect

So far, the 90% ethanol extract of Fructus Malvae and flavonoids—including nortangeretin-8-O-β-d-glucurono pyranoside, isoscutellarein 8-O-β-d-glucuronopyranoside, hypolaetin 8-O-β-d-glucuronopyranoside, herbacetin 8-O-β-d-glucuronopyranoside, herbacetin 3-O-β-d-glucopyranosyl-8-O-β-d-glucuronopyranoside and isoscutellarein 7-O-d-glucopyranoside—separated and identified from the stem, leaf and seed mixture of Malva verticillata L. has shown anti-oxidant activity [31,32]. The DPPH free-radical scavenging test [59,60], ABTS free-radical scavenging test [61,62], total-antioxidant capacity assay (FRAP) [63], oxygen-radical absorbance capacity (ORAC) assay [64] and superoxide scavenging activity assay were used to determine the antioxidant activity of Fructus Malvae and its related active ingredients in vitro. DPPH EC50, ABTS EC50, ORAC, SOD EC50, etc. were calculated as the detection indicators.
For the anti-oxidant study of Fructus Malvae, in the DPPH free-radical scavenging test, the free-radical scavenging activity of 90% ethanol extract of Malva verticillata leaves was 12.62 ± 0.41 mg AAE/g extract, of the stems was 5.15 ± 0.19 mg AAE/g extract and of the seeds was 22.14 ± 0.59 mg AAE/g extract [31]. These results indicated that the seeds of Malva verticillata L. (Fructus Malvae) had a better DPPH free-radical scavenging activity than the stems and leaves. Meanwhile, in the ABTS free-radical scavenging test and total-antioxidant capacity assay (FRAP)—wherein antioxidant activity was evaluated by measuring the absorbance value of the ABTS free-radical working solution at 734 nm and the absorbance value of the FRAP working solution at 539 nm, respectively—the 90% ethanol extract of the leaves showed better antioxidant activity than the stems and seeds [31]. In another study, nortangeretin-8-O-β-d-glucuronopyranoside, isoscutellarein 8-O-β-d-glucuronopyranoside, hypolaetin 8-O-β-d-glucuronopyranoside, herbacetin 8-O-β-d-glucuronopyranoside, and herbacetin 3-O-β-d-glucopyranosyl-8-O-β-d-glucuronopyranoside showed significant antioxidant activity in the ABTS, ORAC, SOD tests [32]. Additionally, the results indicated that the 8-O-glucuronide attached to a flavonoid moiety was a key structure of the antioxidant activity. Due to the presence of a 1,2,3-trihydroxy benzene moiety in the flavonoid A-ring and a 1,2-dihydroxy benzene moiety in the flavonoid B-ring, nortangeretin-8-O-β-d-glucuronopyranoside and hypolaetin 8-O-β-d-glucuronopyranoside showed especially high antioxidant activity in the ABTS and ORAC assays [32].
In a clinical setting, it is widely accepted that antioxidant effects are mostly related to age-related diseases [65], such as cardiovascular disease [66,67], non-alcoholic fatty liver disease [67], vascular dementia [68], Graves’ ophthalmopathy [69], cancer [70,71], diabetes [72], etc. ROS, including hydrogen peroxide (H2O2), hydroxyl radical (•OH), singlet oxygen (1O2), superoxide (O22−), etc., is a group of unstable molecules produced by various cells in the human body. These free radicals could take part in human metabolism, immunity, growth, differentiation and many other homeostatic processes [73,74,75]. The cells and tissues will be damaged oxidatively and stay in a pathological state when ROS is excessively produced in the body [76]. At that time, antioxidative drugs are needed to resist the peroxidative effect of ROS on the human body. The above research and discoveries would be very beneficial and promising for the discovery of new antioxidative drugs.

3.4. Antitumor Effect

The ethyl acetate extract, n-butanol extract, water extract and 17 glycerides identified from Fructus Malvae or the stem, leaf and seed mixture of Malva verticillata L. show significant anti-tumor activity [33,34]. They have all been verified at the cellular level. Splenocytes, natural killer (NK) cells, human liver cancer cells (HepG2) [77], human gastric cancer cells (AGS), human colorectal cancer cells (HCT) and human non-small-cell lung cancer calls (A549) [77,78] were selected as the experimental models to verify the anti-tumor activity of Fructus Malvae. Splenocyte proliferation ability, natural killer (NK) cell activity, AGS cell apoptosis percentage, and the expression of the apoptosis proteins PARP, Cleaved APRP, Caspase-3, Cleaved Caspase-3, Bcl-2, Bax, β-actin, etc. were detected as indicators in the study [33,34]. In addition to the above cell experiments, tumor-bearing mice have also been used to verify anti-tumor activity at the animal experimental level in other studies [79,80,81]. Additionally, tumor volume and mass; thymus index; spleen index; the serum cytokines IL-2, IL-4 and TNF-α; IFN-ɤ levels and tumor histopathology could be detected as detection indicators [82]. Additionally, usually, splenocyte and tumor cells would be cultured in RPMI1640 medium or in DMEM medium, which contains 10% fetal bovine serum (FBS) and 1% penicillin-streptomycin [83,84]. The proliferation ability or the viability of tumor cells can be measured using tetramethylazolyl blue (MTT method) or Cell Counting Kit 8 (CCK8) [83]. The apoptosis of tumor cells can be measured using a Tali apoptosis assay kit. The migration ability of tumor cells can be measured using the scratch method or transwell-migration method. Western blot is generally used to measure the expression of apoptosis, its pathway and other related proteins in tumor cells [85].
For the anti-tumor study of Fructus Malvae, the monoacylglycerides (2S)-1-O-palmitoyl glyceride (compound 34), (2S)-1-O-stearoyl glyceride (compound 35) and (2S)-1-O-linolenoyl glyceride (compound 36), separated and identified from the stem, leaf and seed mixture of Malva verticillata, significantly enhanced the proliferation ability of splenocytes and the activity of natural killer cells against tumor cells at 10 μM [33]. Meanwhile, diacylglyceride (2S)-1,2-di-O-linoleoyl glyceride showed weaker activity. The results indicated that monoacylglycerides exhibited stronger antitumor activity than diacylglycerides. Additionally, the longer the carbon chain of fatty acids, the better the antitumor activity in monoacylglycerides [33]. Additionally, unsaturated fatty acids showed better activity than saturated fatty acids [33]. In another study, 13 glycosylglycerides identified from the stem, leaf and seed mixture of Malva verticillata L. showed cytotoxicity against HepG2, AGS, HCT-15 and A549 human cancer cells in in vitro cell experiments [34]. Among them, the chemical structures of two glycosylglycerides (compounds 38 and 39) contained a unique glycosyl group (6-deoxy-6-sulfo)-α-d-glucopyranosyl) and they showed especially significant cytotoxicity to AGS tumor cell, increasing the apoptosis of AGS cells and affecting the expression of apoptotic proteins [34].
In a clinical setting, surgery, chemotherapy, interventional therapy, immunization and targeted therapy are often used for the treatment of cancers/tumors [86,87]. Cytotoxic drugs such as cyclophosphamide, hormonal drugs such as exemestane, and monoclonal antibodies such as rituximab are often used in the treatment process [88]. However, these therapeutic drugs are often accompanied by serious toxic and side effects, easily resulting in liver and kidney damage [89,90], hair loss [91], drug resistance [87], etc. A study developed by He Zhu et al. found that the combination of traditional Chinese medicine and western medicine can produce a synergistic anti-tumor effect and reduce the toxic and side-effects of the drug [92]. Fructus Malvae may be beneficial in such an application. Furthermore, the above findings would also be beneficial for the discovery of new anti-tumor drugs.

3.5. Treatment of Hair Loss

Extracts of 95% ethanol, ethanol, n-hexane and dichloromethane of Fructus Malvae showed pharmacological activity in treating hair loss [21,22]. Linoleic acid and myristoleic acid were two active compounds. They were all verified at the cellular level by human dermal papilla cells (DPCs) [21,22]. A cell proliferation ability, the expression of Wnt/β-catenin signaling pathway proteins and cell growth factor were detected as detection indicators. Additionally, mice can also be used. For this, the hair on the back of the mice is removed to build a model. The growth rate and appearance of the hair, the number of hair follicles, the hormone levels in the mouse blood, the growth factors in the mouse skin cells, and the histological morphology can be observed or measured to verify the pharmacological activity in the treatment of hair loss.
For the hair-loss-treatment study of Fructus Malvae, a study confirmed that linolenic acid can activate the Wnt/β-catenin signaling pathway and increase the expression of cyclins such as cyclinD1, CDK2 and the cell growth factors VEGF, IGF-1, etc. in a dose-dependent manner [21]. When the administration concentration increased from 10 μg/mL to 30 μg/mL, the HFDPC cell proliferation rate increased by 21.46% [21], while oleic acid showed no relevant pharmacological activity. In addition, another research team found that the dichloromethane extract of Fructus Malvae and the active compound myristoleic acid separated from it also showed a therapeutic effect on hair loss [22]. Similar to the effect of linolenic acid, myristoleic acid can activate the Wnt/β-catenin signaling pathway and promote the proliferation of DPCs cell in the treatment of hair loss [22].
In a clinical setting, due to the advancement of technology, the accelerated pace of life, life pressure, work pressure and unhealthy work and diet habits, hair loss has become an important health problem faced by people. According to a population epidemiological survey, about 70% of the population in China is suffering from hair loss, and the phenomenon of hair loss shows a serious trend in youth [93]. Clinically, alopecia refers to a skin disorder characterized by hair loss, and includes androgenetic alopecia (seborrheic alopecia), alopecia areata and congenital alopecia [93,94]. Minoxidil and finasteride are often used to treat androgenetic alopecia, while steroids and retinoic acid are often used to treat alopecia areata [94]. However, the external use of minoxidil can easily cause dermatitis and increases the amount of body hair; finasteride can easily cause hormonal disorders and sexual dysfunction in the human body; and steroids can easily lead to scalp shrinkage and full-moon face [93,94]. The findings above indicate that Fructus Malvae may become a new choice for the treatment of hair loss.

3.6. Other Pharmacological Effects

In addition to the pharmacological effects above, Fructus Malvae also shows the potential ability to treat pathological bone disease [23], enhancing reticuloendothelial system activity and increasing anti-complement activity [25,26,27,28,29,30]. A study identified 14 compounds using GC-MS analysis from the water extract of Fructus Malvae. The results indicated that the water extract could inhibit the RANKL signaling pathway, and further inhibited osteoclastogenesis and bone resorption. Therefore, Fructus Malvae could also be used as a supplementary alternative drug for the treatment of pathological bone diseases [23]. Most of the polysaccharide components reported in Fructus Malvae showed the effect of enhancing reticuloendothelial system activity and anti-complement activity. More detailed information can be found in references [20,25,26,27,28,29].

4. Summary and Discussion

The outbreak of the COVID-19 pandemic has brought great harm and challenges to the economic development and public health services of many countries and regions [95,96]. In China, traditional Chinese medicine is used in the treatment of COVID-19 and has obtained remarkable success [97]. The Lianhua Qingwen capsule is one of the most widely reported [98]. Additionally, the discovery of artemisinin in Artemisia annua has reduced the incidence of malaria around the world [3]. Therefore, it is becoming urgent and important to establish a novel method of conducting systematic research on Chinese herb medicine, to bring great benefits to human health all over the world.
Fructus Malvae, a kind of Chinese herb medicine, refers to the dried and ripe fruit of Malva verticillata L. [4]. So far, certain studies have been performed at home and abroad that are associated with the chemical composition and biological activity of Fructus Malvae. The chemical composition of Fructus Malvae is varied, mainly including 9 acid compounds (phenolic acids and fatty acids), 21 flavonoids, 3 sterols, 17 glycerides, 24 kinds of volatile oil, 9 kinds of polysaccharide, 15 kinds of amino acid and 5 other compounds. The above compounds and different solvent extracts of Fructus Malvae have shown various pharmacological activities according to the reports, including having diuretic, anti-diabetic, anti-oxidative and anti-tumor effects, treating hair loss, etc.
The mixture of the stems, leaves and seeds of Malva verticillata L. was extracted using 80% methanol at room temperature for 24 h. The extract was filtered and concentrated under reduced pressure to obtain methanol extract, which was dispersed in water, and then, extracted using ethyl acetate and n-butanol in sequence [32,33,34]. Six flavonoids, including nortangeretin-8-O-β-d-glucuronopyranoside (compound 25), isoscutellarein 8-O-β-d-glucuronopyranoside (compound 26), hypolaetin 8-O-β-d-glucurono pyranoside (compound 27), herbacetin-8-O-β-d-glucuronopyranoside (compound 29) and isoscutellarein 7-O-β-d-glucopyranoside (compound 30) were separated and identified from the water extract [32]. Compound 25 is a new compound, and the 5,6,7,8-tetrahydroxy group and the 8-O-glucuronide attached to the A ring of the flavonoid moiety are rarely reported in plants [32]. A total of 17 glycerides were separated from n-butanol extracts [33,34] (compound 34–50), and among them, there are 13 glycosylglycerides (compounds 38–50) [34]. Additionally, tryptophan (compound 85) and 3,5,6,9-tetrahydroxy-7-megastigmene (103) were also identified from n-butanol extracts [35]. Among them, compounds 34, 35 and 36 are monoacylglycerides, while compound 37 is a diacylglyceride [33]. Studies have confirmed that monoacylglycerides are more active than diacylglycerides. Additionally, among monoacylglycerides, the longer the fatty-acid carbon chain, the better the activity, and the unsaturated fatty acid is more active than the saturated fatty acid [33]. 1-O-galactopyranosyl-3-O-isostearoyl glyceride (compound 42) is a novel glycosylglyceride compound. 1-O-(6-deoxy-6-sulfo)-glucopyranosyl-2-O-linolenoyl-3-O-palmitoyl glyceride and 1-O-(6-deoxy-6-sulfo)-glucopyranosyl-2,3-di-O-linolenoyl glyceride (compounds 38, 39) are two sulfoquinovosyl glycerides, and both of them contain a unique chemical structure “(6-deoxy-6-sulfo)-a-d-glucopyranose” which is rarely reported in plants [34]. Tryptophan (85), the precursor of 5-hydroxytryptophan (5-HT) and melatonin, is a kind of essential amino acid [35]. The ratio of compounds 85 and 103 in the n-butanol extract was 1.96:1. Fructus Malvae was extracted using ethanol, and then, extracted using dichloromethane, ethyl acetate, water, n-hexane and other solvents. Myristoleic acid (compound 8) was isolated and identified from dichloromethane extract [22] and linolenic acid was isolated and identified from n-butanol extract [21], which are two polyunsaturated fatty-acid compounds.
In terms of pharmacological activity, the diuretic activity of Fructus Malvae was studied using the rat metabolic-cage diuretic test [18]. The petroleum ether and ethyl acetate extract of Fructus Malva significantly increased the urine output of water-loaded rats. Additionally, the petroleum ether extract also significantly increased their urinary potassium content [18]. In antidiabetic studies, the ethyl acetate, n-butanol, water and n-hexane extracts of Fructus Malva (or of the mixture of stems, leaves and seeds) showed antidiabetic activity [32,35]. The flavonoids nortangeretin-8-O-β-d-glucuronide, hypolaetin8-O-β-d-glucuronopyranoside, herbacetin 8-O-β-d-glucuronopyranoside and isoscutellarein 7-O-β-d-glucopyranoside were able to significantly increase the size of alloxan-injured zebrafish islets, and the study also confirmed that nortangeretin-8-O-β-d-glucuronide and isoscutellarein 7-O-β-d-glucopyranoside were able to block K+ ions channel in islet β cells to increase the size of alloxan-injured zebrafish islets [32]. In addition, 3,5,6,9-tetrahydroxy-7-megastigmene and tryptophan in Fructus Malva also showed significant synergistic antidiabetic activity [35]. When given 1 μg/mL of two compounds, the size of damaged islets in zebrafish was increased by 22.3% and 18.9%, respectively, while their mixture increased the size of damaged islets by 48.6% [35]. The sterol compound β-sitosterol, the neutral polysaccharide MVS-I, the peptidoglycan MVS-V and the peptidoglycan-enriched fraction MVS-V-CH of the polysaccharides also showed activity in the treatment of diabetes [24,29]. For the experimental animal model, in addition to the alloxan-induced zebrafish islet cell-damage model [32,35], a db/db mouse model of type 2 diabetes was also used [24]. In antioxidant research, the DPPH free-radical scavenging assay, the ABTS free-radical scavenging assay, the FRAP total-antioxidant capacity-measurement experiment, the ORAC oxygen-radical absorption capacity-measurement experiment and the SOD superoxide dismutase scavenging assay were used to determine the antioxidant capacity of the of chemical substances in mallow fruit in vitro [31,32]. The 70% ethanol-extracted fraction and six flavonoids identified from Fructus Malvae showed strong antioxidant activity in vitro [31,32]. In a study of anti-tumor activity, the anti-tumor activity of Fructus Malva was verified using immune cells such as splenocytes, natural killer cells (NK), and human tumor cells such as HepG2, AGS, HCT-15 and A549 [33,34]. The glyceride compounds (2S)-1-O-palmitoyl glyceride, (2S)-1-O-stearoyl glyceride and (2S)-1-O-linolenoyl glyceride can significantly increase the proliferation ability of splenocytes and the activity of natural killer cells against tumor cells [33]. Thirteen glycosylglycerides have shown antitumor activity against HepG2, AGS, HCT-15 and A549 human tumor cells [34]. 1-O-(6-deoxy-6-sulfo)-glucopyranosyl-2-O-linolenoyl-3-O-palmitoyl glyceride, 1-O-(6-deoxy-6-sulfo)-glucopyranosyl-2,3-di-O-linolenoyl glyceride and 1-O-6′-O-(-galactopyranosyl)-galactopyranosyl-2,3-di-O-palmitoyl glyceride have particularly significant effects on AGS tumor cells, accelerating tumor cell apoptosis and influencing the expression of apoptosis proteins such as PARR, caspase-3, Bcl-2, Bax and β-actin [34]. In studies of the treatment of hair loss, the 95% ethanol/ethanol, n-hexane and dichloromethane extracts showed a therapeutic effect on hair loss [21,22]. Linolenic acid and myristoleic acid, two kind of fatty acid in Fructus Malva, significantly activated the Wnt/β-catenin signaling pathway and promoted the proliferation of human dermal papilla cell DPCs, which could become a new choice for the treatment of hair loss [21,22].
With the improvement of industrialization, lifestyle changes, unhealthy eating habits, obesity/overweight and other factors, the incidence of diabetes is increasing year by year [99]. Globally, there are 382 million people, about 8.3% of the population, suffering from diabetes. Furthermore, diabetes has become the main cause of death for people under 60 years old [99]. Therefore, it is of great clinical value and prospect to further study the anti-diabetes effect of Fructus Malvae. So far, there have been six flavonoids (compounds 25–30) isolated and identified from the water extract of Fructus Malvae, showing potential antidiabetic effects (Figure 10) [32]. Among them, nortangeretin-8-O-β-d-glucuronopyranoside (compound 25) is a new compound. The 5,6,7,8-tetrahydroxyl and 8-O-glucuronide attached to the A ring of the flavonoid group are novel structures that are rarely reported in plants [32]. Experiments have confirmed that nortangeretin-8-O-β-d-glucuronopyranoside can significantly recover alloxan-induced islet damage and block the K+ channel of islet β-cells in zebrafish. What’s more, so dose isoscutellarein 7-O-β-d-glucopyranoside (compound 30) [32] (as shown in Figure 11). They could be selected as important candidate compounds for a diabetes-treatment drug. Regarding methodological design, male SD rats can also be used instead of the zebrafish mentioned above. They should be fed high-fat and high-sugar diets for 4–6 weeks, and 1% streptozotocin or alloxan should be injected via intraperitoneal injection to build a type 2 diabetes rat model [100,101,102]. Furthermore, db/db mice could also be used directly to verify the anti-diabetic effect of Fructus Malvae [103,104].
Cancer is the leading cause of death in people before the age of 70. According to the “2020 Global Cancer Statistics” released by the American Cancer Society, there were 19.3 million new cancer cases and 10 million cancer deaths worldwide in 2020. There were 4.136 million new cancer cases in China, accounting for 21.0% of the global new cancer cases. The top five cancers, ranked by mortality rate, are lung cancer, colorectal cancer, liver cancer, gastric cancer and female breast cancer [105]. Therefore, it is necessary to further research the anticancer effect of Fructus Malva. Among the 17 glyceride compounds (compounds 34–50) [33,34] identified from the n-butanol extract of Fructus Malva, compounds 38–50 are glycosylglyceride compounds (Figure 10), which show significant cytotoxicity against the human hepatoma cell HepG2, the human gastric cancer cell AGS, the human colorectal cancer cell HCT-15 and the human non-small-cell lung cancer cell A549 [34]. The glycosylglycerides (2S)-1-O-(6-deoxy-6-sulfo)-α-d-glucopyranosyl-2-O-linolenoyl-3-O-palmitoyl glyceride and (2S)-1-O-(6-deoxy-6-sulfo)-α-d-glucopyranosyl-2,3-di-O-linolenoyl glyceride (compounds 38, 39) were isolated from Fructus Malva for the first time and have rarely been reported in plants before. Both compounds contained a unique chemical structure (6-deoxy-6-sulfo)-α-d-glucopyranosyl, which also rarely occurred before. They showed significant cytotoxicity to AGS tumor cells. They accelerated the apoptosis of AGS cells, and significantly affected the expression of apoptotic proteins such as PARP, caspase-3, Bcl-2, Bax and β-actin [34] (Figure 12). They could be further studied as candidate compounds for antitumor drugs. At the same time, monoacylglycerides compounds 34, 35 and 36 significantly enhanced the proliferation ability of spleen cells and the antitumor activity of natural killer cells, and their activity was stronger than that of the diacylglyceride 1,2-di-O-linoleoyl glyceride (compound 37) [33]. Additionally, for the methodological design, in addition to verification at the cellular level, tumor-bearing mice could also be used in research [106]. By evaluating the tumor volume and mass, thymus index, spleen index, serum cytokine levels, tumor histopathology, etc. [82], the anti-tumor activity of Fructus Malva and its active ingredients could be further verified at the level of animal experiments.
At present, some drug standards, including the Chinese Pharmacopoeia (2020 edition), the Traditional Chinese Medicine Processing Specifications of Jiangxi Province (2008 edition), the Traditional Chinese Medicine Processing Specifications of Hunan Province (2010 edition), the Traditional Chinese Medicine Processing Specifications of Guangxi Province (2007 edition), Traditional Chinese Medicine Processing Specifications of Gansu Province (2009 edition), etc. have standardized the production and inspection processes of Fructus Malvae. However, so far, there have still been serious mixed-sales and mixed-use phenomena for Fructus Malva and its confounded medicinal material, Abutili Semen, in the medicinal material market and clinical use, bringing certain obstacles to further research on the medicinal value of Fructus Malvae. At the same time, although Fructus Malva is widely used in clinical settings, its application mainly focuses on the classic pharmacological activity and diuretic effect of Fructus Malvae. Other promising pharmacological activities such as anti-diabetic effect, anti-tumor effect and treatment of hair loss still stay at the level of basic research, which are the focus of current research. This is not only a challenge, but also an opportunity for the development of the medicinal value of Fructus Malvae.

Author Contributions

Conceptualization, X.L. and X.W.; writing—original draft preparation, X.L.; methodology, M.Z.; software, H.Z.; validation, X.L., X.W. and M.Z.; data curation, H.Z.; writing—review and editing, X.L., M.Z. and C.L.; visualization, X.W.; supervision, C.L.; funding acquisition, X.L. and C.L. All authors have read and agreed to the published version of the manuscript.

Funding

This research was funded by the National Key Research and Development Plan of China (No. 2019YFC1711000) and the National Natural Science Foundation of China (No. 81503365, 81873094).

Institutional Review Board Statement

Not applicable.

Informed Consent Statement

Not applicable.

Data Availability Statement

Not applicable.

Conflicts of Interest

The authors declare that there are no conflicts of interest concerning this paper.

References

  1. Gruber, J.; Prinstein, M.J.; Clark, L.A.; Rottenberg, J.; Abramowitz, J.S.; Albano, A.M.; Aldao, A.; Borelli, J.L.; Chung, T.; Davila, J.; et al. Mental health and clinical psychological science in the time of COVID-19: Challenges, opportunities, and a call to action. Am. Psychol. 2021, 76, 409–426. [Google Scholar] [CrossRef] [PubMed]
  2. Guan, W.; Lan, W.; Zhang, J.; Zhao, S.; Ou, J.; Wu, X.; Yan, Y.; Wu, J.; Zhang, Q. COVID-19: Antiviral Agents, Antibody Development and Traditional Chinese Medicine. Virol. Sin. 2020, 35, 685–698. [Google Scholar] [CrossRef] [PubMed]
  3. Tu, Y. Artemisinin-A Gift from Traditional Chinese Medicine to the World (Nobel Lecture). Angew. Chem. Int. Ed. Engl. 2016, 55, 10210–10226. [Google Scholar] [CrossRef] [PubMed]
  4. National Pharmacopoeia Commission, Pharmacopoeia of the People’s Republic of China, (2020 Edition Part one); China Pharmaceutical Science and Technology Press: Beijing, China, 2020; p. 120.
  5. Wu, Z. Identification of Malvae Semen and Abutili Semen. J. Clin. Med. 2018, 5, 184–186. [Google Scholar]
  6. Gao, T.; Xin, T.; Song, J.; Song, J. Identification of Malvae Semen and Abutili Semen using ITS2 DNA barcode. Chin. Tradit. Herb. Drugs 2017, 48, 2740–2745. [Google Scholar]
  7. Ma, Q.; Dong, Y.; Na, S.; Li, X.; Li, S. Determination of Total Phenolic Acid in Fructus malvae. Li Shizhen Med. Mater. Med. Res. 2010, 21, 2583–2584. [Google Scholar]
  8. Zhong, Y. Interpretation of “Shen Nong’s Materia Medica”—Malvae Semen. Yishou Baodian 2018, 34, 40. [Google Scholar]
  9. Cai, Y.; Li, C.; Zou, J. Examination and discussion on some Chinese herb medicine names recorded in “Chinese Pharmacopoeia”. Chin. Tradit. Herb. Drugs 2005, 36, 1104–1106. [Google Scholar]
  10. Qi, Z. The evolution of “Kui” and textual research of its original plant. HeBei J. For. Orchard Res. 2010, 25, 255–262. [Google Scholar]
  11. Ma, Q.; Dong, Y.; Zhu, X.; Li, S. TLC Identification of Mongolia Medicine Fructus Malvae. China Pharm. 2010, 19, 17–18. [Google Scholar]
  12. Dong, Y.; Ma, Q.; Na, S.; Li, X.; Li, S. Quantitative determination of caffeic acid in Dongkuiguo (Fructus Malvae, Mongolian medicated herb) by HPLC. J. Beijing Univ. Tradit. Chin. Med. 2010, 33, 117–119. [Google Scholar]
  13. Wang, H.; Wang, S.; Dong, Y.; Li, S. The experimental study on traditional mongolian materia medica of Fructus Malvae. J. Inn. Mong. Med. Coll. 2012, 34, 69–72. [Google Scholar]
  14. Menghebilige; Wu, X. Research progress of Mongolian medicinal material Fructus Malva. Chin. J. Ethn. Med. 2012, 18, 37–40. [Google Scholar]
  15. Hu, Y.; Li, X.; Shi, H.; Liu, Y.; Mao, Q.; Yan, L. Effects of Different Extraction Methods on the Content of Caffeic Acid and Ferulic Acid in Malvae Fructus. Asia-Pac. Tradit. Med. 2022, 18, 57–60. [Google Scholar]
  16. Zhang, A.; Liu, L.; Luo, S.; Qian, Y. Determination of Ferulic Acid in Malvae Fructus by HPLC. Chin. Pharm. Assoc. 2010, 5, 2752–2756. [Google Scholar]
  17. Wunierqiqige; Liu, B. Disperses the Puncture Vine, the Mallow Fruit quality specification fumble research to Therr Taste Puncture Vines. North. Pharm. 2014, 11, 1–3. [Google Scholar]
  18. He, X. Study on Material Base and Quality Specification of Fruit Malva verticillate; Chengdu University of Chinese Medicine: Chengdu, China, 2006. [Google Scholar]
  19. Gao, F. Analysis on volatile oil of Mongolian medicine Malvae Fructus. J. Med. Pharm. Chin. Minoritie. 2021, 27, 41–43. [Google Scholar]
  20. Li, Z.; Xu, N.; Yang, L.; Zhang, L.; Wang, Q. Analysis on chemical constituents of volatile oil from Mongolian medicine Malvae Fructus. Chin. Tradit. Pat. Med. 2008, 06, 922–924. [Google Scholar]
  21. Ryu, H.S.; Jeong, J.; Lee, C.M.; Lee, K.S.; Lee, J.N.; Park, S.M.; Lee, Y.M. Activation of Hair Cell Growth Factors by Linoleic Acid in Malva verticillata Seed. Molecules 2021, 26, 2117. [Google Scholar] [CrossRef]
  22. Lee, E.Y.; Choi, E.J.; Kim, J.A.; Hwang, Y.L.; Kim, C.D.; Lee, M.H.; Roh, S.S.; Kim, Y.H.; Han, I.; Kang, S. Malva verticillata seed extracts upregulate the Wnt pathway in human dermal papilla cells. Int. J. Cosmet. Sci. 2016, 38, 148–154. [Google Scholar] [CrossRef]
  23. Shim, K.S.; Lee, C.J.; Yim, N.H.; Ha, H.; Ma, J.Y. A water extract of Malva verticillata seeds suppresses osteoclastogenesis and bone resorption stimulated by RANK ligand. BMC Complement. Altern. Med. 2016, 16, 332. [Google Scholar] [CrossRef] [PubMed]
  24. Jeong, Y.-T.; Song, C.-H. Antidiabetic activities of extract from Malva verticillata seed via the activation of AMP-activated protein kinase. J. Microbiol. Biotechnol. 2011, 21, 921–929. [Google Scholar] [CrossRef] [PubMed]
  25. Gonda, R.; Tomoda, M.; Kanari, M.; Shimizu, N.; Yamada, H. Constituents of the seed of Malva verticillata. VI. Characterization and immunological activities of a novel acidic polysaccharide. Chem. Pharm. Bull. (Tokyo) 1990, 38, 2771–2774. [Google Scholar] [CrossRef] [PubMed]
  26. Shimizu, N.; Tomoda, M. Constituents of the seed of Malva verticillata. I. Structural features of the major neutral polysaccharide. Chem. Pharm. Bull. (Tokyo) 1987, 35, 4981–4984. [Google Scholar] [CrossRef] [PubMed]
  27. Tomoda, M.; Shimizu, N.; Gonda, R.; Kanari, M.; Yamada, H.; Hikino, H. Anti-complementary and hypoglycemic activities of the glycans from the seeds of Malva verticillata. Planta Med. 1990, 56, 168–170. [Google Scholar] [CrossRef] [PubMed]
  28. Tomoda, M.; Asahara, H.; Gonda, R.; Takada, K. Constituents of the seed of Malva verticillata. VIII. Smith degradation of MVS-VI, the major acidic polysaccharide, and anti-complementary activity of products. Chem. Pharm. Bull. (Tokyo) 1992, 40, 2219–2221. [Google Scholar] [CrossRef]
  29. Shimizu, N.; Asahara, H.; Tomoda, M.; Gonda, R.; Ohara, N. Constituents of seed of Malva verticillata. VII. Structural features and reticuloendothelial system-potentiating activity of MVS-I, the major neutral polysaccharide. Chem. Pharm. Bull. (Tokyo) 1991, 39, 2630–2632. [Google Scholar] [CrossRef]
  30. Gonda, R.; Tomoda, M.; Shimizu, N.; Kanari, M. Characterization of an acidic polysaccharide from the seeds of Malva verticillata stimulating the phagocytic activity of cells of the RES. Planta Med. 1990, 56, 73–76. [Google Scholar] [CrossRef]
  31. Bao, L.; Bao, X.; Li, P.; Wang, X.; Ao, W. Chemical profiling of Malva verticillata L. by UPLC-Q-TOF-MS and their antioxidant activity in vitro. J. Pharm. Biomed. Anal. 2018, 150, 420–426. [Google Scholar] [CrossRef]
  32. Ko, J.-H.; Nam, Y.H.; Joo, S.-W.; Kim, H.G.; Lee, Y.G.; Kang, T.H.; Baek, N.I. Flavonoid 8-O-Glucuronides from the aerial parts of Malva verticillata and their recovery effects on alloxan-induced pancreatic islets in zebrafish. Molecules 2018, 23, 833. [Google Scholar] [CrossRef]
  33. Ko, J.-H.; Castaneda, R.; Joo, S.-W.; Kim, H.G.; Lee, Y.G.; Lee, Y.H.; Kang, T.H.; Baek, N.I. Glycerides isolated from the aerial parts of Malva verticillata cause immunomodulation effects via splenocyte function and NK anti-tumor activity. Food Sci. Biotechnol. 2018, 27, 1023–1030. [Google Scholar] [CrossRef] [PubMed]
  34. Ko, J.-H.; Cho, S.M.; Joo, S.-W.; Kim, H.G.; Lee, Y.G.; Kang, S.C.; Baek, N.I. Glycosyl glycerides from the aerial parts of Malva verticillata and their chemopreventive effects. Bio. Chem. 2018, 78, 381–392. [Google Scholar] [CrossRef] [PubMed]
  35. Ko, J.-H.; Rodriguez, I.; Joo, S.-W.; Kim, H.G.; Lee, Y.G.; Kang, T.H.; Baek, N.I. Synergistic effect of two major components of Malva verticillata in the recovery of alloxan-damaged pancreatic islet cells in zebrafish. J. Med. Food 2019, 22, 196–201. [Google Scholar] [CrossRef] [PubMed]
  36. Xi, J.; Zhang, G.; Wang, J. Determination of Great and Trace Elements in Mongolia Traditional Herbs Malva verticillata L. Chin. J. Ethn. Med. 2005, 02, 31–45. [Google Scholar]
  37. Felker, G.M.; Ellison, D.H.; Mullens, W.; Cox, Z.L.; Testani, J.M. Diuretic Therapy for Patients With Heart Failure: JACC State-of-the-Art Review. J. Am. Coll. Cardiol. 2020, 75, 1178–1195. [Google Scholar] [CrossRef]
  38. Liu, X. Study on the intensive diuretic effect of Xinshuai No. 1 formula in the treatment of chronic heart failure. Stud. Trace Elem. Health 2018, 35, 8–9. [Google Scholar]
  39. Liu, Q.; Wei, L.; Chen, Y.; Li, W.; Liang, X. Study on the Effect of Abutilon indicum(L.) Sweet on Cirrhotic Ascites and Diuretic. J. Liaoning Univ. TCM 2021, 23, 29–33. [Google Scholar]
  40. Uojima, H.; Hidaka, H.; Nakayama, T.; Sung, J.H.; Ichita, C.; Tokoro, S.; Masuda, S.; Sasaki, A.; Koizumi, K.; Egashira, H.; et al. Efficacy of combination therapy with natriuretic and aquaretic drugs in cirrhotic ascites patients: A randomized study. World J. Gastroenterol. 2017, 23, 8062–8072. [Google Scholar] [CrossRef]
  41. Mariano, L.N.B.; Boeing, T.; Filho, V.C.; Niero, R.; da Silva, L.M.; Souza, P. 1,3,5,6-tetrahydroxyxanthone promotes diuresis, renal protection and antiurolithic properties in normotensive and hypertensive rats. J. Pharm. Pharmacol. 2021, 73, 700–708. [Google Scholar] [CrossRef]
  42. Jing, S.; Gai, Q.; Zhao, X.; Wang, J.; Gong, Y.; Pang, Y.; Peng, C.; Tian, Y.; Wang, Y.; Wang, Z. Physical therapy in the management of stone fragments: Progress, status, and needs. Urolithiasis 2018, 46, 223–229. [Google Scholar] [CrossRef]
  43. Avaid, F.; Mehmood, M.H.; Shaukat, B. Hydroethanolic Extract of A. officinarum Hance Ameliorates Hypertension and Causes Diuresis in Obesogenic Feed-Fed Rat Mode l. Front. Pharmacol. 2021, 12, 670433. [Google Scholar]
  44. Li, M.; Zeng, M.; Zhang, B.; Fan, H.; Wu, G.; La, Z.; Feng, W.; Kuang, H.; Zheng, X. Laboratory Study on Diuretic Effect of Ephedra Decoction and Its Splitting Fractions on Rats. Chin. Arch. Tradit. Chin. Med. 2018, 36, 2203–2206. [Google Scholar]
  45. Ye, X.; Zhu, X.; Liu, T.; Liu, X.; Hui, L.; Feng, W.; Yang, L.; Li, C.; Wang, Z. Diuretic effect and material basis of Clematidis Armandii Caulis in rats. China J. Chin. Mater. Med. 2019, 44, 1889–1894. [Google Scholar]
  46. 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] [PubMed]
  47. Hakim, E.M.; Sivak, K.V.; Kaukhova, I.E. Evaluation of the diuretic effect of crude ethanol and saponin-rich extracts of Herniaria glabra L. in rats. J. Ethnopharmacol. 2021, 273, 113942. [Google Scholar] [CrossRef]
  48. Meng, X.; Chen, Y.; Lili; Bi, L.; Wu, R.; Bai, M. Diuretic mechanism of alcohol extract of Mongolian medicine Althaea rosa on water load model rats. Chin. J. Ethn. Med. 2022, 28, 50–54. [Google Scholar]
  49. Tufer, S.; Engidawork, E.; Ayele, A.G.; Bashea, C. Evaluation of the Diuretic Activity of Aqueous and 80% Methanol Extracts of Croton macrostachyus (Euphorbiaceae) Leaves in Saline-Loaded Rats. J. Exp. Pharmacol. 2021, 13, 213–221. [Google Scholar] [CrossRef] [PubMed]
  50. Zhang, X.; Li, X.Y.; Lin, N.; Zhao, W.L.; Huang, X.Q.; Chen, Y.; Huang, M.Q.; Xu, W.; Wu, S.S. Diuretic Activity of Compatible Triterpene Components of Alismatis rhizoma. Molecules 2017, 22, 1459. [Google Scholar] [CrossRef]
  51. Lu, Q.; Zheng, R.; Zhu, P.; Bian, J.; Liu, Z.; Du, J. Hinokinin alleviates high fat diet/streptozotocin-induced cardiac injury in mice through modulation in oxidative stress, inflammation and apoptosis. Biomed. Pharmacother. 2021, 137, 111361. [Google Scholar] [CrossRef]
  52. Wang, P.; Liu, Y.; Zhang, T.; Yin, C.; Kang, S.Y.; Kim, S.j.; Park, Y.K.; Jung, H.W. Effects of Root Extract of Morinda officinalis in Mice with High-Fat-Diet/Streptozotocin-Induced Diabetes and C2C12 Myoblast Differentiation. ACS Omega 2021, 6, 26959–26968. [Google Scholar] [CrossRef]
  53. Kaul, K.; Tarr, J.M.; Ahmad, S.I.; Kohner, E.M.; Chibber, R. Introduction to diabetes mellitus. Adv. Exp. Med. Biol. 2012, 771, 1–11. [Google Scholar] [PubMed]
  54. Shepard, B.D. Sex differences in diabetes and kidney disease: Mechanisms and consequences. Am. J. Physiol. Renal. Physiol. 2019, 317, F456–F462. [Google Scholar] [CrossRef] [PubMed]
  55. Xiong, J.; Hu, H.; Guo, R.; Wang, H.; Jiang, H. Mesenchymal Stem Cell Exosomes as a New Strategy for the Treatment of Diabetes Complications. Front. Endocrinol. 2021, 12, 646233. [Google Scholar] [CrossRef] [PubMed]
  56. Strain, W.D.; Paldánius, P.M. Diabetes, cardiovascular disease and the microcirculation. Cardiovasc. Diabetol. 2018, 17, 57. [Google Scholar] [CrossRef] [PubMed]
  57. MacPherson, M.; Cranston, K.; Locke, S.; Vis-Dunbar, M.; Jung, M.E. Diet and exercise interventions for individuals at risk for type 2 diabetes: A scoping review protocol. BMJ Open 2020, 10, e039532. [Google Scholar] [CrossRef] [PubMed]
  58. Padhi, S.; Nayak, A.K.; Behera, A. Type II diabetes mellitus: A review on recent drug based therapeutics. Biomed. Pharmacother. 2020, 131, 110708. [Google Scholar] [CrossRef]
  59. Zhang, C.; Yuan, C.; Cheng, Y.; She, R.; Xiao, W. Antioxidant Activity of Alien Invasive Species Eupatorium adenophorum Spreng. Chem. Bioeng. 2022, 39, 35–39, 55. [Google Scholar]
  60. He, W.; Li, X.; Peng, Y.; He, X.; Pan, S. Anti-Oxidant and Anti-Melanogenic Properties of Essential Oil from Peel of Pomelo cv. Guan Xi. Molecules 2019, 24, 242. [Google Scholar] [CrossRef]
  61. Fu, Y.; Wang, Y.; Li, Y.; Zhang, X.; Yuan, P.; Xia, K.; Tan, Z. Study on in vitro anti-inflflammatory and antioxidant activities of flavonoids from sea buckthorn. China Food Addit. 2021, 32, 67–74. [Google Scholar]
  62. Aarland, R.C.; Bañuelos-Hernández, A.E.; Fragoso-Serrano, M.; Sierra-Palacios, E.D.C.; León-Sánchez, F.D.D.; Pérez-Flores, L.J.; Rivera-Cabrera, F.; Mendoza-Espinoza, J. A Studies on phytochemical, antioxidant, anti-inflammatory, hypoglycaemic and antiproliferative activities of Echinacea purpurea and Echinacea angustifolia extracts. Pharm. Biol. 2017, 55, 649–656. [Google Scholar] [CrossRef]
  63. Dżugan, M.; Tomczyk, M.; Sowa, P.; Grabek-Lejko, D. Antioxidant Activity as Biomarker of Honey Variety. Molecules 2018, 23, 2069. [Google Scholar] [CrossRef] [PubMed]
  64. Kuang, X.; Huang, R.; Han, S.; Zhang, Q.; Yan, C.; Li, W. Comparison of Antioxidant Activity of Several Animal Protein-derived Peptides by ORAC. Guangdong Chem. Ind. 2022, 49, 14–15, 52. [Google Scholar]
  65. Xie, J.; Su, T.; Wei, Y.; Li, G.; Wu, J.; Huang, L. Research progress of antioxidant drugs in myocardial ischemiareperfusion injury. Acta Pharm. Sin. 2021, 56, 1845–1855. [Google Scholar]
  66. Choi, S.; Liu, X.; Pan, Z. Zinc deficiency and cellular oxidative stress: Prognostic implications in cardiovascular diseases. Acta Pharm. Sin. 2018, 39, 1120–1132. [Google Scholar] [CrossRef] [PubMed]
  67. Karami, S.; Poustchi, H.; Sarmadi, N.; Radmard, A.R.; Yari, F.A.; Pakdel, A.; Shabani, P. Association of anti-oxidative capacity of HDL with subclinical atherosclerosis in subjects with and without non-alcoholic fatty liver disease. Diabetol. Metab. Syndr. 2021, 13, 121. [Google Scholar] [CrossRef] [PubMed]
  68. Qi, F.X.; Hu, Y.; Li, Y.W.; Gao, J. Levels of anti-oxidative molecules and inflammatory factors in patients with vascular dementia and their clinical significance. Pak. J. Med. Sci. 2021, 37, 1509–1513. [Google Scholar] [CrossRef] [PubMed]
  69. Ko, J.; Kim, J.Y.; Kim, J.W.; Yoon, J.S. Anti-oxidative and anti-adipogenic effects of caffeine in an in vitro model of Graves’ orbitopathy. Endocr. J. 2020, 67, 439–447. [Google Scholar] [CrossRef]
  70. Perillo, B.; Di Donato, M.; Pezone, A.; Di Zazzo, E.; Giovannelli, P.; Galasso, G.; Castoria, G.; Migliaccio, A. ROS in cancer therapy: The bright side of the moon. Exp. Mol. Med. 2020, 52, 192–203. [Google Scholar] [CrossRef]
  71. Srinivas, U.S.; Tan, B.W.Q.; Vellayappan, B.A.; Jeyasekharan, A.D. ROS and the DNA damage response in cancer. Redox Biol. 2019, 25, 101084. [Google Scholar] [CrossRef] [PubMed]
  72. Forrester, S.J.; Kikuchi, D.S.; Hernandes, M.S.; Xu, Q.; Griendling, K.K. Reactive Oxygen Species in Metabolic and Inflammatory Signaling. Circ. Res. 2018, 122, 877–902. [Google Scholar] [CrossRef]
  73. Yang, S.; Lian, G. ROS and diseases: Role in metabolism and energy supply. Mol. Cell. Biochem. 2020, 467, 1–12. [Google Scholar] [CrossRef] [PubMed]
  74. Huang, X.; He, D.; Pan, Z.; Luo, G.; Deng, J. Reactive-oxygen-species-scavenging nanomaterials for resolving inflammation. Mater. Today Bio 2021, 11, 100124. [Google Scholar] [CrossRef] [PubMed]
  75. Li, Q.; Liu, Y.; Dai, X.; Jiang, W.; Zhao, H. Nanozymes Regulate Redox Homeostasis in ROS-Related Inflammation. Front. Chem. 2021, 9, 740607. [Google Scholar] [CrossRef]
  76. Herb, M.; Gluschko, A.; Schramm, M. Reactive Oxygen Species: Not Omnipresent but Important in Many Locations. Front. Cell. Dev. Biol. 2021, 9, 716406. [Google Scholar] [CrossRef] [PubMed]
  77. Li, H.Y.; Li, P.; Yang, H.G.; Wang, Y.Z.; Huang, G.X.; Wang, J.Q.; Zheng, N. Investigation and comparison of the anti-tumor activities of lactoferrin, α-lactalbumin, and β-lactoglobulin in A549, HT29, HepG2, and MDA231-LM2 tumor models. J. Dairy Sci. 2019, 102, 9586–9597. [Google Scholar] [CrossRef]
  78. Xue, X.; Qian, C.; Tao, Q.; Dai, Y.; Lv, M.; Dong, J.; Su, Z.; Qian, Y.; Zhao, J.; Liu, H.; et al. Using bio-orthogonally catalyzed lethality strategy to generate mitochondria-targeting anti-tumor metallodrugs in vitro and in vivo. Natl. Sci. Rev. 2020, 8, nwaa286. [Google Scholar] [CrossRef]
  79. Ju, A.; Du, H.; Yuan, J.; Wan, M.; Zhang, Y.; Li, Z.; Li, D.; Gao, W. Study on anti-tumor effect of Yiqi Fumai Lyophilized Injection combined with cisplatin on breast cancer mice. Drug Eval. Res. 2021, 44, 2372–2378. [Google Scholar]
  80. Zhang, Y.; Yue, Q.; Zhang, L.; Zhang, Y.; Li, P.; Zhang, M. The Effect of Ethanol Extract from Saussurea Medusa Maxim on Anti-tumor Immunity of Lewis Lung Cancer Bearing Mice. Chin. J. Immunol. 2022, 1–17. Available online: http://kns.cnki.net/kcms/detail/22.1126.R.20220303.1819.004.html (accessed on 13 July 2022).
  81. Cao, Y.; Feng, Y.H.; Gao, L.W.; Li, X.Y.; Jin, Q.X.; Wang, Y.Y.; Xu, Y.Y.; Jin, F.; Lu, S.L.; Wei, M.J. Artemisinin enhances the anti-tumor immune response in 4T1 breast cancer cells in vitro and in vivo. Int. Immunol. Pharmacol. 2019, 70, 110–116. [Google Scholar] [CrossRef]
  82. He, S.; Bao, H.; Wei, Y.; Liu, Y.; Liu, J. Antitumor effect and mechanism of different extracts of cultivated Phellinus vaninii on H22 tumor bearing mice. Chin. J. Biotechnol. 2022, 38, 1025–1038. [Google Scholar]
  83. Jin, Y.; Zuo, H.X.; Li, M.Y.; Zhang, Z.H.; Xing, Y.; Wang, J.Y.; Ma, J.; Li, G.; Piao, H.; Gu, P.; et al. Anti-Tumor Effects of Carrimycin and Monomeric Isovalerylspiramycin I on Hepatocellular Carcinoma in Vitro and in Vivo. Front. Pharmacol. 2021, 12, 774231. [Google Scholar] [CrossRef] [PubMed]
  84. Zhao, Y.; Zhang, Y.; Mehdiabad, M.V.; Zhou, K.; Chen, Y.; Li, L.; Guo, J.; Xu, C. Enhanced anti-tumor effect of liposomal Fasudil on hepatocellular carcinoma in vitro and in vivo. PLoS ONE 2019, 14, e0223232. [Google Scholar] [CrossRef] [PubMed]
  85. Youness, R.A.; Gad, A.Z.; Sanber, K.; Ahn, Y.J.; Lee, G.J.; Khallaf, E.; Hafez, H.M.; Motaal, A.A.; Ahmed, N.; Gad, M.Z. Targeting hydrogen sulphide signaling in breast cancer. J. Adv. Res. 2020, 27, 177–190. [Google Scholar] [CrossRef]
  86. Luo, H.; Xue, W.; Lin, H. Discussion on the Statistical Methods of the Therapeutic Modalities of Tumor Cases. Chin. J. Health Inform. Manag. 2018, 15, 550–553. [Google Scholar]
  87. Vasan, N.; Baselga, J.; Hyman, D.M. A view on drug resistance in cancer. Nature 2019, 575, 299–309. [Google Scholar] [CrossRef] [PubMed]
  88. Lv, M.; Ning, W.; Chen, Y.; Lv, H.; Fu, C. Drug Resistance of Antineoplastic Drugs and Clinical Therapeutic Strategies. Chin. J. Mod. Appl. Pharm. 2019, 36, 1721–1727. [Google Scholar]
  89. Ruggiero, A.; Ferrara, P.; Attinà, G.; Rizzo, D.; Riccardi, R. Renal toxicity and chemotherapy in children with cancer. Br. J. Clin. Pharmacol. 2017, 83, 2605–2614. [Google Scholar] [CrossRef] [PubMed]
  90. Huang, S.; Liu, M.; Fu, F.; Liu, H.; He, B.; Xiao, D.; Yang, J. High Serum Estradiol Reduces Acute Hepatotoxicity Risk Induced by Epirubicin Plus Cyclophosphamide Chemotherapy in Premenopausal Women with Breast Cancer. Front. Pharmacol. 2021, 11, 572444. [Google Scholar] [CrossRef] [PubMed]
  91. Freites-Martinez, A.; Shapiro, J.; Goldfarb, S.; Nangia, J.; Jimenez, J.J.; Paus, R.; Lacouture, M.E. Hair disorders in patients with cancer. J. Am. Acad. Dermatol. 2019, 80, 1179–1196. [Google Scholar] [CrossRef]
  92. Zhu, H.; Long, M.-H.; Wu, J.; Wang, M.; Li, X.; Shen, H.; Xu, J.; Zhou, L.; Fang, Z.; Luo, Y.; et al. Ginseng alleviates cyclophosphamide-induced hepatotoxicity via reversing disordered homeostasis of glutathione and bile acid. Sci. Rep. 2015, 5, 17536. [Google Scholar] [CrossRef]
  93. Zhou, L. The Function and Mechanisms of Bioactive Molecules in Regulating the Growth and Cycle of Hair Follicle; Zhejiang University(China): Zhejiang, China, 2019. [Google Scholar] [CrossRef]
  94. Zhang, J. Study on the pharmacological effects of diammonium glycyrrhizinate on hair loss. Zhangjiang Univ. People’s Hosp. Yuyao City Zhejiang Prov. 2015, 12, 15. Available online: https://kns.cnki.net/kcms/detail/detail.aspx?dbcode=SNAD&dbname=SNAD&filename=SNAD000001700741&uniplatform=NZKPT&v=TjRX_0fSS4t-biFKETF6cmWfszyKo1h7jaaTSJLODhI9eFYXao9JJ2G2mu-l6K4m145XZ7KKFaI%3d (accessed on 13 July 2022).
  95. Gao, Z.; Xu, Y.; Sun, C.; Wang, X.; Guo, Y.; Shi, Q.; Ma, K. A systematic review of asymptomatic infections with COVID-19. J. Microbiol. Immunol. Infect. 2021, 54, 12–16. [Google Scholar] [CrossRef] [PubMed]
  96. Hodgson, S.H.; Mansatta, K.; Mallett, G.; Harris, V.; Emary, K.R.W.; Pollard, A.J. What defines an efficacious COVID-19 vaccine? A review of the challenges assessing the clinical efficacy of vaccines against SARS-CoV-2. Lancet Infect. Dis. 2021, 21, e26–e35. [Google Scholar] [CrossRef]
  97. Luo, H.; Gao, Y.; Zou, J.; Zhang, S.; Chen, H.; Liu, Q.; Tan, D.; Han, Y.; Zhao, Y.; Wang, S. Reflections on treatment of COVID-19 with traditional Chinese medicine. Chin. Med. 2020, 15, 94. [Google Scholar] [CrossRef] [PubMed]
  98. Hu, K.; Guan, W.J.; Bi, Y.; Zhang, W.; Li, L.; Zhang, B.; Liu, Q.; Song, Y.; Li, X.; Duan, Z.; et al. Efficacy and safety of Lianhuaqingwen capsules, a repurposed Chinese herb, in patients with coronavirus disease 2019: A multicenter, prospective, randomized controlled trial. Phytomedicine 2021, 85, 153242. [Google Scholar] [CrossRef]
  99. Ley, S.H.; Hamdy, O.; Mohan, V.; Hu, F.B. Prevention and management of type 2 diabetes: Dietary components and nutritional strategies. Lancet 2014, 383, 1999–2007. [Google Scholar] [CrossRef]
  100. Du, S.; Cai, Z.; Yang, K.; Liu, Q. Pancreatic autophagy and protein expression of insulin-related genes in type 2 diabetic rats with Periodontitis. Chin. J. Tissue Eng. Res. 2022, 26, 4605–4610. [Google Scholar]
  101. Tian, M.; Liu, Y.; Xie, L.; Cao, Y.; Lv, H. Protective effffects of tertiary butylhydroquinone on various organs in type 2 diabetic rats. Chin. J. Tissue Eng. Res. 2022, 26, 4616–4623. [Google Scholar]
  102. Cheng, Y.; Yu, X.; Zhang, J.; Chang, Y.; Xue, M.; Li, X.; Lu, Y.; Li, T.; Meng, Z.; Su, L.; et al. Pancreatic kallikrein protects against diabetic retinopathy in KK Cg-Ay/J and high-fat diet/streptozotocin-induced mouse models of type 2 diabetes. Diabetologia 2019, 62, 1074–1086. [Google Scholar] [CrossRef]
  103. Wang, Y.; Dilidaxi, D.; Wu, Y.; Sailike, J.; Sun, X.; Nabi, X. Composite probiotics alleviate type 2 diabetes by regulating intestinal microbiota and inducing GLP-1 secretion in db/db mice. Biomed. Pharmacother. 2020, 125, 109914. [Google Scholar] [CrossRef]
  104. Yu, F.; Han, W.; Zhan, G.; Li, S.; Jiang, X.; Wang, L.; Xiang, S.; Zhu, B.; Yang, L.; Luo, A.; et al. Abnormal gut microbiota composition contributes to the development of type 2 diabetes mellitus in db/db mice. Aging (Albany NY) 2019, 11, 10454–10467. [Google Scholar] [CrossRef] [PubMed]
  105. Sung, H.; Ferlay, J.; Siegel, R.L.; Laversanne, M.; Soerjomataram, I.; Jemal, A.; Bray, F. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J. Clin. 2021, 71, 209–249. [Google Scholar] [CrossRef] [PubMed]
  106. Zhao, M.; Guo, W.; Wu, Y.; Yang, C.; Zhong, L.; Deng, G.; Zhu, Y.; Liu, W.; Gu, Y.; Lu, Y.; et al. SHP2 inhibition triggers anti-tumor immunity and synergizes with PD-1 blockade. Acta Pharm. Sin. B 2019, 9, 304–315. [Google Scholar] [CrossRef] [PubMed]
Molecules 27 05678 g001 550
Figure 1. Pictures of Fructus Malvae.
Figure 1. Pictures of Fructus Malvae.
Molecules 27 05678 g001
Molecules 27 05678 g002 550
Figure 2. The chemical structures of acid compounds identified from Fructus Malvae.
Figure 2. The chemical structures of acid compounds identified from Fructus Malvae.
Molecules 27 05678 g002
Molecules 27 05678 g003 550
Figure 3. The chemical structures of flavonoids identified from Fructus Malvae.
Figure 3. The chemical structures of flavonoids identified from Fructus Malvae.
Molecules 27 05678 g003
Molecules 27 05678 g004 550
Figure 4. The chemical structures of sterol compounds identified from Fructus Malvae.
Figure 4. The chemical structures of sterol compounds identified from Fructus Malvae.
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Molecules 27 05678 g005 550
Figure 5. The chemical structures of glycerides identified from Fructus Malvae.
Figure 5. The chemical structures of glycerides identified from Fructus Malvae.
Molecules 27 05678 g005
Molecules 27 05678 g006 550
Figure 6. The chemical structures of volatile oils identified from Fructus Malvae.
Figure 6. The chemical structures of volatile oils identified from Fructus Malvae.
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Molecules 27 05678 g007 550
Figure 7. The chemical structures of polysaccharides identified from Fructus Malvae.
Figure 7. The chemical structures of polysaccharides identified from Fructus Malvae.
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Molecules 27 05678 g008 550
Figure 8. The chemical structures of amino acids identified from Fructus Malvae.
Figure 8. The chemical structures of amino acids identified from Fructus Malvae.
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Molecules 27 05678 g009 550
Figure 9. The chemical structures of other substances identified from Fructus Malvae.
Figure 9. The chemical structures of other substances identified from Fructus Malvae.
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Molecules 27 05678 g010 550
Figure 10. The typical chemical composition separated and identified from Fructus Malvae.
Figure 10. The typical chemical composition separated and identified from Fructus Malvae.
Molecules 27 05678 g010
Molecules 27 05678 g011 550
Figure 11. The anti-diabetic effect of 2 flavonoids identified from Fructus Malvae.
Figure 11. The anti-diabetic effect of 2 flavonoids identified from Fructus Malvae.
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Molecules 27 05678 g012 550
Figure 12. The anti-tumor effect of 2 glycosylglycerides identified from Fructus Malvae.
Figure 12. The anti-tumor effect of 2 glycosylglycerides identified from Fructus Malvae.
Molecules 27 05678 g012
Table
Table 1. The acid compounds identified from Fructus Malvae.
Table 1. The acid compounds identified from Fructus Malvae.
No.Compound NameMolecular FormulaMedicinal PartsReferences
1Caffeic acidC9H8O4The fruit of Malva verticillata L.[7,11,12,13,14,15]
2Ferulic acidC10H10O4The fruit of Malva verticillata L.[7,15,16,17]
3Quinic acidC7H12O6The stem, leaf and seed mixture of Malva verticillata L.[31]
49,12,13-trihydroxy-octadecadienoic acidC18H32O5The stem, leaf and seed mixture of Malva verticillata L.[31]
59,12,13-trihydroxy-octadecenoic acidC18H34O5The stem, leaf and seed mixture of Malva verticillata L.[31]
6Linolenic acidC18H30O2The stem, leaf and seed mixture of Malva verticillata L.[21,31]
7Oleic acidC18H34O2The seed of Malva verticillata L.[21]
8Myristoleic acid C14H26O2The seed of Malva verticillata L.[22]
9Palmitic acidC16H32O2The seed of Malva verticillata L.[23]
Fructus Malvae refers to the fruit or seed of Malva verticillata L.
Table
Table 2. The flavonoids identified from Fructus Malvae.
Table 2. The flavonoids identified from Fructus Malvae.
No.Chemical Name Molecular FormulaMedicinal PartsReference
10Myricetin-3-hexoside-glucuronideC27H28O19The stem, leaf and seed mixture of Malva verticillata L.[31]
11Quercetin-3-O-hexoside-glucuronideC27H28O18The stem, leaf and seed mixture of Malva verticillata L.[31]
12EpigallocatechinC15H14O7The stem, leaf and seed mixture of Malva verticillata L.[31]
13HyperinC21H20O12The stem, leaf and seed mixture of Malva verticillata L.[31]
14Kaempferol-3-O-rutinosideC27H30O15The stem, leaf and seed mixture of Malva verticillata L.[31]
15Kaempferol-3-O-glucosideC21H20O11The stem, leaf and seed mixture of Malva verticillata L.[31]
16QuercitrinC21H20O11The stem, leaf and seed mixture of Malva verticillata L.[31]
17Quercetin-3-O-glucuronideC21H18O13The stem, leaf and seed mixture of Malva verticillata L.[31]
18CatechinC15H14O6The stem, leaf and seed mixture of Malva verticillata L.[31]
19Kaempferol (or luteolin)-3-O-glucuronid C21H18O12The stem, leaf and seed mixture of Malva verticillata L.[31]
20Kaempferide-3-glucuronideC22H20O12The stem, leaf and seed mixture of Malva verticillata L.[31]
21Biochanin AC16H12O5The stem, leaf and seed mixture of Malva verticillata L.[31]
22Rubone C20H22O7The stem, leaf and seed mixture of Malva verticillata L.[31]
23Robinetin trimethyl etherC18H16O7The stem, leaf and seed mixture of Malva verticillata L.[31]
24RutinC27H30O16The fruit of Malva verticillata L.[18]
25Nortangeretin-8-O-β-d-glucuronideC21H18O13The stem, leaf and seed mixture of Malva verticillata L.[32]
26Isoscutellarein 8-O-glucuronopyranosideC21H18O12The stem, leaf and seed mixture of Malva verticillata L.[32]
27Hypolaetin 8-O-glucuronopyranosideC21H18O13The stem, leaf and seed mixture of Malva verticillata L.[32]
28Herbacetin 8-O-glucuronopyranosideC21H18O13The stem, leaf and seed mixture of Malva verticillata L.[32]
29Herbacetin 3-O-glucopyranosyl-8-O-glucuronopyranoside C27H28O18The stem, leaf and seed mixture of Malva verticillata L.[32]
30Isoscutellarein 7-O-glucopyranosideC21H20O11The stem, leaf and seed mixture of Malva verticillata L.[32]
Fructus Malvae refers to the fruit or seed of Malva verticillata L.
Table
Table 3. The sterol compounds identified from Fructus Malvae.
Table 3. The sterol compounds identified from Fructus Malvae.
No.Chemical NameMolecular FormulaMedicinal PartsReferences
31β-sitosterolC29H50OThe seed of Malva verticillata L.[18,22,23,24]
32VerticillosideC50H80O22The seed of Malva verticillata L.[22]
33DaucosterolC35H60O6The seed of Malva verticillata L.[18,22]
Fructus Malvae refers to the fruit or seed of Malva verticillata L.
Table
Table 4. The Glycerides identified from Fructus Malvae.
Table 4. The Glycerides identified from Fructus Malvae.
No.Chemical NameMolecular FormulaMedicinal PartsReference
341-O-palmitoyl glycerideC19H38O4The stem, leaf and seed mixture of Malva verticillata L.[33]
351-O-stearoyl glycerideC21H42O4The stem, leaf and seed mixture of Malva verticillata L.[33]
361-O-linolenoyl glycerideC21H36O4The stem, leaf and seed mixture of Malva verticillata L.[33]
371,2-di-O-linoleoyl glycerideC39H68O5The stem, leaf and seed mixture of Malva verticillata L.[33]
381-O-(6-deoxy-6-sulfo)-glucopyranosyl-2-O-linolenoyl-3-O-palmitoyl glycerideC43H75O12S−The stem, leaf and seed mixture of Malva verticillata L.[34]
391-O-(6-deoxy-6-sulfo)-glucopyranosyl-2,3-di-O-linolenoyl glycerideC45H73O12S−The stem, leaf and seed mixture of Malva verticillata L.[34]
401-O-galactopyranosyl-3-O-palmitoyl glycerideC25H48O9The stem, leaf and seed mixture of Malva verticillata L.[34]
411-O-galactopyranosyl-3-O-stearoyl glycerideC27H52O9The stem, leaf and seed mixture of Malva verticillata L.[34]
421-O-galactopyranosyl-3-O-isostearoyl glyceride C27H52O9The stem, leaf and seed mixture of Malva verticillata L.[34]
431-O-galactopyranosyl-3-O-linolenoyl glycerideC27H46O9The stem, leaf and seed mixture of Malva verticillata L.[34]
441-O-galactopyranosyl-2,3-di-O-palmitoyl glycerideC41H78O10The stem, leaf and seed mixture of Malva verticillata L.[34]
451-O-galactopyranosyl-2,3-di-O-linolenoyl glyceride C45H74O10The stem, leaf and seed mixture of Malva verticillata L.[34]
461-O-6′-O-(-galactopyranosyl)-galactopyranosyl-3-O-palmitoyl glyceride C31H58O14The stem, leaf and seed mixture of Malva verticillata L.[34]
47O-6′-O-(-galactopyranosyl)-galactopyranosyl-3-O-2-linolenoyl glyceride C33H56O14The stem, leaf and seed mixture of Malva verticillata L.[34]
481-O-6′-O-(-galactopyranosyl)-galactopyranosyl-2,3-di-O-palmitoyl glyceride C47H88O15The stem, leaf and seed mixture of Malva verticillata L.[34]
491-O-(6-O-galactopyranosyl)-galactopyranosyl-2-O-stearolyl-3-O-linolenoyl glycerideC51H90O15The stem, leaf and seed mixture of Malva verticillata L.[34]
501-O-(6-O-galactopyranosyl)-galactopyranosyl-2,3-di-O-linolenoyl glycerideC51H84O15The stem, leaf and seed mixture of Malva verticillata L.[34]
Fructus Malvae refers to the fruit or seed of Malva verticillata L.
Table
Table 5. The volatile oils identified from Fructus Malvae.
Table 5. The volatile oils identified from Fructus Malvae.
No.Chemical NameMolecular FormulaMedicinal PartsReferences
511,1-dichloro-2-hexyl-CyclopropanC9H16Cl2The fruit of Malva verticillata L.[19,20]
523-(Prop-2-enoyloxy)dodecaneC15H28O2The fruit of Malva verticillata L.[19,20]
531-(ethenyloxy)-pentaneC7H14OThe fruit of Malva verticillata L.[19,20]
541-methyl-6,7-Dioxabicyclo[3.2.1]octaneC7H12O2The fruit of Malva verticillata L.[19,20]
552-methyl-5-(1-methylethenyl)-CyclohexanolC10H18OThe fruit of Malva verticillata L.[19,20]
56trans-1,2-CyclopentanediolC5H10O2The fruit of Malva verticillata L.[19,20]
573, 5-Octadien-2-olC10H18OThe fruit of Malva verticillata L.[19,20]
58(Z)-2-Octen-2-olC8H16OThe fruit of Malva verticillata L.[19,20]
59Nona-2-en-1-olC9H18OThe fruit of Malva verticillata L.[19,20]
60(E)-2,6-Dimethyl-3,5,7-octatriene-2-olC10H16OThe fruit of Malva verticillata L.[19,20]
61(1S)-1,7,7-trimethyl-Bicyclo[2.2.1] heptan-2-oneC10H16OThe fruit of Malva verticillata L.[19,20]
62Z,Z-2,5-Pentadecadien-1-olC15H28OThe fruit of Malva verticillata L.[19,20]
63Dihydro-4,4-dimethyl-2(3H)-FuranoC6H10O2The fruit of Malva verticillata L.[19,20]
64Z-1,9-HexadecadieneC16H30The fruit of Malva verticillata L.[19,20]
65(E, E)-2,4-DecadieneC10H18The fruit of Malva verticillata L.[19,20]
66Hexanoic acidC16H12O2The fruit of Malva verticillata L.[19,20]
672-(Prop-2-enoytoxy) tetradecaneC17H32O2The fruit of Malva verticillata L.[19,20]
685-hexyldihydro-2(3H)-FuranoneC10H18O2The fruit of Malva verticillata L.[19,20]
697-Methyl-Z-tetradecen-1-ol acetateC17H32O2The fruit of Malva verticillata L.[19,20]
70DibutylphthalateC16H22O4The fruit of Malva verticillata L.[19,20]
712,5-dihydro-1-nitroso-1H-PyrroleC4H6N2OThe fruit of Malva verticillata L.[19,20]
725-(Prop-2-enoyloxy)pentadecaneC18H34O2The fruit of Malva verticillata L.[19,20]
73(E)-2-OctenalC8H14OThe fruit of Malva verticillata L.[19,20]
74(Z)-2-NonenalC9H16OThe fruit of Malva verticillata L.[19,20]
Fructus Malvae refers to the fruit or seed of Malva verticillata L.
Table
Table 6. The polysaccharides identified from Fructus Malvae.
Table 6. The polysaccharides identified from Fructus Malvae.
No.Chemical NameMolecular FormulaMedicinal PartsReferences
75MVS-I--The seed of Malva verticillata L.[25,26,28,29]
76MVS-IIA--The seed of Malva verticillata L.[25,26,29]
77MVS-IIG--The seed of Malva verticillata L.[25,26,29]
78MVS-IIIA--The seed of Malva verticillata L.[25,26,29]
79MVS-IVA--The seed of Malva verticillata L.[25,26,29,30]
80MVS-VI--The seed of Malva verticillata L.[25,26,27,29]
81MVS-V--The seed of Malva verticillata L.[25,26,29]
82SucroseC12H22O11The seed of Malva verticillata L.[22]
83Raffinose C18H32O16The seed of Malva verticillata L.[22]
Fructus Malvae refers to the fruit or seed of Malva verticillata L.
Table
Table 7. The amino acids identified from Fructus Malvae.
Table 7. The amino acids identified from Fructus Malvae.
No.Chemical NameMolecular FormulaMedicinal PartsReferences
84d-alanineC3H7NO2The seed of Malva verticillata L.[14,18,23]
85tryptophanC11H12N2O2The stem, leaf and seed mixture of Malva verticillata L.[31,35]
86Aspartic acidC4H7NO4The fruit of Malva verticillata L.[14,18]
87ThreonineC4H9NO3The fruit of Malva verticillata L.[14,18]
88SerineC3H7NO3The fruit of Malva verticillata L.[14,18]
89Glutamic acidC5H9NO4The fruit of Malva verticillata L.[14,18]
90ProlineC5H9NO2The fruit of Malva verticillata L.[14,18]
91GlycineC2H5NO2The fruit of Malva verticillata L.[14,18]
92ValineC5H11NO2The fruit of Malva verticillata L.[14,18]
93l-isoleucineC6H13NO2The fruit of Malva verticillata L.[14,18]
94LeucineC6H13NO2The fruit of Malva verticillata L.[14,18]
95TyrosineC9H11NO3The fruit of Malva verticillata L.[14,18]
96PhenylalanineC9H11NO2The fruit of Malva verticillata L.[14,18]
97HistidineC6H9N3O2The fruit of Malva verticillata L.[14,18]
98ArginineC6H14N4O2The fruit of Malva verticillata L.[18]
Table
Table 8. The other substances identified from Fructus Malvae.
Table 8. The other substances identified from Fructus Malvae.
No.Chemical NameMolecular FormulaMedicinal PartsReference
99oleamideC18H35NOThe seed of Malva verticillata L.[23]
1001,3-dihydroxyacetone dimerC6H12O6The seed of Malva verticillata L.[23]
1015-hydroxymethyl furfuralC6H6O3The seed of Malva verticillata L.[23]
1022-hydroxy-gamma-butyrolactoneC4H6O3The seed of Malva verticillata L.[23]
1033,5,6,9-tetrahydroxy-7-megastigmeneC13H24O4The stem, leaf and seed mixture of Malva verticillata L.[35]
Table
Table 9. The research progress on the pharmacological activity of Fructus Malvae.
Table 9. The research progress on the pharmacological activity of Fructus Malvae.
Pharmacological ActivityCompound/ExtractExperimental LevelExperimental ModelAdministration
Method		Dosage/ConcentrationDetection IndicatorEffective DoseReference
Diuretic effectPetroleum ether extractWhole animalWater-loaded rat modelOral administration25 mL/kgUrine volume, urine sodium content, urine potassium content, urine chlorine content (mg)Effective dose:
25 mL/kg		[23]
Ethyl acetate extractWhole animalWater-loaded rat modelOral administration25 mL/kgUrine volume, urine sodium content, urine potassium content, urine chlorine content (mg)Effective dose:
25 mL/kg		[23]
Anti-diabeticEthyl acetate extractWhole animalAlloxan-induced islet damage model in zebrafish larvae Soak absorption25~600 μg/mL,
10 μg/mL		50% lethal concentration LC50; changes in islet area, changes in fluorescence intensity caused by 2-NBDGLC50:91.5 μg/mL;
Effective dose:
10 μg/mL		[18]
n-Butanol extractWhole animalAlloxan-induced islet damage model in zebrafish larvae Soak absorption25~600 μg/mL,
10 μg/mL		50% lethal concentration LC50; changes in islet area, changes in fluorescence intensity caused by 2-NBDGLC50:270.9 μg/mL;
Effective dose:
10 μg/mL		[18]
Whole animalAlloxan-induced islet damage model in zebrafish larvae Soak absorption10 μg/mLChanges in islet area, changes in fluorescence intensity caused by 2-NBDGEffective dose:
10 μg/mL		[30]
Water extractWhole animalAlloxan-induced islet damage model in zebrafish larvaeSoak absorption25~600 μg/mL,
10 μg/mL		50% lethal concentration LC50; changes in islet area, changes in fluorescence intensity caused by 2-NBDGLC50:401.1 μg/mL;
Effective dose:
10 μg/mL		[18]
Nortangeretin-8-O-β-d-glucuronideWhole animalAlloxan-induced islet damage model in zebrafish larvaeSoak absorption0.1 μMChanges in islet area, changes in fluorescence intensity caused by 2-NBDGEffective dose:
0.1 μM		[18]
Hypolaetin 8-O-β-d-glucuronopyranosideWhole animalAlloxan-induced islet damage model in zebrafish larvaeSoak absorption0.1 μMChanges in islet area, changes in fluorescence intensity caused by 2-NBDGEffective dose:
0.1 μM		[18]
Herbacetin 8-O-β-d-glucuronopyranosideWhole animalAlloxan-induced islet damage model in zebrafish larvaeSoak absorption0.1 μMChanges in islet area, changes in fluorescence intensity caused by 2-NBDGEffective dose:
0.1 μM		[18]
Isoscutellarein 7-O-β-d-glucopyranosideWhole animalAlloxan-induced islet damage model in
zebrafish larvae		Soak absorption0.1 μMChanges in islet area, changes in fluorescence intensity caused by 2-NBDGEffective dose:
0.1 μM		[18]
l-tryptophanWhole animalAlloxan-induced islet damage model in
zebrafish larvae		Soak absorption1 μg/mChanges in islet area, changes in fluorescence intensity caused by 2-NBDGEffective dose:
1 μg/mL		[30]
3,5,6,9-tetrahydroxy-7-megastigmeneWhole animalAlloxan-induced islet damage model in
zebrafish larvae		Soak absorption1 μg/mChanges in islet area, changes in fluorescence intensity caused by 2-NBDGEffective dose:
1 μg/mL		[30]
n-hexane extractWhole animalType 2 diabetes db/db miceOral administration10~40 mg/kg weight/dFasting blood glucose levels, non-fasting blood glucose levels, triglycerides, total cholesterol, high-density lipoprotein cholesterol, HTR (high-density lipoprotein cholesterol/total cholesterol), phosphorylation levels of AMPK and ACC in soleus muscle and liverEffective dose:
20 mg/kg		[32]
β-sitosterolCellular levelL6 myotube cells Incubation75~300 μMPhosphorylation levels of AMPK and ACC,
glucose uptake		Effective dose:
75 μM		[32]
Neutral polysaccharide
MVS-Ⅰ		Whole animalMale miceIntraperitoneal injection10~100 mg/kg0 h, 7 h and 24 h plasma glucose levelEffective dose:
10 mg/kg		[28]
Peptidoglycan MVS-VWhole animalMale miceIntraperitoneal injection10~100 mg/kg0 h, 7 h and 24 h plasma glucose levelEffective dose:
100 mg/kg		[28]
Peptidoglycan-enriched fraction MVS-V-CHWhole animalMale miceIntraperitoneal injection10~100 mg/kg0 h, 7 h and 24 h plasma glucose levelEffective dose:
10 mg/kg		[28]
Anti-oxidationNortangeretin-8-O-β-d-glucuronidePhysical and chemical reactionDPPH RS activity,
ABTS RS activity,
oxygen-radical absorbance capacity (ORAC) assay,
superoxide scavenging activity		Incubation0.1 mL,
20 μL,		DPPH EC50,
ABTS EC50,
ORAC,
SOD EC50		DPPH EC50: >50 µM,
ABTS EC50: 2.22 ± 0.05 µM,
ORAC: 14.38 ± 0.35 µmol TE/µmol
SOD EC50: 0.73 ± 0.09 µM 		[18]
Isoscutellarein 8-O-β-d-glucuronopyranosidePhysical and chemical reactionDPPH RS activity,
ABTS RS activity,
oxygen-radical absorbance capacity (ORAC) assay,
superoxide scavenging activity		Incubation DPPH EC50,
ABTS EC50,
ORAC,
SOD EC50		DPPH EC50: >50 µM,
ABTS EC50: 3.38 ± 0.15 µM,
ORAC: 8.06 ± 0.36 µmol TE/µmol,
SOD EC50:1.51 ± 0.15 µM 		[18]
hypolaetin 8-O-β-d-glucuronopyranosidePhysical and chemical reactionDPPH RS activity,
ABTS RS activity,
oxygen-radical absorbance capacity (ORAC) assay,
superoxide scavenging activity		Incubation DPPH EC50,
ABTS EC50,
ORAC,
SOD EC50		DPPH EC50: 5.98 ± 0.24 µM,
ABTS EC50: 1.52 ± 0.04 µM,
ORAC: 12.48 ± 1.27 µmol TE/µmol,
SOD EC50: 0.98 ± 0.13 µM 		[18]
herbacetin 8-O-β-d-glucuronopyranosidePhysical and chemical reactionDPPH RS activity,
ABTS RS activity,
oxygen-radical absorbance capacity (ORAC) assay,
superoxide scavenging activity		Incubation DPPH EC50,
ABTS EC50,
ORAC,
SOD EC50		DPPH EC50: 31.79 ± 2.22 µM,
ABTS EC50: 4.51 ± 0.13 µM,
ORAC:
6.56 ± 0.32 µmol TE/µmol,
SOD EC50: 1.04 ± 0.21 µM 		[18]
herbacetin 3-O-β-d-glucopyranosyl-8-O-β-d-glucuronopyranosidePhysical and chemical reactionDPPH RS activity,
ABTS RS activity,
Oxygen-radical absorbance capacity (ORAC) assay,
superoxide scavenging activity		Incubation DPPH EC50,
ABTS EC50,
ORAC,
SOD EC50		DPPH EC50: 33.80 ± 1.89 µM,
ABTS EC50: 4.05 ± 0.14 µM,
ORAC:
6.42 ± 0.18 µmol TE/µmol,
SOD EC50: 0.70 ± 0.18 µM 		[18]
isoscutellarein
7-O-d-glucopyranoside		Physical and chemical reactionDPPH RS activity,
ABTS RS activity,
oxygen-radical absorbance capacity (ORAC) assay,
superoxide scavenging activity		Incubation DPPH EC50,
ABTS EC50,
ORAC,
SOD EC50		DPPH EC50: >50 µM,
ABTS EC50: 21.62 ± 1.26 µM,
ORAC:
3.83 ± 0.30 µmol TE/µmol,
SOD EC50: 1.31 ± 0.20 µM 		[18]
90% ethanol extractPhysical and chemical reactionDPPH radical scavenging activity assayIncubation100 μL (1–1000 μg/mL)DPPH anion scavenging activity,
ABTS cation scavenging activity,
FRAP 		[17]
AntitumorEthyl acetate extractCellular levelSplenocytes,
natural killer (NK) cells		Incubation10 μg/mLsplenocyte proliferation ability,
natural killer (NK) cell activity		Effective dose:
10 μg/mL		[24]
Cellular levelHepG2, AGS, HCT-15, A549Incubation 50% inhibitory concentration IC50IC50 ± SD:
83.7 ± 3.98 μg/mL,
79.0 ± 1.47 μg/mL,
80.9 ± 1.56 μg/mL,
87.0 ± 0.98 μg/mL,		[33]
n-butanol extractCellular levelSplenocytes,
natural killer (NK) cells		Incubation10 μg/mLsplenocyte proliferation ability,
natural killer (NK) cell activity		Effective dose:
10 μg/mL		[24]
Cellular levelHepG2, AGS, HCT-15, A549Incubation10~40 μg/mL50% inhibitory concentration IC50,
AGS cell apoptosis percentage,
Expression of apoptosis proteins PARP, Cleaved APRP, Caspase-3, Cleaved Caspase-3, Bcl-2, Bax, β-actin		IC50 ± SD:
11.3 ± 0.30 μg/mL,
8.2 ± 0.14 μg/mL,
7.4 ± 0.26 μg/mL,
52.2 ± 4.32 μg/mL,		[33]
Water extractCellular levelSplenocytes,
Natural Killer (NK) cells		Incubation10 μg/mLsplenocyte proliferation ability,
natural killer (NK) cell activity		Effective dose:
10 μg/mL		[24]
Cellular levelHepG2, AGS, HCT-15, A549Incubation 50% inhibitory concentration IC50IC50 ± SD:
86.0 ± 1.66 μg/mL,
90.0 ± 0.14 μg/mL,
91.5 ± 2.76 μg/mL,
96.3 ± 2.24 μg/mL		[33]
(2S)-1-O-palmitoyl glycerideCellular levelSplenocytes,
natural killer (NK) cells		Incubation10 μMsplenocyte proliferation ability,
natural killer (NK) cell activity		Effective dose:
10 μM		[24]
(2S)-1-O-stearoyl glycerideCellular levelSplenocytes,
natural killer (NK) cells		Incubation10 μMsplenocyte proliferation ability,
natural killer (NK) cell activity
Effective dose:
10 μM		[24]
(2S)-1-O-linolenoyl glycerideCellular levelSplenocytes,
natural killer (NK) cells		Incubation10 μMsplenocyte proliferation ability,
natural killer (NK) cell activity		Effective dose:
10 μM		[24]
(2S)-1,2-di-O-linoleoyl glycerideCellular levelSplenocytes,
natural killer (NK) cells		Incubation10 μMsplenocyte proliferation ability,
natural killer (NK) cell activity		Effective dose:
10 μM		[24]
(2S)-1-O-(6-deoxy-6-sulfo)-α-D
glucopyranosyl-2-O-linolenoyl-3-O-palmitoyl glyceride 		Cellular levelHepG2, AGS, HCT-15, A549Incubation25~100 μM50% inhibitory concentration IC50,
AGS cell apoptosis percentage,
Expression of apoptosis proteins PARP, Cleaved APRP, Caspase-3, Cleaved Caspase-3, Bcl-2, Bax, β-actin		IC50 ± SD:
63.7 ± 2.43 μM,
33.7 ± 0.64 μM,
49.6 ± 0.24 μM,
81.8 ± 2.19 μM		[33]
(2S)-1-O-(6-deoxy-6-sulfo)-α-d-glucopyranosyl-2,3-di-O-linolenoyl glycerideCellular levelHepG2, AGS, HCT-15, A549Incubation20~80 μM50% inhibitory concentration IC50,
AGS cell apoptosis percentage,
Expression of apoptosis proteins PARP, Cleaved APRP, Caspase-3, Cleaved Caspase-3, Bcl-2, Bax, β-actin		IC50 ± SD:
34.7 ± 2.26 μM,
11.1 ± 0.07 μM,
49.2 ± 5.16 μM,
76.0 ± 2.62 μM		[33]
(2S)-1-O-β-d-
galactopyranosyl-3-O-palmitoyl glyceride		Cellular levelHepG2, AGS, HCT-15, A549Incubation 50% inhibitory concentration IC50IC50 ± SD:
83.4 ± 0.55 μM,
86.7 ± 2.02 μM,
>100 μM,
96.1 ± 2.23 μM		[33]
(2S)-1-O-β-d-galactopyranosyl-3-O
stearoyl glyceride		Cellular levelHepG2, AGS, HCT-15, A549Incubation 50% inhibitory concentration IC50IC50 ± SD:
71.1 ± 2.04 μM,
77.7 ± 6.22 μM,
>100 μM,
87.5 ± 3.98 μM		[33]
(2S)-1-O-β-d-galactopyranosyl-3-O-isostearoyl glycerideCellular levelHepG2, AGS, HCT-15, A549Incubation 50% inhibitory concentration IC50IC50 ± SD:
77.3 ± 1.76 μM,
89.5 ± 0.88 μM,
>100 μM,
91.5 ± 1.76 μM		[33]
(2S)-1-O-β-d-galactopyranosyl-3-O-linolenoyl glycerideCellular levelHepG2, AGS, HCT-15, A549Incubation 50% inhibitory concentration IC50IC50 ± SD:
74.9 ± 1.89 μM,
89.3 ± 1.21 μM,
91.8 ± 2.43 μM,
89.9 ± 1.61 μM		[33]
(2S)-1-O-β-d-galactopyranosyl-2,3-di-O-palmitoyl glyceride Cellular levelHepG2, AGS, HCT-15, A549Incubation 50% inhibitory concentration IC50IC50 ± SD:
83.1 ± 0.48 μM,
90.6 ± 1.00 μM,
90.6 ± 1.00 μM,
87.9 ± 2.69 μM		[33]
(2S)-1-O-β-d-galactopyranosyl-2,3-di-O-linolenoyl glyceride Cellular levelHepG2, AGS, HCT-15, A549Incubation 50% inhibitory concentration IC50IC50 ± SD:
76.3 ± 1.23 μM,
64.8 ± 2.24 μM,
77.5 ± 4.64 μM,
>100 μM		[33]
(2S)-1-O-6′-O-(α-d-galactopyranosyl)-β-d-galactopyra-nosyl-3-O-palmitoyl glycerideCellular levelHepG2, AGS, HCT-15, A549Incubation 50% inhibitory concentration IC50IC50 ± SD:
74.4 ± 0.78 μM,
70.6 ± 1.00 μM,
85.9 ± 3.33 μM,
87.8 ± 4.53 μM		[33]
(2S)-1-O-6′-O-(α-d-galactopyranosyl)-β-d-galactopyran-osyl-3-O-linolenoyl glycerideCellular levelHepG2, AGS, HCT-15, A549Incubation 50% inhibitory concentration IC50IC50 ± SD:
79.3 ± 1.46 μM,
85.4 ± 1.74 μM,
91.3 ± 3.28 μM,
98.3 ± 0.67 μM 		[33]
(2S)-1-O-6′-O-(α-d-galactopyranosyl)-β-d-galactopyrano-syl-2,3-di-O-palmitoyl glycerideCellular levelHepG2, AGS, HCT-15, A549Incubation10~40 μM 50% inhibitory concentration IC50,
AGS cell apoptosis percentage,
Expression of apoptosis proteins PARP, Cleaved APRP, Caspase-3, Cleaved Caspase-3, Bcl-2, Bax, β-actin		IC50 ± SD:
10.0 ± 0.45 μM,
10.6 ± 0.10 μM,
15.3 ± 1.12 μM,
7.1 ± 0.12 μM 		[33]
(2S)-1-O-(6-O-α-d-galactopyranosyl)-β-d-galactopyran-osyl-2-O-stearolyl-3-O-linolenoyl
glyceride		Cellular levelHepG2, AGS, HCT-15, A549Incubation 50% inhibitory concentration IC50IC50 ± SD:
72.8 ± 2.41 μM,
88.2 ± 1.59 μM,
97.1 ± 5.18 μM,
>100 μM 		[33]
(2S)-1-O-(6-O-α-d-galactopyranosyl)-β-d-Galactopyrano syl-2-O-stearolyl-3-O-linolenoyl glycerideCellular levelHepG2, AGS, HCT-15, A549Incubation 50% inhibitory concentration IC50IC50 ± SD:
71.3 ± 0.46 μM,
66.3 ± 1.96 μM,
74.6 ± 1.93 μM,
83.1 ± 3.66 μM 		[33]
Hair-loss treatment95% ethanol extractCellular levelHFDPC cellsIncubation3~100 μg/mLCell proliferation rateEffective dose:
100 μg/mL		[31]
n-hexane extractCellular levelHFDPC cellsIncubation3~100 μg/mLCell proliferation rateEffective dose:
30 μg/mL		[31]
Linoleic acidCellular levelHFDPC cellsIncubation3~30 μg/mLCell proliferation rate, Wnt/β-catenin signaling pathway proteins GSK-3β, β-catenin; Cyclin D1, CDK2, GAPDH; cell growth factor VEGF, IGF-1, HGF, KGF, GAPDHEffective dose:
10 μg/mL		[31]
Ethanol extractCellular levelHuman dermal papilla cells (DPCs)Incubation0~50 μg/mLWnt reporter activity, expression of intracellular proteins β-catenin and GAPDHEffective dose:
10 μg/mL		[21]
Dichloromethane extractCellular levelHuman dermal papilla cells DPCs)Incubation10~100 μg/mLWnt reporter activity, expression of intracellular proteins β-catenin and GAPDHEffective dose:
10 μg/mL		[21]
Myristoleic acidCellular levelHuman dermal papilla cells (DPCs)Incubation0~100 μg/mLWnt reporter activity, cell number, expression of cytokines IGF-1, KGF, VEGF, HGF, GAPDH,
Phosphorylation levels of cell-signaling molecules p-38, ERK, CREB, Akt		Effective dose:
10 μg/mL		[21]
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Li, X.; Wang, X.; Zhao, M.; Zhang, H.; Liu, C. The Chemical and Pharmacological Research Progress on a Kind of Chinese Herbal Medicine, Fructus Malvae. Molecules 2022, 27, 5678. https://doi.org/10.3390/molecules27175678

AMA Style

Li X, Wang X, Zhao M, Zhang H, Liu C. The Chemical and Pharmacological Research Progress on a Kind of Chinese Herbal Medicine, Fructus Malvae. Molecules. 2022; 27(17):5678. https://doi.org/10.3390/molecules27175678

Chicago/Turabian Style

Li, Xiaoyu, Xianglei Wang, Menglu Zhao, He Zhang, and Chao Liu. 2022. "The Chemical and Pharmacological Research Progress on a Kind of Chinese Herbal Medicine, Fructus Malvae" Molecules 27, no. 17: 5678. https://doi.org/10.3390/molecules27175678

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