MOLECULES
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2021
·Vol. 26
·期 14
·4300
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IF 4.412
Lin Yang,Yangping Liu,Wenhui Zhang,Yujie Hua,Ban Chen,Quanzhou Wu,Dongfeng Chen,Shuqin Liu,Xican Li
The search for a safe and effective inhibitor of ferroptosis, a recently described cell death pathway, has attracted increasing interest from scientists. Two hydrolyzable tannins, chebulagic acid and chebulinic acid, were selected for the study. Their optimized conformations were calculated using computational chemistry at the B3LYP-D3(BJ)/6-31G and B3LYP-D3(BJ)/6-311 + G(d,p) levels. The results suggested that (1) chebulagic acid presented a chair conformation, while chebulinic acid presented a skew-boat conformation; (2) the formation of chebulagic acid requires 762.1729 kcal/mol more molecular energy than chebulinic acid; and (3) the 3,6-HHDP (hexahydroxydiphenoyl) moiety was shown to be in an (R)- absolute stereoconfiguration. Subsequently, the ferroptosis inhibition of both tannins was determined using a erastin-treated bone marrow-derived mesenchymal stem cells (bmMSCs) model and compared to that of ferrostatin-1 (Fer-1). The relative inhibitory levels decreased in the following order: Fer-1 > chebulagic acid > chebulinic acid, as also revealed by the in vitro antioxidant assays. The UHPLC–ESI-Q-TOF-MS analysis suggested that, when treated with 16-(2-(14-carboxytetradecyl)-2-ethyl-4,4-dimethyl-3-oxazolidinyloxy free radicals, Fer-1 generated dimeric products, whereas the two acids did not. In conclusion, two hydrolyzable tannins, chebulagic acid and chebulinic acid, can act as natural ferroptosis inhibitors. Their ferroptosis inhibition is mediated by regular antioxidant pathways (ROS scavenging and iron chelation), rather than the redox-based catalytic recycling pathway exhibited by Fer-1. Through antioxidant pathways, the HHDP moiety in chebulagic acid enables ferroptosis-inhibitory action of hydrolyzable tannins.Keywords:ferroptosis-inhibition;ferrostatin-1;chebulagic acid;chebulinic acid;hydrolyzable tannin;HHDP
研究领域:
生物化学
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细胞生物学
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药理学
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产品关联
DOI
PubMed
高影响因子
Frontiers in Microbiology
·
2024
·
IF 4
Feng Zhong,Li Hui,Hao Yajie,Peng Chang,Ou Ling,Jia Junwei,Xun Mingjin,Zou Yuanjing,Chen Meiyun,Zhang Guimin,Yao Meicun
Background: Helicobacter pylori (H. pylori) is thought to primarily colonize the human stomach and lead to various gastrointestinal disorders, such as gastritis and gastric cancer. Currently, main eradication treatment is triple or quadruple therapy centered on antibiotics. Due to antibiotic resistance, the eradication rate of H. pylori is decreasing gradually. Therefore, searching for anti-H. pylori drugs from herbal sources has become a strategy for the treatment. Our team proposed a Hezi Qingyou Formula (HZQYF), composed of Chebulae Fructus, Ficus hirta Vahl and Cloves, and studied its anti-H. pylori activity and mechanism.Methods: Chemical components of HZQYF were studied using UHPLC–MS/MS and HPLC. Broth microdilution method and agar dilution method were used to evaluate HZQYF’s antibacterial activity. The effects of HZQYF on expression of adhesion genes (alpA, alpB, babA), urease genes (ureE, ureF), and flagellar genes (flaA, flaB) were explored using Reverse Transcription-quantitative Polymerase Chain Reaction (RT-qPCR) technology. Effects on morphology and permeability of the extracellular membrane were studied using scanning electron microscopy (SEM) and N-phenylnaphthalen-1-amine (NPN) uptake. Effect on urease activity was studied using a urease kinetics analysis in vitro. Immunofluorescence staining method was used to examine the effect on adhesion. Western blot was used to examine the effect on cagA protein.Results: Minimum inhibitory concentration (MIC) values of the formula against H. pylori clinical strains and standard strains were 80–160 μg/mL, and minimum bactericidal concentration (MBC) values were 160–320 μg/mL. The formula could down-regulate the expression of adhesion genes (alpA, alpB, babA), urease genes (ureE, ureF) and flagellar genes (flaA, flaB), change the morphology of H. pylori, increase its extracellular membrane permeability, and decrease its urease activity.Conclusion: Present studies confirmed that HZQYF had promising in vitro anti-H. pylori activities and demonstrated its possible mechanism of action by down-regulating the bacterial adhesion, urease, and flagellar gene expression, which provided scientific bases for further clinical investigations.
研究领域:
微生物学
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药理学
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中医药
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分子生物学
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DOI
PubMed
高影响因子
WORLD JOURNAL OF GASTROENTEROLOGY
·
2020
·
IF 3.665
Xiao Meng,Guo-Yi Tang,Cai-Ning Zhao,Qing Liu,Xiao-Yu Xu,Shi-Yu Cao
BACKGROUND Alcoholic liver disease (ALD) is a worldwide health problem, and natural products have been shown to improve ALD due to their antioxidant activities. Some parts of Hovenia dulcis ( H. dulcis ), such as roots, peduncles, and stems, provide health benefits. Nevertheless, the effects and mechanisms of H. dulcis seeds on ALD have not yet been fully elucidated. AIM To determine H. dulcis antioxidant activity, evaluate its effects against ALD, and investigate the related mechanisms via network pharmacology. METHODS The antioxidant activity of H. dulcis seed was determined by both ferric-reducing antioxidant power and trolox equivalent antioxidant capacity assays. The total phenolic and flavonoid contents were determined by Folin–Ciocalteu method and aluminum chloride colorimetry, respectively, and polysaccharide was determined by phenol-sulfuric acid method. The effects of H. dulcis seeds against alcoholic liver injury were investigated in mice with water extract pretreatment for 7 days followed by alcohol administration. Moreover, the mechanisms of action were explored with network pharmacology. RESULTS The results showed that H. dulcis seeds possessed strong antioxidant activity (245.11 ± 10.17 μmol Fe 2+ /g by ferric-reducing antioxidant power and 284.35 ± 23.57 μmol TE/g by trolox equivalent antioxidant capacity) and contained remarkable phenols and flavonoids, as well as a few polysaccharides. H. dulcis seeds attenuated alcohol-induced oxidative liver injury, showing reduced serum alanine and aspartate aminotransferases, alkaline phosphatase, and triglyceride, elevated hepatic glutathione, increased activities of superoxide dismutase and catalase, and reduced malondialdehyde and hepatic triglyceride. The results of network pharmacology analysis indicated that kaempferol, stigmasterol, and naringenin were the main bioactive compounds in H. dulcis seeds and that modulation of oxidative stress, inflammation, gut-derived products, and apoptosis were underlying mechanisms of the protective effects of H. dulcis seeds on ALD. CONCLUSION The results of this study demonstrate that H. dulcis seeds could be a good natural antioxidant source with protective effects on oxidative diseases such as ALD.
研究领域:
药理学
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肝病学
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天然产物化学
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DOI
PubMed
高影响因子
Antioxidants
·
2023
·Vol. 12
·期 12
·2093
·
IF 7
Xiangdong Wang,Jian Xu,Li-Hua Zhang,Wenzhi Yang,Huijuan Yu,Min Zhang,Yuefei Wang,Hong-Hua Wu
An integrative strategy of UHPLC/IM-QTOF-MS analysis, MS/MS molecular networking (MN), in-house library search, and a collision cross-section (CCS) simulation and comparison was developed for the rapid characterization of the chemical constituents in Chebulae Fructus (CF). A total of 122 Constituents were identified, and most were phenolcarboxylic and tannic compounds. Subsequently, 1,3,6-tri-O-galloyl-β-d-glucose, terflavin A, 1,2,6-tri-O-galloyl-β-d-glucose, punicalagin B, chebulinic acid, chebulagic acid, 1,2,3,4,6-penta-O-galloyl-β-d-glucose, and chebulic acid, among the 23 common constituents of CF, were screened out by UPLC-PDA fingerprinting and multivariate statistical analyses (HCA, PCA, and OPLS-DA). Then, Pearson’s correlation analysis and a grey relational analysis were performed for the spectrum-effect correlation between the UPLC fingerprints and the antioxidant capacity of CF, which was finally validated by an UPLC-DPPH•analysis for the main antioxidant constituents. Our study provides a global identification of CF constituents and contributes to the quality control and development of functional foods and preparations dedicated to CF.Keywords:Terminalia chebula;Chebulae Fructus;tannins;molecular networking;spectrum-effect relationship
研究领域:
药用植物学
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分析化学
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药学
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食品科学
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产品关联
DOI
PubMed
高影响因子
MOLECULES
·
2024
·Vol. 29
·期 10
·2399
·
IF 4.2
Jian Xu,Xiangdong Wang,Huijuan Yu,Xin Chai,Min Zhang,Hong-Hua Wu,Yuefei Wang
Chebulae Fructus (CF) is known as one of the richest sources of hydrolyzable tannins (HTs). In this study, ultra-performance liquid chromatography coupled with a photodiode array detector method was established for simultaneous determination of the 12 common phenolcarboxylic and tannic constituents (PTCs). Using this method, quantitative analysis was accomplished in CF and other four adulterants, including Terminaliae Belliricae Fructus, Phyllanthi Fructus, Chebulae Fructus Immaturus, and Canarii Fructus. Based on a quantitative analysis of the focused compounds, discrimination of CF and other four adulterants was successfully accomplished by hierarchical cluster analysis and principal component analysis. Additionally, the total contents of the 12 compounds that we focused on in this study were unveiled as 148.86 mg/g, 96.14 mg/g, and 18.64 mg/g in exocarp, mesocarp, and endocarp and seed of CF, respectively, and PTCs were witnessed to be the most abundant in the exocarp of CF. Noticeably, the HTs (chebulagic acid, chebulanin acid, chebulinic acid, and punicalagin) were observed to be ultimately degraded to chebulic acid, gallic acid, and ellagic acid during sunlight-drying of the fresh fruits. As a result, our study indicated that CF and its adulterants could be distinguished by the observed 12 PTCs, which were mainly distributed in the exocarp of the fruits. The HTs were prone to degrade into the three simple phenolcarboxylic acids during drying or processing, allowing us to obtain a more comprehensive understanding of the PTCs, with great significance in the improved quality of CF and related products.
研究领域:
生药学
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分析化学
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植物化学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2024
·
IF 4.8
Hong Xiang,Yu Zhang,Jiaming Li,Li Li,Ziwei Li,Rui Ni,Dan Peng,Lining Jiang,Jianhong Chen,Yao Liu
Ethnopharmacological relevance Terminalia bellirica (Gaertn.) Roxb. (TBR) , a popular herbal remedy in India and Southeast Asia, has been demonstrated to possess multiple pharmacological activities. However, systematic studies on the medicinal effects and mechanism of TBR for the androgenetic alopecia (AGA) treatment are deficient. Materials and methods Human Umbilical Vein Endothelial Cells (HUVECs) and testosterone-induced AGA mice were used to evaluate the hair regrowth activity of TBR extracts. Chemical constituents and potential active components of TBR extracts were analyed by UPLC-Q-TOF-MS in vitro / vivo . The hair regrowth mechanisms of TBR were elucidated through network pharmacology and experimental validation. Results Totally 28 chemical constituents in TBR were identified, of which 15 were predicted as potential active components for AGA therapy. TBR could significantly scavenge ROS, promote VEGF level/cell migration of HUVECs, and inhibiting type II 5α-reductase activity (the inhibit rate: 82.35 ± 1.02 %). Pharmacodynamic evaluation suggested that TBR effectively led to hair regrowth in C57BL6 mice compared to minoxidil. TBR promoted the hair follicle (HF) transition from the telogen phase to anagen phase by decreasing MDA levels, increasing VEFG expression and up-regulating phosphorylated P38/ERK protein levels in the MAPK signalling pathway. Conclusions TBR reversed AGA via inhibiting SRD5A2 activity and stimulating the MAPK pathway. Meantime, TBR could remodel the follicle microenvironment by reducing oxidative stress and increasing angiogenesis.
研究领域:
药理学
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民族药理学
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分子生物学
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细胞生物学
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皮肤科
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产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）