JOURNAL OF ETHNOPHARMACOLOGY
·
2023
·
IF 5.4
Kun Ren,Xuanmeng Zhang,Ruijie Wang,Shumeng Ren,Huiming Hua,Dongmei Wang,Yingni Pan,Xiaoqiu Liu
Ethnopharmacological relevance Euodiae Fructus (EF), the dried, unripe, scented fruit of Tetradium ruticarpum (A. Juss, T.G.Hartley), is a traditional food and herb with mild toxicity. In Asia, it is processed with licorice (EFP), which has been used for centuries to alleviate pain and suppress cough. Pharmacological studies have reported that this herb could cause liver injury by activating the P450 3A enzyme, thus carrying the risk of clinical application. Processing with licorice is an effective method to reduce EF toxicity. It is urgent to explore the toxic components of EF and the attenuation mechanism of licorice. Aim of the study This study aimed to indicate the specific pathway of EF-induced damage and identify the mechanism of action of licorice in reducing P450 activation and resulting in reduced liver damage. Materials and methods Male C57BL-6 mice were used to investigate the toxicity of EF to the liver and determine the attenuation effect on P450 from licorice ingestion. Glutathione (GSH) was used to capture the metabolic activation intermediates of EF. The key component reducing the EF toxicity of licorice was investigated by comparing the differences in chemical components and inhibition on the EF metabolism of licorice from different habitats. Results The intermediate product of evodiamine (EVO) in EF was found to be activated by the P450 enzyme during metabolism, causing liver injury and inflammation. Isoliquiritigenin and liquiritigenin in licorice produced by intestinal bacterial metabolism and glycyrrhizin inhibited the metabolic activation of EF. Glycosides in licorice are metabolized into aglycones by intestinal bacteria , inhibiting the metabolic activation of EF and alleviating hepatotoxicity. Conclusions By combining with GSH, the electrophilic intermediates produced by the P450 enzyme's metabolic activation of the indole ring of EVO might cause hepatotoxicity. Glycyrrhizin from licorice and the liquiritigenin and isoliquiritigenin generated by intestinal bacterial metabolism play an attenuated function by inhibiting the P450 enzyme and preventing the metabolic activation of EF.
研究领域:
药理学
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毒理学
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中医药学
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产品关联
DOI
PubMed
高影响因子
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
·
2025
·Vol. 66
·期 3
·44-44
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IF 4.7
Boda Li,Junpeng Liu,Di Zhang,Yiran Chu,Zeying Chen,Jiaruei Tsao,Taige Chen,Jiaxuan Jiang,Kai Hu
Purpose:This study aims to explore the therapeutic efficacy of evodiamine (EVO) in the treatment of dry eye disease (DED).Methods:Mouse models of DED was developed using benzalkonium chloride eye drops and subcutaneous atropine injections. Corneal epithelial defects were assessed by fluorescein sodium staining, and tear secretion was measured with the phenol red thread test. For the in vitro model, human corneal epithelial cells were cultured in a sodium chloride–enriched medium. Phenotypic and mechanistic analyses were conducted using real-time quantitative PCR, Western blotting, flow cytometry, and immunofluorescence staining.Results:The administration of EVO eye drops significantly enhanced tear secretion in mice, ameliorated ocular surface damage, decreased the expression of corneal inflammatory factors, and increased the density of conjunctival goblet cells. Furthermore, EVO reduced oxidative stress by promoting autophagy. Mechanistically, EVO-induced autophagy was mediated via the p53/mammalian target of rapamycin pathway.Conclusions:These findings suggest that EVO is a potential therapeutic agent for the treatment of DED, with its beneficial effects attributed to the activation of autophagy through the p53/mammalian target of rapamycin pathway.
研究领域:
眼科
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药理学
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细胞生物学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
XENOBIOTICA
·
2021
·
IF 1.908
Xian-Mei Song,Bing-Jie Li,Yan-Yan Zhang,Wen-Jing Ge,She-Feng Zhang,Wei-Feng Cui,Geng-Sheng Li,Rui-Feng Liang
Diabetes mellitus is a chronic metabolic disorder with multiple complications, patients who receive metformin may have a simultaneous intake of herbal medicine containing rutaecarpine due to cardiovascular protection and hypolipidemic effects of rutaecarpine. There might be drug interactions between metformin and rutaecarpine. This study aimed to investigate the effects of rutaecarpine on the pharmacodynamics and pharmacokinetics of metformin in diabetic rats.The diabetic rat model was induced with high-fat diet and low dose streptozotocin. Metformin with or without rutaecarpine was administered by oral gavage for 42 days. Pharmacodynamics and pharmacokinetics parameters were evaluated.The pharmacodynamics results revealed that co-administration of rutaecarpine with metformin resulted in a remarkable reduction of serum glucose and lipid profiles in diabetic rats compared to metformin treated alone. The pharmacokinetics results showed that co-treatments of rutaecarpine with metformin did not affect the systemic exposure and renal distribution of metformin, but increased metformin concentration in liver. Furthermore, rutaecarpine increased Oct1-mediated metformin uptake into hepatocytes by upregulation of Oct1 expression in the liver.The above data indicate that rutaecarpine enhanced the anti-diabetic effect of metformin, which may be associated with the increased hepatic distribution of metformin through up-regulation of Oct1 in response to rutaecarpine.
研究领域:
药理学
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内分泌学
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糖尿病研究
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产品关联
DOI
PubMed
高影响因子
PEST MANAGEMENT SCIENCE
·
2025
·
IF 3.8
Wenhao Liang,Xiaoxiao Xu,Tong Shi,Shengyang Xu,Qizhi Wang,Bi Wang
BACKGROUND Phytophthora capsici is a devastating oomycete pathogen with major economic concern. However, the use of traditional chemical fungicides is associated with environmental pollution, and fungicide resistance is increasingly prevalent. Consequently, developing safe, effective, and environmentally friendly alternatives is critically required. Evodiamine (EVO), a bioactive alkaloid from plants, has been extensively investigated for its anti-cancer properties. However, its inhibitory effects against phytopathogens have not yet been fully elucidated. This study evaluated EVO's antimicrobial activity toward P. capsici and its potential mode of action. RESULTS EVO significantly inhibited P. capsici mycelial growth and spore germination, with median effective concentration (EC 50 ) values of 6.48 μg mL −1 and 7.13 μg mL −1 respectively, across 108 P. capsici isolates. EVO exerted its antimicrobial effects by disrupting the cellular integrity of P. capsici , specifically targeting both the cell membrane and wall. Furthermore, EVO exhibited strong protective and curative efficacies in pepper leaves and seedlings. Genome-wide transcriptional analysis revealed that EVO treatment significantly altered the gene expression profile of P. capsici , especially affecting genes relevant to cell membrane integrity and transporter activity. CONCLUSION Overall, this study revealed that EVO showed great control efficacy against P. capsici and held promise as a novel botanical fungicide. © 2025 Society of Chemical Industry.
研究领域:
植物病理学
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农业微生物学
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分子植物-病原互作
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天然产物药理学
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农药学
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产品关联
DOI
PubMed
高影响因子
Chemical Biology & Drug Design
·
2023
·Vol. 102
·期 1
·101-114
·
IF 3
Meiya Mao,Xiaojiao Zheng,Yuehua Sheng,Jinghan Chai,Huiqing Ding
Evodiamine (EVO) has been demonstrated to promote apoptosis of ovarian cancer cells, and upregulate miR-152-3p level in colorectal cancer. Here, we explore part of the network mechanism of EVO and miR-152-3p in ovarian cancer. The bioinformatics website, dual luciferase reporter assay, and quantitative real-time polymerase chain reaction were applied to analyze the network among EVO, lncRNA, miR-152-3p, and mRNA. The effect and mechanism of EVO on ovarian cancer cells were determined using cell counting kit-8, flow cytometry, TUNEL, Western blot, and rescue experiments. As a result, EVO dose-dependently attenuated cell viability, induced G2/M phase arrest and apoptosis, promoted miR-152-3p level (4.5- or 2-fold changes), and inhibited expressions of NEAT1 (0.225- or 0.367-fold changes), CDK8 (0.625- or 0.571-fold changes), and CDK19 (0.25- or 0.147-fold changes) in OVCAR-3 and SKOV-3 cells. In addition, EVO decreased Bcl-2 expression, but increased the expressions of Bax and c-caspase-3. NEAT1 targeted miR-152-3p which bound to CDK19. The impacts of EVO on cell viability, cycle, apoptosis, and apoptosis-related proteins were partially reversed by miR-152-3p inhibitor, NEAT1 overexpression, or CDK19 overexpression. Furthermore, miR-152-3p mimic offset the effects of NEAT1 or CDK19 overexpression. The role of NEAT1 overexpression in the biological phenotype of ovarian cancer cells was counteracted by shCDK19. In conclusion, EVO attenuates ovarian cancer cell progression via the NEAT1-miR-152-3p-CDK19 axis.
研究领域:
肿瘤学
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分子生物学
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药理学
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产品关联
DOI
PubMed
高影响因子
Pharmaceuticals
·
2025
·Vol. 18
·期 3
·426
·
IF 4.8
Zhimin Song,Meijing Li,Ziwei Zhou,Xiaomeng Guo,Qi Wang,Zekuan Zhang,Keshu Wang,Qixiang Zheng,Wenjing Gou,Sha Wu,Hui Zhao,Muxin Gong
Background:Chronic migraine (CM) is a common complex nervous system disease, often accompanied by symptoms of the digestive tract that interact with each other, leading to prolonged and difficult-to-cure migraines. These symptoms are associated with abnormalities in 5-HT and its receptors. Wuzhuyu decoction (WZYD) is a traditional Chinese medicine prescription commonly used in clinics to treat CM; it relieves gastrointestinal symptoms, such as nausea and vomiting; however, its mechanism is still unclear. Investigating the differences in the role of WZYD compared to existing drugs targeting 5-HT receptors in the treatment of CM not only helps elucidate its pathogenesis but also provides possibilities for the development of new therapeutic approaches.Methods:An inflammation soup (IS)-induced CM male rat model was established. Based on a preliminary experiment, the target of WZYD in treating CM was determined by network pharmacology, and verified by molecular docking. ELISA, immunofluorescence, western blot, and real-time quantitative polymerase chain reaction (RT-qPCR) were used to evaluate the expression levels of CM-related indicators (5-HT, calcitonin gene-related peptide (CGRP), and c-Fos) to ensure the successful establishment of the CM model and the effectiveness of the drug. On this basis, the protein expression levels of 5-HT1A/3A receptors and their cAMP-response element binding protein (CREB) signaling pathway were detected by western blot and immunohistochemistry. The role of 5-HT1A/3A receptors in the treatment of CM by WZYD was validated using a 5-HT1A receptor antagonist (WAY 100635) and a 5-HT3A receptor agonist (SR 57227).Results:The results showed that WZYD increased the expression of 5-HT in the brain, decreased the expression of CGRP, c-Fos, ionized calcium-binding adapter molecule 1 (Iba1), and relieved CM. At the same time, WZYD also increased the expression of the 5-HT1A receptor and decreased the expression of the 5-HT3A receptor in the brain and colon of CM rats. Subsequently, WZYD further exerted its brain-gut integrated therapeutic effects by regulating the CREB signaling pathway mediated by 5-HT1A/3A receptors in the brain and colon of CM rats.Conclusions:WZYD not only regulates neurotransmitters in the brain and colon at the same time, but also specifically regulates 5-HT1A/3A receptors in the brain and colon, which explains the characteristics and advantages of WZYD from a new perspective. While effectively relieving headache symptoms, it also improves related gastrointestinal symptoms, which is more conducive to the treatment of CM.
研究领域:
神经科学
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药理学
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中医药学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2021
·
IF 6.953
Gaoyin Xiong,Lisha Ma,Han Zhang,Yanping Li,Wanshuang Zou,Xiaofan Wang,Quansheng Xu,Jingteng Xiong,Yanping Hu,Xiaoyin Wang
In this study, polysaccharides from Evodiae fructus were extracted by water, 0.5 M HCl, 0.5 M NaOH, water + 0.5 M HCl and water + 0.5 M NaOH, which were named as ERP-W, ERP-AC, ERP-AK, ERP-W-AC and ERP-W-AK, respectively. Their physicochemical properties, antioxidant activities and α-glucosidase inhibitory effects were investigated and compared. Physico-chemical analysis showed that they were acidic heteropolysaccharides, which had α- and β-configurations. ERP-W, ERP-AK and ERP-W-AK were mainly composed of Rha, Ara, Gal, Glc and Gal-UA, while ERP-AC and ERP-W-AC were dominantly made up of Rha, Gal and Gal-UA. ERP-AK had the highest yield (24.5%) and the best thermal stability, ERP-AC and ERP-W-AC showed better homogeneity and lower molecular weight (83.6 and 41.6 kDa), and ERP-W possessed the highest neutral sugar content (50.7%) and molecular weight. Biological evaluation indicated that ERP-W, ERP-AK and ERP-W-AK had relatively stronger antioxidant activities, including ABTS, DPPH, OH and O 2 − radicals scavenging activities, Fe 2+ chelating ability and α-glucosidase inhibitory effects. Moreover, these actions were considerably related to their physicochemical properties especially monosaccharide composition and molecular weight. Therefore, polysaccharides extracted by water and alkaline solvents from Evodiae fructus could be developed as promising natural antioxidants and α-glucosidase inhibitors in the food and medicine industries.
研究领域:
药学
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食品科学
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生物化学
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产品关联
DOI
PubMed
高影响因子
Drug Design Development and Therapy
·
2023
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IF 4.8
Zhen Yu,Shixin Chan,Xu Wang,Rui Sun,Ming Wang,Zhenglin Wang,Xiaomin Zuo,Jiajie Chen,Huabing Zhang,Wei Chen
Purpose To evaluate the effect of 5-fluorouracil (5-FU) combined with rutaecarpine (RUT) on the antiproliferative, anti-migratory, and apoptosis-promoting ability of colorectal cancer (CRC) cells and explore the underlying mechanism.Methods The antiproliferative effects of RUT and 5-FU on CRC cells were evaluated using MTT and colony formation assays. Anti-migration was assessed by cell scratch and transwell tests. The synergistic effect of RUT and 5-FU was assessed by isobologram and combination index analysis using CompuSyn software. The effects of RUT and 5-FU on cell apoptosis were detected by flow cytometry. Differences in protein expression levels with or without RUT and/or 5-FU treatment were assessed by Western blot. Moreover, a mouse xenograft model of CRC was established to investigate the antitumor effect of RUT and 5-FU in vivo, and Ki67 and cleaved caspase-3 expression was detected by immunofluorescence.Results In this study, we found that 5-FU combined with RUT can inhibit the proliferative, migratory, and antiapoptotic abilities of CRC cells to a significantly greater extent than either RUT or 5-FU alone both in vivo and in vitro. Western blot analysis showed that the level of signal transducer and activator of transcription 3 (STAT3) phosphorylation in CRC cells was significantly reduced after combination therapy compared with that seen with the respective monotherapies. In addition, combination therapy influenced the STAT3 signaling pathway, namely, it inhibited the expression of c-Myc, CDK4, and Bcl-2 while enhancing that of the proapoptotic protein cleaved caspase-3. Immunofluorescence staining further showed that the expression of Ki67 and cleaved caspase-3 was significantly downregulated and upregulated, respectively, in tumor tissues of mice treated with combination therapy compared with that observed with 5-FU treatment alone.Conclusion Combined therapy with 5-FU and RUT exerted a superior curative effect in CRC than treatment with either single drug alone and has potential as a novel therapeutic modality for the treatment of CRC.
研究领域:
肿瘤学
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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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产品关联
DOI
PubMed
高影响因子
Journal of Cancer
·
2022
·
IF 4.478
Shixin Chan,Rui Sun,Xucan Tu,Manyu Guo,Qianqian Yuan,Zhen Yu,Zhenglin Wang,Shaocheng Hong,Wei Han,Bingbing Zou,Zeng Li,Huabing Zhang,Wei Chen
Colorectal cancer (CRC) is a malignant disease that is a serious threat to human health. Rutaecarpine (RUT) is an important bioactive alkaloid of Evodia rutaecarpa. According to previous studies, RUT suppressed the proliferation of several human tumors. However, its role in colorectal tumorigenesis remained unknown. The aim of the present study was to determine the functions of RUT in CRC. Here, we have demonstrated that RUT inhibited the proliferation, migration and invasion of CRC cells in vitro . Further, RUT was found to induce the apoptosis of CRC cells. Mechanistically, RUT decreased the phosphorylation levels of NF-κB and STAT3. Moreover, treatment with RUT upregulated the expression of cleaved-Caspase3 and downregulated the expression of Bcl-2 in CRC. In addition, our findings suggested that RUT inhibited the growth and lung metastasis of CRC Cells in vivo . Based on immunofluorescence analysis, the expression of Ki67 was downregulated while that of cleaved-Caspase3 was upregulated in RUT-treated tumors compared with control-treated tumors. Taken together, our findings indicate that RUT can inhibit the proliferation and migration of CRC cells, and induce the apoptosis of CRC cells by inactivating NF-κB/STAT3 signaling. Our study highlights the potential clinical application of RUT for the treatment of CRC.
研究领域:
肿瘤学
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药理学
·
分子生物学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
MEDICAL ONCOLOGY
·
2016
·Vol. 33
·期 2
·1-9
·
IF 2.486
Li Yang-ling,Pan Yi-ni,Wu Wen-jue,Mao Shi-ying,Sun Jiao,Zhao Yi-ming,Dong Jing-yin,Zhang Da-yong,Pan Jian-ping,Zhang Chong,Lin Neng-ming
Erlotinib is effective in NSCLC patients with known drug-sensitizing EGFR mutations, but its clinical efficacy in patients with wild-type EGFR or acquired resistance to erlotinib remains modest. Evodiamine is a chemical extracted from the Evodia rutaecarpa (Juss.) Benth, we showed that evodiamine could induce anti-proliferation and apoptosis in four wild-type EGFR NSCLC cell lines, and combining evodiamine with erlotinib might successfully inhibit cell proliferation and survival in wild-type EGFR NSCLC cells, characterized as erlotinib-resistant. In addition, evodiamine plus erlotinib significantly increased the apoptotic rate of NSCLC cells, as compared to single agent treatment alone. Further investigation of the mechanism underlying these effects revealed that evodiamine plus erlotinib might downregulate Mcl-1 expression through the mTOR/S6K1 control of its translation. Thus, our study has revealed evodiamine as a pertinent sensitizer to erlotinib and the strategy of combining erlotinib with evodiamine appears to be an attractive option for reversing resistance to erlotinib.
研究领域:
肿瘤学
·
药理学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PHARMACEUTICAL BIOLOGY
·
2022
·
IF 3.889
Ruifeng Liang,Wenjing Ge,Bingjie Li,Weifeng Cui,Xiaofan Ma,Yuying Pan,Gengsheng Li
Context Patients with non-alcoholic steatohepatitis (NASH) may have a simultaneous intake of pravastatin and evodiamine-containing herbs.Objective The effect of evodiamine on the pharmacokinetics of pravastatin and its potential mechanisms were investigated in NASH rats.Materials and methods The NASH model was conducted with feeding a methionine choline-deficient (MCD) diet for 8 weeks. Sprague-Dawley rats were randomised equally (n = 6) into NASH group, evodiamine group (10 mg/kg), pravastatin group (10 mg/kg), and evodiamine (10 mg/kg) + pravastatin (10 mg/kg) group. Normal control rats were fed a standard diet. Effects of evodiamine on the pharmacokinetics, distribution, and uptake of pravastatin were investigated.Results Evodiamine decreased Cmax (159.43 ± 26.63 vs. 125.61 ± 22.17 μg/L), AUC0-t (18.17 ± 2.52 vs. 14.91 ± 2.03 mg/min/L) and AUC0-∞ (22.99 ± 2.62 vs. 19.50 ± 2.31 mg/min/L) of orally administered pravastatin in NASH rats, but had no significant effect in normal rats. Evodiamine enhanced the uptake (from 154.85 ± 23.17 to 198.48 ± 26.31 pmol/mg protein) and distribution (from 736.61 ± 108.07 to 911.89 ± 124.64 ng/g tissue) of pravastatin in NASH rat liver. The expression of Oatp1a1, Oatp1a4, and Oatp1b2 was up-regulated 1.48-, 1.38-, and 1.51-fold by evodiamine. Evodiamine decreased the levels of IL-1β, IL-6, and TNF-α by 27.82%, 24.76%, and 29.72% in NASH rats, respectively.Discussion and conclusions Evodiamine decreased the systemic exposure of pravastatin by up-regulating the expression of OATPs. These results provide a reference for further validation of this interaction in humans.
研究领域:
药理学
·
肝病学
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药代动力学
·
炎症
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
·
2025
·
IF 3.1
Chujun Tao,Wenjing Ren,Yongsong Zhai,Feng Qiu
Viticis fructus (VF) is the dry and ripe fruit of Vitex trifolia L. var. simplicifolia Cham or Vitex trifolia L., which contains several flavonoids exhibiting promising pharmacological effects. However, the pharmacokinetic behaviors of these flavonoids and their metabolites remain unclear. This study aimed to comprehensively evaluate the pharmacokinetics of five flavonoids from VF in rats using ultra-high-performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry (UHPLC–ESI–MS/MS) and the Iceberg pharmacokinetic strategy. After gavage administration of VF extract to rats, only small amounts of free vitexicarpin, chrysosplenol D and luteolin were detected in rat plasma, while the contents of free quercetin and kaempferol were both lower than their corresponding lower limits of quantification. In contrast, enzymatic hydrolysis with β-glucosidase revealed significant amounts of quercetin, kaempferol, vitexicarpin, chrysosplenol D, and luteolin. The maximum plasma concentration (C max ) and the area under the curve from time zero to the last measurable concentration (AUC 0–t ) values of total vitexicarpin, chrysosplenol D and luteolin after enzymatic hydrolysis were all significantly higher than those free values before enzymatic hydrolysis, respectively ( P < 0.05). These findings indicate that most flavonoids from VF primarily exist as phase II metabolites in rat plasma, which can prolong their residence time in the body through intestinal hepatic circulation and other pathways. These phase II metabolites with higher concentrations may be an essential material basis for their pharmacological effects.
研究领域:
药理学
·
分析化学
✓ 已验证
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）