JOURNAL OF ETHNOPHARMACOLOGY
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2024
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IF 4.8
Zhiyuan Zhang,Guoqiang Guan,Zixuan Tang,Weimin Wan,Zhipeng Huang,Yuefeng Wang,Jianzhao Wu,Bo Li,Mingli Zhong,Kefeng Zhang,Lixian Nong,Ya Gao,Houkang Cao
A B S T R A C T Ethnopharmacological relevance Cholestatic liver disease (CLD) is a disease characterized by cholestasis. Farnesoid X receptor (FXR) is a nuclear receptor that maintains homeostasis in bile acid metabolism. Studies have shown that gut microbiota interfered with the FXR pathway. Modulation of FXR to inhibit cholestasis has become a key measure in the treatment of CLD. In traditional folk medicine, Desmodium styracifolium (Osb.) Merr. was used as a primary treatment for gallstones, gonorrhea, jaundice, cholecystitis and other diseases. Modern pharmacological studies had also found that the herb has anti-calculus, anti-inflammatory, antioxidant, diuretic and liver damage. Therefore, we speculated that Desmodium styracifolium (Osb.) Merr. extracts (DME) could alleviate CLD through the FXR pathway and might be associated with the gut microbiota. However, studies of DME alleviating CLD through the FXR pathway have not been reported. Aim of study To study the effect and mechanism of DME in relieving CLD through in vivo and in vitro experiments. Materials and methods First, mice were administrated with alpha-naphthyl isothiocyanate (ANIT) to establish a CLD model in vivo . Meanwhile, HepG2 cells were induced by lithocholic acid (LCA) to establish the CLD model in vitro . To evaluate the therapeutic effect of DME on CLD mice, hematoxylin-eosin (HE) staining, and biochemical indicators were performed. The prototype of the blood components in mice serum was detected by ultra-high-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). 16S rDNA sequencing was used to analyze the gut microbiota. Finally, the protein and mRNA expression of the FXR pathway in mice liver tissues or HepG2 cells were detected by Western blot, qRT-PCR, or immunofluorescence. Results Pathological testing and biochemical indexes showed that DME significantly reduced serum ALT, AST, ALP, TBIL, DBIL, TBA and liver TBA levels, and attenuated liver tissue injury, necrosis and jaundice in CLD mice. In addition, MetagenomeSeq analysis of gut microbiota showed that DME significantly up-regulated the abundance of Parvibacter , down-regulated the abundance of Paenalcaligenes , and regulated bile acid homeostasis. In terms of mRNA expression, DME significantly upregulated the mRNA levels of Nr1h4, Abcb11, Cyp7a1 and Slc10a1. Meanwhile, in terms of protein expression, DME significantly up-regulated the protein expression levels of FXR, BSEP, CYP7A1 and NTCP, which regulated bile acid homeostasis. Finally, the molecular docking results showed that the components of DME, such as Lumichrome, Daidzein and Folic acid, all had good binding ability with FXR, and the surface plasmon resonance (SPR) results also showed that both Lumichrome and Daidzein had a relatively high affinity with FXR. Conclusion DME alleviated CLD through the FXR pathway, and the mechanisms might be associated with the gut microbiota.
研究领域:
药理学
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肝病学
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分子生物学
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微生物学
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DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
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2024
·
IF 4.8
Guoqiang Guan,Houkang Cao,Zixuan Tang,Kefeng Zhang,Mingli Zhong,Rui Lv,Weimin Wan,Fengyue Guo,Yongwang Wang,Ya Gao
Ethnopharmacological relevance Polygala fallax Hemsl. is a traditional folk medicine commonly used by ethnic minorities in the Guangxi Zhuang Autonomous Region, and has a traditional application in the treatment of liver disease. Polygala fallax Hemsl . polysaccharides (PFPs) are of interest for their potential health benefits. Aim of this study This study explored the impact of PFPs on a mouse model of cholestatic liver injury (CLI) induced by alpha-naphthyl isothiocyanate (ANIT), as well as the potential mechanisms. Materials and methods A mouse CLI model was constructed using ANIT (80 mg/kg) and intervened with different doses of PFPs or ursodeoxycholic acid. Their serum biochemical indices, hepatic oxidative stress indices, and hepatic pathological characteristics were investigated. Then RNA sequencing was performed on liver tissues to identify differentially expressed genes and signaling pathways and to elucidate the mechanism of liver protection by PFPs. Finally, Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting were used to verify the differentially expressed genes. Results Data analyses showed that PFPs reduced the levels of liver function-related biochemical indices, such as ALT, AST, AKP, TBA, DBIL, and TBIL. PFPs up-regulated the activities of SOD and GSH, down-regulated the contents of MDA, inhibited the release of IL-1β, IL-6, and TNF-α, or promoted IL-10. Pathologic characterization of the liver revealed that PFPs reduced hepatocyte apoptosis or necrosis. The RNA sequencing indicated that the genes with differential expression were primarily enriched for the biosynthesis of primary bile acids, secretion or transportation of bile, the reactive oxygen species in chemical carcinogenesis, and the NF-kappa B signaling pathway. In addition, the results of qRT-PCR and Western blotting analysis were consistent with those of RNA sequencing analysis. Conclusions In summary, this study showed that PFPs improved intrahepatic cholestasis and alleviated liver damage through the modulation of primary bile acid production, Control of protein expression related to bile secretion or transportation, decrease in inflammatory reactions, and inhibition of oxidative pressure. As a result, PFPs might offer a hopeful ethnic dietary approach for managing intrahepatic cholestasis.
研究领域:
药理学
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分子生物学
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肝病学
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民族药理学
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DOI
PubMed
高影响因子
RSC Advances
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2023
·Vol. 13
·期 4
·2635-2648
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IF 3.9
Ying Li,Yingxin Tian,Qixue Wang,Xinyi Gu,Long Chen,Yiqun Jia,Shan Cao,Ting Zhang,Mingmei Zhou,Xiaojun Gou
Gynura segetum (Lour.) Merr. (GS), has been widely used in Chinese folk medicine and can promote circulation, relieve pain and remove stasis. In recent years, the hepatotoxicity caused by GS has been reported, however its mechanism is not fully elucidated. Metabolomic techniques are powerful means to explore the toxicological mechanism and therapeutic effects of traditional Chinese medicine. The purpose of this study was to establish a serum metabolomics method based on Gas Chromatography-Mass Spectrometry (GC-MS) to explore the hepatotoxicity mechanism of different exposure times and doses of GS in rats. Sprague Dawley (SD) rats were administered daily with distilled water, 7.5 g kg−1 GS, or 15 g kg−1 GS by intragastrical gavage for either 10 or 21 days. The methods adopted included enzyme-linked immunosorbent assay (ELISA), Hematoxylin and Eosin (H&E) staining and GC-MS-based serum metabolomics. Serum biochemistry analysis showed that the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), triglycerides (TG), total bilirubin (TBIL) and total bile acid (TBA) significantly (P < 0.05) increased while the levels of albumin (ALB) and high-density lipoprotein (HDL) significantly (P < 0.05) decreased in GS-treated groups, compared with the control group. Interestingly, the ALT, AST, TG and ALB levels changed in a time- and dose-dependent manner. The results of H&E staining showed the degree of liver damage after administration of GS gradually deepened with the extension of administration time and the increase of the dose. According to the results of metabolomics analysis, 26 differential metabolites were identified, which were involved in 8 metabolic pathways including phenylalanine metabolism, glyoxylic acid and dicarboxylic acid metabolism and so on. Meanwhile, the number of differential metabolites in different GS-treated groups was associated with GS exposure time and dose. Therefore, we concluded that GS might induce hepatotoxicity depending on the exposure time and dose.
研究领域:
药理学
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毒理学
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代谢组学
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传统中药
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2019
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IF 4.784
Hang Qu,Xin Gao,Zhen-Yu Wang,Juan-Juan Yi
A novel polysaccharide (PNP80b-2) was obtained from Pinus koraiensis pine nut, which has been proved to possess good hepatoprotective effects in vitro . This study comprehensively investigated its hepatoprotective activities against different types of chemical-induced liver injury in vivo . Carbon tetrachloride, alcohol and acetaminophen were used as hepatic toxicants to establish chemical pollutant-induced liver injury (CILI) model, alcohol induced-liver injury (AILI) model and drug-induced liver injury (DILI) model, respectively. The results showed that PNP80b-2 prevented elevation of biomarkers for liver injury in each model, including alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and total bilirubin (TBIL). The expression of cytochrome P450 in damaged hepatocytes was also downregulated. Additionally, PNP80b-2 enhanced hepatic antioxidant capacity through upregulating the expression of NRF2 and HO-1, thereby increasing superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT) activities and decreasing malondialdehyde (MDA) levels. The uncontrolled production of inflammatory factors including tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6) and cyclooxygenase-2 (COX-2) in CILI, AILI and DILI models was also suppressed by PNP80b-2. By contrast, PNP80b-2 exerted the strongest hepatoprotection against AILI model, through improving hepatic antioxidant capacity via NRF2/ARE pathway and regulating inflammation response. Thus, PNP80b-2 is a promising functional food to prevent AILI.
研究领域:
药理学
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肝病学
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功能性食品
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毒理学
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产品关联
DOI
PubMed
高影响因子
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