Frontiers in Pharmacology
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2024
·
IF 4.4
Zhang Hui,Cui Xiao,Liu Wei,Xiang Zheng,Ye Ji-Feng
Introduction: Alcoholic liver disease (ALD) was the second leading cause of liver injury. Penthorum chinense Pursh (GHC) is an important Miao ethnic drug of traditional Chinese medicine for the treatment of liver disease, but the pathogenesis is not clear.Aim of the study: To analysis the intestinal microflora and metabolic pathway of GHC on ALD mice.Methods: An HPLC-QTOF-MS method was used to identified the components from GHC extract, firstly. 60 mice were divided into six groups including blank group, model group, positive group and GHC groups (0.29, 0.87 and 2.61 g/kg). ALD mice was treated with GHC for 12 days. ALT, AST, TC and TG in serum were determined, liver index and pathological analysis were achieved. 16S rRNA gene sequencing was used to detect the intestinal microbial diversity. Finally, UPLC-QTOF-MS was used to analysis the metabolic pathways.Results: 38 ingredients were identified in GHC extract. Compared with the model group, liver index of the positive group and GHC (2.61 g/kg) group was significantly reduced. Compared with the model group, contents of ALT, AST, TC and TG of GHC groups reduced in a dose-dependent manner. Intestinal microbial diversity analysis indicated that Chao1, Observed species, Pielou_e, and Shannon indexes in GHC group (2.61 g/kg) were lower than those in model group. Principal coordinate analysis indicated that the intestinal microbial composition between blank group and model group, the model group and GHC (2.61 g/kg) group changed significantly. Compared with the model group, proportion of Firmicutes decreased, and the proportion of Bacteroidetes increased significantly in GHC group, which were 50.84% and 40.15%. The more prominent bacteria in the GHC group were odoribacteraceae, turicibacter, deferribacteraceae, and the intestinal beneficial symbiotic bacteria mucispirillum. Metabolic analysis indicated that, compared with blank group, 90 metabolites in model group changed significantly, and 68 metabolites were significantly callback in GHC group.Discussion: GHC has a therapeutic effect on ALD by regulating intestinal flora imbalance and metabolic pathways including Glycine, serine and threonine metabolism, Glutathione metabolism, Arginine and proline metabolism, Alanine, aspartate and glutamate metabolism, Butanoate metabolism and primary bile acid biosynthesis.
研究领域:
药理学
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微生物学
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代谢组学
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高影响因子
Food Science & Nutrition
·
2024
·
IF 3.5
Ruixi Luo,Yudie Hu,La Wang,Zunli Ke,Wenjia Wang,Ping Wang,Weiyi Tian
The primary catalyst for nonalcoholic fatty liver disease (NAFLD) is widely recognized as the induction of lipotoxicity in hepatocytes by an excess of fatty acids. In China, Penthorum chinense Pursh (PcP) is commonly employed as a functional food due to its known hepatoprotective properties. The present study aimed to investigate the influence of PcP extract on in vivo and in vitro models of NAFLD. We found that PcP extract can attenuate palmitic acid (PA)-induced lipotoxicity in HepG2 cells. PA was observed to trigger pyroptosis, as indicated by the increased expression of NLRP3 and GSDMD/N, activation of Caspase-1, and subsequent release of IL-1β and IL-18. However, these changes were reversed after PcP was administered. Furthermore, the application of an NLRP3 agonist inhibited the protective effects of PcP on lipotoxicity, indicating that PcP decreased lipotoxicity by inhibiting the NLRP3/Caspase-1/GSDMD pathway. Ultimately, we established a rat model of NAFLD through the administration of a high-fat diet (HFD), followed by the oral delivery of PcP extracts. The results demonstrated that the administration of PcP extract effectively decreased dyslipidemia and hepatic steatosis, which coincided with a decrease in hepatic pyroptosis through modulation of the NLRP3/Caspase-1/GSDMD pathway in liver tissues. Overall, our findings provide insight into the mechanism by which PcP extracts alleviate hepatic steatosis, highlighting the potential significance of modulating the NLRP3/Caspase-1/GSDMD pathway in the context of pyroptosis.
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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细胞生物学
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高影响因子
Food & Function
·
2020
·Vol. 11
·期 9
·7925-7934
·
IF 4.171
Yi-Chao Du,Li Lai,Hao Zhang,Fu-Rui Zhong,Huan-Li Cheng,Bao-Lin Qian,Peng Tan,Xian-Ming Xia,Wen-Guang Fu
Acetaminophen (APAP) is one of the safest and most effective over-the-counter (OTC) analgesics and antipyretics, but excessive doses of APAP will induce hepatotoxicity with high morbidity and mortality worldwide. Kaempferol (KA), a flavonoid compound derived from the medicinal and edible plant of Penthorum chinense Pursh, has been reported to exert a profound anti-inflammatory and antioxidant activity. In this study, we explored the protective effect and novel mechanism of KA against APAP-induced hepatotoxicity. The results revealed that KA pretreatment significantly reduced the levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT), relieved hepatocellular damage and apoptosis, attenuated the exhaustion of glutathione (GSH) and accumulation of malondialdehyde (MDA), increased the expression of antioxidative enzymes (e.g., heme oxygenase 1 (HO-1) and NADPH quinone oxidoreductase 1 (NQO1)), and thus restrained APAP-induced oxidative damage in the liver. KA suppressed the expression of NLRP3 and reduced the levels of pro-inflammatory factors, including interleukin-1 beta (IL-1β), tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6). Moreover, KA remarkably inhibited high-mobility group box 1 (HMGB1) and toll-like receptor 4 (TLR4) expression as well as nuclear factor kappa-B (NF-κB) activation for liver protection against APAP-induced inflammatory responses and apoptosis. Taken together, our findings suggested that KA could effectively protect hepatocytes from APAP hepatotoxicity through the up-regulation of HO-1 and NQO1 expression, the down-regulation of NLRP3 expression, and the inhibition of the HMGB1/TLR4/NF-κB signaling pathway.
研究领域:
药理学
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毒理学
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分子生物学
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高影响因子
MICROCHEMICAL JOURNAL
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2023
·
IF 4.8
Li-Li Yang,Ting Li,Dan-Dan Yang,Yan-Jun Li,Jia-Yuan He,Lian-Di Zhou,Qi-Hui Zhang,Chong-Zhi Wang,Chun-Su Yuan
In this work, a novel dummy molecularly imprinted polymer (MIP/CS/Fe 3 O 4 ) was successfully prepared for the selective enrichment of flavonoids in Penthorum chinense Pursh. The molecularly imprinted polymer was synthesized on the surface of chitosan-modified Fe 3 O 4 nanoparticles with naringenin as the dummy template and then it was used as a solid adsorbent for the analyte enrichment. Compared with structural analogues, the MIP/CS/Fe 3 O 4 presented quick binding kinetic behavior, satisfying selectivity and high adsorption capacity toward pinocembrin. The adsorption capacity and the imprinting factor of MIP/CS/Fe 3 O 4 could reach 8.56 mg·g −1 and 1.7, respectively. Finally, MIP/CS/Fe 3 O 4 was applied to enrich flavonoids in the crude extract from Penthorum chinense Pursh and 11 flavonoids were successfully detected, indicating the MIP/CS/Fe 3 O 4 was a promising adsorbent for separation and enrichment of flavonoids. Many favorable properties of the synthesized dummy molecularly imprinted polymer can also provide a new direction for the simultaneous enrichment of structural similarities.
研究领域:
化学
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材料科学
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药物分析
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环境科学
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高影响因子
Chinese Medicine
·
2026
·Vol. 21
·期 1
·40
·
IF 5.7
Yao Qianfang,Hu Guishan,Yin Can,Wu Anguo,Hu Guangqiang,Qin Dalian,Zhou Xiaogang,Law Betty Yuen-Kwan,Du Xi,Chen Li,Li Jianqiao,Lin Hong,Long Xin,Wu Jianming,Yu Lu
Background Cerebral ischemia/reperfusion injury (CI/RI) remains a critical barrier to effective ischemic stroke (IS) treatment. While mitophagy activation has been shown to attenuate apoptosis and pyroptosis, thereby ameliorating CI/RI, the therapeutic potential of natural compounds targeting this pathway remains underexplored. Penthorum chinense Pursh (PCP), a traditional hepatoprotective herb, contains Thonningianin A (TA), a bioactive compound with reported autophagic properties. However, the role and mechanisms of TA in CI/RI mitigation remain unclear. Methods In vivo, a middle cerebral artery occlusion/reperfusion (MCAO/R) rat model was established to evaluate TA’s neuroprotective effects via TTC staining, Longa neurological scoring, and immunofluorescence staining. In vitro, oxygen–glucose deprivation/reoxygenation (OGD/R)-treated HT22 and BV2 cells were used to assess TA’s impact on cell viability (MTT, Hoechst/PI staining), mitochondrial oxidative stress (DHE, TMRM, JC-1, Mito-Tracker staining and Western blot), apoptosis (flow cytometry, immunofluorescence staining, Hochest and PI staining and Western blot), and pyroptosis (EthD-2/YO-PRO-1 staining and Western blot). Autophagy and mitophagy modulation was investigated using rapamycin (Rap), 3-MA (autophagy inhibitor), CCCP (mitophagy inducer), and AC220 (mitophagy inhibitor) in EGFP-LC3-U87 and mCherry-GFP-FIS1-293T cells. Co-localization immunofluorescence and Western blotting were employed to validate PINK1/Parkin pathway involvement. Results TA administration significantly improved neurological function, reduced cerebral infarct volume, and attenuated neuronal damage in MCAO/R rats. In vitro, TA suppressed OGD/R-induced mitochondrial oxidative stress and apoptosis in HT22 cells while mitigating pyroptosis in BV2 microglia. Mechanistically, TA activated PINK1/Parkin-dependent mitophagy, as evidenced by enhanced LC3-II/I ratio, and increased mitochondrial-autophagosome co-localization. Crucially, TA’s anti-apoptotic and anti-pyroptotic effects were abolished upon mitophagy inhibition. These findings were corroborated in the MCAO/R model, where TA upregulated PINK1/Parkin signaling and mitigated cell damage. Conclusion This study identifies TA as a novel natural agent alleviating CI/RI by activating PINK1/Parkin-mediated mitophagy, thereby concurrently suppressing apoptosis and pyroptosis. These findings provide the first elucidating the molecular mechanis underlying TA's potential as a therapeutic candidate for IS. Graphical
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Frontiers in Microbiology
·
2023
·
IF 5.2
Junyuan Qin,Lei Yu,Fu Peng,Xin Ye,Gangmin Li,Chen Sun,Fang Cheng,Cheng Peng,Xiaofang Xie
Staphylococcus aureus is an opportunistic pathogen. Due to the widespread use and abuse of antibiotics, various drug-resistant strains of S. aureus have emerged, with methicillin-resistant Staphylococcus aureus (MRSA) being the most prevalent. Bacterial biofilm is a significant contributor to bacterial infection and drug resistance. Consequently, bacterial biofilm formation has emerged as a therapeutic strategy. In this study, the chemical constituents, antimicrobial and antibiofilm properties of tannins isolated from Penthorum chinense Pursh (TPCP) were investigated. In vitro , TPCP exhibited antimicrobial properties. The minimum inhibitory concentrations (MIC) and minimum bactericidal concentrations (MBC) for methicillin-sensitive Staphylococcus aureus (MSSA) and MRSA were 156.25 and 312.5 μg/mL, and 312.5 and 625 μg/mL, respectively. According to the growth curves, TPCP significantly inhibited the growth of MSSA and MRSA. The results of the crystal violet biofilm assay in conjunction with confocal laser scanning and scanning electron microscopy demonstrated that TPCP destroyed preformed MSSA and MRSA biofilms. TPCP significantly decreased the secretion of exopolysaccharides and extracellular DNA. Subsequently, the mechanism was investigated using RT-PCR. Examining the expression of ica A, cid A, sig B, agr A, and sar A genes in MRSA, we discovered that TPCP inhibited biofilm formation by affecting the quorum-sensing system in bacteria. Our study demonstrates that TPCP exerts antibacterial effects by disrupting the formation of bacterial biofilms, suggesting that TPCP has clinical potential as a novel antibacterial agent for the prevention and treatment of MSSA and MRSA infections.
研究领域:
微生物学
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药理学
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生物技术
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传染病学
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高影响因子
Frontiers in Pharmacology
·
2023
·
IF 5.6
Sujuan Wang,Wenqing Li,Wenxiu Liu,Lei Yu,Fu Peng,Junyuan Qin,Lin Pu,Yunli Tang,Xiaofang Xie,Cheng Peng
Background: Penthorum chinense Pursh (PCP) is widely utilized in China to treat a variety of liver diseases. It has been shown that flavonoids inhibit inflammation and have the potential to attenuate tissue damage and fibrosis. However, the mechanisms underlying how total flavonoids isolated from PCP (TFPCP) exert their anti-fibrotic effects remain unclear. Methods: The chemical composition of TFPCP was determined using UHPLC–Q-Orbitrap HRMS. Subsequently, rats were randomly assigned to a control group (Control), a carbon tetrachloride (CCl 4 )-induced hepatic fibrosis model group (Model), a positive control group [0.2 mg/(kg∙day)] of Colchicine), and three TFPCP treatment groups [50, 100, and 150 mg/(kg∙day)]. All substances were administered by gavage and treatments lasted for 9 weeks. Simultaneously, rats were intraperitoneally injected with 10%–20% CCl 4 for 9 weeks to induce liver fibrosis. At the end of the experiment, the liver ultrasound, liver histomorphological, biochemical indicators, and inflammatory cytokine levels were tested respectively. The underlying mechanisms were assessed using Western blot, immunohistochemistry, immunofluorescence, RT-qPCR, and metabolomics. Results: Fourteen flavonoids were identified in TFPCP. Compared with control animals, CCl 4 -treated rats demonstrated obvious liver injury and fibrosis, manifested as increases in gray values, distal diameter of portal vein (DDPV) and a decrease in blood flow velocity (VPV) in the ultrasound analysis; increased biochemical index values (serum levels of ALT, AST, TBIL, and ALP); marked increases in the contents of fibrotic markers (PC III, COL4, LN, HA) and inflammatory factors (serum TNF-α, IL-6, and IL-1β); and significant pathological changes. However, compared with the Model group, the ultrasound parameters were significantly improved and the serum levels of inflammatory cytokines were reduced in the TFPCP group. In contrast, the expression of TGF-β 1 , TLR4, and MyD88, as well as the p-P65/P65 and p-IκBα/IκBα ratios, were considerably reduced following TFPCP treatment. In addition, we identified 32 metabolites exhibiting differential abundance in the Model group. Interestingly, TFPCP treatment resulted in the restoration of the levels of 20 of these metabolites. Conclusion: Our findings indicated that TFPCP can ameliorate hepatic fibrosis by improving liver function and morphology via the inactivation of the TLR4/MyD88-mediated NF-κB pathway and the regulation of liver metabolism.
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高影响因子
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