Objective:To investigate the effects of a crude extract from Gnetum montanum Markgr.on ethanol-induced hepatotoxicity and metabolic disorders.Methods:Alcoholic liver disorder was induced in mice by administering incre...Objective:To investigate the effects of a crude extract from Gnetum montanum Markgr.on ethanol-induced hepatotoxicity and metabolic disorders.Methods:Alcoholic liver disorder was induced in mice by administering increasing doses of ethanol via oral gavage.Biomarkers of liver injury and oxidative stress were assessed at the end of the study.Liver tissue damage and fat deposition were evaluated using hematoxylin and eosin and oil red O staining,respectively.In addition,key biomarkers were examined in acetaldehyde-treated HepG2 cells.Results:Ethanol consumption induced characteristic pathological changes,including elevated serum markers of liver injury,hepatic lipid accumulation,and oxidative stress in liver tissues.Oral administration of Gnetum montanum extract(175 and 350 mg/kg)decreased serum aspartate aminotransferase,alanine aminotransferase,γ-glutamyl transferase,and bilirubin levels in ethanol-treated mice.The extract also lowered triglyceride levels in serum and liver tissue in a dose-dependent manner.Furthermore,it mitigated malondialdehyde levels,preserved reduced glutathione levels,and enhanced catalase activity and total antioxidant capacity in liver tissue homogenates.Additionally,ethanol-induced hyperuricemia was suppressed by Gnetum montanum extract by inhibiting xanthine oxidase activity.Similar effects were observed in Gnetum montanum extract-treated HepG2 cells.Conclusions:This study demonstrates that Gnetum montanum extract alleviates ethanol-induced hepatic injury by alleviating oxidative stress and inhibiting xanthine oxidase activity.展开更多
BACKGROUND Inhibition of liver fibrosis plays a crucial role in curbing the advancement of chronic disease to cirrhosis and even liver cancer.However,modern medicine currently lacks direct anti-fibrotic drugs.He-He-Sh...BACKGROUND Inhibition of liver fibrosis plays a crucial role in curbing the advancement of chronic disease to cirrhosis and even liver cancer.However,modern medicine currently lacks direct anti-fibrotic drugs.He-He-Shu-Yang formula(HHSY)is a renowned Chinese medicine for the treatment of liver fibrosis.However,its mechanism of action has not been fully unraveled.AIM To explore the efficacy and mechanism of action of HHSY through in vitro and in vivo experiments.METHODS A liver fibrosis rat model(carbon tetrachloride-induced)was treated with low-or high-dose HHSY(10.42 g/kg or 20.84 g/kg)or with colchicine(1 mg/kg)for 9 weeks.In vitro,LX-2 human hepatic stellate cells(HSCs)were activated using transforming growth factor-β1 and subsequently treated with HHSY-containing serum or a nicotinamide adenine dinucleotide phosphate oxidase 4(NOX4)inhibitor.Through high-performance liquid chromatography,histopathology(hematoxylin and eosin,Masson),immunohistochemistry,western blot,and quantitative reverse transcription polymerase chain reaction analyses,we demonstrated that HHSY inhibited HSC activation and suppressed the NOX4/reactive oxygen species(ROS)/nucleotide binding oligomerization domain-like receptor family pyrin domain-containing 3(NLRP3)pathway.RESULTS In vivo,HHSY improved liver function and alleviated liver pathology,including reducing inflammatory cell infiltration,and liver fibrosis in carbon tetrachloride rats.with more significant effects at higher doses.Immunohistochemistry revealed that HHSY could decrease alpha-smooth muscle actin,NOX4,and NLRP3 expression,as well as serum ROS levels(O_(2)-and H_(2)O_(2),P<0.05).Western blot analysis confirmed HHSY also reduced NLRP3 protein levels(P<0.05).In vitro,HHSY at 1.25%or 2.5%reduced the levels of ACTA2 mRNA,NOX4 protein and NOX4 mRNA,ROS production,and NLRP3 and IL-1βmRNA in activated LX-2 cells(P<0.05).CONCLUSION HHSY effectively treats liver fibrosis,likely by inhibiting HSC activation through the NOX4/ROS/NLRP3 pathway.This underscores HHSY’s clinical relevance as a potential therapeutic option for liver fibrosis.展开更多
AIM: To investigate the total cytochrome P450 (CYP) content, microsomal mixed-function oxidase (MFO) activity, and expression of mRNAs for various CYP isozymes in a simple rat model of reversible obstructive jaundice....AIM: To investigate the total cytochrome P450 (CYP) content, microsomal mixed-function oxidase (MFO) activity, and expression of mRNAs for various CYP isozymes in a simple rat model of reversible obstructive jaundice. METHODS: Obstructive jaundice was created in male rats by causing bile duct obstruction with polyester tape. In another group of rats, bile duct obstruction was followed by internal biliary drainage after releasing the tape. The expression of various CYP isozyme mRNAs was semi-quantitatively assessed by competitive RT- PCR. RESULTS: The total CYP content and microsomal MFO activity showed a significant decrease after biliary obstruction, but returned to respective control levels after biliary drainage. A marked reduction in the expression of CYP1A2, 2B1/2, 2C11, 2E1, 3A1, and 3A2 mRNA was detected during biliary obstruction, while expression increased significantly toward the control level after biliary drainage. Although expression of CYP4A1 mRNA showed no reduction during biliary obstruction, it still increased significantly after biliary drainage. CONCLUSION: These results suggest that not only obstructive jaundice, but also the subsequent internal biliary drainage may affect regulatory medications of the synthesis of individual CYP isozymes differently.展开更多
目的观察大蒜素对大鼠肝星状细胞(HSC-T6)增殖及细胞外基质合成酶-单胺氧化酶(MAO)的影响,探讨大蒜素抗肝纤维化的作用及其机制。方法体外培养大鼠肝星状细胞株HSC-T6。以MTT法检测大蒜素作用下对大鼠肝星状细胞增殖的影响,real time RT...目的观察大蒜素对大鼠肝星状细胞(HSC-T6)增殖及细胞外基质合成酶-单胺氧化酶(MAO)的影响,探讨大蒜素抗肝纤维化的作用及其机制。方法体外培养大鼠肝星状细胞株HSC-T6。以MTT法检测大蒜素作用下对大鼠肝星状细胞增殖的影响,real time RT-PCR检测肝星状细胞的MAO m RNA的表达水平、Western blot检测肝星状细胞的MAO蛋白的表达水平。结果 HSC-T6大蒜素处理组与空白对照组比较,增殖抑制率明显提高,差异有统计学意义(P<0.05);MAO的m RNA及蛋白表达水平均明显下调,并且大蒜素浓度增高时,MAO的m RNA及蛋白表达水平则逐渐下调,DATS高浓度实验组(24μg/ml)对MAO的抑制作用明显强于溶剂对照组,差异有统计学意义(P<0.05)。结论大蒜素对HSC-T6的增殖和MAO的表达均有抑制作用,且对MAO的表达抑制作用具有剂量依赖性,可为临床开发抗肝纤维化的新药物提供理论基础。展开更多
基金funded by Vietnam National Foundation for Science and Technology Development under grant number 108.05-2023.23.
文摘Objective:To investigate the effects of a crude extract from Gnetum montanum Markgr.on ethanol-induced hepatotoxicity and metabolic disorders.Methods:Alcoholic liver disorder was induced in mice by administering increasing doses of ethanol via oral gavage.Biomarkers of liver injury and oxidative stress were assessed at the end of the study.Liver tissue damage and fat deposition were evaluated using hematoxylin and eosin and oil red O staining,respectively.In addition,key biomarkers were examined in acetaldehyde-treated HepG2 cells.Results:Ethanol consumption induced characteristic pathological changes,including elevated serum markers of liver injury,hepatic lipid accumulation,and oxidative stress in liver tissues.Oral administration of Gnetum montanum extract(175 and 350 mg/kg)decreased serum aspartate aminotransferase,alanine aminotransferase,γ-glutamyl transferase,and bilirubin levels in ethanol-treated mice.The extract also lowered triglyceride levels in serum and liver tissue in a dose-dependent manner.Furthermore,it mitigated malondialdehyde levels,preserved reduced glutathione levels,and enhanced catalase activity and total antioxidant capacity in liver tissue homogenates.Additionally,ethanol-induced hyperuricemia was suppressed by Gnetum montanum extract by inhibiting xanthine oxidase activity.Similar effects were observed in Gnetum montanum extract-treated HepG2 cells.Conclusions:This study demonstrates that Gnetum montanum extract alleviates ethanol-induced hepatic injury by alleviating oxidative stress and inhibiting xanthine oxidase activity.
基金Supported by the Guangdong Basic and Applied Basic Research Fund Project,No.2022A1515110825 and No.2023A1515011092the Incubation Program for the Science and Technology Development of Chinese Medicine Guangdong Laboratory,No.HQL2024PZ033+5 种基金the Chi Xiaoling National Famous Traditional Chinese Medicine Expert Inheritance Studio,Teaching Letter from the State Traditional Chinese Medicine Office[2022],No.75the Advantage Disease Project of Guangdong Provincial Hospital of Traditional Chinese Medicine[2020],No.37the Science and Technology Planning Project of Guangdong Province,No.2023B1212060063the Project of Guangdong Provincial Key Laboratory of Chinese Medicine for Prevention and Treatment of Refractory Chronic Diseases,No.YN2023MB04the Clinical Research Projects of Guangdong Provincial Hospital of Chinese Medicine,No.YN2022QN05the Guangzhou Basic Research Program for Young Doctors in Basic and Applied Basic Research,No.2024A04J3004.
文摘BACKGROUND Inhibition of liver fibrosis plays a crucial role in curbing the advancement of chronic disease to cirrhosis and even liver cancer.However,modern medicine currently lacks direct anti-fibrotic drugs.He-He-Shu-Yang formula(HHSY)is a renowned Chinese medicine for the treatment of liver fibrosis.However,its mechanism of action has not been fully unraveled.AIM To explore the efficacy and mechanism of action of HHSY through in vitro and in vivo experiments.METHODS A liver fibrosis rat model(carbon tetrachloride-induced)was treated with low-or high-dose HHSY(10.42 g/kg or 20.84 g/kg)or with colchicine(1 mg/kg)for 9 weeks.In vitro,LX-2 human hepatic stellate cells(HSCs)were activated using transforming growth factor-β1 and subsequently treated with HHSY-containing serum or a nicotinamide adenine dinucleotide phosphate oxidase 4(NOX4)inhibitor.Through high-performance liquid chromatography,histopathology(hematoxylin and eosin,Masson),immunohistochemistry,western blot,and quantitative reverse transcription polymerase chain reaction analyses,we demonstrated that HHSY inhibited HSC activation and suppressed the NOX4/reactive oxygen species(ROS)/nucleotide binding oligomerization domain-like receptor family pyrin domain-containing 3(NLRP3)pathway.RESULTS In vivo,HHSY improved liver function and alleviated liver pathology,including reducing inflammatory cell infiltration,and liver fibrosis in carbon tetrachloride rats.with more significant effects at higher doses.Immunohistochemistry revealed that HHSY could decrease alpha-smooth muscle actin,NOX4,and NLRP3 expression,as well as serum ROS levels(O_(2)-and H_(2)O_(2),P<0.05).Western blot analysis confirmed HHSY also reduced NLRP3 protein levels(P<0.05).In vitro,HHSY at 1.25%or 2.5%reduced the levels of ACTA2 mRNA,NOX4 protein and NOX4 mRNA,ROS production,and NLRP3 and IL-1βmRNA in activated LX-2 cells(P<0.05).CONCLUSION HHSY effectively treats liver fibrosis,likely by inhibiting HSC activation through the NOX4/ROS/NLRP3 pathway.This underscores HHSY’s clinical relevance as a potential therapeutic option for liver fibrosis.
文摘AIM: To investigate the total cytochrome P450 (CYP) content, microsomal mixed-function oxidase (MFO) activity, and expression of mRNAs for various CYP isozymes in a simple rat model of reversible obstructive jaundice. METHODS: Obstructive jaundice was created in male rats by causing bile duct obstruction with polyester tape. In another group of rats, bile duct obstruction was followed by internal biliary drainage after releasing the tape. The expression of various CYP isozyme mRNAs was semi-quantitatively assessed by competitive RT- PCR. RESULTS: The total CYP content and microsomal MFO activity showed a significant decrease after biliary obstruction, but returned to respective control levels after biliary drainage. A marked reduction in the expression of CYP1A2, 2B1/2, 2C11, 2E1, 3A1, and 3A2 mRNA was detected during biliary obstruction, while expression increased significantly toward the control level after biliary drainage. Although expression of CYP4A1 mRNA showed no reduction during biliary obstruction, it still increased significantly after biliary drainage. CONCLUSION: These results suggest that not only obstructive jaundice, but also the subsequent internal biliary drainage may affect regulatory medications of the synthesis of individual CYP isozymes differently.
文摘目的观察大蒜素对大鼠肝星状细胞(HSC-T6)增殖及细胞外基质合成酶-单胺氧化酶(MAO)的影响,探讨大蒜素抗肝纤维化的作用及其机制。方法体外培养大鼠肝星状细胞株HSC-T6。以MTT法检测大蒜素作用下对大鼠肝星状细胞增殖的影响,real time RT-PCR检测肝星状细胞的MAO m RNA的表达水平、Western blot检测肝星状细胞的MAO蛋白的表达水平。结果 HSC-T6大蒜素处理组与空白对照组比较,增殖抑制率明显提高,差异有统计学意义(P<0.05);MAO的m RNA及蛋白表达水平均明显下调,并且大蒜素浓度增高时,MAO的m RNA及蛋白表达水平则逐渐下调,DATS高浓度实验组(24μg/ml)对MAO的抑制作用明显强于溶剂对照组,差异有统计学意义(P<0.05)。结论大蒜素对HSC-T6的增殖和MAO的表达均有抑制作用,且对MAO的表达抑制作用具有剂量依赖性,可为临床开发抗肝纤维化的新药物提供理论基础。
