Herbal-induced liver injury(HILI)is an important and increasingly concerning cause of liver toxicity,and this study presents recent updates to the literature.An extensive literature review was conducted encompassing S...Herbal-induced liver injury(HILI)is an important and increasingly concerning cause of liver toxicity,and this study presents recent updates to the literature.An extensive literature review was conducted encompassing September 2019 through March 2021.Studies with clinically significant findings were analyzed and included in this review.We emphasized those studies that provided a causality assessment methodology,such as Roussel Uclaf Causality Assessment Method scores.Our review includes reports of individual herbals,including Garcinia cambogia,green tea extract,kratom as well as classes such as performance enhancing supplements,Traditional Chinese medicine,Ayurvedic medicine and herbal contamination.Newly described herbals include ashwagandha,boldo,skyfruit,and‘Thermo gun’.Several studies discussing data from national registries,including the United States Drug-Induced Liver Injury(DILI)Network,Spanish DILI Registry,and Latin American DILI Network were incorporated.There has also been a continued interest in hepatoprotection,with promising use of herbals to counter hepatotoxicity from anti-tubercular medications.We also elucidated the current legal conversation surrounding use of herbals by presenting updates from the Federal Drug Administration.The highlights of the literature over the past year indicate interest in HILI that will continue as the supplement industry in the United States grows.展开更多
The prevalence of alcoholic liver disease and non-alcoholic liver disease patients has nearly doubled over the past decades worldwide. Alcoholic liver disease among patients with chronic liver disease has increased wi...The prevalence of alcoholic liver disease and non-alcoholic liver disease patients has nearly doubled over the past decades worldwide. Alcoholic liver disease among patients with chronic liver disease has increased with arisen due to alcohol consumption and obesity. The diagnosis plays a crucial role in treating such conditions based on the stages of liver functioning. The elevated liver enzymes are the key characterizing of identifying the alcoholic liver disease (ALD) and NAFLD. Later on, there is a progression of the disease conditions by developing fibrosis and cirrhosis, leading to liver carcinoma. The other state, steatohepatitis, is associated with an increase in liver-related and can lead to mortality. Risk factors for both diseases are growing, leading to various complications in health. There is no specific treatment up to date for these conditions, but statins play a crucial role in managing several liver disease conditions. The commonly used drug is hydroxymethylglutaryl coenzyme A (HMG Co-A) reductase inhibitors. It is also known as statins, which help normalize liver enzymes in patients with elevated plasma aminotransferases. As a result, external liver damage is considered safe for the liver as the Statin medication at low to moderate dose usage. OBJECTIVES: The main scope of this review is to study the various factors like pharmacological actions, adverse events, and biochemical and liver cell imaging results in patients with ALD and NAFLD. The different types of statins used in alcoholic and non-alcoholic patients’ clinical data for the safety of the statin therapy were concluded in this review. Fatty liver changes of both liver disease conditions were studied using different drugs. The other liver enzymes like Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma-glutamyl Transferase (GGT), and the effectiveness of Statin therapy are considered vital concepts in this review.展开更多
Objective:Objective:To analyze and explore the key targets and molecular mechanisms of action of Radix Paeoniae Alba against Toosendan Fructus-induced hepatotoxicity and the relationship between corresponding compound...Objective:Objective:To analyze and explore the key targets and molecular mechanisms of action of Radix Paeoniae Alba against Toosendan Fructus-induced hepatotoxicity and the relationship between corresponding compounds based on network pharmacology.Methods:Using network pharmacology,a"traditional Chinese medicine-chemical composition-key target-pathway"analysis was conducted on Radix Paeoniae Alba for the treatment of Toosendan Fructus-induced hepatotoxicity.The possible mechanism of action was analyzed in terms of function.Results:The core targets,such as interleukin(IL)-6,tumor necrosis factor(TNF),heat shock protein 90 alpha family class A member 1(HSP90AA1),peroxisome proliferator-activated receptor gamma(PPARG),prostaglandin-endoperoxide synthase 2(PTGS2),heme oxygenase 1(HMOX1),Jun proto-oncogene(JUN),caspase-3,estrogen receptor 1(ESR1),and aryl hydrocarbon receptor(AHR)were screened from the targets of Radix Paeoniae Alba against Toosendan Fructus-induced hepatotoxicity.Biological process(BP)of toxic targets(BP terms)involved"response to drug;activation of cysteine-type endopeptidase activity involved in apoptotic process,”positive regulation of transcription.Cellular components(CC terms)mainly involved cytosol and membrane rafts.Molecular function(MF)terms included"protein homodimerization activity,"RNA polymerase II transcription factor activity and enzyme binding,etc."The Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway included the TNF signaling pathway,cancer pathways,and apoptosis.Conclusion:Radix Paeoniae Alba might alleviate Toosendan Fructus-induced hepatotoxicity through IL6,TNF,HSP90AA1,PPARG,PTGS2,HMOX1,and other targets,possibly via the activation of cysteine-type endopeptidase activity involved in these pathways.展开更多
Microplastics(MPs)have become a significant concern for their potential toxicity.However,the correlation between the size of plastic particles and their toxicity remains inconclusive.Here,we investigate the toxic effe...Microplastics(MPs)have become a significant concern for their potential toxicity.However,the correlation between the size of plastic particles and their toxicity remains inconclusive.Here,we investigate the toxic effects of different sizes(80 nm,800 nm,8μm and 80μm)polystyrene MPs(PS-MPs)on the model organism Nile tilapia(Oreochromis niloticus).The results of bioluminescent imaging indicate that the 80 nm PS-MPs are more likely to invade the body.H&E staining shows severe damage on the intestinal villi and distinct hepatic steatosis in the 80 nm group.Ed U labeling shows that the proliferation activity of intestinal and liver cells reduces significantly in the 80 nm group.The gut microbiome analysis shows a severe imbalance of gut microbiota homeostasis in the 80 nm group.The analysis of liver transcriptomics and metabolomics shows that the liver lipid metabolism is disordered in the 80 nm group.In conclusion,this study confirms that the 80 nm PS-MPs are more likely to induce intestinal and liver toxicity.All the above lay the foundation for further study on the pathological damage of MPs to other organisms.展开更多
The incidence of inflammatory bowel diseases(IBD)is rising worldwide.The therapeutic options for IBD are expanding,and the number of drugs with new targets will rapidly increase in coming years.A rapid step-up approac...The incidence of inflammatory bowel diseases(IBD)is rising worldwide.The therapeutic options for IBD are expanding,and the number of drugs with new targets will rapidly increase in coming years.A rapid step-up approach with close monitoring of intestinal inflammation is extensively used.The fear of side effects represents one the most limiting factor of their use.Despite a widespread use for years,drug induced liver injury(DILI)management remains a challenging situation with Azathioprine and Methotrexate.DILI seems less frequent with anti-tumor necrosis factor agents and new biologic therapies.The aim of this review is to report incidence,physiopathology and practical guidelines in case of DILI occurrence with the armamentarium of old and new drugs in the field of IBD.展开更多
Inflammatory bowel diseases(IBD)are associated with various hepatobiliary disorders.They can occur at any moment in the course of the disease or associated with the treatment.The prevalence of liver dysfunction can re...Inflammatory bowel diseases(IBD)are associated with various hepatobiliary disorders.They can occur at any moment in the course of the disease or associated with the treatment.The prevalence of liver dysfunction can reach up to 50%in different studies.Nonalcoholic fatty liver disease is considered the most common hepatobiliary complication in IBD,while primary sclerosing cholangitis is the most specific.Management of hepatic manifestations in IBD involves a multidisciplinary approach that includes a high index of suspicion and joint management with hepatologists.The medical confrontation with abnormal liver tests must include an exhaustive study to determine if these patterns can be related to IBD,associated diseases or to the therapies used.展开更多
Serum palmitic acid(PA), a type of saturated fatty acid, causes lipid accumulation and induces toxicity in hepatocytes.Ethanol(Et OH) is metabolized by the liver and induces hepatic injury and inflammation. Herein, we...Serum palmitic acid(PA), a type of saturated fatty acid, causes lipid accumulation and induces toxicity in hepatocytes.Ethanol(Et OH) is metabolized by the liver and induces hepatic injury and inflammation. Herein, we analyzed the effects of Et OH on PA-induced lipotoxicity in the liver. Our results indicated that Et OH aggravated PA-induced apoptosis and lipid accumulation in primary rat hepatocytes in dose-dependent manner. Et OH intensified PA-caused endoplasmic reticulum(ER) stress response in vitro and in vivo, and the expressions of CHOP, ATF4, and XBP-1 in nucleus were significantly increased. Et OH also increased PA-caused cleaved caspase-3 in cytoplasm. In wild type and CHOP–/– mice treated with Et OH and high fat diet(HFD), Et OH worsened the HFD-induced liver injury and dyslipidemia, while CHOP knockout blocked toxic effects of Et OH and PA. Our study suggested that targeting UPR-signaling pathways is a promising, novel approach to reducing Et OH and saturated fatty acid-induced metabolic complications.展开更多
The development of molecular medicine has greatly promoted the research and development (R&D) of innovative drugs. However,drug design and development for those novel targets remains a big challenge with low succe...The development of molecular medicine has greatly promoted the research and development (R&D) of innovative drugs. However,drug design and development for those novel targets remains a big challenge with low success rates and high attrition of drug candidates1. The current methodology of new drug R&D is deeply influenced by the idea of allopathic medicine, which directly inhibits biological targets.展开更多
文摘Herbal-induced liver injury(HILI)is an important and increasingly concerning cause of liver toxicity,and this study presents recent updates to the literature.An extensive literature review was conducted encompassing September 2019 through March 2021.Studies with clinically significant findings were analyzed and included in this review.We emphasized those studies that provided a causality assessment methodology,such as Roussel Uclaf Causality Assessment Method scores.Our review includes reports of individual herbals,including Garcinia cambogia,green tea extract,kratom as well as classes such as performance enhancing supplements,Traditional Chinese medicine,Ayurvedic medicine and herbal contamination.Newly described herbals include ashwagandha,boldo,skyfruit,and‘Thermo gun’.Several studies discussing data from national registries,including the United States Drug-Induced Liver Injury(DILI)Network,Spanish DILI Registry,and Latin American DILI Network were incorporated.There has also been a continued interest in hepatoprotection,with promising use of herbals to counter hepatotoxicity from anti-tubercular medications.We also elucidated the current legal conversation surrounding use of herbals by presenting updates from the Federal Drug Administration.The highlights of the literature over the past year indicate interest in HILI that will continue as the supplement industry in the United States grows.
文摘The prevalence of alcoholic liver disease and non-alcoholic liver disease patients has nearly doubled over the past decades worldwide. Alcoholic liver disease among patients with chronic liver disease has increased with arisen due to alcohol consumption and obesity. The diagnosis plays a crucial role in treating such conditions based on the stages of liver functioning. The elevated liver enzymes are the key characterizing of identifying the alcoholic liver disease (ALD) and NAFLD. Later on, there is a progression of the disease conditions by developing fibrosis and cirrhosis, leading to liver carcinoma. The other state, steatohepatitis, is associated with an increase in liver-related and can lead to mortality. Risk factors for both diseases are growing, leading to various complications in health. There is no specific treatment up to date for these conditions, but statins play a crucial role in managing several liver disease conditions. The commonly used drug is hydroxymethylglutaryl coenzyme A (HMG Co-A) reductase inhibitors. It is also known as statins, which help normalize liver enzymes in patients with elevated plasma aminotransferases. As a result, external liver damage is considered safe for the liver as the Statin medication at low to moderate dose usage. OBJECTIVES: The main scope of this review is to study the various factors like pharmacological actions, adverse events, and biochemical and liver cell imaging results in patients with ALD and NAFLD. The different types of statins used in alcoholic and non-alcoholic patients’ clinical data for the safety of the statin therapy were concluded in this review. Fatty liver changes of both liver disease conditions were studied using different drugs. The other liver enzymes like Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma-glutamyl Transferase (GGT), and the effectiveness of Statin therapy are considered vital concepts in this review.
文摘Objective:Objective:To analyze and explore the key targets and molecular mechanisms of action of Radix Paeoniae Alba against Toosendan Fructus-induced hepatotoxicity and the relationship between corresponding compounds based on network pharmacology.Methods:Using network pharmacology,a"traditional Chinese medicine-chemical composition-key target-pathway"analysis was conducted on Radix Paeoniae Alba for the treatment of Toosendan Fructus-induced hepatotoxicity.The possible mechanism of action was analyzed in terms of function.Results:The core targets,such as interleukin(IL)-6,tumor necrosis factor(TNF),heat shock protein 90 alpha family class A member 1(HSP90AA1),peroxisome proliferator-activated receptor gamma(PPARG),prostaglandin-endoperoxide synthase 2(PTGS2),heme oxygenase 1(HMOX1),Jun proto-oncogene(JUN),caspase-3,estrogen receptor 1(ESR1),and aryl hydrocarbon receptor(AHR)were screened from the targets of Radix Paeoniae Alba against Toosendan Fructus-induced hepatotoxicity.Biological process(BP)of toxic targets(BP terms)involved"response to drug;activation of cysteine-type endopeptidase activity involved in apoptotic process,”positive regulation of transcription.Cellular components(CC terms)mainly involved cytosol and membrane rafts.Molecular function(MF)terms included"protein homodimerization activity,"RNA polymerase II transcription factor activity and enzyme binding,etc."The Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway included the TNF signaling pathway,cancer pathways,and apoptosis.Conclusion:Radix Paeoniae Alba might alleviate Toosendan Fructus-induced hepatotoxicity through IL6,TNF,HSP90AA1,PPARG,PTGS2,HMOX1,and other targets,possibly via the activation of cysteine-type endopeptidase activity involved in these pathways.
基金supported by China Agriculture Research System (No.CARS-46)the Central Public-interest Scienti?c Institution Basal Research Fund,CAFS (No.YFI202208)the National Natural Science Foundation of China (Nos.31872554and 32172952)
文摘Microplastics(MPs)have become a significant concern for their potential toxicity.However,the correlation between the size of plastic particles and their toxicity remains inconclusive.Here,we investigate the toxic effects of different sizes(80 nm,800 nm,8μm and 80μm)polystyrene MPs(PS-MPs)on the model organism Nile tilapia(Oreochromis niloticus).The results of bioluminescent imaging indicate that the 80 nm PS-MPs are more likely to invade the body.H&E staining shows severe damage on the intestinal villi and distinct hepatic steatosis in the 80 nm group.Ed U labeling shows that the proliferation activity of intestinal and liver cells reduces significantly in the 80 nm group.The gut microbiome analysis shows a severe imbalance of gut microbiota homeostasis in the 80 nm group.The analysis of liver transcriptomics and metabolomics shows that the liver lipid metabolism is disordered in the 80 nm group.In conclusion,this study confirms that the 80 nm PS-MPs are more likely to induce intestinal and liver toxicity.All the above lay the foundation for further study on the pathological damage of MPs to other organisms.
文摘The incidence of inflammatory bowel diseases(IBD)is rising worldwide.The therapeutic options for IBD are expanding,and the number of drugs with new targets will rapidly increase in coming years.A rapid step-up approach with close monitoring of intestinal inflammation is extensively used.The fear of side effects represents one the most limiting factor of their use.Despite a widespread use for years,drug induced liver injury(DILI)management remains a challenging situation with Azathioprine and Methotrexate.DILI seems less frequent with anti-tumor necrosis factor agents and new biologic therapies.The aim of this review is to report incidence,physiopathology and practical guidelines in case of DILI occurrence with the armamentarium of old and new drugs in the field of IBD.
文摘Inflammatory bowel diseases(IBD)are associated with various hepatobiliary disorders.They can occur at any moment in the course of the disease or associated with the treatment.The prevalence of liver dysfunction can reach up to 50%in different studies.Nonalcoholic fatty liver disease is considered the most common hepatobiliary complication in IBD,while primary sclerosing cholangitis is the most specific.Management of hepatic manifestations in IBD involves a multidisciplinary approach that includes a high index of suspicion and joint management with hepatologists.The medical confrontation with abnormal liver tests must include an exhaustive study to determine if these patterns can be related to IBD,associated diseases or to the therapies used.
基金supported by National Natural Science Foundation of China(Nos.81273569,81001465)Natural Science Foundation of Jiangsu Province,China(No.BK2012726)the Ph.D. Programs Foundation of Ministry of Education of China(No.20100091120028)
文摘Serum palmitic acid(PA), a type of saturated fatty acid, causes lipid accumulation and induces toxicity in hepatocytes.Ethanol(Et OH) is metabolized by the liver and induces hepatic injury and inflammation. Herein, we analyzed the effects of Et OH on PA-induced lipotoxicity in the liver. Our results indicated that Et OH aggravated PA-induced apoptosis and lipid accumulation in primary rat hepatocytes in dose-dependent manner. Et OH intensified PA-caused endoplasmic reticulum(ER) stress response in vitro and in vivo, and the expressions of CHOP, ATF4, and XBP-1 in nucleus were significantly increased. Et OH also increased PA-caused cleaved caspase-3 in cytoplasm. In wild type and CHOP–/– mice treated with Et OH and high fat diet(HFD), Et OH worsened the HFD-induced liver injury and dyslipidemia, while CHOP knockout blocked toxic effects of Et OH and PA. Our study suggested that targeting UPR-signaling pathways is a promising, novel approach to reducing Et OH and saturated fatty acid-induced metabolic complications.
文摘The development of molecular medicine has greatly promoted the research and development (R&D) of innovative drugs. However,drug design and development for those novel targets remains a big challenge with low success rates and high attrition of drug candidates1. The current methodology of new drug R&D is deeply influenced by the idea of allopathic medicine, which directly inhibits biological targets.
