Hepatoprotective effects of berberine on acetaminophen-induced hepatotoxicity in mice. 2018

Zheng Zhao, and Qingyan Wei, and Weiwei Hua, and Yunxin Liu, and Xiang Liu, and Yubing Zhu
Department of Pharmacy, Nanjing First Hospital, Nanjing Medical University, Nanjing 210006, China; School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing 210009, China.

Acetaminophen (APAP) hepatotoxicity remains the leading cause of drug-induced liver injury due to the lack of safe and effective therapeutic agents. Berberine (BBR) is a natural alkaloid derived from traditional medicine Rhizoma Coptidis and possesses various pharmacological properties. The aim of this study was to explore the hepatoprotective effects and underlying mechanisms of BBR on APAP-induced hepatotoxicity. Our results indicated that BBR pretreatment significantly ameliorated APAP-induced hepatic pathological abnormalities and attenuated the elevations of serum aminotransferases and liver/body weight ratio. Compared to APAP group, BBR notably increased the levels of hepatic UDP-glucuronosyltransferases and sulfotransferases, whereas failed to ameliorate APAP-induced GSH depletion. Pretreatment with BBR significantly reduced hepatic MDA and MPO levels, inhibited JNK phosphorylation and up-regulated the expression of nuclear Nrf-2 and its downstream gene Mn-SOD. Additionally, BBR obviously prevented APAP-induced DNA fragmentation. Furthermore, BBR pretreatment dramatically reduced the expression of pro-inflammatory cytokines, HMGB1, p-p65 and cleaved caspase-1 and inhibited the infiltration of macrophages and neutrophils. Taken these results together, BBR exhibits notable preventive effects on APAP-induced hepatotoxicity by inhibiting oxidative stress, hepatocyte necrosis and inflammatory response.

UI MeSH Term Description Entries
D007249 Inflammation A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function. Innate Inflammatory Response,Inflammations,Inflammatory Response, Innate,Innate Inflammatory Responses
D008099 Liver A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances. Livers
D008297 Male Males
D008810 Mice, Inbred C57BL One of the first INBRED MOUSE STRAINS to be sequenced. This strain is commonly used as genetic background for transgenic mouse models. Refractory to many tumors, this strain is also preferred model for studying role of genetic variations in development of diseases. Mice, C57BL,Mouse, C57BL,Mouse, Inbred C57BL,C57BL Mice,C57BL Mice, Inbred,C57BL Mouse,C57BL Mouse, Inbred,Inbred C57BL Mice,Inbred C57BL Mouse
D000082 Acetaminophen Analgesic antipyretic derivative of acetanilide. It has weak anti-inflammatory properties and is used as a common analgesic, but may cause liver, blood cell, and kidney damage. Acetamidophenol,Hydroxyacetanilide,Paracetamol,APAP,Acamol,Acephen,Acetaco,Acetominophen,Algotropyl,Anacin-3,Datril,N-(4-Hydroxyphenyl)acetanilide,N-Acetyl-p-aminophenol,Panadol,Tylenol,p-Acetamidophenol,p-Hydroxyacetanilide,Anacin 3,Anacin3
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001599 Berberine An alkaloid from Hydrastis canadensis L., Berberidaceae. It is also found in many other plants. It is relatively toxic parenterally, but has been used orally for various parasitic and fungal infections and as antidiarrheal. Umbellatine
D053938 DNA Fragmentation Splitting the DNA into shorter pieces by endonucleolytic DNA CLEAVAGE at multiple sites. It includes the internucleosomal DNA fragmentation, which along with chromatin condensation, are considered to be the hallmarks of APOPTOSIS. DNA Degradation, Apoptotic,Apoptotic DNA Degradation,Fragmentation, DNA
D056486 Chemical and Drug Induced Liver Injury A spectrum of clinical liver diseases ranging from mild biochemical abnormalities to ACUTE LIVER FAILURE, caused by drugs, drug metabolites, herbal and dietary supplements and chemicals from the environment. Drug-Induced Liver Injury,Liver Injury, Drug-Induced,Acute Liver Injury, Drug-Induced,Chemically-Induced Liver Toxicity,Drug-Induced Acute Liver Injury,Drug-Induced Liver Disease,Hepatitis, Drug-Induced,Hepatitis, Toxic,Liver Injury, Drug-Induced, Acute,Toxic Hepatitis,Acute Liver Injury, Drug Induced,Chemically Induced Liver Toxicity,Chemically-Induced Liver Toxicities,Disease, Drug-Induced Liver,Diseases, Drug-Induced Liver,Drug Induced Acute Liver Injury,Drug Induced Liver Disease,Drug Induced Liver Injury,Drug-Induced Hepatitides,Drug-Induced Hepatitis,Drug-Induced Liver Diseases,Drug-Induced Liver Injuries,Hepatitides, Drug-Induced,Hepatitides, Toxic,Hepatitis, Drug Induced,Injuries, Drug-Induced Liver,Injury, Drug-Induced Liver,Liver Disease, Drug-Induced,Liver Diseases, Drug-Induced,Liver Injuries, Drug-Induced,Liver Injury, Drug Induced,Liver Toxicities, Chemically-Induced,Liver Toxicity, Chemically-Induced,Toxic Hepatitides,Toxicities, Chemically-Induced Liver,Toxicity, Chemically-Induced Liver
D018384 Oxidative Stress A disturbance in the prooxidant-antioxidant balance in favor of the former, leading to potential damage. Indicators of oxidative stress include damaged DNA bases, protein oxidation products, and lipid peroxidation products (Sies, Oxidative Stress, 1991, pxv-xvi). Anti-oxidative Stress,Antioxidative Stress,DNA Oxidative Damage,Nitro-Oxidative Stress,Oxidative Cleavage,Oxidative DNA Damage,Oxidative Damage,Oxidative Injury,Oxidative Nitrative Stress,Oxidative Stress Injury,Oxidative and Nitrosative Stress,Stress, Oxidative,Anti oxidative Stress,Anti-oxidative Stresses,Antioxidative Stresses,Cleavage, Oxidative,DNA Damage, Oxidative,DNA Oxidative Damages,Damage, DNA Oxidative,Damage, Oxidative,Damage, Oxidative DNA,Injury, Oxidative,Injury, Oxidative Stress,Nitrative Stress, Oxidative,Nitro Oxidative Stress,Nitro-Oxidative Stresses,Oxidative Cleavages,Oxidative DNA Damages,Oxidative Damage, DNA,Oxidative Damages,Oxidative Injuries,Oxidative Nitrative Stresses,Oxidative Stress Injuries,Oxidative Stresses,Stress Injury, Oxidative,Stress, Anti-oxidative,Stress, Antioxidative,Stress, Nitro-Oxidative,Stress, Oxidative Nitrative,Stresses, Nitro-Oxidative

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