Platycodin D protects acetaminophen-induced hepatotoxicity by inhibiting hepatocyte MAPK pathway and apoptosis in C57BL/6J mice
| Autor: | Chen Chen, Yu-Fang He, Ying Liu, Wei Li, Jing Leng, Jing Zhang, Zi Wang, Cheng-lin Fu |
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| Rok vydání: | 2018 |
| Předmět: |
Male
0301 basic medicine Platycodon MAP Kinase Signaling System p38 mitogen-activated protein kinases Apoptosis Pharmacology Protective Agents medicine.disease_cause Mice 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Malondialdehyde medicine Animals Acetaminophen Inflammation Liver injury Platycodin D digestive oral and skin physiology General Medicine Analgesics Non-Narcotic Saponins medicine.disease Glutathione Triterpenes Mice Inbred C57BL Oxidative Stress 030104 developmental biology medicine.anatomical_structure Liver chemistry 030220 oncology & carcinogenesis Hepatocyte Hepatocytes Tumor necrosis factor alpha Chemical and Drug Induced Liver Injury Oxidative stress medicine.drug |
| Zdroj: | Biomedicine & Pharmacotherapy. 107:867-877 |
| ISSN: | 0753-3322 |
| Popis: | The root of Platycodon grandiflorus (Jacq.) A. DC. (P. grandiflorus), Platycodonis Radix, has been commonly applied to prevent and treat human diseases including bronchitis, asthma and excessive phlegm. Platycodin D (PD), one of the most important therapeutic components of P. grandiflorus, has been reported to possess protective effect against alcohol and carbon tetrachloride induced hepatotoxicity. In this study, we examined the protective efficacy of PD on acetaminophen (APAP)-induced liver injury and possible underlying mechanisms in C57BL/6J mice. Administration of PD prior to APAP intoxication significantly ameliorated the increase in serum transferases, interleukin 1β (IL-1β), IL-6, tumor necrosis factor alpha (TNF-α), and hepatic malondialdehyde (MDA) and the depletion of glutathione (GSH) in mice. PD pretreatment decreased the expression of heme oxygenase-1 (HO-1), cyclooxygenase-2 (COX-2) and nuclear factor kappa B (NF-κB) in presence of APAP. Moreover, PD treatment noticeably reduced APAP-induced hepatocyte necrosis and apoptosis evidenced by evaluating physiological and histological hepatocyte changes in mice. Finally, PD pretreatment significantly diminished c-Jun NH2-terminal kinase (JNK), extracellular signal-regulated kinases 1 and 2 (ERK1/2), and p38 phosphorylation induced by APAP. Collectively, PD pretreatment effectively protects hepatocytes against APAP-induced hepatotoxicity in mice through ameliorating oxidative stress, inflammatory response, and hepatocyte apoptosis. |
| Databáze: | OpenAIRE |
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