Paeonia lactiflora Pall. regulates the NF‐κB‐NLRP3 inflammasome pathway to alleviate cholestasis in rats

• Published in: Journal of pharmacy and pharmacology 2018-12, Vol.70 (12), p.1675-1687
• Main Authors: Ma, Xiao, Wen, Jian‐Xia, Gao, Si‐Jia, He, Xuan, Li, Peng‐Yan, Yang, Yu‐Xue, Wei, Shi‐zhang, Zhao, Yan‐Ling, Xiao, Xiao‐He
• Format: Article
• Language: English
• Subjects: 1-Naphthylisothiocyanate - pharmacology; Animals; anti‐inflammatory; Biomarkers; Caspase; Cholestasis; Cholestasis - chemically induced; Cirrhosis; Disease Models, Animal; Dose-Response Relationship, Drug; Gallbladder diseases; Gene Expression; Health risks; Herbal medicine; Humans; Inflammasomes; Inflammasomes - drug effects; Inflammation; Inflammation Mediators - metabolism; Liver - drug effects; Liver - metabolism; Liver cirrhosis; Liver diseases; Liver Function Tests; Medicine, Chinese Traditional; NF-kappa B - biosynthesis; NLRP3; nuclear factor‐kappa B; Paeonia; Paeonia lactiflora; Paeonia lactiflora Pall; Plant Extracts - pharmacology; Rats; Rats, Sprague-Dawley; Risk factors; RNA, Messenger; Traditional Chinese medicine
• ISSN: 0022-3573; 2042-7158
• DOI: 10.1111/jphp.13008

Objectives Cholestasis is a critical risk factor for severe hepatic disease or cirrhosis. The anti‐inflammatory effect of Paeonia lactiflora Pall. (PLP), named Chishao in traditional Chinese medicine (TCM), on alpha‐naphthylisothiocyanate (ANIT)‐induced cholestasis model was tried to be elucidated in this research. Methods Therapeutic effect indices on hepatic function, including ALT, AST, TBIL, DBIL, ALP, TBA and γ‐GT, were measured. To further investigate the protective mechanism of PLP, the mRNA and protein expression levels of NF‐κB‐NLRP3 inflammasome pathway were detected. Results Our results showed that compared with the model group, PLP could significantly reduce the increased serum indices such as ALT, AST, TBIL, DBIL, ALP, TBA and γ‐GT induced by ANIT in a dose‐dependent way. Moreover, we found that PLP downregulated the mRNA expression levels including IKK, p65, NLRP3, caspase‐1 and IL‐1β, especially at the large dose. Furthermore, PLP also significantly inhibited NF‐κB‐NLRP3 inflammasome pathway by decreasing the protein levels of p65, p‐p65, p‐IKK, NLRP3, caspase‐1 and IL‐1β. Conclusions The results indicated that PLP could ameliorate ANIT‐induced cholestasis in rats and the anti‐inflammatory effect of PLP might be related to regulating NF‐κB‐NLRP3 inflammasome pathway. This study will provide scientific evidence for PLP as a potential drug candidate for cholestasis.