Paeoniflorin alleviates non-alcoholic steatohepatitis in rats: Involvement with the ROCK/NF-κB pathway

• Published in: International immunopharmacology Vol. 38; pp. 377 - 384
• Main Authors: Ma, Zhihong, Chu, Li, Liu, Hongying, Li, Jieru, Zhang, Yuanyuan, Liu, Wentai, Dai, Jun, Yi, Jianfeng, Gao, Yue
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01-09-2016
• Subjects: Alanine Transaminase - blood; Animals; Anti-Inflammatory Agents - therapeutic use; Aspartate Aminotransferases - blood; Cholesterol - blood; Diet; Disease Models, Animal; Glucosides - therapeutic use; Humans; Male; Monoterpenes - therapeutic use; NF-kappa B - metabolism; NF-κB; Non-alcoholic Fatty Liver Disease - drug therapy; Non-alcoholic steatohepatitis; Paeonia - immunology; Paeoniflorin; Rats; Rats, Sprague-Dawley; Rhizome; Rho kinase; rho-Associated Kinases - genetics; rho-Associated Kinases - metabolism; Signal Transduction - drug effects; Transforming Growth Factor beta1 - genetics; Transforming Growth Factor beta1 - metabolism; Tumor Necrosis Factor-alpha - metabolism; AST; ROCK; Rho kinase; ALT; NASH; TC; HDL; NF-κB; Paeoniflorin; TG; TNF-α; LDL; PF; TGF-β; Non-alcoholic steatohepatitis
• ISSN: 1567-5769; 1878-1705
• DOI: 10.1016/j.intimp.2016.06.023

Paeoniflorin (PF) is one of the major active ingredients of Paeonia lactiflora and has been suggested as a dietary therapy for non-alcoholic steatohepatitis (NASH); however, the involved mechanism remains obscure. The present work investigates the anti-inflammatory effects of PF and explores the possible mechanisms in a rat model of NASH. Male Sprague-Dawley rats were fed a high-cholesterol and high-fat (HCF) diet for 12weeks to induce the NASH model, and PF (20mg/kg/d) was orally administered to the NASH rats during the last four weeks of the study. Our results showed that PF significantly decreased serum alanine transferase (ALT) and aspartate transferase (AST) activities and also significantly decreased total levels of cholesterol (TC), low-density lipoprotein (LDL), and tumor necrosis factor alpha (TNF-α) (all P<0.05). Moreover, PF ameliorated the hepatic steatosis and inflammation and inhibited CD68 and transforming growth factor beta (TGF-β)-1 expression (both P<0.05). PF also down-regulated the activity of Rho kinase (ROCK) and suppressed the activation of the nuclear factor (NF)-κB signaling pathway in liver tissue. PF has liver protective and anti-inflammatory effects in HCF diet-induced NASH rats. The possible mechanisms may be associated with inhibition of the ROCK/NF-κB signaling pathway in the NASH liver.
•Paeoniflorin is the major active component of Paeonia lactiflora rhizome.•Administration of paeoniflorin alleviates non-alcoholic steatohepatitis (NASH) in rats.•Paeoniflorin inhibits Kupffer cell infiltration and activation in the NASH liver.•Paeoniflorin inhibits Rho kinase/NF-κB signaling in the NASH liver.