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Trolline Ameliorates Liver Fibrosis by Inhibiting the NF-κB Pathway, Promoting HSC Apoptosis and Suppressing Autophagy.

Research paper by Facheng F Bai, Quanfang Q Huang, Jinlan J Nie, Shengjuan S Lu, Chunyuan C Lu, Xunshuai X Zhu, Yuxin Y Wang, Lang L Zhuo, Zhongpeng Z Lu, Xing X Lin

Indexed on: 16 Nov '17Published on: 16 Nov '17Published in: Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology



Abstract

Previous studies have shown that trolline possesses various forms of pharmacological activity, including antibacterial and antiviral potency. The present paper addressed the putative hepatoprotective effects of trolline.Rats received 2 ml/kg CCl4 (mixed 1: 1 in peanut oil) intragastrically twice a week for 8 weeks to induce hepatic fibrosis. The animals were then treated with trolline for additional 4 weeks. Liver pathology and collagen accumulation were observed by hematoxylin-eosin and Masson's trichrome staining, respectively. Serum transaminase activity and collagen-related indicator level were determined by commercially available kits. NF-κB pathway activation was also examined. Moreover, the effects of trolline on hepatic stellate cell (HSC-T6) apoptosis, mitochondrial membrane potential (MMP), and autophagy were assessed.Trolline significantly alleviated CCl4-induced liver injury and notably reduced the accumulation of collagen in liver tissues. Trolline treatment also markedly decreased inflammatory cytokines levels by inhibiting the NF-κB pathway. Trolline strongly inhibited HSC-T6 activation and notably induced cell apoptosis by modulating the Bax/Bcl-2 ratio, caspase activity, and MMP. Moreover, trolline significantly inhibited HSC-T6 autophagy, as evidenced by the decrease in the formation of autophagic vacuoles and the number of autophagosomes, by regulating the expression levles of LC3, Beclin-1, P62, Atg 5 and 7.Our study demonstrates that trolline ameliorates liver fibrosis, possibly by inhibiting the NF-κB pathway, promoting HSCs apoptosis and suppressing autophagy.