1. Jinlida granules ameliorate the high-fat-diet induced liver injury in mice by antagonising hepatocytes pyroptosis
- Author
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Yuan-yuan Hao, Wen-wen Cui, Huai-lin Gao, Ming-ye Wang, Yan Liu, Cui-ru Li, Yun-long Hou, and Zhen-hua Jia
- Subjects
Male ,hepg2 ,nafl ,Pharmaceutical Science ,RM1-950 ,Diet, High-Fat ,Mice ,Non-alcoholic Fatty Liver Disease ,Drug Discovery ,Pyroptosis ,Animals ,Humans ,pyroptosis pathway ,Pharmacology ,Body Weight ,Hep G2 Cells ,General Medicine ,Mice, Inbred C57BL ,Glucose ,Complementary and alternative medicine ,traditional chinese medicine ,Hepatocytes ,Molecular Medicine ,Therapeutics. Pharmacology ,Insulin Resistance ,Drugs, Chinese Herbal - Abstract
Context Jinlida (JLD) as a traditional Chinese medicine formula has been used to treat type 2 diabetes mellitus (T2DM) and studies have shown its anti-obesity effect. Objective To investigate the therapeutic effects of JLD in a mouse model of non-alcoholic fatty liver (NAFL). Materials and methods C57BL/6J mice were divided into three groups and fed a low-diet diet (LFD), high-fat diet (HFD), or HFD + JLD (3.8 g/kg) for 16 weeks, respectively. The free fatty acids-induced lipotoxicity in HepG2 cells were used to evaluate the anti-pyroptotic effects of JLD. The pharmacological effects of JLD on NAFL were investigated by pathological examination, intraperitoneal glucose and insulin tolerance tests, western blotting, and quantitative real-time PCR. Results In vivo studies showed that JLD ameliorated HFD-induced liver injury, significantly decreased body weight and enhanced insulin sensitivity and improved glucose tolerance. Furthermore, JLD suppressed both the mRNA expression of caspase-1 (1.58 vs. 2.90), IL-1β (0.93 vs. 3.44) and IL-18 (1.34 vs. 1.60) and protein expression of NLRP3 (2.04 vs. 5.71), pro-caspase-1 (2.68 vs. 4.92) and IL-1β (1.61 vs. 2.60). In vitro, JLD inhibited the formation of lipid droplets induced by 2 mM FFA (IC50 = 2.727 mM), reduced the protein expression of NLRP3 (0.74 vs. 2.27), caspase-1 (0.57 vs. 2.68), p20 (1.67 vs. 3.33), and IL-1β (1.44 vs. 2.41), and lowered the ratio of p-IKB-α/IKB-α (0.47 vs. 2.19). Conclusion JLD has a protective effect against NAFLD, which may be related to its anti-pyroptosis, suggesting that JLD has the potential as a novel agent in the treatment of NAFLD.
- Published
- 2022