Jinlida granules ameliorate the high-fat-diet induced liver injury in mice by antagonising hepatocytes pyroptosis.

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.

• Authors: Yuan-Yuan Hao, Wen-Wen Cui, Huai-Lin Gao, Ming-Ye Wang, Yan Liu, Cui-Ru Li, Yun-Long Hou, Zhen-Hua Jia
• Journal: Pharmaceutical biology (Pharm Biol) Vol. 60 Issue 1 Pg. 274-281 (Dec 2022) ISSN: 1744-5116 [Electronic] England
• PMID: 35138995 (Publication Type: Journal Article)

Chemical References

• Drugs, Chinese Herbal
• jinlida
• Glucose

Topics

• Animals
• Body Weight (drug effects)
• Diet, High-Fat
• Drugs, Chinese Herbal (pharmacology)
• Glucose (metabolism)
• Hep G2 Cells
• Hepatocytes (drug effects, pathology)
• Humans
• Insulin Resistance
• Male
• Mice
• Mice, Inbred C57BL
• Non-alcoholic Fatty Liver Disease (prevention & control)
• Pyroptosis (drug effects)