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金利达颗粒通过拮抗肝细胞焦亡改善高脂饮食诱导的小鼠肝损伤。

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

机构信息

College of Integrative Medicine, Hebei University of Chinese Medicine, Hebei, China.

Hebei Yiling Pharmaceutical Research Institute, Hebei, China.

出版信息

Pharm Biol. 2022 Dec;60(1):274-281. doi: 10.1080/13880209.2022.2029501.

DOI:10.1080/13880209.2022.2029501
PMID:35138995
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8843117/
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

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). , JLD inhibited the formation of lipid droplets induced by 2 mM FFA (IC = 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 -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.

摘要

背景

金利达(JLD)作为一种中药方剂,已被用于治疗 2 型糖尿病(T2DM),研究表明其具有抗肥胖作用。

目的

探讨 JLD 在非酒精性脂肪性肝病(NAFL)小鼠模型中的治疗效果。

材料和方法

将 C57BL/6J 小鼠分为三组,分别给予低饮食(LFD)、高脂肪饮食(HFD)或 HFD+JLD(3.8g/kg)喂养 16 周。采用游离脂肪酸诱导的 HepG2 细胞脂毒性来评价 JLD 的抗细胞焦亡作用。通过病理检查、腹腔内葡萄糖和胰岛素耐量试验、western blot 和实时定量 PCR 研究 JLD 对 NAFL 的药理作用。

结果

研究表明,JLD 改善了 HFD 诱导的肝损伤,显著降低了体重,增强了胰岛素敏感性,改善了葡萄糖耐量。此外,JLD 抑制了 caspase-1(1.58 对 2.90)、IL-1β(0.93 对 3.44)和 IL-18(1.34 对 1.60)的 mRNA 表达,以及 NLRP3(2.04 对 5.71)、前半胱天冬酶-1(2.68 对 4.92)和 IL-1β(1.61 对 2.60)的蛋白表达。JLD 抑制了 2mM FFA 诱导的脂滴形成(IC=2.727mM),降低了 NLRP3(0.74 对 2.27)、半胱天冬酶-1(0.57 对 2.68)、p20(1.67 对 3.33)和 IL-1β(1.44 对 2.41)的蛋白表达,降低了-IKB-α/IKB-α 的比值(0.47 对 2.19)。

结论

JLD 对 NAFLD 具有保护作用,这可能与其抗细胞焦亡有关,提示 JLD 有可能成为治疗 NAFLD 的新型药物。

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