PMID- 35138995 OWN - NLM STAT- MEDLINE DCOM- 20220304 LR - 20220501 IS - 1744-5116 (Electronic) IS - 1388-0209 (Print) IS - 1388-0209 (Linking) VI - 60 IP - 1 DP - 2022 Dec TI - Jinlida granules ameliorate the high-fat-diet induced liver injury in mice by antagonising hepatocytes pyroptosis. PG - 274-281 LID - 10.1080/13880209.2022.2029501 [doi] AB - 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-1beta (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-1beta (1.61 vs. 2.60). In vitro, JLD inhibited the formation of lipid droplets induced by 2 mM FFA (IC(50) = 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-1beta (1.44 vs. 2.41), and lowered the ratio of p-IKB-alpha/IKB-alpha (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. FAU - Hao, Yuan-Yuan AU - Hao YY AUID- ORCID: 0000-0001-8573-5433 AD - College of Integrative Medicine, Hebei University of Chinese Medicine, Hebei, China. FAU - Cui, Wen-Wen AU - Cui WW AUID- ORCID: 0000-0003-0391-4150 AD - College of Integrative Medicine, Hebei University of Chinese Medicine, Hebei, China. AD - Hebei Yiling Pharmaceutical Research Institute, Hebei, China. FAU - Gao, Huai-Lin AU - Gao HL AUID- ORCID: 0000-0002-4952-680X AD - College of Integrative Medicine, Hebei University of Chinese Medicine, Hebei, China. AD - Hebei Yiling Hospital, Hebei, China. FAU - Wang, Ming-Ye AU - Wang MY AUID- ORCID: 0000-0001-9507-4181 AD - College of Integrative Medicine, Hebei University of Chinese Medicine, Hebei, China. FAU - Liu, Yan AU - Liu Y AUID- ORCID: 0000-0002-9592-4710 AD - Xianghe Hospital of Traditional Chinese Medicine, Hebei, China. FAU - Li, Cui-Ru AU - Li CR AUID- ORCID: 0000-0001-9896-0904 AD - College of Integrative Medicine, Hebei University of Chinese Medicine, Hebei, China. AD - National Key Laboratory of Luobing Research and Innovative Chinese Medicine, Hebei, China. FAU - Hou, Yun-Long AU - Hou YL AUID- ORCID: 0000-0002-6989-8221 AD - College of Integrative Medicine, Hebei University of Chinese Medicine, Hebei, China. AD - Hebei Yiling Pharmaceutical Research Institute, Hebei, China. FAU - Jia, Zhen-Hua AU - Jia ZH AUID- ORCID: 0000-0001-5132-1099 AD - Hebei Yiling Hospital, Hebei, China. AD - National Key Laboratory of Luobing Research and Innovative Chinese Medicine, Hebei, China. LA - eng PT - Journal Article PL - England TA - Pharm Biol JT - Pharmaceutical biology JID - 9812552 RN - 0 (Drugs, Chinese Herbal) RN - 0 (jinlida) RN - IY9XDZ35W2 (Glucose) SB - IM MH - Animals MH - Body Weight/drug effects MH - Diet, High-Fat MH - Drugs, Chinese Herbal/*pharmacology MH - Glucose/metabolism MH - Hep G2 Cells MH - Hepatocytes/*drug effects/pathology MH - Humans MH - Insulin Resistance MH - Male MH - Mice MH - Mice, Inbred C57BL MH - Non-alcoholic Fatty Liver Disease/*prevention & control MH - Pyroptosis/*drug effects PMC - PMC8843117 OTO - NOTNLM OT - HepG2 OT - NAFL OT - pyroptosis pathway OT - traditional Chinese medicine COIS- The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2022/02/10 06:00 MHDA- 2022/03/05 06:00 PMCR- 2022/02/09 CRDT- 2022/02/09 17:12 PHST- 2022/02/09 17:12 [entrez] PHST- 2022/02/10 06:00 [pubmed] PHST- 2022/03/05 06:00 [medline] PHST- 2022/02/09 00:00 [pmc-release] AID - 2029501 [pii] AID - 10.1080/13880209.2022.2029501 [doi] PST - ppublish SO - Pharm Biol. 2022 Dec;60(1):274-281. doi: 10.1080/13880209.2022.2029501.