Yanggan Jiangmei Formula alleviates hepatic inflammation and lipid accumulation in non-alcoholic steatohepatitis by inhibiting the NF-κB/NLRP3 signaling pathway

IF 4 2区 医学 Q1 INTEGRATIVE & COMPLEMENTARY MEDICINE
Yuanyuan WU , Jingwen ZHOU , Xinchen ZUO , Yufeng KUANG , Lixia SUN , Xiaolong ZHANG
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Abstract

The role of NF-κB and the NLRP3 inflammasome in the chronic inflammatory microenvironment of non-alcoholic steatohepatitis (NASH) has been posited as crucial. The Yanggan Jiangmei Formula (YGJMF) has shown promise in ameliorating hepatic steatosis in NASH patients, yet its pharmacological mechanisms remain largely unexplored. This study was conducted to investigate the efficacy of YGJMF in NASH and to elucidate its pharmacological underpinnings. To simulate NASH both in vivo and in vitro, high-fat-diet (HFD) rats and HepG2 cells stimulated with free fatty acids (FFAs) were utilized. The severity of liver injury and lipid deposition was assessed using serum indicators, histopathological staining, micro-magnetic resonance imaging (MRI), and the liver-to-muscle signal intensity ratio (SIRL/M). Furthermore, a combination of enzyme-linked immunosorbent assay (ELISA), immunohistochemistry (IHC), immunofluorescence, real-time quantitative polymerase chain reaction (RT-qPCR), and Western blotting analyses was employed to investigate the NF-κB/NLRP3 signaling pathway and associated cytokine levels. The results from liver pathology, MRI assessments, and biochemical tests in rat models demonstrated YGJMF's significant effectiveness in reducing liver damage and lipid accumulation. Additionally, YGJMF markedly reduced hepatocyte inflammation by downregulating inflammatory cytokines in both liver tissue and serum. Furthermore, YGJMF was found to disrupt NF-κB activation, consequently inhibiting the assembly of the NLRP3 inflammasome in both the in vitro and in vivo models. The preliminary findings of this study suggest that YGJMF may alleviate hepatic steatosis and inhibit the NF-κB/NLRP3 signaling pathway, thereby exerting anti-inflammatory effects in NASH.

杨干姜梅方通过抑制NF-κB/NLRP3信号通路减轻非酒精性脂肪性肝炎的肝脏炎症和脂质蓄积
NF-κB和NLRP3炎症小体在非酒精性脂肪性肝炎(NASH)的慢性炎症微环境中的作用被认为是至关重要的。杨干姜梅方(YGJMF)在改善非酒精性脂肪性肝炎(NASH)患者肝脏脂肪变性方面显示出良好的前景,但其药理机制在很大程度上仍未得到探索。本研究旨在探讨茵陈姜梅方对 NASH 的疗效,并阐明其药理基础。为了在体内和体外模拟 NASH,研究人员利用高脂饮食(HFD)大鼠和游离脂肪酸(FFAs)刺激的 HepG2 细胞。利用血清指标、组织病理学染色、显微磁共振成像(MRI)和肝肌信号强度比(SIRL/M)评估肝损伤和脂质沉积的严重程度。此外,还采用了酶联免疫吸附试验(ELISA)、免疫组织化学(IHC)、免疫荧光、实时定量聚合酶链反应(RT-qPCR)和 Western 印迹分析等方法来研究 NF-κB/NLRP3 信号通路和相关细胞因子水平。大鼠模型的肝脏病理学、核磁共振成像评估和生化测试结果表明,YGJMF 在减少肝损伤和脂质积累方面具有显著效果。此外,YGJMF 通过下调肝组织和血清中的炎症细胞因子,明显减轻了肝细胞炎症。此外,研究还发现 YGJMF 能破坏 NF-κB 的活化,从而抑制 NLRP3 炎性体在体外和体内模型中的组装。这项研究的初步结果表明,YGJMF 可减轻肝脏脂肪变性,抑制 NF-κB/NLRP3 信号通路,从而在 NASH 中发挥抗炎作用。
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来源期刊
Chinese Journal of Natural Medicines
Chinese Journal of Natural Medicines INTEGRATIVE & COMPLEMENTARY MEDICINE-PHARMACOLOGY & PHARMACY
CiteScore
7.50
自引率
4.30%
发文量
2235
期刊介绍: The Chinese Journal of Natural Medicines (CJNM), founded and sponsored in May 2003 by China Pharmaceutical University and the Chinese Pharmaceutical Association, is devoted to communication among pharmaceutical and medical scientists interested in the advancement of Traditional Chinese Medicines (TCM). CJNM publishes articles relating to a broad spectrum of bioactive natural products, leading compounds and medicines derived from Traditional Chinese Medicines (TCM). Topics covered by the journal are: Resources of Traditional Chinese Medicines; Interaction and complexity of prescription; Natural Products Chemistry (including structure modification, semi-and total synthesis, bio-transformation); Pharmacology of natural products and prescription (including pharmacokinetics and toxicology); Pharmaceutics and Analytical Methods of natural products.
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