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岩石紫堇总生物碱通过调节小鼠肝内 PI3K/Akt 和 TLR4/NF-κB 通路改善饮食诱导的非酒精性脂肪性肝炎。

Corydalis saxicola Bunting Total Alkaloids ameliorate diet-induced non-alcoholic steatohepatitis by regulating hepatic PI3K/Akt and TLR4/NF-κB pathways in mice.

机构信息

Department of Pharmacology of Chinese Materia Medica, China Pharmaceutical University, 639 Longmian avenue, Nanjing, PR China.

Department of Pharmacology of Chinese Materia Medica, China Pharmaceutical University, 639 Longmian avenue, Nanjing, PR China; Nanjing Zhongshan Pharmaceutical Co, Ltd., 21 Hengfa Road, Nanjing Economic and Technological Development Zone, Nanjing, PR China.

出版信息

Biomed Pharmacother. 2022 Jul;151:113132. doi: 10.1016/j.biopha.2022.113132. Epub 2022 May 25.

DOI:10.1016/j.biopha.2022.113132
PMID:35623174
Abstract

Corydalis saxicola Bunting (Yanhuanglian), distributed in Southwest China, is mainly used for treatment of hepatitis, oral mucosal erosion, conjunctivitis, dysentery, acute abdominal pain and hemorrhoids in the folk. Corydalis saxicola Bunting Total Alkaloids (CSBTA) are the active ingredients extracted from the root of C. saxicola bunting. Non-alcoholic steatohepatitis (NASH) is the hinge between steatosis and cirrhosis in the spectrum of Non-alcoholic fatty liver disease (NAFLD), which has become one of the most common chronic liver diseases in the world. CSBTA can reduce tumors and brain diseases through anti-inflammatory and antioxidant pathways. Our study was designed to clarify the effects of CSBTA on the HFHC (High fat and high carbohydrate drinking) diet induced mice. In our research, A HFHC diet induced NASH mice model was applied to investigate the effects of CSBTA in vivo and obeticholic acid (OA) was set as positive control. Moreover, the underlying mechanisms were explored by palmitic acid (PA) and lipopolysaccharide (LPS) stimulated HepG2 cells in vitro. The in vivo study illustrated that CSBTA could alleviate mice away from the onset of NASH, and reduce intrahepatocellular lipid accumulation and hepatocyte inflammation under high fat condition. Further in vitro analysis confirmed that CSBTA attenuated inflammation and hepatic lipid accumulation by improving hepatic PI3K/Akt and suppressing hepatic TLR4/NF-κB pathways. In summary, this study demonstrated that CSBTA might be a promising compound for the treatment of NAFLD.

摘要

中国西南地区特有的紫堇属植物岩石紫堇(岩黄连),在民间主要用于治疗肝炎、口腔黏膜糜烂、结膜炎、痢疾、急性腹痛和痔疮。岩石紫堇总生物碱(CSBTA)是从岩石紫堇根部提取的有效成分。非酒精性脂肪性肝炎(NASH)是非酒精性脂肪性肝病(NAFLD)谱中脂肪变性和肝硬化的枢纽,已成为世界上最常见的慢性肝病之一。CSBTA 通过抗炎和抗氧化途径可以减少肿瘤和脑部疾病。我们的研究旨在阐明 CSBTA 对 HFHC(高脂肪和高碳水化合物饮食)诱导的小鼠的作用。在我们的研究中,应用 HFHC 饮食诱导的 NASH 小鼠模型来研究 CSBTA 在体内的作用,并将奥贝胆酸(OA)作为阳性对照。此外,通过体外棕榈酸(PA)和脂多糖(LPS)刺激 HepG2 细胞来探讨潜在的机制。体内研究表明,CSBTA 可以减轻小鼠 NASH 的发病,并在高脂肪条件下减少肝细胞内脂质积累和肝细胞炎症。进一步的体外分析证实,CSBTA 通过改善肝脏 PI3K/Akt 并抑制肝脏 TLR4/NF-κB 途径来减轻炎症和肝脂质积累。总之,这项研究表明 CSBTA 可能是治疗 NAFLD 的一种有前途的化合物。

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