人参皂苷 Rg5 通过 Notch1 信号通路抑制 NASH 小鼠的脂质积累和肝细胞凋亡。
Ginsenoside Rg5 inhibits lipid accumulation and hepatocyte apoptosis via the Notch1 signaling pathway in NASH mice.
机构信息
Shaanxi Key Laboratory of Degradable Biomedical Materials, School of Chemical Engineering, Northwest University, China; Shaanxi R&D Center of Biomaterials and Fermentation Engineering, School of Chemical Engineering, Northwest University, Xi'an 710069, China; Biotech & Biomed Research Institute, Northwest University, 229 North Taibai Road, Xi'an 710069, China.
Shaanxi Key Laboratory of Degradable Biomedical Materials, School of Chemical Engineering, Northwest University, China; Shaanxi R&D Center of Biomaterials and Fermentation Engineering, School of Chemical Engineering, Northwest University, Xi'an 710069, China; Biotech & Biomed Research Institute, Northwest University, 229 North Taibai Road, Xi'an 710069, China.
出版信息
Phytomedicine. 2024 Feb;124:155287. doi: 10.1016/j.phymed.2023.155287. Epub 2023 Dec 16.
BACKGROUND
Non-alcoholic steatohepatitis (NASH) is a prevalent chronic liver disease that lacks an FDA-approved treatment medicine. Despite the known antitumor and hypoglycemic properties of Ginsenoside Rg5, its effects and underlying mechanisms in the context of NASH remain largely unexplored.
PURPOSE
This study aims to investigate the effect of Rg5 on NASH mice induced by a high-fat diet and CCl.
STUDY DESIGN
In vivo experiments, a mouse NASH model was established by a HFHC diet plus intraperitoneal injection of low-dose CCl. In vitro experiments, a cellular steatosis model was established using free fatty acids (FFA) induced HepG2 cells. In addition, a fibrogenesis model was established using HSC-LX2 cells.
METHODS
The effects of Ginsenoside Rg5 on lipid accumulation and oxidative damage were analyzed by ELISA kit, H&E staining, Oil Red O staining, flow cytometry and Western blot. The effects of Ginsenoside Rg5 on liver fibrosis were analyzed by Masson staining, Sirus Red staining, immunohistochemistry and Western blot. The effect of Ginsenoside Rg5 on Notch1 signaling pathway in liver was studied by protein Oil Red staining, protein immunoblotting and immunofluorescence.
RESULTS
In terms of lipid accumulation, Rg5 has the ability to regulate key proteins related to lipogenesis, thereby inhibiting hepatic lipid accumulation and oxidative stress. Additionally, Rg5 can reduce the occurrence of hepatocyte apoptosis by regulating the p53 protein. Moreover, after Rg5 intervention, the presence of fibrotic proteins (α-SMA, Collagen 1, TGF-β) in the liver is significantly suppressed, thus inhibiting liver fibrosis. Lastly, Rg5 leads to a decrease in the expression levels of Notch1 and its ligand Jagged-1 in the liver.
CONCLUSION
In summary, the regulatory effects of Rg5 on the Notch1 signaling pathway play a crucial role in modulating hepatic lipid metabolism and preventing hepatocyte apoptosis, thereby impeding the progression of NASH. These findings highlight the potential of Rg5 as a promising natural product for interventions targeting NASH.
背景
非酒精性脂肪性肝炎（NASH）是一种常见的慢性肝病，目前尚无获得 FDA 批准的治疗药物。尽管人参皂苷 Rg5 已被证实具有抗肿瘤和降血糖作用，但它在 NASH 中的作用和潜在机制仍知之甚少。
目的
本研究旨在探讨 Rg5 对高脂饮食联合小剂量 CCl 诱导的 NASH 小鼠的作用。
设计
体内实验采用 HFHC 饮食联合小剂量 CCl 腹腔注射建立小鼠 NASH 模型，体外实验采用游离脂肪酸（FFA）诱导 HepG2 细胞建立细胞脂肪变性模型，采用 HSC-LX2 细胞建立肝纤维化模型。
方法
采用 ELISA 试剂盒、HE 染色、油红 O 染色、流式细胞术和 Western blot 分析 Ginsenoside Rg5 对脂质蓄积和氧化损伤的影响；采用 Masson 染色、天狼猩红染色、免疫组化和 Western blot 分析 Ginsenoside Rg5 对肝纤维化的影响；采用蛋白油红染色、蛋白免疫印迹和免疫荧光分析 Ginsenoside Rg5 对肝脏 Notch1 信号通路的影响。
结果
在脂质蓄积方面，Rg5 能够调节脂生成相关的关键蛋白，从而抑制肝内脂质蓄积和氧化应激。此外，Rg5 可通过调节 p53 蛋白减少肝细胞凋亡的发生。此外，Rg5 干预后，肝内纤维化蛋白（α-SMA、胶原 1、TGF-β）的表达明显受到抑制，从而抑制肝纤维化。最后，Rg5 导致肝脏中 Notch1 及其配体 Jagged-1 的表达水平降低。
结论
综上所述，Rg5 对 Notch1 信号通路的调节作用在调节肝内脂质代谢和防止肝细胞凋亡方面发挥着重要作用，从而阻碍 NASH 的进展。这些发现表明 Rg5 作为一种有前途的天然产物，可能成为 NASH 干预的靶点。
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