基于网络药理学和实验验证探讨三花降脂颗粒治疗高脂血症的潜在机制。

Exploration of potential mechanism of Sanhua Jiangzhi granules for the treatment of hyperlipidemia based on network pharmacology and experimental verification.

机构信息

Shaanxi Province Key Laboratory of New Drugs and Chinese Medicine Foundation Research, Pharmacy College, Shaanxi University of Chinese Medicine, Xianyang 712046, China.

Weinan Testing Institute, 714000, China.

出版信息

Fitoterapia. 2024 Dec;179:106271. doi: 10.1016/j.fitote.2024.106271. Epub 2024 Oct 24.

Abstract

Sanhua Jiangzhi Granules (SJG) is a traditional Chinese patent medicine known for regulating lipid metabolism. In this study, we utilized UPLC-TOF-MS to analyze the components of SJG and, in conjunction with network pharmacology, identified 125 core chemical constituents. These components were individually queried and intersected with targets related to hyperlipidemia, resulting in the identification of 312 core targets. KEGG and GO analyses suggested that the mechanism of SJG in treating hyperlipidemia may primarily involve the PPAR signaling pathway. To further validate the efficacy and underlying signaling mechanisms of SJG, we conducted experiments using 60 rats. The results indicated that SJG significantly reduced body weight, lowered serum levels of total cholesterol (TC), triglycerides (TG), and low-density lipoprotein cholesterol (LDL-C), while increasing high-density lipoprotein cholesterol (HDLC) levels. Enzyme-linked immunosorbent assay (ELISA) results demonstrated that SJG decreased hepatic TC and TG levels and mitigated lipid accumulation in the liver. Hematoxylin and eosin (HE) staining indicated that SJG improved liver pathological morphology and reduced the risk of fatty liver disease. Western blot analyses showed that treatment with SJG down-regulated the expression of stearoyl-CoA desaturase (SCD), 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), phospholipid transfer protein (PLTP), and fatty acid-binding protein 1 (FABP1), while up-regulating the expression of cholesterol 7α-hydroxylase (CYP7A1), carnitine palmitoyltransferase 1 (CPT-1), and PPARα by activating the PPAR signaling pathway. In conclusion, this study demonstrated that SJG activates the PPAR signaling pathway, leading to decreased body weight, lowered blood lipid levels, reduced hepatic TC and TG, and improved liver pathology in rats.

摘要

三花降脂颗粒(SJG)是一种传统的中药,以调节脂质代谢而闻名。在本研究中,我们利用 UPLC-TOF-MS 分析了 SJG 的成分,并结合网络药理学,鉴定了 125 个核心化学成分。这些成分分别进行了查询,并与高脂血症相关的靶点进行了交集,鉴定出 312 个核心靶点。KEGG 和 GO 分析表明,SJG 治疗高脂血症的机制可能主要涉及 PPAR 信号通路。为了进一步验证 SJG 的疗效和潜在的信号机制,我们用 60 只大鼠进行了实验。结果表明,SJG 能显著降低体重,降低血清总胆固醇(TC)、甘油三酯(TG)和低密度脂蛋白胆固醇(LDL-C)水平,同时升高高密度脂蛋白胆固醇(HDLC)水平。酶联免疫吸附测定(ELISA)结果表明,SJG 降低了肝组织 TC 和 TG 水平,减轻了肝内脂质堆积。苏木精和伊红(HE)染色表明,SJG 改善了肝组织病理形态,降低了脂肪肝的发病风险。Western blot 分析表明,SJG 通过下调硬脂酰辅酶 A 去饱和酶(SCD)、3-羟-3-甲基戊二酰辅酶 A 还原酶(HMGCR)、磷脂转移蛋白(PLTP)和脂肪酸结合蛋白 1(FABP1)的表达,上调胆固醇 7α-羟化酶(CYP7A1)、肉碱棕榈酰转移酶 1(CPT-1)和 PPARα的表达,激活了 PPAR 信号通路。综上所述,本研究表明 SJG 通过激活 PPAR 信号通路,降低体重,降低血脂水平,减少肝组织 TC 和 TG,改善大鼠肝组织病理学。

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