Quantitative Proteomics Reveal the Role of Matrine in Regulating Lipid Metabolism

分类： 药物科学 >> 生物化学 提交时间： 2024-06-14

Huixu Feng Guobin Liu Luhan Li Xuelian Ren Yue Jiang Wanting Hou Ruilong Liu Kun Liu Hong Liu He Huang

摘要： Hyperlipidemia (HLP) is a prevalent systemic metabolic disorder characterized by disrupted lipid metabolism. Statin drugs have long been the primary choice for managing lipid levels, but intolerance issues have prompted the search for alternative treatments. Matrine, a compound derived from the traditional Chinese medicine Kushen, exhibits anti-inflammatory and lipid-lowering properties. Nevertheless, the mechanism by which matrine modulates lipid metabolism remains poorly understood. Here, we investigated the molecular mechanisms underlying matrine’s regulation of lipid metabolism. Employing quantitative proteomics, we discovered that matrine increases the expression of LDL receptor (LDLR) in HepG2 and A549 cells, with subsequent experiments validating its role in enhancing LDL uptake. Notably, in hyperlipidemic hamsters, matrine effectively lowered lipid levels without affecting body weight, which highlights LDLR as a critical target for matrine’s impact on hyperlipidemia. Moreover, matrine’s potential inhibitory effects on tumor cell LDL uptake hint at broader applications in cancer research. Additionally, Thermal Proteome Profiling (TPP) analysis identified lipid metabolism-related proteins that may interact with matrine. Together, our study reveals matrine’s capacity to upregulate LDLR expression and highlights its potential in treating hyperlipidemia. These findings offer insights into matrine’s mechanism of action and open new avenues for drug research and lipid metabolism regulation.

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