Wang Hui, Wang Hua, Zhang Jin, Luo Jiahui, Peng Caidong, Tong Xiaoyun, Chen Xudong
The First Affiliated Hospital of Yunnan University of Chinese Medicine, Kunming 650021, Yunnan, China.
Department of Psychiatry, National Clinical Research Center for Mental Disorders, The Second Xiangya Hospital of Central South University, Changsha 410011, Hunan, China.
Evid Based Complement Alternat Med. 2022 Jun 8;2022:4891370. doi: 10.1155/2022/4891370. eCollection 2022.
Dyslipidemia has become a critical global issue for public health, with elevating prevalence and morbidity closely related to many cardiovascular diseases (CVD) with high incidence rates. Crataegi Folium (known as Shanzhaye in China, SZ, the leaves of Bge. var. major N.E. Br. or Bge) and Alisma rhizoma (known as Zexie in China, ZX, the dried tuber of (Sam.) Juzep or Linn), a classic combination of herbs, have been widely used to treat dyslipidemia. However, the therapeutic mechanism of this pair still remains unclear. Hence, this study aimed to elucidate the molecular mechanism of the Shanzhaye-Zexie herb pair (SZHP) in the treatment of dyslipidemia with the use of a network pharmacology analysis approach.
Active compounds, targets of the SZHP, and targets for dyslipidemia were screened based on the public database. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment were performed on the database for annotation, visualization, and integrated discovery (DAVID 6.8). The compound-target-disease-pathway network was visualized using the Cytoscape software, and SYBYL was used for molecular docking.
Twelve active compounds in the SZHP were screened out, which were closely connected to 186 dyslipidemia-related targets. The network analysis revealed that sitosterol, stigmasterol, isorhamnetin, kaempferol, and quercetin might be candidate agents and CCND1, CASP3, HIF1A, and ESR1 genes were potential drug targets. GO analysis revealed 856 biological processes (BP), 139 molecular functions (MF), and 89 cellular components (CC). The KEGG pathway enrichment analysis indicated that the lipid level and atherosclerosis might influence the treatment of dyslipidemia. Molecular docking showed that quercetin bound well to CCND1, HIF1A, MYC, AKT1, and EGFR genes. These findings were in accord with the prediction obtained through the network pharmacology approach.
This study revealed the primary pharmacological effects and relevant mechanisms of the SZHP in treating dyslipidemia. Our findings may facilitate the development of the SZHP or its active compounds as an alternative therapy for dyslipidemia. Still, more pharmacological experiments are needed for verification.
血脂异常已成为一个关键的全球公共卫生问题，其患病率不断上升，发病率与许多高发性心血管疾病密切相关。山楂叶（在中国称为山楂叶，SZ，山里红或山楂的叶子）和泽泻（在中国称为泽泻，ZX，东方泽泻或泽泻的干燥块茎），这一经典的药对，已被广泛用于治疗血脂异常。然而，这一药对的治疗机制仍不清楚。因此，本研究旨在利用网络药理学分析方法阐明山楂叶 - 泽泻药对（SZHP）治疗血脂异常的分子机制。
基于公共数据库筛选SZHP的活性成分、靶点以及血脂异常的靶点。利用数据库注释、可视化与综合发现工具（DAVID 6.8）对基因本体论（GO）和京都基因与基因组百科全书（KEGG）通路进行富集分析。使用Cytoscape软件对化合物 - 靶点 - 疾病 - 通路网络进行可视化，并使用SYBYL进行分子对接。
筛选出SZHP中的12种活性成分，它们与186个血脂异常相关靶点紧密相连。网络分析表明，甾醇、豆甾醇、异鼠李素、山柰酚和槲皮素可能是候选药物，而细胞周期蛋白D1（CCND1）、半胱天冬酶3（CASP3）、缺氧诱导因子1α（HIF1A）和雌激素受体1（ESR1）基因是潜在药物靶点。GO分析揭示了856个生物学过程（BP）、139个分子功能（MF）和89个细胞成分（CC）。KEGG通路富集分析表明，脂质水平和动脉粥样硬化可能影响血脂异常的治疗。分子对接显示，槲皮素与CCND1、HIF1A、MYC、蛋白激酶B1（AKT1）和表皮生长因子受体（EGFR）基因结合良好。这些发现与通过网络药理学方法获得的预测结果一致。
本研究揭示了SZHP治疗血脂异常的主要药理作用及相关机制。我们的研究结果可能有助于将SZHP或其活性成分开发为血脂异常的替代疗法。不过，仍需要更多药理实验进行验证。
