Gong Zhaohui, Yang Haixin, Gao Li, Liu Yi, Chu Qingmin, Luo Chuanjin, Kang Liang, Zhai Huiqi, Xu Qiang, Wu Wei, Li Nan, Li Rong
Department of Cardiovascular Medicine, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, 510405, China.
The First Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, 510405, China.
BMC Complement Med Ther. 2025 Jan 27;25(1):28. doi: 10.1186/s12906-025-04760-x.
Atherosclerosis serves as the fundamental pathology for a variety of cardiovascular disorders, with its pathogenesis being closely tied to the complex interplay among lipid metabolism, oxidative stress, and inflammation. Wogonoside is a natural flavonoid extracted from Scutellaria baicalensis with a variety of biological activities, including anti-inflammatory, hypolipidemic, and cardiac function improvement properties. Despite these known effects, the specific role of wogonoside in the context of atherosclerosis remains to be elucidated.
To validate the efficacy of wogonoside in the treatment of atherosclerosis and to investigate its possible therapeutic mechanisms.
Network pharmacology was used to obtain the core targets and signaling pathways that may be efficacious in the treatment of atherosclerosis with wogonoside, which were validated using molecular docking and molecular dynamics simulations. To further validate the core targets in the signaling pathway, we performed in vivo experiments using apolipoprotein E (ApoE)-/- mice. This included pathological morphology and lipid deposition analysis of mouse aorta, serum lipid level analysis, Elisa analysis, oxidative stress analysis, reactive oxygen species (ROS) fluorescence assay, immunohistochemical analysis and protein blot analysis.
Predictions were obtained that wogonoside treatment of atherosclerosis has 31 core targets, which are mainly focused on pathways such as Toll-like receptor (TLR) signaling pathway and NF-kappa B (NF-κB ) signaling pathway. Molecular docking and molecular dynamics simulations showed that wogonoside has good binding properties to the core targets. In vivo experimental results showed that wogonoside significantly inhibited aortic inflammatory response and lipid deposition, significantly reduced the release levels of total cholesterol (TC), triglycerides (TG), low-density-lipoprotein cholesterol (LDL-C), oxidized low density (ox-LDL) and free fatty acid (FFA), and significantly inhibited the release of inflammatory factors TNF-α, IL-1β, IL-6 and oxidative stress in ApoE-/- mice. Further molecular mechanism studies showed that wogonoside significantly inhibited the activation of TLR4/NF-κB signaling pathway in ApoE-/- mice.
Wogonoside may be an effective drug monomer for the treatment of atherosclerosis, and its mechanism of action is closely related to the inhibition of the activation of the TLR4/NF-κB signaling pathway.
动脉粥样硬化是多种心血管疾病的基本病理基础，其发病机制与脂质代谢、氧化应激和炎症之间的复杂相互作用密切相关。汉黄芩苷是从黄芩中提取的一种天然黄酮类化合物，具有多种生物学活性，包括抗炎、降血脂和改善心脏功能等特性。尽管有这些已知作用，但汉黄芩苷在动脉粥样硬化背景下的具体作用仍有待阐明。
验证汉黄芩苷治疗动脉粥样硬化的疗效，并探讨其可能的治疗机制。
采用网络药理学方法获取可能对汉黄芩苷治疗动脉粥样硬化有效的核心靶点和信号通路，并通过分子对接和分子动力学模拟进行验证。为进一步验证信号通路中的核心靶点，我们使用载脂蛋白E（ApoE）基因敲除小鼠进行体内实验。这包括对小鼠主动脉的病理形态和脂质沉积分析、血清脂质水平分析、酶联免疫吸附测定（ELISA）分析、氧化应激分析、活性氧（ROS）荧光检测、免疫组织化学分析和蛋白质印迹分析。
预测得出汉黄芩苷治疗动脉粥样硬化有31个核心靶点，主要集中在Toll样受体（TLR）信号通路和核因子κB（NF-κB）信号通路等途径。分子对接和分子动力学模拟表明汉黄芩苷与核心靶点具有良好的结合特性。体内实验结果表明，汉黄芩苷显著抑制主动脉炎症反应和脂质沉积，显著降低ApoE基因敲除小鼠血清总胆固醇（TC）、甘油三酯（TG）、低密度脂蛋白胆固醇（LDL-C）、氧化型低密度脂蛋白（ox-LDL）和游离脂肪酸（FFA）的释放水平，并显著抑制炎症因子肿瘤坏死因子-α（TNF-α）、白细胞介素-1β（IL-1β）、白细胞介素-6（IL-6）的释放以及氧化应激。进一步的分子机制研究表明，汉黄芩苷显著抑制ApoE基因敲除小鼠中TLR4/NF-κB信号通路的激活。
汉黄芩苷可能是治疗动脉粥样硬化的有效药物单体，其作用机制与抑制TLR4/NF-κB信号通路的激活密切相关。
