Henan University of Chinese Medicine, Zhengzhou, Henan, China.
The Third Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou, Henan, China.
Biomed Pharmacother. 2022 Sep;153:113503. doi: 10.1016/j.biopha.2022.113503. Epub 2022 Aug 16.
Arctium lappa (A. lappa) leaves are widely used in various traditional Chinese herbal formulae to ameliorate atherosclerosis (AS) and its complications such as stroke; however, there is no literature reporting the anti-atherosclerotic effect and mechanism of A. lappa leaves thus far. In the present study, we used network pharmacology and molecular docking approaches to examine the protective effect and potential mechanism of A. lappa leaves against AS in vivo and in vitro. From the network pharmacology, PPARG, HMGCR and SREBF2 were identified as the core targets of A. lappa leaves against AS. Further enrichment analyses of GO and KEGG pathways suggested that A. lappa leaves might play an anti-AS role by regulating metabolic processes and PPAR signalling pathways. The results of molecular docking experiment revealed that the major components of A. lappa leaves interacted with cholesterol efflux-regulating core proteins (PPARG, LXRα, ABCA1, and ABCG1), AMPK and SIRT1. Both in vivo and in vitro experimental results demonstrated that treatment with A. lappa leaves significantly lowered TC and LDL-C, increased HDL-C, and reduced cholesterol accumulation in the liver and aorta of the AS rat model and the foam cell model. Importantly, both in vivo and in vitro experimental results demonstrated that A. lappa leaves regulate the activity of the PPARG/LXRα signalling and AMPK/SIRT1 signalling pathways. Moreover, after treatment with the AMPK inhibitor Compound C in vitro, the improvement induced by A. lappa leaves was significantly reversed. In conclusion, A. lappa leaves attenuated AS-induced cholesterol accumulation by targeting the AMPK-mediated PPARG/LXRα pathway and promoting cholesterol efflux.
牛蒡叶广泛用于各种中药方剂中，以改善动脉粥样硬化（AS）及其并发症如中风；然而，目前尚无文献报道牛蒡叶的抗动脉粥样硬化作用及其机制。本研究采用网络药理学和分子对接方法，研究了牛蒡叶在体内和体外对动脉粥样硬化的保护作用及其潜在机制。通过网络药理学分析，发现 PPARG、HMGCR 和 SREBF2 是牛蒡叶抗动脉粥样硬化的核心靶点。GO 和 KEGG 通路的进一步富集分析表明，牛蒡叶可能通过调节代谢过程和 PPAR 信号通路发挥抗动脉粥样硬化作用。分子对接实验结果表明，牛蒡叶的主要成分与胆固醇流出调节核心蛋白（PPARG、LXRα、ABCA1 和 ABCG1）、AMPK 和 SIRT1 相互作用。体内和体外实验结果均表明，牛蒡叶治疗可显著降低 AS 大鼠模型和泡沫细胞模型中 TC 和 LDL-C，升高 HDL-C，并减少肝脏和主动脉中的胆固醇积累。重要的是，体内和体外实验结果均表明，牛蒡叶调节 PPARG/LXRα 信号通路和 AMPK/SIRT1 信号通路的活性。此外，体外用 AMPK 抑制剂 Compound C 处理后，牛蒡叶的改善作用明显逆转。综上所述，牛蒡叶通过靶向 AMPK 介导的 PPARG/LXRα 通路和促进胆固醇流出，减轻 AS 诱导的胆固醇积累。
