School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, Liaoning, 110016, China; Shenzhen Institute for Drug Control, Shenzhen, Guangdong, 518057, China; NMPA Key Laboratory for Quality Research and Evaluation of Traditional Chinese Medicine, Shenzhen Institute for Drug Control, Shenzhen, Guangdong, 518057, China; Shenzhen Key Laboratory of Drug Quality Standard Research, Shenzhen Institute for Drug Control, Shenzhen, Guangdong, 518057, China.
Shenzhen Institute for Drug Control, Shenzhen, Guangdong, 518057, China; NMPA Key Laboratory for Quality Research and Evaluation of Traditional Chinese Medicine, Shenzhen Institute for Drug Control, Shenzhen, Guangdong, 518057, China; Shenzhen Key Laboratory of Drug Quality Standard Research, Shenzhen Institute for Drug Control, Shenzhen, Guangdong, 518057, China.
J Ethnopharmacol. 2022 Aug 10;294:115345. doi: 10.1016/j.jep.2022.115345. Epub 2022 May 6.
Rhodiola crenulata (Hook.f. & Thomson) H.Ohba has a long history of clinical application for the prevention and treatment of acute mountain sickness (AMS) in traditional Chinese medicine. However, gaps in knowledge still exist in understanding the underlying mechanisms of Rhodiola crenulata against AMS.
To address this problem, a comprehensive method was established by combining UHPLC-Q-TOF-MS/MS analysis and network pharmacology.
The ingredients of Rhodiola crenulata were comprehensively analyzed using UHPLC-Q-TOF-MS/MS method. On this basis, a network pharmacology method incorporated target prediction, protein-protein interaction network, gene enrichment analysis and components-targets-pathways network was performed. Finally, the possible mechanisms were verified through molecular docking, in vitro and in vivo experiments.
A total of 106 constituents of Rhodiola crenulata were charactered via UHPLC-Q-TOF-MS/MS. The 98 potentially active compounds out of 106 were screened and corresponded to 53 anti-AMS targets. Gene enrichment analysis revealed that hypoxia and inflammation related genes may be the central factors for Rhodiola crenulata to modulate AMS. Molecular docking revealed that TNF, VEGFA and HIF-1α had high affinities to Rhodiola crenulata compounds. Subsequently, Rhodiola crenulata extract was indicated to inhibit the protein expression level of TNF in hypoxia induced H9c2 cells. Lastly, Rhodiola crenulata extract was further verified to ameliorate heart injury and decreased the heart levels of TNF, VEGFA and HIF-1α in acute hypoxia-induced rats.
This study used UHPLC-Q-TOF-MS/MS analysis and a network pharmacology to provide an important reference for revealing the potential mechanism of Rhodiola crenulata in the prevention and treatment of AMS.
红景天（Hook.f. & Thomson）H.Ohba 在传统中医中用于预防和治疗急性高山病（AMS）已有很长的临床应用历史。然而，在理解红景天防治 AMS 的潜在机制方面，知识仍存在差距。
为了解决这个问题，采用了一种综合方法，结合 UHPLC-Q-TOF-MS/MS 分析和网络药理学。
采用 UHPLC-Q-TOF-MS/MS 方法对红景天的成分进行全面分析。在此基础上，采用网络药理学方法进行了靶标预测、蛋白质-蛋白质相互作用网络、基因富集分析和成分-靶标-通路网络分析。最后，通过分子对接、体外和体内实验验证了可能的机制。
通过 UHPLC-Q-TOF-MS/MS 共鉴定出 106 种红景天成分。从 106 种成分中筛选出 98 种潜在活性化合物，对应 53 种抗 AMS 靶标。基因富集分析表明，缺氧和炎症相关基因可能是红景天调节 AMS 的核心因素。分子对接表明，TNF、VEGFA 和 HIF-1α 与红景天化合物具有较高的亲和力。随后，红景天提取物被表明可抑制缺氧诱导的 H9c2 细胞中 TNF 的蛋白表达水平。最后，进一步验证了红景天提取物可改善急性缺氧诱导大鼠的心脏损伤，并降低心脏中 TNF、VEGFA 和 HIF-1α 的水平。
本研究采用 UHPLC-Q-TOF-MS/MS 分析和网络药理学为揭示红景天防治 AMS 的潜在机制提供了重要参考。
