Xie Jiamei, Yang Yang, Du Yuhang, Su Xiaohua, Zhao Yige, An Yongcheng, Mao Xin, Wang Menglu, Shan Ziyi, Huang Zhiyun, Liu Shuchang, Zhao Baosheng
School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 102488, China.
Guangzhou Baiyunshan Xingqun Pharmaceutical Co., Ltd., Guangzhou 510288, China.
Pharmaceuticals (Basel). 2025 Aug 2;18(8):1153. doi: 10.3390/ph18081153.
: Acute mountain sickness (AMS) is a prevalent and potentially life-threatening condition caused by rapid exposure to high-altitude hypoxia, affecting pulmonary and neurological functions. Tongqiao Jiuxin Oil (TQ), a traditional Chinese medicine formula composed of aromatic and resinous ingredients such as sandalwood, agarwood, frankincense, borneol, and musk, has been widely used in the treatment of cardiovascular and cerebrovascular disorders. Clinical observations suggest its potential efficacy against AMS, yet its pharmacological mechanisms remain poorly understood. The chemical profile of TQ was characterized using UHPLC-Q-Exactive Orbitrap HRMS. Network pharmacology was applied to predict the potential targets and pathways involved in AMS. A rat model of AMS was established by exposing animals to hypobaric hypoxia (~10% oxygen), simulating an altitude of approximately 5500 m. TQ was administered at varying doses. Physiological indices, oxidative stress markers (MDA, SOD, GSH), histopathological changes, and the expression of hypoxia- and apoptosis-related proteins (HIF-1α, VEGFA, EPO, Bax, Bcl-2, Caspase-3) in lung and brain tissues were assessed. : A total of 774 chemical constituents were identified from TQ. Network pharmacology predicted the involvement of multiple targets and pathways. TQ significantly improved arterial oxygenation and reduced histopathological damage in both lung and brain tissues. It enhanced antioxidant activity by elevating SOD and GSH levels and reducing MDA content. Mechanistically, TQ downregulated the expression of HIF-1α, VEGFA, EPO, and pro-apoptotic markers (Bax/Bcl-2 ratio, Caspase-3), while upregulated Bcl-2, the anti-apoptotic protein expression. : TQ exerts protective effects against AMS-induced tissue injury by improving oxygen homeostasis, alleviating oxidative stress, and modulating hypoxia-related and apoptotic signaling pathways. This study provides pharmacological evidence supporting the potential of TQ as a promising candidate for AMS intervention, as well as the modern research method for multi-component traditional Chinese medicine.
急性高原病（AMS）是一种因快速暴露于高海拔低氧环境而引发的常见且可能危及生命的病症，会影响肺部和神经功能。通窍救心油（TQ）是一种由檀香、沉香、乳香、冰片和麝香等芳香和树脂成分组成的中药配方，已广泛用于治疗心血管和脑血管疾病。临床观察表明其对急性高原病具有潜在疗效，但其药理机制仍知之甚少。使用超高效液相色谱-四极杆-静电场轨道阱高分辨质谱（UHPLC-Q-Exactive Orbitrap HRMS）对通窍救心油的化学特征进行了表征。应用网络药理学预测急性高原病涉及的潜在靶点和途径。通过将动物暴露于低压低氧环境（约10%氧气）建立急性高原病大鼠模型，模拟海拔约5500米的环境。以不同剂量给予通窍救心油。评估了生理指标、氧化应激标志物（丙二醛、超氧化物歧化酶、谷胱甘肽）、组织病理学变化以及肺和脑组织中缺氧和凋亡相关蛋白（缺氧诱导因子-1α、血管内皮生长因子A、促红细胞生成素、 Bax、Bcl-2、半胱天冬酶-3）的表达。共从通窍救心油中鉴定出774种化学成分。网络药理学预测了多个靶点和途径的参与。通窍救心油显著改善了动脉氧合，并减少了肺和脑组织的组织病理学损伤。它通过提高超氧化物歧化酶和谷胱甘肽水平并降低丙二醛含量来增强抗氧化活性。从机制上讲，通窍救心油下调了缺氧诱导因子-1α、血管内皮生长因子A、促红细胞生成素和促凋亡标志物（Bax/Bcl-2比值、半胱天冬酶-3）的表达，同时上调了抗凋亡蛋白Bcl-2的表达。通窍救心油通过改善氧稳态、减轻氧化应激以及调节缺氧相关和凋亡信号通路，对急性高原病诱导的组织损伤发挥保护作用。本研究提供了药理学证据，支持通窍救心油作为急性高原病干预的有前景候选药物的潜力，以及多成分中药的现代研究方法。
