Northwest Institute of Plateau Biology, Chinese Academy of Sciences, Xining 810008, Qinghai, China; Key Laboratory of Tibetan Medicine Research, Chinese Academy of Sciences, Xining 810008, Qinghai, China; Key Laboratory of Tibetan Medicine Research of Qinghai Province, Xining 810008, Qinghai, China; University of Chinese Academy of Sciences, Beijing 100049, China.
Northwest Institute of Plateau Biology, Chinese Academy of Sciences, Xining 810008, Qinghai, China; Key Laboratory of Tibetan Medicine Research, Chinese Academy of Sciences, Xining 810008, Qinghai, China; Key Laboratory of Tibetan Medicine Research of Qinghai Province, Xining 810008, Qinghai, China.
Phytomedicine. 2018 Jan 1;38:175-182. doi: 10.1016/j.phymed.2017.12.008. Epub 2017 Dec 8.
In previous investigation, we have identified antioxidative effects of water-soluble ethanolic extracts (named as AKE) from Arenaria kansuensis and inferred that these extracts or their constituents may also have antihypoxic activity. A. kansuensis has been widely used in traditional Tibetan medicine for altitude sickness (AS) and has been known as the herb of anti-inflammatory and hypoxia resistance for a long time.
The purpose of this study is to evaluate protective effects of AKE and its major constituents against hypoxia-induced lethality in mice and RSC96 cells.
Hypoxia-induced lethality in mice was investigated by 3 experimental animal models of hypoxia. Meanwhile, we established a RSC96 cell model of hypoxia which applied to screen and assess the anti-hypoxic activity of compounds isolated from A. kansuensis.
Results indicated that AKE dose-dependently prolonged survival time of hypoxia induced lethality in mice compared to vehicle group and exhibited significantly anti-hypoxic effect. AKE also enhanced the number of red blood cells (RBC) and the concentration of hemoglobin (HB). 8 compounds were bio-guided separated and purified from AKE based on the animal model and cell model of hypoxia. Among which pyrocatechol (C16) and tricin 7-O-β-d-glucopyranoside (C13) were confirmed to express better protective effects on cell damage induced by hypoxia, suggesting that these two compounds are major active constituents of AKE for anti-hypoxia.
This study demonstrated that pyrocatechol and tricin 7-O-β-d-glucopyranoside could be therapeutic candidates for treatment of AS. It is the first time to find the major active constituents of AKE for anti-hypoxia. Meanwhile, a RSC96 cell model of hypoxia was established to screen anti-hypoxic activity of compounds for the first time.
在之前的研究中，我们已经发现来自甘肃蚤缀的水溶性乙醇提取物（命名为 AKE）具有抗氧化作用，并推断这些提取物或其成分可能也具有抗缺氧活性。甘肃蚤缀在传统藏医中被广泛用于治疗高原病（AS），长期以来一直被认为是一种具有抗炎和抗缺氧作用的草药。
本研究旨在评估 AKE 及其主要成分对小鼠和 RSC96 细胞缺氧诱导致死的保护作用。
通过 3 种缺氧动物模型研究缺氧诱导的小鼠致死作用，同时建立了 RSC96 细胞缺氧模型，用于筛选和评估从甘肃蚤缀中分离得到的化合物的抗缺氧活性。
结果表明，与对照组相比，AKE 剂量依赖性地延长了缺氧诱导的小鼠致死时间，表现出显著的抗缺氧作用。AKE 还增加了红细胞（RBC）的数量和血红蛋白（HB）的浓度。根据缺氧动物模型和细胞模型，从 AKE 中生物导向分离和纯化了 8 种化合物。其中，邻苯二酚（C16）和木樨草素 7-O-β-d-吡喃葡萄糖苷（C13）被证实对缺氧诱导的细胞损伤具有更好的保护作用，表明这两种化合物是 AKE 抗缺氧的主要活性成分。
本研究表明，邻苯二酚和木樨草素 7-O-β-d-吡喃葡萄糖苷可能是治疗 AS 的治疗候选药物。这是首次发现 AKE 抗缺氧的主要活性成分。同时，首次建立了 RSC96 细胞缺氧模型来筛选化合物的抗缺氧活性。
