Zhang Siyue, Wang Xixin, Yang Qing, Xia Qing, Zhao Ye, Zheng Xiaohui, Zhang Yun, Liu Kechun
Biology Institute, Qilu University of Technology (Shandong Academy of Sciences), Jinan, Shandong, PR China.
Biology Institute, Qilu University of Technology (Shandong Academy of Sciences), Jinan, Shandong, PR China; Department of Surgery, Li Ka Shing Faculty of Medicine, Pokfulam, The University of Hong Kong, Hong Kong.
Biomed Pharmacother. 2023 May;161:114570. doi: 10.1016/j.biopha.2023.114570. Epub 2023 Mar 20.
Isopropyl 3-(3,4-dihydroxyphenyl)-2-hydroxypropanoate (IDHP) is the core active substance of salvia miltiorrhiza in disease treatment. The significance of our work lies in evaluating the ameliorating effects of IDHP on hypoxia-induced injury and investigating its mechanisms. We examined the morphology, dopamine neurons (DANs), cerebral vessels, and behavior of zebrafish larvae administrated by IDHP/VHC after hypoxia-induction. We next sought to explore its anti-hypoxic mechanisms via transcriptome analysis and qPCR experiments. The results indicated that hypoxia-induced injuries, including decreased length of DANs, number of cereal vessels, total swimming distance, and average swimming speed, were all alleviated by IDHP. Furthermore, transcriptome analysis provided a sign that IDHP most likely played the anti-hypoxic role through the neuroactive ligand-receptor interaction (NLRI) signaling pathway. Consistently, expression of related genes, such as f2rl1.1, p2ry10, npy1r, ptger2b, ptger2b, pth2rb, and nmur1a, was downregulated by hypoxia induction and recovered after IDHP administration. Therefore, we speculated that, via regulating NLRI, IDHP reduced inflammation, promoted angiogenesis, modulated blood pressure and flow, and inhibited cell apoptosis, and eventually played an anti-hypoxic role.
3-(3,4-二羟基苯基)-2-羟基丙酸异丙酯（IDHP）是丹参在疾病治疗中的核心活性物质。我们工作的意义在于评估IDHP对缺氧诱导损伤的改善作用并探究其机制。我们检测了缺氧诱导后经IDHP/VHC处理的斑马鱼幼体的形态、多巴胺神经元（DANs）、脑血管和行为。接下来，我们试图通过转录组分析和qPCR实验探索其抗缺氧机制。结果表明，IDHP减轻了缺氧诱导的损伤，包括DANs长度缩短、脑血管数量减少、总游动距离和平均游动速度降低等。此外，转录组分析表明IDHP很可能通过神经活性配体-受体相互作用（NLRI）信号通路发挥抗缺氧作用。一致地，缺氧诱导下调了f2rl1.1、p2ry10、npy1r、ptger2b、ptger2b、pth2rb和nmur1a等相关基因的表达，而IDHP处理后这些基因的表达得以恢复。因此，我们推测，IDHP通过调节NLRI，减轻炎症、促进血管生成、调节血压和血流并抑制细胞凋亡，最终发挥抗缺氧作用。
