Lu Hongmei, Xie Dengpiao, Qu Bo, Li Mingquan, He Yuhua, Liu Weijing
Dongzhimen Hospital Affiliated to Beijing University of Chinese Medicine, Beijing University of Chinese Medicine, Beijing, 100700, China.
Department of Clinical Medicine, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, 610072, China.
Heliyon. 2023 Apr 22;9(5):e15682. doi: 10.1016/j.heliyon.2023.e15682. eCollection 2023 May.
Previous evidence indicated that emodin has significant advantages for preventing acute kidney injury (AKI). However, the mechanisms responsible for these effects of emodin have yet to be elucidated.
We first used network pharmacology and molecular docking to identify the core targets of emodin for AKI and performed a range of experiments to validate this result. Pretreatment with emodin for 7 days, the rats were treated with bilateral renal artery clipping for 45 min to identify the prevention effect. Hypoxia/reoxygenation (H/R), and vancomycin - induced renal tubular epithelial cells (HK-2 cells) were treated with emodin to explore the related molecular mechanism.
Network pharmacology and molecular docking showed that anti-apoptosis might be the core mechanism responsible for the action of emodin on AKI; this anti-apoptotic effect appears to because by regulation p53-related signaling pathway. Our data showed that pretreatment with emodin significantly improved renal function and renal tubular injury in renal I/R model rats ( < 0.05. The prevention effect of emodin was proved to be related to anti - apoptosis of HK-2 cells, possibly by downregulating the levels of p53, cleaved-caspase-3, pro-caspase-9, and upregulated the levels of Bcl-2. The efficacy and mechanism of emodin on anti - apoptosis was also confirmed in vancomycin - induced HK-2 cells. Meanwhile, the data also showed that emodin promoted angiogenesis in I/R damaged kidneys and H/R-induced HK-2 cells, which was associated with decreasing HIF-1α levels and increasing VEGF levels.
Our findings indicated that the preventive effect of emodin on AKI is probably attributable to anti-apoptosis response and promoting angiogenesis effect.
先前的证据表明，大黄素在预防急性肾损伤（AKI）方面具有显著优势。然而，大黄素产生这些作用的机制尚未阐明。
我们首先使用网络药理学和分子对接来确定大黄素对AKI的核心靶点，并进行了一系列实验来验证这一结果。用大黄素预处理7天，然后对大鼠进行双侧肾动脉夹闭45分钟以确定预防效果。用大黄素处理缺氧/复氧（H/R）和万古霉素诱导的肾小管上皮细胞（HK-2细胞），以探索相关分子机制。
网络药理学和分子对接表明，抗凋亡可能是大黄素对AKI起作用的核心机制；这种抗凋亡作用似乎是通过调节p53相关信号通路实现的。我们的数据表明，大黄素预处理显著改善了肾缺血/再灌注（I/R）模型大鼠的肾功能和肾小管损伤（P<0.05）。大黄素的预防作用被证明与HK-2细胞的抗凋亡有关，可能是通过下调p53、裂解的半胱天冬酶-3、前半胱天冬酶-9的水平，并上调Bcl-2的水平。大黄素在万古霉素诱导的HK-2细胞中抗凋亡的功效和机制也得到了证实。同时，数据还表明，大黄素促进了I/R损伤肾脏和H/R诱导的HK-2细胞中的血管生成，这与降低缺氧诱导因子-1α（HIF-1α）水平和增加血管内皮生长因子（VEGF）水平有关。
我们的研究结果表明，大黄素对AKI的预防作用可能归因于抗凋亡反应和促进血管生成的作用。
