Wu Yizhan, Guo Fei, Li Jiajia, Shi Wenhui, Song Laiyang, Liu Jiangwei
Department of Graduate School, Xinjiang Medical University, Urumqi, 830000, Xinjiang Uygur Autonomous Region, China.
Department of Emergency Trauma Surgery, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, 830054, Xinjiang Uygur Autonomous Region, China.
Naunyn Schmiedebergs Arch Pharmacol. 2025 Apr;398(4):4617-4632. doi: 10.1007/s00210-024-03572-z. Epub 2024 Nov 9.
Heatstroke (HS) poses a significant threat to public health. Curcumin, a polyphenolic compound, has been reported to possess anti-inflammatory and antioxidant properties. This study aimed to investigate the potential therapeutic effects of curcumin on HS-induced lung injury and to elucidate its underlying molecular mechanisms. We utilized network pharmacology to predict the potential targets of curcumin and determine its possible protective effects against HS. Molecular docking was performed to assess the affinity of curcumin to proteins. Forty mice were used for in vivo experiments to evaluate the therapeutic effects of curcumin, divided into four groups (n = 10 per group): normal control (NC), high-temperature control (HTC), low-dose curcumin heatstroke (H100c, 100 mg/kg/day), and high-dose curcumin heatstroke (H200c, 200 mg/kg/day). Furthermore, we evaluated lung pathology, ultrastructural alterations, and protein expression levels of key molecules. Molecular docking indicated a high binding affinity between curcumin and PIK3R1, AKT, and CASP3. In vivo experiments confirm that curcumin pretreatment significantly mitigates HS-induced lung tissue pathology and ultrastructural damage, with the H200c group showing notably greater improvement. Furthermore, curcumin pretreatment markedly enhances the activation of the PI3K/AKT pathway and suppresses the expression of cleaved caspase3, particularly in the H200c group. Our study suggests curcumin may alleviate HS-induced lung injury via the PI3K/AKT pathway, but limitations exist. We did not test key protein knockdown/overexpression, and PI3K/AKT may not be the only pathway. Human and mouse pharmacokinetic differences could affect clinical translation.
中暑（HS）对公众健康构成重大威胁。姜黄素是一种多酚类化合物，据报道具有抗炎和抗氧化特性。本研究旨在探讨姜黄素对中暑诱导的肺损伤的潜在治疗作用，并阐明其潜在的分子机制。我们利用网络药理学预测姜黄素的潜在靶点，并确定其对中暑的可能保护作用。进行分子对接以评估姜黄素与蛋白质的亲和力。四十只小鼠用于体内实验以评估姜黄素的治疗效果，分为四组（每组n = 10）：正常对照组（NC）、高温对照组（HTC）、低剂量姜黄素中暑组（H100c，100 mg/kg/天）和高剂量姜黄素中暑组（H200c，200 mg/kg/天）。此外，我们评估了肺病理学、超微结构改变以及关键分子的蛋白质表达水平。分子对接表明姜黄素与PIK3R1、AKT和CASP3之间具有高结合亲和力。体内实验证实姜黄素预处理可显著减轻中暑诱导的肺组织病理学和超微结构损伤，H200c组改善尤为明显。此外，姜黄素预处理显著增强PI3K/AKT途径的激活并抑制裂解的caspase3的表达，特别是在H200c组。我们的研究表明姜黄素可能通过PI3K/AKT途径减轻中暑诱导的肺损伤，但存在局限性。我们未测试关键蛋白的敲低/过表达，且PI3K/AKT可能不是唯一途径。人和小鼠的药代动力学差异可能会影响临床转化。
