Curcumin ameliorates heatstroke-induced lung injury by activating the PI3K/AKT pathway

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.