Andrographolide mitigates paraquat-induced pulmonary injury via PI3K/Akt/PPAR? pathway-mediated regulation of EMT and oxidative stress

Background: Paraquat (PQ) poisoning causes acute pulmonary injury via oxidative stress and epithelial-mesenchymal transition (EMT), with limited treatment options. Objectives: This study investigated whether andrographolide (Andro) alleviates PQ-induced lung damage and the underlying mechanisms. Methods: PQ-induced pulmonary injury was established in C57BL/6J mice. Animals were assigned to Control, Andro, PQ and PQ +Andro groups. Lung pathology, oxidative stress markers (MPO, ROS, MDA, SOD, CAT), EMT markers (E-cadherin, ?-SMA), and PI3K/Akt/PPAR? pathway proteins were assessed in vivo and in MLE-12 cells, with PI3K inhibition using LY294002. Results: Andro significantly improved survival, reduced alveolar injury and collagen deposition, and suppressed oxidative stress by downregulating ROS/MDA/MPO and enhancing SOD/CAT. It suppressed EMT by upregulating E-cadherin and reducing ?-SMA. Andro inhibited PI3K/Akt activation and increased PPAR? expression. LY294002 partially reproduced these effects, supporting pathway involvement. Conclusion: Andro mitigates PQ-induced lung damage by limiting oxidative stress and EMT via the PI3K/Akt/PPAR? pathway. These findings provide preclinical evidence for its further investigation as a candidate protective agent.