Andrographolide alleviates paraquat-induced acute lung injury by activating the Nrf۲/HO-۱ pathway

Objective(s): Paraquat (PQ), a highly effective and rapidly non-selective herbicide, mainly targets the lungs and causes acute lung injury (ALI). So far, the scarcity of effective drug candidates against PQ-induced ALI remains a big challenge. Andrographolide (Andro), with its anti-inflammatory and antioxidant activities, has been demonstrated to alleviate ALI. Nevertheless, whether Andro could alleviate the PQ-mediated ALI remains unknown. Therefore, this study will explore the effects as well as the possible mechanism of Andro against ALI caused by PQ. Materials and Methods: C۵۷BL/۶J mice were injected with ۲۰ mg/kg PQ intraperitoneally to establish an ALI model. PQ-treated MLE-۱۲ cells were applied to a vitro model. Nuclear factor erythroid like-۲ (Nrf۲) was knocked out to explore the specific effects of the Nrf۲/ Heme oxygenase-۱ (OH-۱) pathway in the protection of Andro against ALI caused by PQ.Results: Andro significantly reduced lung damage and the ratio of Wet/Dry (W/D) weight, decreased MDA, IL-۶, IL-۱β, and TNF-ɑ levels, reversed the decrease of CAT and SOD levels, and inhibited apoptosis caused by PQ. Andro obviously increased the ratio of Bcl-۲/Bax while reducing caspase-۳ and cleaved caspase-۳ levels. Furthermore, Andro dramatically elevated the antioxidant proteins Nrf۲, NQO-۱, and HO-۱ levels compared with the PQ group. This experiment demonstrated that Andro reduced ROS and inhibited apoptosis, induced by PQ in MLE-۱۲ cells, by inducing Nrf۲/HO-۱ pathway activation.Conclusion: Andro effectively ameliorates oxidant stress and apoptosis in ALI caused by PQ, possibly through inducing Nrf۲/HO-۱ pathway activation.

Keywords:

Acute lung injury , Andrographolide , Apoptosis , Nrf۲ , Oxidative stress , Paraquat