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Andrographolide alleviates paraquat-induced acute lung injury by activating the Nrf2/HO-1 pathway
- Source :
- Iranian Journal of Basic Medical Sciences, Vol 26, Iss 6, Pp 653-661 (2023)
- Publication Year :
- 2023
- Publisher :
- Mashhad University of Medical Sciences, 2023.
-
Abstract
- 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: C57BL/6J mice were injected with 20 mg/kg PQ intraperitoneally to establish an ALI model. PQ-treated MLE-12 cells were applied to a vitro model. Nuclear factor erythroid like-2 (Nrf2) was knocked out to explore the specific effects of the Nrf2/ Heme oxygenase-1 (OH-1) 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-6, IL-1β, 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-2/Bax while reducing caspase-3 and cleaved caspase-3 levels. Furthermore, Andro dramatically elevated the antioxidant proteins Nrf2, NQO-1, and HO-1 levels compared with the PQ group. This experiment demonstrated that Andro reduced ROS and inhibited apoptosis, induced by PQ in MLE-12 cells, by inducing Nrf2/HO-1 pathway activation.Conclusion: Andro effectively ameliorates oxidant stress and apoptosis in ALI caused by PQ, possibly through inducing Nrf2/HO-1 pathway activation.
- Subjects :
- acute lung injury
andrographolide
apoptosis
nrf2
oxidative stress
paraquat
Medicine
Subjects
Details
- Language :
- English
- ISSN :
- 20083866 and 20083874
- Volume :
- 26
- Issue :
- 6
- Database :
- Directory of Open Access Journals
- Journal :
- Iranian Journal of Basic Medical Sciences
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.3cbc5ed73d2d45e881afa94ab2f1710b
- Document Type :
- article
- Full Text :
- https://doi.org/10.22038/ijbms.2023.68827.15000