Diterpene Coronarin Attenuates Lipopolysaccharide-Induced Acute Lung Injury in Both In Vivo and In Vitro Models

Abstract

Acute lung injury (ALI) is a clinical condition occurs due to severe systemic inflammatory response for clinical stimulus like pneumonia, sepsis, trauma, aspiration, inhalation of toxic gases, and pancreatitis. Disruption of alveolar barriers, activation of macrophages, infiltration of neutrophils, and proinflammatory cytokines are the vital events occurs during ALI. The drugs which inhibit these inflammatory response can protect lungs from inflammatory insults. In this study, we examined the potency of phytochemical coronarin, a diterpene which have been proven to possess anti-inflammatory, antioxidant, antiangiogenic, and antitumor activities. Healthy BALB/c mice were induced to acute lung injury with intra-tracheal administration of LPS and then treated with 5 and 10 mg/kg concentration of coronarin. The wet/dry lung weight of mice were estimated to assess the induction of pulmonary edema. BALF fluid was analyzed for protein concentrations and immune cells count. Myeloperoxidase activity and levels of chemokines MCP-2 and MIP-2, iNOS, COX-2, and PGE-2 were quantified to assess the immunomodulatory effect of coronarin against LPS-induced ALI. The levels of proinflammatory cytokines was measured to examine the anti-inflammatory property of coronarin, and it was confirmed with histopathological analysis of the lung tissue. Murine RAW 264.7 cells were utilized for the in vitro analysis. Cell cytoxicity and cytoprotective property of coronarin was assessed with MTT assay in LPS-treated Murine RAW 264.7. The anti-inflammatory property of coronarin was further confirmed in in vitro condition by estimating the levels of pro-inflammatory cytokines in coronarin-treated and untreated LPS-induced cells. Overall, our in vivo and in vitro results confirm coronarin significantly inhibited the infiltration of neutrophils prevented immunodulatory activity and synthesis of proinflammatory cytokines and alleviated the acute lung injury induced by LPS. Coronarin is a potent anti-inflammatory drug which can be subjected to further research to be prescribed as drug for ALI.