Anti-inflammatory and anti-oxidant activities of Gymnema sylvestre extract rescues acute respiratory distress syndrome in rats via modulating the NF-κB/MAPK pathway

Abstract Acute respiratory distress syndrome (ARDS) is one of the major cause of mortality in COVID-19 patients, due to limited therapeutic options. This prompted us to explore natural sources to mitigate this condition. Gymnema sylvestre (GS) is an ancient medicinal plant known to have various therapeutic effects. In this investigation, Gymnema sylvestre hydroalcoholic extract (HAEGS) was examined against lipopolysaccharide (LPS) induced lung injury and ARDS in in vitro and in vivo models. UHPLC-HRMS/GC-MS was employed for characterizing the HAEGS and identified several active derivatives including gymnemic acid, gymnemasaponins, gymnemoside, gymnemasin, quercetin, and long fatty acids. Gene expression by RTqPCR and DCFDA analysis by flow-cytometry revealed that several inflammatory cytokine/chemokine, cell injury markers, and reactive-oxygen-species (ROS) levels were highly upregulated in LPS control and were significantly reduced upon HAEGS treatment. Consistent with the in vitro studies, we found that in LPS induced ARDS model, pre-treatment with HAEGS significantly suppressed the LPS-induced elevation of inflammatory cell infiltrations, cytokine/chemokine marker expression, ROS levels, and lung injury in a dose dependent manner. Further mechanistic studies suggested that the HAEGS ameliorates the ARDS through the NF-κB/MAPK signaling pathway. Additional fractionation results revealed that fraction-6 which has the exclusive composition of gymnemic acid derivatives showed anti-inflammatory effects which is similar to the HAEGS. Overall, HAEGS significantly mitigated the LPS-induced lung injury and ARDS by targeting NF-κB/MAPK signaling pathway. Thus, our work unravels the protective role of HAEGS for the first time in managing ARDS.