Assessment of lapachol's anti-inflammatory effectiveness in mitigating sepsis-induced acute lung injury.

Sepsis-induced Acute Lung Injury (ALI) and Acute Respiratory Distress Syndrome (ARDS) pose life-threatening risks due to an excessive activation of proinflammatory cytokines via the JAK pathway. Currently, no confirmed drug treatment exists for ALI. In this study, we explored JAK1 as a potential therapeutic target to address this issue. This study evaluates lapachol, a bioactive secondary metabolite, for its potential in treating sepsis-induced Acute Lung Injury (ALI). Lapachol was selected based on in-silico analyses such as binding energy, RMSD, RMSF, H-bond graphs, and lig plots supported the hypothesis that Lapachol binds to JAK1 in a manner similar to Tofacitinib JAK1/3 inhibitor (Positive control). Lapachol, derived from the heartwood of Tecomella undulata, was used in this investigation. Swiss albino mice were categorized into control, LPS treated, positive control (Tofacitinib), and experimental groups (Lapachol at 20 and 40 mg/kg doses). Throughout the experiment, mice behaviour was monitored, and euthanasia was performed at 12 and 24-h intervals. Various analyses, including body weight, W/D ratio, lung weight/body weight ratio, flow cytometry of BAL fluid (at 12 and 24 h), histology, myeloperoxidase assays were performed. Results indicated that both Tofacitinib and Lapachol significantly reduced ALI markers, including lung weight/body weight ratio, cell counts, and granulocytes in bronchoalveolar lavage fluid. Moreover, histopathology and MPO analysis suggested that Lapachol, particularly at 40 mg/kg, exhibited anti-inflammatory effects comparable to Tofacitinib. Conclusively, the findings suggest that Lapachol possesses the potential to inhibit JAK1 kinase domains and mitigate ALI associated with sepsis similar to Tofacitinib.
Competing Interests: Declaration of competing interest The authors declares no other conflicts of interest related to this research.
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