Repurposing of digoxin in pain and inflammation: An evidence-based study

In recent years, the drug repositioning strategy has gained considerable attention in the drug discovery process that involves establishing new therapeutic uses of already known drugs. In line with this, we have identified digoxin a cardiac glycoside, as a potent inhibitor of soluble epoxide hydrolase (sEH) enzyme employing in silico high throughput screening protocols and further confirmed using in vitro cell-free sEH inhibitory assay and in vivo preclinical studies in rodents for its repurposing in hyperalgesia, inflammation, and related disorders. Oral administration of digoxin at dose 0.2 mg/kg significantly reduced (p < .0001) the allodynia in mice induced by using hot plate (3.6 ± 1.9) and tail-flick test (7.58 ± 0.9). In addition, digoxin at a dose of 0.2 mg/kg showed marked reduction (94%, p < .0001) in acetic acid-induced abdominal contraction in rats. Further, digoxin also demonstrated antipyretic activity (37.04 ± 0.2, p < .0001) and showed notable reduction (0.60 ± 0.06) in carrageenan-induced paw edema in rats. Also, the histopathological evaluation revealed that digoxin treatment attenuated the edema, neutrophil infiltration, and alveolar septal thickening in lung tissue. These findings are novel and highlight the newer insights towards repurposing digoxin as a new lead in the treatment of hyperalgesia, inflammation, and related disorders.