Molecular simulations probing Kushecarpin A as a new lipoxygenase inhibitor

Zizyphus oxyphylla Edgew is used in Pakistan as a folk medicinal remedy for inflammatory conditions, pains especially rheumatic pain, fevers, allergy and diabetes. The aim of the current study was to scientifically validate the folk use of Z. oxyphylla Edgew by using the isolated compound in vitro and in vivo levels. Kushecarpin A was isolated from ethyl acetate fraction of the plant crude extract. Molecular docking simulations predicted Kushecarpin A as a potential new lipoxygenase (LOX) inhibitor. Kushecarpin A showed significant lipoxygenase inhibition (IC50: 7.2 ± 0.02 μM) thus validated computational prediction. It also exhibited significant and highly significant inhibition (p < 0.05 and p < 0.01) of carrageenan-induced hind paw oedema at the doses of 5, 10 and 20 mg/kg. Kushecarpin A seems to be a potentially new anti-inflammatory compound responsible for anti-inflammatory activities of Z. oxyphylla Edgew. In vitro and in vivo anti-inflammatory inflammatory activities were found in good agreement with the folk medicinal use of Z. oxyphylla Edgew in inflammatory disorders.

Kushecarpin A isolated from Zizyphus oxyphylla Edgew showed significant lipoxygenase inhibition (IC50: 7.2 ± 0.02 μM). It also exhibited significant inhibition of carrageenan-induced hind paw oedema in animals.368Highlights► Zizyphus oxyphylla Edgew. is traditionally used in diabetes and inflammation. ► Kushecarpin A was isolated from crude extract of Z. oxyphylla. ► Molecular docking simulations predicted Kushecarpin A as new LOX inhibitor. ► LOX inhibitory activity validated the computational prediction. ► Kushecarpin A also showed significant in-vivo anti-inflammatory activity.