Abstract
Isoniazid and rifampin are antituberculosis drugs with a side effect in hepatotoxicity. An antioxidant can neutralize the toxic effects of these drugs on the liver. Jackfruit leaf (Arthocarpus heterophyllus Lam.) was identified as a rich source of antioxidants. This study aims to determine the effect of the ethanolic extract of jackfruit leaf (EEJL) on the liver histopathological structure of the rats induced by isoniazid-rifampin and analyze the molecular docking interaction of Arthocarpus heterophyllus Lam. active compound toward targeted receptor. The histological structure was determined using the Hematoxylin-Eosin staining method. Fifteen male Wistar rats were divided into five groups. Group 1 is a negative group with 1% sodium carboxymethyl cellulose. Group 2, as a positive control, was given a Curliv®, and the treatment groups 3, 4, and 5 were given EEJL at a dose of 100, 200, and 300 mg/kg body weight (BW), respectively. Before being treated, the rats were induced with an isoniazid-rifampin dose of 300 mg/kg BW orally for three days. The extract was administered orally once a day for seven days. On the eighth day, the liver was collected for histologic observation. Molecular docking was performed using the AutoDock Vina package to estimate the interaction of the ligand-receptor complex using 1HD2 and 3NT1 corresponding to antioxidant and COX-1 receptors, respectively. The results revealed that the treatment of EEJL affected repairing the structure of damaged liver cells in rats. Histological observation revealed that the group dose of 300 mg/kg BW had a better effect than other groups because only sinusoid dilatation was seen in the liver section. The molecular docking study showed that the ΔG produced between the test ligands toward 1HD2 is at a lower level (-6.134 to -6.881 kcal/mol) compared to the native ligand, which is only -4.701 kcal/mol. Besides, the interaction of test ligands toward targeted receptor 3NT1 exhibited a higher level than the native ligand. Therefore, the EEJL has shown significant improvement in the histology of rat liver, which might be due to its high stability interaction of active compounds toward 1HD2 and 3NT1 corresponding to antioxidant and COX-1 receptors, respectively.
Published Version
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