Molecular Interaction of Naringin and Its Metabolite Naringenin to Human Liver Fibrosis Proteins: An In Silico Approach

Background: Naringin, pharmaceutically active flavonoid, rapidly metabolizes in liver into naringenin. Both naringin and naringenin have significant biological activity and less toxicity. Objective: In the present study, in silico molecular interactions of naringin and its metabolite naringenin have been evaluated against different human liver fibrosis proteins. Materials and Methods: The major human therapeutic protein targets such as epidermal growth factor receptor (EGFR), vascular endothelial growth factor receptor‑2 (VEGFR‑2), fibroblast growth factor receptor‑1 (FGFR1), Kelch‑like ECH‑associated protein‑1 (Kaep1), transforming growth factor beta receptor I (TGFBR‑1), angiotensin II receptor type‑1 (Angio‑II‑Type‑1), Janus kinase‑2 (JAK‑2), Zeta‑chain‑associated protein kinase‑70 (ZAP‑70) have been selected for the docking studies. This computational study was performed using Schrödinger Suite Maestro 10.3 Glide software 2015. Results: The studies demonstrated comparable binding affinities of naringin and naringenin with human therapeutic protein targets such as JAK‑2, ZAP‑70 Kinase, Angio‑II‑Type 1, TGFBR1, Kaep1, EGFR, VEGFR‑2, and FGFR1 when compared to their respective standard drugs such as gefitinib, regorafenib, dovitinib, bardoxolone methyl, SB‑431542, olmesartan, and ruxolitinib. Naringin showed better glide score ranging from −8.5 to −13.3 kcal/mol whereas its metabolite Naringenin also showed comparable glide score ranging from −5.4 to −9.3 kcal/mol. The binding of target proteins with respective standard drugs showed −2.2 to −10.12 kcal/mol. Conclusion: The observed in silico human protein interactions of naringin and its metabolite naringenin could be exploited for the anti-liver fibrosis therapy. The results derived from this pioneering virtual study may advance further mechanistic in vitro and preclinical in vivo studies.