Phytochemical investigation, structural elucidation, in silico study and anti-psoriatic activity of potent bioactive from Betula utilis
Abstract
Psoriasis is a chronic autoimmune pathological condition characterized by hyperactivation of proinflammatory cytokines (IL-6, TNF-α, IL-17, IL-23, etc.). Severe drug-associated toxicities like hepatotoxicity and nephrotoxicity (Methotrexate), teratogenicity (Tazarotene), hypercholesterolemia (Cyclosporine) and hypercalcemia (tacalcitol), are the forefront challenges that demand an alternative approach for the treatment of psoriasis. In the present study, a natural lead molecule 'Betulin' (BE, lup-20(29)-ene-3b,28-diol) was isolated from Betula utilis and subsequently, structure-based molecular docking was employed to identify the molecular target for psoriasis. The computational analysis reflects better affinity of BE towards pro-inflammatory cytokine as compared to standard drugs. Apart from this BE shows a greater affinity towards the overexpressed Glut-1 receptor in comparison to standard drug Metformin (Met). Based on the in silico screening the isolated lead compound was further processed for the evaluation of anti-psoriatic activity via imiquimod (IMQ 5%) induced psoriasis-like skin inflammation model. In vivo screening models were characterized by different parameters (psoriasis area and severity index (PASI) scores, macroscopically and behavioral evaluation, splenomegaly, cytokine levels and histological changes) and compared among the experimental groups. The experimental finding reflects comparable results of PASI score, i.e., 57.14% and 61.9% recovery of test…
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