28‑Homocastasterone: A Dietary Plant Keto Oxysterol Positively Modulating Hexokinase mRNA Expression and Catalytic Activity in Diabetic Male Rat
Background and Aim: 28‑homocastasterone (28‑HC) is a keto oxysteroid comes under the brassinosteroid family phytohormone. 28‑HC exhibited structural similarity with mammalian oxysteroid such as OH‑cholesterol. Humans were exposed to 28‑HC through diet and herbal‑based medicine. Therefore, in the present study, we investigated the influence of 28‑HC on hexokinase catalytic activity and mRNA expression in liver, kidney, and testicular tissues in normal and diabetic male rat. Methods: Induction of diabetes was achieved by single peritoneal injection of streptozotocin (60 mg/kg bwt) followed by 28‑HC (333.33 μg/kg b.wt) which was fed orally for 15 days. At 16th day, tissues were removed followed by hexokinase activity, and mRNA expression was analyzed. In silico, docking study was performed to 28‑HC against glucokinase and hexokinase proteins carried out using docking application AutoDock 4.0 suite docking simulations. Results: 28‑HC‑treated rat tissues showed significantly elevated hexokinase catalytic activity and mRNA expression (P < 0.05). On the other hand, in silico molecular, docking study was performed to recognize the binding affinity of 28‑HC to glucokinase and hexokinase proteins. 28‑HC was bound to the drug binding pocket of glucokinase and hexokinase. The glide energy score is − 6.23 and − 6.43 for glucokinase and hexokinase. Conclusion: 28‑HC has high binding affinity for both glucokinase and hexokinase equally. Upregulation of hexokinase activity resulted in cellular glycolysis. Hence, it is suggested that 28‑HC supplemented diets were suitable for higher energy‑related work activities in human and animals.