Browsing by Author "Ologe, M.O., Agede, O.A., Okoro, P.N"

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    Lipid Lowering Efficacy between Morning and Evening Rosuvastatin Treatment and the In-silico Mechanistic Insight
    (Faculty of Basic Medical Sciences, University of Ibadan, 2024-09-10) Ologe, M.O., Agede, O.A., Okoro, P.N
    Rosuvastatin, a potent inhibitor of HMG-CoA reductase, disrupts cholesterol production. With a plasma half-life of 19 hours, it surpasses atorvastatin (15 hours) and simvastatin (2-3 hours). There are limited information on whether morning or evening administration affects its efficacy. This study compares the lipid-lowering effects of morning and evening rosuvastatin to simvastatin, the statin with the shortest half-life. Rats acclimated for two weeks were fed conventional rat chow. Blood samples were collected from tail veins to assess serum lipid profiles. Randox kits measured total cholesterol, HDL, LDL, and triglycerides. In rats on a high-fat diet, LDL levels were significantly lower in the evening rosuvastatin group compared to the morning group at the 4th week (19.871±2.31 mmol/l vs. 24.2±1.40 mmol/l, p = 0.00199). Similarly, mean cholesterol was significantly lower in the evening group at the 4th week (28.271±1.4874 mmol/l vs. 31.2±1.5113 mmol/l, p = 0.00514). In silico docking revealed six rosuvastatin binding orientations within the HMG-CoA reductase site, with favorable interactions at binding mode 1. Hydrogen bonding with ASN-658, halogen interaction, and electrostatic interactions with ASP-767 were observed. However, unlike simvastatin studies, no significant differences in lipid levels were found between morning and evening rosuvastatin administration in hyperlipidemic rats at the 12th week. This suggests potential phenotypic variations in rosuvastatin response due to its extended half-life. Hydrogen bonding, particularly with ASN-658, emerges as critical in rosuvastatin-HMG-CoA reductase interaction