From Nutraceutical to Molecular Targets: Antidiabetic Effects of Spirulina maxima Validated by In Vivo and In Silico Studies.

Abstract

BackgroundSpirulina maxima is a cyanobacterium, which has been a staple food in Mexico since 16th century. Presently this nutraceutical alga has been explored for its antioxidant, anticancer, hepatoprotective and antilipemic properties. The present study is focused on the antihyperglycemic effect of S.maxima in streptozotocin induced diabetes mellitus. The molecular characterization of S. maxima and the anti-diabetic targets are deduced from in-silico analysis. MethodsThe anti-hyperglycemic potential of S. maxima was evaluated in male Wistar rats injected with streptozotocin (45 mg/kg (i.p)). The Animals were grouped based on the blood levels into Normal control (n=6); Normal control administered with S. maxima (n=6), Diabetic control, Diabetic group treated with S. maxima(n=6),, the diabetic group treated with Glibenclamide (600{micro}g/kg b.w.) (n=6), S. maxima (500mg/kg) was administrated orally for 15 days, and the variations in blood glucose levels along with the lipid levels and the antioxidant status were determined.The lipids content of S. maxima was characterized through GCMS. The lipids identified were docked in-silico with AMPK molecule and PPAR{gamma}, potential targets for antidiabetic drugs. Results and conclusionsS. maxima administration in diabetic rats significantly reduced the blood glucose levels by 62.76% while the cholesterol, triglycerides, and VLDL level were marginally reduced. The HDL levels were significantly enhanced by 32.4%. The antioxidant markers such as catalase, SOD and GSH levels, were elevated by 13.8, 25 and 7.47%. The TBARS levels were reduced up to 15.1%. The functional group analysis showed characteristic vibrations of polysaccharides proteins, lipids and aromatic compounds. The GCMS characterization of S. maxima showed the presence of C8, C9 and C13 lipids at a concentration less than 1% of total lipids, while C5, C11, C16 and C20 lipids were 1-10% of total lipid content while C6, C10, C15 and C22 lipids were above 10% of total lipids. The docking results revealed the binding affinity of C5, C6, C10, C11 and C18 with regulatory gamma subunit of AMPK while C5, C6 and C11 lipids had the binding affinity with PPAR-{gamma} receptor. The study revealed, the antidiabetic potential of S. maxima, and hypothesized AMPK and PPAR-{gamma} as a potential target in maintaining blood glucose homeostasis.