5‑Methyltetrahydrofolate and aqueous extract of Spirulina (Arthrospira) ameliorate diabetes and associated complications in STZ‑induced diabetic rats

The present study evaluated the effects of 5-methyltetrahydrofolate (5-MTHF) and Spirulina aqueous extract on diabetes. An
in silico docking study with select Spirulina bioactive compounds showed strong binding affinities of folates with glucose
metabolism-related proteins. In vitro assay showed 5-MTHF’s superior inhibitory activity on alpha-amylase compared to
folic acid. The protective effect of Spirulina aqueous extract and 5-MTHF were validated in vivo using an STZ-induced dia-
betic Wistar rat model. Supplementation with Spirulina extract through diet, and a higher dose of 5-MTHF through gavage
effectively lowered fasting blood glucose levels and improved oral glucose tolerance and amylase content. Supplementation
also countered hyperlipidemia, improved the levels of antioxidant enzymes, and reduced the inflammatory markers. Weight
loss prevention, mitigation of kidney enlargement, and normalisation of the histology of the pancreas, kidney, and liver were
also observed. The ameliorative effect of a higher dose of 5-MTHF was comparatively superior to Spirulina aqueous extract
and a corresponding higher dose of folic acid. An increase in serum folate levels on supplementation with Spirulina aqueous
extract suggests Spirulina to be a source of bioavailable folate. The positive effect of Spirulina aqueous extract suggests a
potential synergistic role for folate along with its other bioactive phytochemicals. The study highlights the potential amelio-
rative effects of Spirulina aqueous extract and 5-MTHF as a dietary supplement on diabetes and associated complications.