Antidiabetic and antihyperlipidemic effects of crude fractions and isolated compound from Striga orobanchioides Benth on streptozotocin induced diabetic rats

Striga orobanchioides Benth is a traditionally used Ayurvedic medicinal plant for the treatment of diabetes. Scientific validation of the claim is studied in this research. The significant bioactivity of the plant components is obligatory for its use in medicine.The present work is to extract bioactive fractions and chemicals, biological activity of the chemicals and to identify potentially bioactive compound(s) from ethanolic extract of the plant.Ethanolic extract of the authenticated plant was fractionated and subjected to in vitro and in vivo antidiabetic and antihyperlipidemic activity. In vitro α-amylase and α-glucosidase enzyme activity was carried out on digestive enzyme. Streptozotocin (STZ) induced diabetes mellitus in rats model was preferred for in vivo activity where antidiabetic parameters body weight, urine volume, blood glucose level, glycosylated hemoglobin, serum insulin, liver glycogen and lipid profile as an antihypertensive parameters were assessed. Isolation of bioactive compounds was carried out by chromatographic techniques and identification of the compound was done by FTIR, Mass spectrometry and NMR spectroscopy. The molecular docking study with α-amylase, α-glucosidase, dipeptidyl peptidase-IV (DPP-IV), glucokinase (GK) as diabetic markers and on 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) and Niemann-Pick C1-Like 1 (NPC1L1) was carried out.Ethyl acetate-methanol fraction of the ethanol extract showed presence of pentacyclic triterpenoids (81.5% w/w) in GC-HRMS study. Spectroscopic analysis of the isolated compound revealed presence betulin. In vitro antidiabetic activity pointed out robust inhibition of the digestive enzymes by the fractions known as bioactive fraction and betulin. Betulin at a dose of 40 mg/kg treated group showed significant improvement of diabetic conditions. The gene expression studies revealed that betulin in 40 mg/kg dose has positive effects for carbohydrate metabolism in liver, lowers the hepatic inflammation and increases insulin secretion. The plant compound demonstrated significant inhibitory potential on α-amylase, α-glucosidase, DPP-IV and GK enzymes in silico.The biological study reveals that betulin could dominate the succession of diabetes in dose dependent manner. The plant and specifically Betulin exerts a significant antidiabetic and antihyperlipidemic effects that are more possibly through stimulation of insulin secretion, increase in PPAR-α level with an increase in GRIA2 mRNA expression.