Metabolic alterations in streptozotocin-nicotinamide-induced diabetic rats treated with Muntingia calabura L. extract via 1H-NMR-based metabolomics.

Diabetes mellitus (DM) is a metabolic endocrine disorder caused by decreased insulin concentration or poor insulin response. Muntingia calabura (MC) has been used traditionally to reduce blood glucose levels. This study aimed to support the traditional claim of MC as a functional food and blood-glucose-lowering regimen. The antidiabetic potential of MC has been tested on a streptozotocin-nicotinamide (STZ-NA) induced diabetic rat model by using the 1H-NMR-based metabolomic approach. Serum biochemical analyses revealed that treatment with 250 mg/kg body weight (bw) standardized freeze dried (FD) 50% ethanolic MC extract (MCE 250) showed favorable serum creatinine (37.77 ± 3.53 µM), urea (5.98 ± 0.84 mM) and glucose (7.36 ± 0.57 mM) lowering capacity, which was comparable to the standard drug, metformin. The clear separation between diabetic control (DC) and normal group in principal component analysis indicated the successful induction of diabetes in the STZ-NA-induced type 2 diabetic rat model. A total of nine biomarkers, including allantoin, glucose, methylnicotinamide, lactate, hippurate, creatine, dimethylamine, citrate and pyruvate were identified in rats' urinary profile discriminating DC and normal groups through orthogonal partial least squares-discriminant analysis. Induction of diabetes by STZ-NA was due to alteration in the tricarboxylic acid (TCA) cycle, gluconeogenesis pathway, pyruvate metabolism and nicotinate and nicotinamide metabolism. Oral treatment with MCE 250 in STZ-NA induced diabetic rats showed improvement in the altered carbohydrate metabolism, cofactor and vitamin metabolic pathway, as well as purine and homocysteine metabolism.