Inhibition and kinetic studies of phytochemical constituents of Goniothalamus wynaadensis and their isoxazoline derivatives on α-glucosidase.

α-Glucosidase, an enzyme involved in post-prandial hyperglycaemia, was used as a target to study the effect of compound(s) isolated from Goniothalamus wynaadensis and its isoxazoline derivatives. Among thirteen compounds screened, compounds 1, 3a and 3j exhibited significant inhibition with IC50 values of 63.42, 61.36 and 58.89 µg/mL, respectively, outperforming acarbose (71.72 µg/mL). Kinetic studies revealed competitive binding for compound 1 and uncompetitive/non-competitive binding for 3a and 3j. Fluorescence quenching showed a linear relationship between I0/I at different inhibitor concentrations. The binding sites in α-glucosidase were ≤ 1. The binding constants 3a (0.7307) > 3j (0.6563) > 1 (0.5415) displayed strong interactions. Docking study revealed binding affinities; 3j (-8.9) > 3a (-7.7) > 1 (-7), and acarbose, 1, 3a and 3j had ARG-312, PHE-157 interactions in common to α-glucosidase. The toxicity profile showed compounds fell in classes IV and V. Overall, the results indicate that compounds 1, 3a and 3j are effective against α-glucosidase.

Nesfatin-1-like peptide is a novel metabolic factor that suppresses feeding, and regulates whole-body energy homeostasis in male Wistar rats.

Nucleobindin-1 has high sequence similarity to nucleobindin-2, which encodes the anorectic and metabolic peptide, nesfatin-1. We previously reported a nesfatin-1-like peptide (NLP), anorectic in fish and insulinotropic in mice islet beta-like cells. The main objective of this research was to determine whether NLP is a metabolic regulator in male Wistar rats. A single intraperitoneal (IP) injection of NLP (100 µg/kg BW) decreased food intake and increased ambulatory movement, without causing any change in total activity or energy expenditure when compared to saline-treated rats. Continuous subcutaneous infusion of NLP (100 µg/kg BW) using osmotic mini-pumps for 7 days caused a reduction in food intake on days 3 and 4. Similarly, water intake was also reduced for two days (days 3 and 4) with the effect being observed during the dark phase. This was accompanied by an increased RER and energy expenditure. However, decreased whole-body fat oxidation, and total activity were observed during the long-term treatment (7 days). Body weight gain was not significantly different between control and NLP infused rats. The expression of mRNAs encoding adiponectin, resistin, ghrelin, cholecystokinin and uncoupling protein 1 (UCP1) were significantly upregulated, while leptin and peptide YY mRNA expression was downregulated in NLP-treated rats. These findings indicate that administration of NLP at 100 µg/kg BW reduces food intake and modulates whole body energy balance. In summary, NLP is a novel metabolic peptide in rats.

Metabolic and Cardiovascular Actions of Nesfatin-1: Implications in Health and Disease.

BACKGROUND: Metabolic homeostasis is achieved by proper functioning of a complex endocrine milieu, comprising of signals arising from the brain and peripheral tissues. Our knowledge of the factors regulating such balance is rapidly evolving, as new signaling molecules are being characterized. Of central interest is nesfatin-1, owing to its multifunctional tissue specific actions regulating food intake, body weight, blood glucose and cardiac functions. METHOD: This review discusses the tissue/system wide distribution and actions of nesfatin-1 in regulating metabolic and cardiovascular functions in healthy conditions and diseases. RESULTS: Nesfatin-1 is an 82 amino acid peptide encoded in the secreted precursor, nucleobinin-2 (NUCB2). It was first reported as a novel anorexigen and a fat reducing orphan ligand. Research to date has established nesfatin-1 in the regulation of food intake via modulation of neuropeptides in the feeding centers of brain. Nesfatin-1 expression was also reported to have a spectrum of peripheral tissue specific actions, which includes insulin secretion (pancreas), fat and glucose modulation (adipocyte), gastric motility and gastric acid secretion (stomach), hormone secretion and transit time (intestine) and mean arterial pressure and cardiac injury (heart). Abnormal levels of nesfatin-1 in circulation and/or variations in tissue specific expression have been observed in obesity, diabetes and cardiovascular diseases. CONCLUSION: The multifunctional biological actions of nesfatin-1 propelled this peptide as a therapeutic target, and as a potential biomarker of diseases. However, a better and comprehensive understanding of tissue specific effects of nesfatin-1 is critical prior to exploring its possible use in the detection and treatment of diseases.

Antidiabetic and antioxidant potency evaluation of different fractions obtained from Cucumis prophetarum fruit.

CONTEXT: Cucumis prophetarum Linn. (Cucurbitaceae) fruit is used for inflammatory-related problems and is proved to be possessing anticancer and hepatoprotective effects. OBJECTIVE: The present investigation was to study the effect of different fractions of C. prophetarum on antidiabetic and antioxidant activity. MATERIALS AND METHODS: Aqueous crude extract (CE) of C. prophetarum fruits was fractionated into water soluble fraction 1 (F1), chloroform fraction 2 (F2), basic fraction 3 (F3), and neutral fraction 4 (F4) by acid-base extraction. CE and its fractions at different doses (0.02-0.1 mg/mL) were subjected to antidiabetic (α-amylase and α-glucosidase inhibition assays) and antioxidant (DPPH, superoxide radical scavenging (SO) and metal chelation) evaluation. RESULTS: F1 exhibited effective antidiabetic activity (p < 0.05) with an IC50 value of 20.6 and 59.9 µg/mL. The activity decreased in the order of CE > F4 > F3 > F2, according to α-amylase assay, which were the same, with the exception of the rank order of F4 and CE, as the α-glucosidase assay. Furthermore, F1 (IC50 = 73 µg/mL) showed better reducing ability than CE >F4 >F2 > F3 (IC50 = 78-272 µg/mL), according to the DPPH assay. In SO and metal chelation assays, F1 showed the highest activity (IC50 = 101 and 147 µg/mL), respectively; the activity decreased in the order of CE >F4 >F3 > F2 (IC50 = 126-469 µg/mL) for SO and 194-944 µg/mL for metal chelation assay. CONCLUSION: The results indicate that F1 possesses potent in vitro antidiabetic and antioxidant activities.