Identification of potential human pancreatic α-amylase inhibitors from natural products by molecular docking, MM/GBSA calculations, MD simulations, and ADMET analysis.

Human pancreatic α-amylase (HPA), which works as a catalyst for carbohydrate hydrolysis, is one of the viable targets to control type 2 diabetes. The inhibition of α-amylase lowers blood glucose levels and helps to alleviate hyperglycemia complications. Herein, we systematically screened the potential HPA inhibitors from a library of natural products by molecular modeling. The modeling encompasses molecular docking, MM/GBSA binding energy calculations, MD simulations, and ADMET analysis. This research identified newboulaside B, newboulaside A, quercetin-3-O-ß-glucoside, and sasastilboside A as the top four potential HPA inhibitors from the library of natural products, whose Glide docking scores and MM/GBSA binding energies range from -9.191 to -11.366 kcal/mol and -19.38 to -77.95 kcal/mol, respectively. Based on the simulation, among them, newboulaside B was found as the best HPA inhibitor. Throughout the simulation, with the deviation of 3Å (acarbose = 3Å), it interacted with ASP356, ASP300, ASP197, THR163, ARG161, ASP147, ALA106, and GLN63 via hydrogen bonding. Additionally, the comprehensive ADMET analysis revealed that it has good pharmacokinetic properties having not acutely toxic, moderately bioavailable, and non-inhibitor nature toward cytochrome P450. All the results suggest that newboulaside B might be a promising candidate for drug discovery against type 2 diabetes.

Protective effect of Blumea lacera DC aerial parts in indomethacin-induced enterocolitis in rats.

Traditionally Blumea lacera DC is used to treat inflammation and bowel ailments. Lack of specific, curative treatment for IBD enticed us to investigate the therapeutic efficacy of ethanolic extract of aerial parts of Blumea lacera DC (EEBL) against indomethacin-induced enterocolitis. Male Wistar rats were divided into six groups (n = 5) and different doses of EEBL (100 and 200 mg/kg, p.o) and sulphasalazine (100 mg/kg, p.o) were administered for seven days. Enterocolitis was induced by two subsequent doses of indomethacin (7.5 mg/kg, s.c) on 7th and 8th day. Treatments were continued up to 12th day and sacrificed. The protective effect was assessed on the basis of macroscopic scores of ileum strips, changes in biochemical parameters such as serum lactate dehydrogenase (LDH), tissue myeloperoxidase (MPO), lipid peroxidation (LPO), and total thiols (TT). Further, activity was ascertained by histopathological evaluations. HPLC fingerprinting profiling of EEBL was also carried out. Pre-treatment with EEBL or sulphasalazine significantly attenuated the indomethacin-induced proximal ileal damage, elevated levels of serum LDH, tissue MPO, LPO and lower levels of TT. Further, observed activity of EEBL was well correlated with histopathological alterations. The results revealed the protective action of the title plant against the indomethacin-induced enterocolitis in rats, which might be attributed by its antioxidant, anti-inflammatory, antimicrobial, and membrane-stabilizing properties.