Molecular docking and molecular dynamics studies of bioactive compounds contained in noni fruit (Morinda citrifolia L.) against human pancreatic α-amylase.

Human pancreatic α-amylase inhibition is currently a promising therapeutic target against type 2 diabetes (DMT2) because it can reduce aggressive digestion of carbohydrates into absorbable monosaccharides. In Indonesia, medicinal plants, e.g. Morinda citrifolia fruit, have been empirically utilized as a blood-sugar reducer, however, the inhibitory activity of compounds in this plant against human pancreatic α-amylase is still limited or none. Therefore, this study aimed to test the interaction of 7 compounds (americanin, asperulosidic acid, damnacanthal, quercetin, rutin, scopoletin, and ursolic acid) contained in noni fruit against human pancreatic α-amylase by molecular docking and molecular dynamics and compared their binding modes with that of acarbose. Results of the molecular docking simulation indicated that the ursolic acid compound possesses the best binding energy (-8.58 kcal/mol) and comparable to that of acarbose (-8.59 kcal/mol). The molecular dynamics study at 100 ns simulation, the values of RMSD, RMSF, the radius of gyration (Rg), the solvent-accessible surface area (SASA), principal component analysis (PCA), and MM-PBSA binding free energy were stable and identical to those of acarbose. It could be concluded that ursolic acid might be potential in inhibiting human pancreatic α-amylase, thus, potential to be developed as an anti-DMT2 drug candidate. Communicated by Ramaswamy H. Sarma.

Antibacterial activity and subchronic toxicity of Cassia fistula L. barks in rats.

Increasing incidence of antibiotic resistance necessitates the development of more potent antibiotics. The aim of this work was to evaluate the antibacterial activity of Cassia fistula L. barks as an alternative agent for resistant pathogenic bacteria. The C. fistula barks were extracted with ethanol, followed by partition of the extract to give n-hexane, ethyl acetate and water fractions. An in vitro antibacterial assay was conducted to evaluate inhibitory activity of the extract and fractions against Salmonella typhosa and Shigella dysenteriae. An in vivo antibacterial activity was examined using S. typhosa-infected mouse models, in which the colony number of S. typhosa were counted from the infected rats' feces. Assesment on safety of the extract was conducted by a subchronic toxicity test which mainly examined alteration occured in biochemical parameters and hystopatological conditions of livers and kidneys. The results showed that the ethanol extract inhibited the growth of both S. typhosa and S. dysenteriae with the MIC of 0.3125% w/v, and the ethyl acetate fraction with the MIC of 0.625% b/v. In the in vivo antibacterial assay, the extract at three doses decreased the colony number of S. typhosa significantly, and after the fourth to sixth days, the precentage of decrease reached more than 90% by 1000 mg/kg dose. The subchronic toxicity test revealed that after the extract exposured for 90 days, a dose of 1000 mg/kg induced liver and kidney damages histologically, however, it returned to normal condition after 30 days of recovery. The results of this study indicated that the extract of C. fistula L. barks had potent in vivo antibacterial activity against S. typhosa as sample of resistant bacteria, and is safe to be used as a herbal medicine, preferably at a dose lower than 1000 mg/kg.