Understanding the Anti-Diarrhoeal Properties of Incomptines A and B: Antibacterial Activity against Vibrio cholerae and Its Enterotoxin Inhibition.

Incomptines A (IA) and B (IB) are two sesquiterpene lactones with antiprotozoal, antibacterial, cytotoxic, antitumor, spermicidal, and phytotoxic properties. The antibacterial activity of IA and IB against bacteria causing diarrhoea have been reported; however, no information is available regarding their antibacterial activity on Vibrio cholerae. In this work, both compounds were evaluated for their anti-diarrhoeal potential using the bacterium V. cholerae, sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) analysis on cholera toxin, and a cholera toxin-induced diarrhoea model in male Balb/c mice. In addition, a molecular docking study was carried out to understand the interaction of IA and IB with cholera toxin. In terms of antibacterial activity, IB was three times more active than IA on V. cholerae. In the case of SDS-PAGE analysis and the in silico study, IA was most effective, revealing its potential binding mode at a molecular level. In terms of anti-diarrhoeal activity, IA was 10 times more active than IB and racecadotril, an antisecretory drug used as positive control; the anti-diarrheal activity of IB was also closer than racecadotril. The results obtained from in vitro, in vivo, and computational studies on V. cholerae and cholera toxin support the potential of IA and IB as new anti-diarrhoeal compounds.

Antihyperglycemic and Lipid Profile Effects of Salvia amarissima Ortega on Streptozocin-Induced Type 2 Diabetic Mice.

Salvia amarissima Ortega was evaluated to determinate its antihyperglycemic and lipid profile properties. Petroleum ether extract of fresh aerial parts of S. amarissima (PEfAPSa) and a secondary fraction (F6Sa) were evaluated to determine their antihyperglycemic activity in streptozo-cin-induced diabetic (STID) mice, in oral tolerance tests of sucrose, starch, and glucose (OSTT, OStTT, and OGTT, respectively), in terms of glycated hemoglobin (HbA1c), triglycerides (TG), and high-density lipoprotein (HDL). In acute assays at doses of 50 mg/kg body weight (b.w.), PEfAPSa and F6Sa showed a reduction in hyperglycemia in STID mice, at the first and fifth hour after of treatment, respectively, and were comparable with acarbose. In the sub-chronic test, PEfAPSa and F6Sa showed a reduction of glycemia since the first week, and the effect was greater than that of the acarbose control group. In relation to HbA1c, the treatments prevented the increase in HbA1c. In the case of TG and HDL, PEfAPSa and F6Sa showed a reduction in TG and an HDL increase from the second week. OSTT and OStTT showed that PEfAPSa and F6Sa significantly lowered the postprandial peak at 1 h after loading but only in sucrose or starch such as acarbose. The results suggest that S. amarissima activity may be mediated by the inhibition of disaccharide hydrolysis, which may be associated with an α-glucosidase inhibitory effect.

Antihyperglycemic Activity of the Leaves from Annona cherimola Miller and Rutin on Alloxan-induced Diabetic Rats.

BACKGROUND: Annona cherimola, known as "chirimoya" has been reported in Mexican traditional medicine for the treatment of diabetes. OBJECTIVE: The aims of the present study were to validate and assess the traditional use of A. cherimola as an antidiabetic agent. MATERIALS AND METHODS: The ethanol extract from A. cherimola (300 mg/kg, EEAc), subsequent fractions (100 mg/kg), and rutin (30 mg/kg) were studied on alloxan-induced type 2 diabetic (AITD) and normoglycemic rats. In addition, oral glucose tolerance test (OGTT) and oral sucrose tolerance test (OSTT) were performed in normoglycemic rats. Molecular docking technique was used to conduct the computational study. RESULTS: Bioassay-guided fractionation of EEAc afforded as major antihyperglycemic compound, rutin. EEAc attenuated postprandial hyperglycemia in acute test using AITD rats (331.5 mg/dL) carrying the glycemic levels to 149.2 mg/dL. Rutin after 2 h, attenuated postprandial hyperglycemia in an acute assay using AITD rats such as EEAc, with maximum effect (150.0 mg/dL) being seen at 4 h. The antihyperglycemic activities of EEAc and rutin were comparable with acarbose (151.3 mg/dL). In the subchronic assay on AITD rats, the EEAc and rutin showed a reduction of the blood glucose levels since the 1st week of treatment, reaching levels similar to normoglycemic state (116.9 mg/kg) that stayed constant for the rest of the assay. OGTT and OSTT showed that EEAc and rutin significantly lowered blood glucose levels in normoglycemic rats at 2 h after a glucose or sucrose load such as acarbose. Computational molecular docking showed that rutin interacted with four amino acids residues in the enzyme α-glucosidase. CONCLUSION: The results suggest that rutin an α-glucosidase inhibitor was responsible in part of the antihyperglycemic activity of A. cherimola. Its in vivo antihyperglycemic activity is in good agreement with the traditional use of A. cherimola for the treatment of diabetes. SUMMARY: The ethanol extract from Annona cherimola (300 mg/kg, EEAc), subsequent fractions (100 mg/kg) and rutin (30 mg/kg) were studied on alloxan-induced type 2 diabetic (AITD) and normoglycemic rats. The results suggest that rutin; an α-glucosidase inhibitor was responsible in part of the antihyperglycemic activity of A. cherimola. Its in vivo antihyperglycemic activity is in good agreement with the traditional use of A. cherimola for the treatment of diabetes. Abbreviations Used: EEAc: The ethanol extract from Annona cherimola, AITD: Alloxan-induced type 2 diabetic rats, OGTT: Oral glucose tolerance test, OSTT: Oral sucrose tolerance test, DM: Diabetes mellitus.