Salacia Chinensis Extract (SCE) Modulates Carbohydrates and Lipid Metabolism: in vitro and in vivo Models

Abstract

Background: Salacia Chinensis (SC) is herbal medicine in Ayurvedic medicine. The extract of Salacia chinensis showed preventive effects on various metabolic health disorders. Objective: The aim of this study was to elucidate the therapeutic efficacy of the extract of Salacia chinensis extract (SCE) and modulation of carbohydrate and lipid metabolism in in vitro and in vivo models. Methods: In vitro studies were conducted to study the effect of Salacia chinensis extract (SCE, OmniLeanTM) on alpha-glucosidase, pancreatic lipase and HMG-CoA reductase. The activity of α-glucosidase was assessed using mammalian α-glucosidase extracted from rat intestinal acetone powder (Sigma) and p-nitrophenyl L-D glucopyranoside (PNPG) as an artificial substrate. Pancreatic lipase activity was assessed using pancreatic porcine lipase and 4-methylumbelliferyl oleate (MU Oleate) as substrate. Lipase activity was measured using a fluorescence kinetic assay. HMG-CoA reductase was the rate-limiting step in cholesterol synthesis. The activity of HMG-CoA reductase was assessed using HMG-CoA reductase assay kit (Sigma CS1090). Nutrigenomics study was conducted to study the effect of SCE on fatty acids, PPAR gamma and C/EBP α. In an in vivo model, fifty-six (56) male C57BL/6 mice were purchased from Charles River Labs, at the age of 5 weeks. The mice were housed individually in mouse cages in a temperature-controlled room with a 12-hour light and dark cycle and free access to regular rodent chow and water. After a week of adaptation, the mice were divided into 3 groups with 8 mice in each group. All mice were fed a high-fat diet (60% energy from fat) to induce obesity. One of the group was administered with low (100mg/kg/d) and high (500mg/kg/d) doses of SCE suspending in 0.5% carboxymethyl cellulose, respectively for 7.5 weeks (52 days). One group was used as the obese control (N=24) and gavage with the vehicle control. Body weights were obtained daily and food intake was recorded thrice every week. Body weights and food intake were recorded thrice every week. Fecal samples were collected during week 6 and 7. Serum lipid analysis, glycerol, free fatty acids, hormonal assays (ghrelin, adiponectin, leptin, insulin, glucose and GLP), fecal crude lipids and histopathology changes were assessed. Results: Salacia chinensis extract (SCE) showed a significant inhibitory effect on α-glucosidase. SCE demonstrated a significant inhibitory effect against pancreatic lipase, compared to orlistat. SCE inhibited HMG-C0A only at higher concentration (1mg/ml). In nutrigenomics model, SCE upregulated C/EBP alpha and down regulated ACC, PPARG and SCD-1. SCE at the dose of 500mg/kg/d significantly slowed body weight gain, reduced food intake, increased adiponectin, decreased fat pads mass and increased fecal fat excretion in animal model. SCE significantly decreased significantly serum glycerol levels (by 69%) and free fatty acids levels (by 77%) compared to control group. Treatment with SCE decreased by 20% leptin levels and by 21% insulin levels and increases by 16% adiponectin but did not affect glucose or GLP-1 levels. Conclusions: In vitro results suggest the effects of SCE in modulating gastrointestinal carbohydrate and lipid digestion and absorption, may be advocated as a candidate for obesity-diabetes prevention and phytotherapy. Animal study (in vivo) results suggest the inhibition of fat absorption slows weight gain and reducing effects of metabolic risk factors with SCE. More experiments need to be performed to optimize the optimal concentration that has an effect in vivo on body weight or food intake.