Hypoglycemic Activity of Rice Resistant-Starch Metabolites: A Mechanistic Network Pharmacology and In Vitro Approach.

Rice (Oryza sativa L.) is one of the primary sources of energy and nutrients needed by the body, and rice resistant starch (RRS) has been found to have hypoglycemic effects. However, its biological activity and specific mechanisms still need to be further elucidated. In the present study, 52 RRS differential metabolites were obtained from mouse liver, rat serum, canine feces, and human urine, and 246 potential targets were identified through a literature review and database analysis. A total of 151 common targets were identified by intersecting them with the targets of type 2 diabetes mellitus (T2DM). After network pharmacology analysis, 11 core metabolites were identified, including linolenic acid, chenodeoxycholic acid, ursodeoxycholic acid, deoxycholic acid, lithocholic acid, lithocholylglycine, glycoursodeoxycholic acid, phenylalanine, norepinephrine, cholic acid, and L-glutamic acid, and 16 core targets were identified, including MAPK3, MAPK1, EGFR, ESR1, PRKCA, FYN, LCK, DLG4, ITGB1, IL6, PTPN11, RARA, NR3C1, PTPN6, PPARA, and ITGAV. The core pathways included the neuroactive ligand-receptor interaction, cancer, and arachidonic acid metabolism pathways. The molecular docking results showed that bile acids such as glycoursodeoxycholic acid, chenodeoxycholic acid, ursodeoxycholic acid, lithocholic acid, deoxycholic acid, and cholic acid exhibited strong docking effects with EGFR, ITGAV, ITGB1, MAPK3, NR3C1, α-glucosidase, and α-amylase. In vitro hypoglycemic experiments further suggested that bile acids showed significant inhibitory effects on α-glucosidase and α-amylase, with CDCA and UDCA having the most prominent inhibitory effect. In summary, this study reveals a possible hypoglycemic pathway of RRS metabolites and provides new research perspectives to further explore the therapeutic mechanism of bile acids in T2DM.

Studies on the Changes of Fermentation Metabolites and the Protective Effect of Fermented Edible Grass on Stress Injury Induced by Acetaminophen in HepG2 Cells.

In this study, gas chromatography-mass spectrometry (GC-MS) based untargeted metabolomics was used to describe the changes of metabolites in edible grass with Lactobacillus plantarum (Lp) fermentation durations of 0 and 7 days, and subsequently to investigate the protective effect of fermented edible grass on acetaminophen-induced stress injury in HepG2 cells. Results showed that 53 differential metabolites were identified, including 31 significantly increased and 22 significantly decreased metabolites in fermented edible grass. Fermented edible grass protected HepG2 cells against acetaminophen-induced stress injury, which profited from the reduction in lactate dehydrogenase (LDH) and malondialdehyde (MDA) levels and the enhancement in superoxide dismutase (SOD) activity. Cell metabolomics analysis revealed that a total of 13 intracellular and 20 extracellular differential metabolites were detected. Fermented edible grass could regulate multiple cell metabolic pathways to exhibit protective effects on HepG2 cells. These findings provided theoretical guidance for the formation and regulation of bioactive metabolites in fermented edible grass and preliminarily confirmed the protective effects of fermented edible grass on drug-induced liver damage.