Dietary Ginsenoside T19 Supplementation Regulates Glucose and Lipid Metabolism via AMPK and PI3K Pathways and Its Effect on Intestinal Microbiota

Abstract

Ginseng, as a functional food, is widely used worldwide because of its multifarious benefits. Studies have verified that 25-hydroxyl-protopanaxatriol (T19) is a new ginsenoside from ginseng, which had an important inhibitory effect on α-glucosidase and protein tyrosine phosphatase 1B in vitro. This study aims to assess the regulation of T19 against glycolipid metabolism by insulin-resistant HepG2 cells and diabetes mice induced with high-fat diet combined with streptozotocin (STZ). T19 effectively lowered the levels of blood glucose and lipid, alleviated insulin resistance, and improved histological pathology of liver and pancreas. Further study demonstrated that regulation of AMP-activated protein kinase-and phosphoinositide-3-kinase-signaling pathways was involved in the potential mechanism of T19 efficiency. Simultaneously, high-throughput sequencing of 16S rDNA revealed that T19 remarkably ameliorated the high-fat diet/STZ-induced disorders of intestinal microbiota by decreasing the value of Firmicutes/ Bacteroidetes, and remarkably raised the relative abundance of the Lachnospiraceae family, which are the beneficial bacteria that can regulate glucose and lipid metabolism. The results may provide clues for further understanding the mechanism of T19 in regulating glycolipid metabolism, and may provide a scientific basis for ginseng as a potential dietary food to prevent metabolic diseases.

Antidiabetic Function of Lactobacillus fermentum MF423-Fermented Rice Bran and Its Effect on Gut Microbiota Structure in Type 2 Diabetic Mice

“…Glucose consumption was detected in HepG2 cells treated with PA and OA to verify whether FLRB could improve insulin resistance. The IR-HepG2 cell model was developed following the above method ( Xu et al, 2020 ). As shown in Figure 1B , the glucose consumption of cells treated with DMEM containing PA (0.15 μM) and OA (0.2 μM) was significantly lower than that of cells treated with normal DMEM, indicating that coincubation with PA and OA could induce insulin resistance in HepG2 cells.…”

“…To investigate the effect of FLRB on glucose and lipid metabolism, an insulin resistant (IR) HepG2 cell model was established according to a method with slight modifications ( Xu et al, 2020 ). Briefly, HepG2 cells were seeded in 96-well plates (3 × 10 3 cells per well) and cultured at 37°C for 24 h. Then, IR cells were induced with PA (0.15 μM) plus OA (0.20 μM) in serum-free and phenol red-free medium for 12 h. FLRB was dissolved in sterile water and diluted to various concentrations at 25, 50 and 100 μg/mL with DMEM and added to IR cells for 24 h. The concentration of RB was 100 μg/mL, and non-treated cells were used as a blank control.…”

Strategies for Remodeling the Tumor Microenvironment Using Active Ingredients of Ginseng—A Promising Approach for Cancer Therapy

“…In accordance with these concepts, previous studies indicated that the efficacy of oral ginseng was related to gut microbiome-mediated metabolic transformation involving two types of ginsenoside biotransformation: conversion of protopanaxadiol-type ginsenosides to form compound K and ginsenoside Rh2; conversion of protopanaxatriol-type ginsenosides to form ginsenosides Rh1 and protopanaxatriol ( Kim, 2018 ). Interestingly, ginsenosides and ginseng polysaccharides have also been used to regulate the structure of the gut microbiome for treating a variety of diseases, such as obesity ( Song et al, 2014 ; Lee et al, 2021 ), diabetes ( Li J. et al, 2018 ; Xu et al, 2020 ), colitis ( Wang et al, 2016 ; Chen L. et al, 2020 ), and antibiotic-related diarrhea ( Qu et al, 2021 ). With regard to cancer, a recent study showed that oral ginseng polysaccharides combined with anti-PD-1-mAb could improve therapeutic sensitivity of anti-PD-1-mAb in patients with NSCLC.…”

Gut Microbiota: Therapeutic Targets of Ginseng Against Multiple Disorders and Ginsenoside Transformation

“…Current results have confirmed that ginseng plays a role in improving blood glucose level and insulin sensitivity in patients with T2DM ( Gui et al., 2016 ). It proved that the treatment with ginsenoside T19 in C57BL/6 mice model induced by high-fat diet combined with streptozotocin could exert therapeutic effect for treating T2DM by reducing the relative abundance of pathogenic bacteria such as Coprobacillus and decreasing the ratio of Firmicutes and Bacteroidetes , as well as enhancing the relative abundance of probiotics such as Bacteroidetes ( Xu et al., 2020 ). Ginsenoside Rg5 can also reverse the disordered gut microbiota, alleviate metabolic endotoxemia, repair intestinal barrier, inhibit nuclear factor kappaB (NF-κB) and other related inflammatory pathways to improve T2DM of Db/Db mice ( Wei et al., 2020 ).…”