Ginsenoside Rg3 induces apoptosis and inhibits proliferation by down-regulating TIGAR in rats with gastric precancerous lesions

Abstract

Background Ginsenoside Rg3 (GRg3) is one of the main active ingredients in Chinese ginseng extract and has various biological effects, such as immune-enhancing, antitumour, antiangiogenic, immunomodulatory and anti-inflammatory effects. This study aimed to investigate the therapeutic effect of GRg3 on gastric precancerous lesion (GPL) induced by N-methyl-N′-nitro-N-nitrosoguanidine (MNNG) and the potential mechanism of action. Methods The MNNG–ammonia composite modelling method was used to establish a rat model of GPL. Histopathological changes in the rat gastric mucosa were observed by pathological analysis using haematoxylin–eosin staining to assess the success rate of the composite modelling method. Alcian blue–periodic acid Schiff staining was used to observe intestinal metaplasia in the rat gastric mucosa. Apoptosis was detected in rat gastric mucosal cells by terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling staining. The production level of reactive oxygen species (ROS) was determined by the dihydroethidium fluorescent probe method, and that of TP53-induced glycolysis and apoptosis regulator (TIGAR) protein was determined by immunohistochemical staining and western blotting. The production levels of nicotinamide adenine dinucleotide phosphate (NADP) and glucose-6-phosphate dehydrogenase (G6PDH) were determined by an enzyme-linked immunosorbent assay, and that of glutathione (GSH) was determined by microanalysis. Results GRg3 significantly alleviated the structural disorganization and cellular heteromorphism in the form of epithelial glands in the gastric mucosa of rats with GPL and retarded the progression of the disease. Overexpression of TIGAR and overproduction of NADP, GSH and G6PDH occurred in the gastric mucosal epithelium of rats with GPL, which in turn led to an increase in the ROS concentration. After treatment with GRg3, the expression of TIGAR and production of NADP, GSH G6PDH decreased, causing a further increase in the concentration of ROS in the gastric mucosal epithelium, which in turn induced apoptosis and played a role in inhibiting the abnormal proliferation and differentiation of gastric mucosal epithelial cells. Conclusion Grg3 can induce apoptosis and inhibit cell proliferation in MNNG-induced GPL rats. The mechanism may be related to down-regulating the expression levels of TIGAR and production levels of GSH, NADP and G6PD, and up-regulating the concentration of ROS.

The effect of phytochemicals in N-methyl-N-nitro-N-nitroguanidine promoting the occurrence and development of gastric cancer

“…Verification through experiments found that Erianin, the main active ingredients of Dendrobium officinale, could significantly induce cell apoptosis triggered by MNNNG in a dose-dependent manner through the HRAS-PI3K-AKT pathway ( Wang et al, 2021 ). Lv et al (2022) found that Ginsenoside Rg3 could suppress TIGAR and induce cell apoptosis in MNNG induced gastric precancerous lesion rats. Nariman et al reported that MGN-3/biological bran exerts chemopreventive effects on gastric carcinogenesis in rats by regulating gastric cancer cell apoptosis ( Badr El-Din et al, 2016 ).…”

“…Ginsenoside Rg3 is one of the most effective active ingredients in ginseng extract, with a variety of biological effects. Lv et al (2022) reported that Ginsenoside Rg3 could inhibit cell proliferation in MNNG induced gastric precancerous lesion rats. They found that after GRg3 treatment, the expression of TIGAR and the production of NADP, GSH G6PDH decreased, leading to the increase of ROS in the gastric mucosal epithelium, thereby inhibiting abnormal proliferation of gastric mucosal epithelial cells.…”

Gastric Mucosa Pathology in Rats with Precancerous Lesions of Gastric Cancer with Spleen Deficiency and Blood Stasis

“…Atrophic gastritis with IM and/or Dys is referred to as precancerous lesions of GC (PLGC) because of its high risk of cancer [ 5 , 6 ]. Blocking or delaying PLGC progression has been proven to be an effective way to prevent GC [ 7 ]. Traditional Chinese medicine states that if the spleen is weak, food is not digested.…”

Correction: Ginsenoside Rg3 induces apoptosis and inhibits proliferation by down-regulating TIGAR in rats with gastric precancerous lesions

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Following publication of the original article [1], the authors identified an error in Figs. 3 and 5.

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