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.

Oxygen-glucose deprivation (OGD) is widely used as an in vitro model for stroke. The present study aimed to explore the mechanisms of action of long non-coding RNA (lncRNA) maternally expressed gene 3 (Meg3) in angiogenesis following OGD. The human brain microvascular endothelial cell line, hCMEC/D3, was used to establish the OGD model. lncRNA Meg3 was highly expressed in hCMEC/D3 cells subjected to OGD. Furthermore, it was found that the overexpression of lncRNA Meg3 decreased the proliferation, migration and angiogenesis of hCMEC/D3 cells subjected to OGD, and increased cell apoptosis. Meg3 silencing exerted the opposite effects. Subsequently, lncRNA Meg3 increased the expression of NDRG family member 3 (NDRG3) by directly binding to miR-122-5p. The overexpression of miR-122-5p and the knockdown of NDRG3 reversed the inhibitory effects of Meg3 overexpression on the proliferation, migration and angiogenesis of hCMEC/D3 cells subjected to OGD, as well as the promoting effects of Meg3 overexpression on cell apoptosis. The present study demonstrated that lncRNA Meg3 functions as a competing endogenous RNA by targeting the miR-122-5p/NDRG3 axis in regulating OGD injury.

Vascular cognitive impairment (VCI) has emerged as the second major disease responsible for dementia, and there is still a lack of effective treatment methods for this disorder to date. Clinical medications have found that Yisui Fuyongtang (YSFYT) Decoction is effective in improving neurological signs and learning-memory functions in patients who develop white matter lesions and whole brain atrophy. To clarify the effect and molecular regulation mechanism of YSFYT Decoction on model rats, this research analyzed the influence of YSFYT Decoction on the learning-memory ability and lipid metabolism of rats based on behavioral and biochemical analysis. Further pathology and protein detection methods were adopted to investigate the action of YSFYT Decoction on the neurons in the hippocampus of model rats and the regulation of the brain derived neurotrophic factor (BDNF)-tyrosine protein kinase receptor B (TrkB) signaling pathway. Compared with the VCI group, after YSFYT Decoction administration, the ratio of swimming time in the platform, number of crossing the platform, number of active avoidance, and proportion of active avoidance of the rats were markedly increased, whereas the response latency was substantially reduced ( p < 0.05 ). Biochemical tests indicated that contents of lipoprotein lipase (LPL), triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) of the model rats in YSFYT Decoction treatment group were greatly reduced, whereas those of total antioxidant capacity (T-AOC), glutathione peroxidase (GSH-PX), catalase (CAT), malondialdehyde (MDA), and superoxide dismutase (SOD) were elevated ( p < 0.05 ). Additionally, Bcl-2 expression in YSFYT Decoction treatment group was significantly increased, but neuron apoptosis of the hippocampus tissue was reduced. Meanwhile, neuron number was apparently higher than that in VCI model group. Following Yisui Decoction treatment, expressions of growth-associated protein 43 (GAP43), synaptophysin (SYP), postsynaptic density 95 (PSD95), NMDAR subunit 2B (NR2B), BDNF, TrkB, phospho-mitogen-activated protein kinase (p-MAPK), extracellular signal-regulated kinase (ERK), phosphatidylinositol 3-kinase (PI3K), and phospho-protein kinase B (p-AKT) were markedly elevated. Taken together, YSFYT Decoction could activate the BDNF-TrkB signaling pathway, elevate Bcl-2 expression, and minimize neuronal apoptosis in hippocampus, thereby improving the behavioral characteristics and biochemical indicators of the VCI rat model.

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 expression 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 expression 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, 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, NADP, GSH and 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, GSH, NADP and G6PD, up regulating the concentration of ROS and inducing apoptosis.