Basic Medical College, Chengdu University of Traditional Chinese Medicine, Chengdu, China.
Department of Gastrointestinal Surgery, Sichuan Cancer Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China.
BMC Complement Med Ther. 2022 Jul 15;22(1):188. doi: 10.1186/s12906-022-03669-z.
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.
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.
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.
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.
人参皂苷 Rg3（GRg3）是人参提取物中的主要活性成分之一，具有多种生物学效应，如增强免疫、抗肿瘤、抗血管生成、免疫调节和抗炎作用。本研究旨在探讨 GRg3 对 N-甲基-N'-硝基-N-亚硝基胍（MNNG）诱导的胃癌前病变（GPL）的治疗作用及其潜在作用机制。
采用 MNNG-氨复合建模法建立大鼠 GPL 模型。通过苏木精-伊红染色的病理分析观察大鼠胃黏膜的组织学变化，评估复合建模方法的成功率。采用阿尔辛蓝-过碘酸希夫染色观察大鼠胃黏膜的肠上皮化生。采用末端脱氧核苷酸转移酶介导的 dUTP 缺口末端标记染色检测大鼠胃黏膜细胞的凋亡。通过二氢乙啶荧光探针法测定活性氧（ROS）的产生水平，免疫组织化学染色和 Western blot 法测定 TP53 诱导的糖酵解和凋亡调节因子（TIGAR）蛋白的产生水平。通过酶联免疫吸附试验测定烟酰胺腺嘌呤二核苷酸磷酸（NADP）和葡萄糖-6-磷酸脱氢酶（G6PDH）的产生水平，通过微分析测定谷胱甘肽（GSH）的产生水平。
GRg3 显著缓解了 GPL 大鼠胃黏膜上皮腺体结构紊乱和细胞异型性，并延缓了疾病的进展。GPL 大鼠胃黏膜上皮中 TIGAR 过度表达，NADP、GSH 和 G6PDH 过度产生，导致 ROS 浓度升高。GRg3 治疗后，TIGAR 表达降低，NADP、GSH、G6PDH 产生减少，导致胃黏膜上皮 ROS 浓度进一步升高，进而诱导凋亡，抑制胃黏膜上皮细胞异常增殖和分化。
GRg3 可诱导 MNNG 诱导的 GPL 大鼠细胞凋亡，抑制细胞增殖。其机制可能与下调 TIGAR 的表达水平和 GSH、NADP 和 G6PD 的产生水平，上调 ROS 浓度有关。
