Effect Of Ginsenoside Rh1 Research Articles

Mechanism of Ginsenoside Rh1 in Regulating Breast Cancer Cell Extravasation Based on CCL20-CCR6

Objective: To explore the regulatory mechanism of ginsenoside Rh1 on breast cancer cell extravasation based on CCL20-CCR6. Methods: In 2021, a total of 34 patients with breast cancer were treated in Baoding First Central Hospital. During hospitalization, pathological examinations were performed, and all the patients were diagnosed with invasive ductal carcinoma. Out of the 34 cases, 16 cases were found to have CCR6 expression in breast cancer tissues, in which they were recorded as the CCR6 expression group, whereas 18 cases did not have CCR6 expression; these cases were recorded as the CCR6 non-expression group. During the same period, 21 normal patients were selected as the control group. The peripheral blood CCL20 level and the expression of CCR6 on the surface of CD3+ T lymphocytes were analyzed. The extracts of cancer cells were collected, purified, and cultured, and the effect of ginsenoside Rh1 on the invasion and metastasis of breast cancer cells was analyzed. Results: The peripheral blood CCL20 level in the CCR6 expression group was significantly higher than that in the CCR6 non-expression group and the control group, in which p < 0.05, indicating that the difference was statistically significant; at 12, 24, and 48 hours, the cell survival rate of each dose group was significantly higher than that of the blank control group and the dimethyl sulfoxide (DMSO) group (p < 0.05). At 48 hours, comparing the low-dose group with the high-dose group, the cell survival rate significantly decreased (p < 0.05). Compared with the blank control group and DMSO group, the invasion ability of breast cancer cells could be reduced in both, high- and medium-dose groups, where p < 0.05, indicating that the difference was statistically significant. Conclusion: CCL20 may play a role in the pathogenesis of certain breast cancers, and ginsenoside Rh1 can effectively regulate the invasion and migration of breast cancer cells.

Effect of Ginsenoside Rh1 on Proliferation, Apoptosis, and Oxidative Stress in Vascular Endothelial Cells by Regulation of the Nuclear Erythroid 2-related Factor-2/Heme Oxygenase-1 Signaling Pathway.

:This study aimed to investigate the role of ginsenoside Rh1 in regulating the proliferation, apoptosis, and oxidative stress in oxidized low-density lipoprotein (ox-LDL)-treated human vascular endothelial cells (VECs) and the underlying mechanisms. VECs were treated with ox-LDL to generate an in vitro atherosclerosis model. The effect of ginsenoside Rh1 on cell viability and proliferation was examined by MTT and colony formation assays, respectively, and cell apoptosis was determined by flow cytometry and transferase dUTP nick end-labeling assay. The levels of reactive oxygen species, malondialdehyde, and superoxide dismutase activity were detected using biological assays. Finally, the effect of ginsenoside Rh1 on the levels of BAX and BCL-2 and the nuclear erythroid 2-related factor-2/heme oxygenase (HO)-1 signaling pathway was determined by quantitative real-time polymerase chain reaction and western blot assays. Treatment with ginsenoside Rh1 significantly increased the proliferation and decreased the apoptosis of ox-LDL–treated VECs in a dose-dependent manner. Moreover, ginsenoside Rh1 also relieved oxidative stress in ox-LDL–treated VECs by activating the Nrf2/HO-1 signaling pathway. Thus, ginsenoside Rh1 affects the proliferation, apoptosis, and oxidative stress in ox-LDL–treated VECs by activating the Nrf2/HO-1 signaling pathway.

Ginsenoside Rh1 Induces MCF-7 Cell Apoptosis and Autophagic Cell Death through ROS-Mediated Akt Signaling.

Simple SummaryBreast cancer (BC) is the most common cause of cancer-related deaths among women worldwide, and its incidence has been increasing. However, current therapeutic approaches, such as chemotherapy, radiation, and hormonal therapy, have become increasingly ineffective because of their severe adverse effects and multidrug resistance. Therefore, the discovery of new potential candidates for BC therapy is essential. Here, we investigated whether ginsenoside Rh1 exhibits anticancer effects on BC. We found that this ginsenoside effectively inhibited the growth of BC cells in both cell cultures and mice. Therefore, ginsenoside Rh1 is a promising candidate for BC treatment.Breast cancer (BC) is the leading cause of cancer-related deaths among women worldwide. Ginsenosides exhibit anticancer activity against various cancer cells. However, the effects of ginsenoside Rh1 on BC and the underlying mechanisms remain unknown. Here, we investigated the anticancer effects of Rh1 on human BC MCF-7 and HCC1428 cells and the underlying signaling pathways. The anticancer effects of Rh1 in vitro were evaluated using sulforhodamine B (SRB), 3-(4, 5-dimethylthiazole-2-yl)-2, 5-diphenyltetrazolium bromide (MTT), clonogenic assay, propidium iodide (PI)/Hoechst staining, Western blotting, flow cytometry, and immunofluorescence analysis. The in vivo effects of Rh1 were determined using a xenograft model via hematoxylin and eosin and the immunohistochemistry staining of tumor tissues. We found that Rh1 exerted cytotoxicity in the cells by increasing cell apoptosis, autophagy, and cell cycle arrest. These effects were further enhanced by a phosphatidylinositol 3-kinase (PI3K) inhibitor but were rescued by the inhibition of reactive oxygen species (ROS). Moreover, enhanced ROS generation by Rh1 inhibited the activation of the PI3K/Akt pathway. Consistently, Rh1 treatment significantly reduced tumor growth in vivo and increased the ROS production and protein expression of LC3B and cleaved caspase-3 but decreased the phosphorylation of Akt and retinoblastoma (Rb) in tumor tissues. Taken together, Rh1 exerted a potential anticancer effect on BC cells by inducing cell cycle arrest, apoptosis, and autophagy via inhibition of the ROS-mediated PI3K/Akt pathway.

Ginsenoside Rh1 induces mouse osteoblast growth and differentiation through the bone morphogenetic protein 2/runt-related gene 2 signalling pathway.

This study aimed to investigate the stimulative and pharmacological effects of ginsenoside Rh1 (hereinafter referred to as: Rh1) on differentiation and mineralization of osteoblast and its possible mechanism of action on the expression of bone morphogenetic protein 2 (BMP-2)/Runt-related gene 2 (Runx2) signalling pathways using mouse preosteoblastic MC3T3-E1 cell line as in-vitro model. An in-vitro stimulative activity of Rh1 was assessed by analyzing alkaline phosphatase activity (ALP), type-I collagen (Coll-I) synthesis, mineralization and glutathione content. Its antioxidant activity was measured by evaluating the reactive oxygen species (ROS) production in the presence of antimycin A (AMA), one of the mitochondrial dysfunction factors. The level of BMP-2/Runx2 signal-regulated osteoblast-specific proteins such as osteocalcin (OCN), Coll-I and ALP were detected using Western blot analysis. Rh1 was capable to stimulate cell growth, ALP activity, Coll-I synthesis, mineralization and glutathione content in the MC3T3-E1 cells. BMP-2 and Runx2 expression were also increased by Rh1 concentration dependently. Additionally, Rh1 also showed inhibitory action on the level of ROS production enhanced by AMA in MC3T3-E1 cells. Rh1 could increase the expression level of BMP-2/Runx2 signal-regulated osteogenic markers such as ALP, Coll-I and OCN. Rh1, a protopanaxatriol type's active ingredients of Panax ginseng Meyer, possesses osteoblast differentiation, osteogenic stimulatory and anti-oxidative activity.

Ginsenoside-Rh1 and Rh2 inhibit the induction of nitric oxide synthesis in murine peritoneal macrophages.

The effects of ginsenoside-Rh1 and Rh2 in the induction of nitric oxide (NO) synthesis by IFN-gamma plus LPS were investigated using murine peritoneal macrophages. The NO production from rIFN gamma plus LPS-treated macrophages was markedly reduced by ginsenoside-Rh1 or Rh2 in a dose dependent manner, but had no inhibitory effects by ginsenoside-Rb1, Rc or Re. In addition, treatment of the cells with ginsenoside-Rh2 6 hr before the stimulation with IFN-gamma plus LPS showed more inhibitory effect than the treatment with ginsenoside-Rh2 6 hr after or simultaneously with the stimulation with IFN-gamma plus LPS in the NO production. Ginsenoside-Rh2 also effectively inhibited IFN-gamma induced NO production when the cells were treated with IFN-gamma 6 hr after the treatment with ginsenoside-Rh2. Our findings suggest that this phenomenon might be caused by inhibition of priming signal such as IFN-gamma for the synergistic induction of NO synthesis.