Search

Background: Ginsenoside Rh2 (GRh2) is the main bioactive component in American ginseng, a commonly used herb, and its antitumor activity had been studied in previous studies. PDZ-binding kinase/T-LAK cell-originated protein kinase (PBK/TOPK), a serine/threonine protein kinase, is highly expressed in HCT116 colorectal cancer cells. Methods: We examined the effect of GRh2 on HCT116 cells ex vivo. Next, we performed in vitro binding assay and in vitro kinase assay to search for the target of GRh2. Furthermore, we elucidated the underlying molecular mechanisms for the antitumor effect of GRh2 ex vivo and in vivo. Results: The results of our in vitro studies indicated that GRh2 can directly bind with PBK/TOPK and GRh2 also can directly inhibit PBK/TOPK activity. Ex vivo studies showed that GRh2 significantly induced cell death in HCT116 colorectal cancer cells. Further mechanistic study demonstrated that these compounds inhibited the phosphorylation levels of the extracellular regulated protein kinases 1/2 (ERK1/2) and (H3) in HCT116 colorectal cancer cells. In vivo studies showed GRh2 inhibited the growth of xenograft tumors of HCT116 cells and inhibited the phosphorylation levels of the extracellular regulated protein kinases 1/2 and histone H3. Conclusion: The results indicate that GRh2 exerts promising antitumor effect that is specific to human HCT116 colorectal cancer cells through inhibiting the activity of PBK/TOPK.

Ginsenoside Rh2, an intermediate metabolite of ginseng, but not naturally occurring, has recently drawn attention because of its anticancer effect. However, it is not clear if and how Rh2 inhibits preadipocytes differentiation. In the present study, we hypothesized that ginsenoside Rh2 attenuates adipogenesis through regulating the peroxisome proliferator-activated receptor gamma (PPAR-γ) pathway both in cells and obese mice. Different concentrations of Rh2 were applied both in 3T3-L1 cells and human primary preadipocytes to determine if Rh2 inhibits cell differentiation. Dietary Rh2 was administered to obese mice to determine if Rh2 prevents obesity in vivo. The mRNA and protein expression of PPAR-γ pathway molecules in cells and tissues were measured by real-time polymerase chain reaction (RT-PCR) and Western blot, respectively. Our results show that Rh2 dose-dependently (30–60 μM) inhibited cell differentiation in 3T3-L1 cells (44.5% ± 7.8% of control at 60 μM). This inhibitory effect is accompanied by the attenuation of the protein and/or mRNA expression of adipogenic markers including PPAR-γ and CCAAT/enhancer binding protein alpha, fatty acid synthase, fatty acid binding protein 4, and perilipin significantly (p < 0.05). Moreover, Rh2 significantly (p < 0.05) inhibited differentiation in human primary preadipocytes at much lower concentrations (5–15 μM). Furthermore, dietary intake of Rh2 (0.1 g Rh2/kg diet, w/w for eight weeks) significantly (p < 0.05) reduced protein PPAR-γ expression in liver and hepatic glutathione reductase and lowered fasting blood glucose. These results suggest that ginsenoside Rh2 dose-dependently inhibits adipogenesis through down-regulating the PPAR-γ pathway, and Rh2 may be a potential agent in preventing obesity in vivo.

Panax ginseng is widely used as a functional food in Asia because of its bioactivities. Here, we report that ginsenoside Rh2, an extract of red Panax ginseng, suppressed growth of uterine leiomyomas (ULs) in a rat model and decreased serum hormone levels in a dose-dependent manner. Rh2 also inhibited the growth of cultured human UL cells in vitro. After Rh2 treatment, cells showed morphological changes that were consistent with apoptosis. Using ELISA, real-time RT-PCR, and Western blot methods, we found that Rh2 significantly reduced the activity of oestrogen receptor alpha (ERα) and c-Src, increased p38 MAPK activity, and reversed ERα activity mediated by PP2 and SB203580, specific inhibitors of c-Src and p38 MAPK, respectively, in UL cells. These findings provide a novel mechanism for the anti-proliferative efficacy of Rh2 that likely involves regulating ERα/Src/p38 MAPK activity.

Background: Acute myocardial infarction (AMI) is one of the most important causes of mortality among patients with cardiovascular disease. Ginsenoside Rh2 plays a protective role in cardiovascular diseases. Furthermore, pyroptosis reportedly participates in regulating the occurrence and development of AMI. However, whether ginsenoside Rh2 contributes to mitigating AMI by regulating cardiomyocyte pyroptosis remains unknown., Methods: In the present study, we established an AMI model in rats. Next, we determined the effects of ginsenoside Rh2 on AMI by examining the myocardial infarct area, while regulation of myocardial pyroptosis was determined by assessing related factors. We established a cardiomyocyte model using hypoxia/reoxygenation (H/R) treatment. The expression of pyroptosis-related factors was determined following ginsenoside Rh2 treatment. In addition, we evaluated the correlation between ginsenoside Rh2 and the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) pathway at the mechanistic level., Results: Herein, we observed that ginsenoside Rh2 alleviated AMI in rats and cells. Notably, the expression levels of inflammatory factors were reduced in AMI rats and cells. Furthermore, AMI rats and cells exhibited high expression levels of cleaved caspase-1 and gasdermin D, which were downregulated following treatment with ginsenoside Rh2. Further analysis revealed that ginsenoside Rh2 could inhibit cardiomyocyte pyroptosis by regulating the PI3K/AKT signaling pathway., Conclusions: Collectively, the findings of the present study demonstrated that ginsenoside Rh2 regulates pyroptosis in cardiomyocytes to alleviate AMI in vivo and in vitro , thereby affording a novel therapeutic approach to treat AMI.

Highlights • Novel nanodelivery systems for a sinsititve drug, ginsenoside Rh2, were synthesized. • The designed systems were characterized by TEM, FTIR, and Raman. • The effects of nanosystems on RBCs, blood coagulation and cardiovascular tissue were investigated. • The nanosystems enhanced anticancer potency of ginsenoside Rh2 and its side effects. Abstract In this study, blood- and cardio-toxicity of Rh2–treated graphene oxide (GO-Rh2), lysine-treated graphene oxide (GO-Lys), arginine-treated GO (GO-Arg), Rh2–treated GO-Lys (GO-Lys-Rh2) and Rh2–treated GO-Arg (GO-Arg-Rh2) were evaluated. Two concentrations of each nanostructures (200 and 1000 µg/ml) was injected to rats. After 2 weeks, the effects of agents were evaluated on heart tissue by histopathological assays. Cytotoxicity of all designed nanostructures was investigated on blood cancer cells (K562) by MTT assay. Toxicity of designed nanostructures was also investigated on Red Blood Cells (RBCs), Prothrombin Time (PT) and Partial Thromboplastin Time (PTT). The results demonstrated increase of anticancer activity for GO-Arg-Rh2 and GO-Lys-Rh2 in comparison with free Rh2 and GO. GO, GO-Rh2, GO-Lys, GO-Arg, GO-Lys-Rh2, and GO-Arg-Rh2 had 50% hemolysis at concentrations 250, 360, 420, 435, 500, and 575 µg/ml, respectively. GO led to RBCs aggregation and morphological change at 5–100 µg/ml, but other functionalized nanostructures did not show these changes. All nanostructures had slight effect on intrinsic and extrinsic coagulation system, especially on PTT. GO-Arg-Rh2 and GO-Lys-Rh2 had lower effect on blood coagulation system in comparison with other examined nanosystems. Besides, GO-Rh2, GO-Arg-Rh2, and GO-Lys-Rh2 had lowest toxicity on heart tissue than other synthesized nanostructures. Functionalization of GO with Arg, Lys, and especially, Rh2 led to decrease the destruction of heart tissue. So, modified GO with Rh2 and basic amino acids may be a potential and promising strategy to enhance the therapeutic index for GO because of the reduction of side effects on normal cells. Graphical abstract Image, graphical abstract [ABSTRACT FROM AUTHOR]

Liver cancer is one of the leading causes of malignancy‑associated mortality worldwide and its clinical therapy remains very challenging. Ginsenoside Rh2 (Rh2) has been reported to have antitumor effects on some types of cancer, including liver cancer. However, its regulatory mechanism has not been extensively evaluated. In the present study, Rh2 increased the expression of microRNA (miR)‑200b‑5p, miR‑224‑3p and miR‑146a‑5p, and decreased the expression of miR‑26b‑3p and miR‑29a‑5p. Of the three upregulated miRs, miR‑146a‑5p exhibited the highest fold elevation. In accordance with a previous study, Rh2 effectively inhibited the survival of liver cancer cells in vitro and in a mouse model. In addition, it was observed that Rh2 markedly promoted liver cancer apoptosis and inhibited colony formation. Cell apoptosis and the inhibition of cell survival as well as colony formation induced by Rh2 were enhanced and weakened by miR‑146a‑5p overexpression and inhibition, respectively. The results of the present study provide further evidence of the antitumor effect of Rh2 in liver cancer and also demonstrate that this effect may be mediated via the regulation of miR‑146a‑5p expression in the liver cancer cell line HepG2. The results indicated that miR‑146a‑5p may be a promising regulatory factor in Rh2‑mediated effects in liver cancer. [ABSTRACT FROM AUTHOR]

Sleep deprivation (SD) negatively caused cognitive deficit, which was associated with oxidative stress induced damage. Ginsenoside Rh2 had the ability to protect against damage caused by reactive oxygen species in vitro , showing antioxidant property. Therefore, it was hypothesized that Ginsenoside Rh2 could prevent SD-induced cognitive deficit via its antioxidant properties. In this study, the effect of Ginsenoside Rh2 on memory impairment induced by sleep deprivation was investigated. The mice were sleep deprived continuously for 14 days using our self-made Sleep Interruption Apparatus (SIA). Ginsenoside Rh2 was administered intraperitoneally at two doses (20 and 40 μmol/kg) for 20 days. Thereafter, behavioral studies were conducted to test the learning and memory ability using object location recognition (OLR) experiment and passive avoidance (PA) test. Additionally, the oxidative stress parameters in the serum and the brain tissues (cortex and hippocampus) were assessed, including the superoxide dismutase (SOD) enzyme activity, the total antioxidant reactivity (TAR), the malondialdehyde (MDA) level, the glutathione (GSH) level, and the lipid peroxidation (LPO) content. The results revealed that SD impaired both spatial and non-spatial memory (P < 0.05). Treatment with Ginsenoside Rh2 at both doses prevented memory impairment induced by SD. Moreover, Ginsenoside Rh2 normalized the reduction of SOD and TAR activities in the serum (P < 0.01) and the decrease of GSH content in both the cortex and hippocampus (P < 0.05) induced by SD. Furthermore, Ginsenoside Rh2 significantly decreased the MDA level in the serum (P < 0.05) and the LPO content in both the cortex and hippocampus (P < 0.05) compared to SD group. In conclusion, sleep deprivation impaired both spatial and non-spatial memory and Ginsenoside Rh2 reversed this impairment, probably by preventing the oxidative stress damage in the body, including the serum and brain during sleep deprivation. [ABSTRACT FROM AUTHOR]

Corilagin content from different parts of longan ( Dimocarpus longan Lour.) was determined by ultra performance liquid chromatography (UPLC) method. Additionally, the potential synergistic effects of corilagin + ginsenoside Rh2 (Rh2), and corilagin + 5-fluorouracil (5-FU) on ovarian cancer cells, and cancer-preventing activities, including inhibition of tyrosinase, properties of antioxidant and nitrite-scavenging, and blocking of nitrosamine synthesis were investigated. The results showed the content of corilagin from different parts of longan varied widely, while corilagin content in longan seed was high with a value of 542.15 ± 10.30 μg/g. Then the corilagin from longan seed was chosen for further study, since longan seed was easily obtained from by-product of longan fruit processing with low cost. Furthermore, the combinations of corilagin + Rh2, and corilagin + 5-FU showed an increased synergistic cytotoxicity on SKOv3ip and Hey cells. Moreover, corilagin inhibited exhibited effects of inhibiting tyrosinase, antioxidation, scavenging nitrite and blocking nitrosamine synthesis. [ABSTRACT FROM AUTHOR]

Recent studies hint that Ginsenoside is involved in cancer prevention and treatment. In this study, we investigated the effect of Ginsenoside Rh2 on drug resistance in human colorectal carcinoma (CRC) cells and its mechanism. The resistance reversion effect of Ginsenoside Rh2 in CRC cells was analyzed using CCK-8 assay. After treating with Ginsenoside Rh2, the cell cycle distribution and cellular apoptosis were analyzed by flow cytometry, cell migration was determined by transwell migration assay, the expression of drug-resistance genes and proteins were evaluated using quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot, respectively. Ginsenoside Rh2 could enhance the cytotoxicity of 5-FU in drug-resistant CRC cells (LoVo/5-FU and HCT-8/5-FU). Treatment with Ginsenoside Rh2 could result in an increase of cell numbers in G0/G1 phase accompanied with a decrease in S-phase, and induced cellular apoptosis in drug-resistant CRC cells. In addition, the migration process and EMT process of drug-resistant CRC cells were suppressed by treatment of Ginsenoside Rh2. Compared to control group, expression of drug-resistance genes, such as MRP1, MDR1, LRP and GST, were negatively correlated to Ginsenoside Rh2. All these results indicated that Ginsenoside Rh2 could effectively reverse drug resistance in human colorectal carcinoma cell and its mechanism involved the prevention of cellular proliferation and migration, the promotion of cellular apoptosis and the alteration of drug-resistance genes, which suggested that Ginsenoside Rh2 may act as a promising candidate for drug resistance in human colorectal carcinoma chemotherapy. [ABSTRACT FROM AUTHOR]

Ginsenoside Rh2 (G-Rh2), the main bioactive component in American ginseng, is known to exert a wide variety of biological activities. Accumulating evidence suggests that G-Rh2 inhibits cell proliferation and induces apoptosis of tumor cells. However, the possible mechanism through which G-Rh2 exerts its action on malignant glioma cells have not been completely elucidated. The findings of the present study demonstrated that G-Rh2 decreased the viability of glioma cells in a dose- and time-dependent manner, and induced cell cycle arrest. G-Rh2-induced cell cycle arrest was accompanied by the downregulation of cyclin-dependent kinase 4 and Cyclin E. In addition, G-Rh2 markedly reduced the expression of total-RAC-α serine/threonine-protein kinase (Akt) and the levels of phosphorylated-Akt. These findings provide mechanistic details of how G-Rh2 acts on glioma cells and suggest that G-Rh2 may function as a potential anti-cancer drug for glioma treatment. [ABSTRACT FROM AUTHOR]

Ginsenoside Rh2 (Rh2) is one of the major bioactive ginsenosides in Panax ginseng . However, the oral bioavailability of Rh2 is low, with P-glycoprotein (P-gp) and CYP3A4 being reported to be the main factors. The purpose of the present study was to determine the enhancing effect of piperine on the oral bioavailability as well as bioactivity of Rh2. The inhibitory effect of piperine on P-gp and CYP3A4 was determined using a Caco-2 monolayer model and a recombinant CYP3A4 metabolic system, respectively. The pharmacokinetics of oral Rh2 (10 mg·kg −1 ) administered alone or in combination with piperine (10 and 20 mg·kg −1 ) was performed in rats. The immune boosting effect of Rh2 was assessed in rats by measuring IL-12 level after treated by Rh2 alone or co-administered with piperine. The results indicated that piperine significantly increased the permeability of Rh2 and inhibited the metabolism of Rh2. The pharmacokinetic study results showed that the AUC of Rh2 was significantly increased in combination with piperine at high dose (20 mg·kg −1 ) when compared to the control group, with relative bioavailability of 196.8%. The increase of Rh2 exposure led to increased serum levels of IL-12. In conclusion, piperine may be used as a bioenhancer to improve pharmacological effect of Rh2 when given orally. [ABSTRACT FROM AUTHOR]

Sustained liver fibrosis may lead to cirrhosis. Activated hepatic stellate cells (HSCs) are crucial for liver fibrosis development. Ferroptosis, a newly iron-dependent regulated cell death, has been demonstrated to be involved in HSC inactivation. Ginsenoside Rh2 (GRh2), a natural bioactive product derived from ginseng, has been shown to promote HSC inactivation. However, the effect of GRh2 on HSC ferroptosis remains unclear. We explored the effects of GRh2 on liver fibrosis in vivo and in vitro. RNA-sequence analysis was performed in HSCs after GRh2 treatment. The crosstalk between ferroptotic HSCs and macrophages was also explored. GRh2 alleviated liver fibrosis in vivo. In vitro , GRh2 reduced HSC proliferation and activation via ferroptosis, with increased intracellular iron, reactive oxygen species, malondialdehyde and glutathione depletion. The expression of SLC7A11, a negative regulator of ferroptosis, was obviously reduced by GRh2. Interestingly, interferon regulatory factor 1 (IRF1), a transcription factor, was predicted to bind the promoter region of SCL7A11. The interaction between IRF1 and SCL7A11 was further confirmed by the results of chromatin immunoprecipitation and luciferase reporter assays. Furthermore, loss of IRF1 led to an increase in SCL7A11, which contributed to the suppression of HSC ferroptosis and the enhancement of HSC activation in GRh2-treated HSCs. Further studies revealed that GRh2-induced HSC ferroptosis contributed to the inhibition of macrophage recruitment via regulation of inflammation-related genes. Moreover, GRh2 caused a reduction in liver inflammation in vivo. Collectively, GRh2 up-regulates IRF1 expression, resulting in the suppression of SLC7A11, which contributes to HSC ferroptosis and inactivation. GRh2 ameliorates liver fibrosis through enhancing HSC ferroptosis and inhibiting liver inflammation. GRh2 may be a promising drug for treating liver fibrosis. [Display omitted] [ABSTRACT FROM AUTHOR]

Ginseng is well-known as one of the most valuable and commonly used Chinese medicines not only in ancient China but also worldwide including East, Russia, Southeast Asia, North America and some Western European countries. Ginsenosides, as one of the main high active components of Ginseng, have various pharmacological activities, such as anti-inflammatory, antianaphylaxis, anti-depression, and anticancer activities. Ginsenoside Rh2 (Rh2), one of the major bioactive ginsenosides in Panax ginseng , also exhibits versatile pharmacological activities, such as increasing non-specific resistance and specific immune response, improving cardiac function and fibrosis, anti-inflammatory effects and antitumor effects, which may serve as an excellent medicinal potential. As one of hundreds of ginsenosides being identified from ginseng, Rh2 exerts a markedly pharmacological effect on various diseases without severe toxicity, it has attracted many researchers 'attention. Although Rh2 plays important roles in some animal models and cell lines to simulate human diseases, its underlying molecular mechanisms have yet to be determined. During the past ten years, nearly 450 studies on Rh2 in the treatment of complex disease have been reported, however, up to now, no comprehensive reviews about the roles of Rh2 in animal models and cellular lines of human nonmalignant and malignant diseases have been conducted. We searched articles on ginsenoside-related diseases from December 2010 to February 2023 in peer-reviewed and nonclinical databases, which include Web of Science, Scopus, PubMed, China national knowledge internet and Medline, and using the following keywords: Ginsenoside Rh2, Human diseases, Cancer, Mechanisms, Chinese herbal medicine, Natural products and Signaling pathway. Therefore, in this review, we make a comprehensive summary on the roles of Rh2 and support the potential mechanisms of Rh2 according to the disease classification, including nonmalignant disease such as ulcerative colitis, neuropathic pain, Asthma, myocardial injury, depression and malignant disease such as breast cancer, colorectal cancer, hepatocellular carcinoma and gastric cancer. Finally, the combination therapy of Rh2 and other medications in human diseases are summarized, apart from that, there are other problems such as the bioavailability of oral administration Rh2 to be overcome in following research. These findings provide strong evidence that Ginsenoside Rh2 plays important roles in the treatment of nonmalignant and malignant diseases. [ABSTRACT FROM AUTHOR]

Suppressive effects of ginsenoside Rh2 (Rh2), (24R)-pseudo-ginsenoside HQ (R-PHQ), and (24S)-pseudo-ginsenoside HQ (S-PHQ) against lipopolysaccharide (LPS)-induced depression-like behavior were evaluated using the forced swimming test (FST) and tail suspension test (TST) in mice. Pretreatment with Rh2, R-PHQ, and S-PHQ significantly decreased immobility time in FST and TST with clear dose-dependence, and significantly downregulated levels of serum tumor necrosis factor-α and interleukin-6, and upregulated superoxide dismutase activity in the hippocampus of LPS-challenged mice. Furthermore, R-PHQ and S-PHQ significantly increased the expression of the brain-derived neurotrophic factor (BDNF), tropomyosin-related kinase B (TrkB), sirtuin type 1 (Sirt1), and nuclear-related factor 2, and inhibited the phosphorylation of inhibitor of κB-α and nuclear factor-κB (NF-κB) in the hippocampus of LPS-challenged mice. Additionally, the antidepressant-like effect of R-PHQ was found related to the dopaminergic (DA), γ-aminobutyric acid (GABA)ergic, and noradrenaline systems, while the antidepressive effect of S-PHQ was involved in the DA and GABAergic systems. Taken together, these results suggested that Rh2, R-PHQ, and S-PHQ produced significant antidepressant-like effects, which may be related to the BDNF/TrkB and Sirt1/NF-κB signaling pathways.

Background Anticancer effect of ginsenoside Rh2 has been found in various cancer cells. However, the anticancer effect of Rh2 in endometrial cancer cells is still unclear. We aimed to determine the anticancer effect of Rh2 and elucidate its mechanism in endometrial cancer cells, using HEC1A and Ishikawa cell lines, in this study. Methods Cell proliferation was assessed by MTT assay, and cell apoptosis was visualized by TdT mediated-dUTP Nick-End Labeling (TUNEL) method. Western blot were performed to detect the expression of apoptosis and epithelial-mesenchymal transition (EMT)-related proteins. Further, cell invasion and migration assays were conducted to estimate cell migration and invasion abilities. Results Rh2 treatment significantly suppressed cell proliferation in HEC1A and Ishikawa cells, in dose-dependent manner. Levels of cleaved poly adenosine diphosphate-ribose polymerase (PARP) and cleaved caspase-3 increased in the both cell lines with Rh2 compared with control. In Western blotting analysis after Rh2 treatment, the expression of E-cadherin increased, while the expression of EMT-related proteins including vimentin, TGF-β, and Snail markedly decreased in both cell lines. The cell invasion and migration assays results indicated that Rh2 inhibited the cell invasion and migration in HEC1A cells. Conclusions Our findings suggested that Rh2 exerts the anticancer effect in endometrial cancer cells through the apoptosis induction and EMT inhibition. [ABSTRACT FROM AUTHOR]

This study aims to provide basic data on useful functional ingredients in red ginseng by studying the anti-inflammatory and anti-cancer effects of convergence of ginsenoside Rh2(Rh2) and compound K(CK) isolated from amplified red ginseng. Therefore we examined cytotoxicity in Hep3B, activity of IL-6 induced STAT3 luciferase and survival concentration of cells in B16F10 and HaCa T. According to the experimental results, when the Rh2 and CK mixture were 10 ug/ml, there was no cytotoxicity in Hep3B cells and the anti-inflammatory effect of IL-6 reduction ratio was 102%. In addition, Rh2 and CK mixture were observed to be toxic in melanoma cell line B16F10 and HaCa T (human keratinocyte) at 50 uM. FACS(fluorescence activated cell sorting) analysis showed that annexin V was not expressed and melanoma cells and keratinocyte were desorbed and killed. It can be assumed that the mechanism of killing through this phenomenon is due to the cell death of anoikis-type, and it is necessary to study the changes of cell adhesion proteins in the future in order to clarify the cell death signal system. [ABSTRACT FROM AUTHOR]

Gold nanoparticles (GNPs) are forecasted to provide an attractive platform in biomedicine and catalysis with their potentials of combining a variety of biophysicochemical properties into an integrated nanodevice with great therapeutic and optical functions. There are several reports of crude plant extracts mediating the conversion of metal ions into nanoparticles. However, we aimed to investigate the capability of single bioactive compounds, namely ginsenosides compound K (C-K) and Rh2, to accommodate a synergistic chemical reduction of gold salts by one-pot green chemistry. Ginsenosides C-K and Rh2 are unique triterpenoid saponins present in Panax ginseng Meyer, a perennial plant traditionally used as an oriental medicinal herbal with long history. C-K and Rh2 have demonstrated diverse pharmacological properties such as anticancer, anti-inflammation, anti-aging, and neuroprotective properties. The reduction of gold ions by these ginsenosides led to the production of nontoxic GNPs as tested in mouse macrophage (J774A.1) and human kidney epithelial (HEK-293) in vitro. The kinetics of the bioreduction and the influence of pH were examined by an ultraviolet-visible (UV-Vis) spectrophotometer. GNPs were characterized by field emission transmission electron microscopy (FE-TEM), X-ray diffraction (XRD), dynamic light scattering (DLS), and Fourier transform infrared (FTIR) spectroscopy. Ginsenoside loading efficiency of C-K-GNPs and Rh2-GNPs was determined to be approximately 62.83% and 54.91%, respectively, by thermogravimetric analysis (TGA). These results suggest that one-pot synthesis by ginsenosides C-K and Rh2 may be useful for producing ginsenoside-loaded gold nanocarriers. [ABSTRACT FROM AUTHOR]

Ginsenoside Rh2 (Rh2) is an active principal ingredient contained in ginseng (Panax ginseng Meyer), a medicinal herb used to enhance health worldwide. The present study is designed to investigate the effect of Rh2 on myocardial fibrosis in diabetic rats. In a streptozotocin-induced model of type-1 diabetic rats (STZ-diabetic rats), the increased fasting blood glucose levels and heart weight/body weight (HW/BW) ratio were substantially alleviated by Rh2. Moreover, Rh2 improved cardiac performance in STZ-diabetic rats. Histological results from Masson staining showed that Rh2 attenuated cardiac fibrosis in STZ-diabetic rats. The effects of Rh2 were reversed by GSK0660 at a dose sufficient to inhibit peroxisome proliferator-activated receptor δ (PPARδ) in STZ-diabetic rats. The role of PPARδ was subsequently investigated in vitro. Rh2 restored the decreased PPARδ expression level in high glucose-cultured cardiomyocytes. Moreover, increased protein levels of fibrotic signals, including signal transducer and activator of transcription 3 (STAT3), connective tissue growth factor (CCN2) and fibronectin, were reduced by Rh2 in high glucose-cultured cardiomyocytes. These effects of Rh2 were reversed by GSK0660 or siRNA specific for PPARδ Taken together, PPARδ activation may inhibit STAT3 activation to reduce CCN2 and fibronectin expression in diabetic rats with cardiac fibrosis. Moreover, Rh2 improves cardiac function and fibrosis by increasing PPARδ signaling. Therefore, Rh2 is suitable to develop as an alternative remedy for cardiac fibrosis. [ABSTRACT FROM AUTHOR]

The current study highlights the fabrication of drug delivery system by utilizing 200 nm mesoporous silica nanoparticles (MSNPs) with 4-nm pore size, as a carrier system for delivery ginsenoside compound K (CK) and Rh2 to enhance their efficacy. The two pharmacologically imperative ginsenosides, CK and Rh2, were loaded to the MSNPs to prepare MSNPs-CK and MSNPs-Rh2, respectively. A fluorescein isothiocyanate (FITC) fluorescent dye was combined in the MSNPs carrier system, in order to trace the cellular uptake of ginsenoside-loaded nanoparticles for in vitro studies. Following purification, the so-prepared MSNPs-CK-FITC and MSNPs-Rh2-FITC were characterized by several analytical techniques, which includes, high-pressure liquid chromatography (HPLC), H NMR, field emission transmission electron microscopy (FE-TEM), Fourier transform infrared spectroscopy (FT-IR), x-ray diffraction (XRD), thermogravimetric analysis (TGA), and dynamic light scattering (DLS). In vitro cytotoxicity assay in HaCaT skin cells, A549 lung cancer cells, HepG2 liver carcinoma cells, and HT-29 colon cancer cell lines were tested for MSNPs-CK-FITC and MSNPs-Rh2-FITC. The results demonstrate the excellent biocompatibility of nanoparticles in normal cell lines (HaCaT skin cells) and anticancer efficacy in all the tested cancer cell lines at 10-μM concentration. Additionally, the in vitro anti-inflammatory behavior of MSNPs-CK-FITC and MSNPs-Rh2-FITC were checked in RAW264.7 (murine macrophage) cell lines. The outcomes showed higher anti-inflammatory efficacy of MSNPs-CK-FITC and MSNPs-Rh2-FITC as compared to standard ginsenosides CK and Rh2 in RAW264.7 cell lines. Thus, with 200 nm MSNPs carrier system for the delivery ginsenosides CK and Rh2, a high amount of loading and increasing in vitro pharmacological efficacies of ginsenosides were realized. This study may provide useful insights for designing and improving the applicability of MSNPs for ginsenoside delivery. [ABSTRACT FROM AUTHOR]

Ginsenoside Rh2 (GRh2) and ginsenoside Rg3 (GRg3) are primary bioactive components in Panax ginseng. The present study aimed to investigate the underlying mechanisms of apoptotic cell‑death induced by GRh2 and GRg3 in human leukemia Jurkat cells. The Cell Counting kit‑8 assay was used to determine cell proliferation. Apoptosis was detected by nuclear morphologic observation by Hoechst 33342 staining and Annexin V‑allophycocyanin and 7‑amino‑actinomycin D assay. mitoTEMPO, a mitochondrial reactive oxygen species (ROS) scavenger, was used to examine the effects of mitochondrial ROS on cell viability and mitochondrial membrane potential (MMP). Finally, the expression levels of numerous mitochondrial‑associated apoptosis proteins were assessed by western blot analysis. These results demonstrated that GRh2 and GRg3 inhibited cell growth and induced apoptosis, and that GRh2 had greater cytotoxicity than GRg3. GRh2 induced generation of more mitochondrial ROS compared with GRg3 in Jurkat cells;however, this effect was ameliorated by subsequent treatment with mitoTEMPO. Furthermore, excess mitochondrial ROS induced by GRh2 was more potent than GRg3 in inhibiting cell proliferation and reducing MMP. In addition, expression levels of apoptosis‑associated proteins were significantly increased in Jurkat cells treated with GRh2 than GRg3. In conclusion, these findings suggested that GRh2 and GRg3 induce mitochondrial‑associated apoptosis by increasing mitochondrial ROS in human leukemia Jurkat cells. GRh2 may more effectively inhibit cell growth and accelerate apoptosis than GRg3. This study provides a potential novel strategy for the treatment of acute lymphoblastic leukemia. [ABSTRACT FROM AUTHOR]

Ginsenoside Rh2 is a major metabolite from ginseng that has antitumor activity. Previously, we reported that Rh2-O, an octyl ester derivative of ginsenoside Rh2, had a higher anti-cancer activity than Rh2 in human HepG2 cells. The aim of the present study was to compare the antitumor and immunomodulatory effects of ginsenoside Rh2 and Rh2-O using an animal model. Experiments using H22 tumor-bearing mice demonstrated that the antitumor effect of Rh2-O (10 mg/kg) was better than that of Rh2 (10 mg/kg) with inhibitory rates of 50.6% and 28.2%, respectively (p < 0.05). Both Rh2 and Rh2-O induced tumor cells apoptosis by regulating the expression of the Bcl-2 family proteins and the activation of the caspase family proteins. Additionally, Rh2 and Rh2-O treatment increased the serum IL-2 levels, TNF-α production, T lymphocyte counts, CD4 + /CD8 + ratio, and NK cell levels. Furthermore, immune-histochemical and western blot analyses demonstrated that Rh2 and Rh2-O inhibited vascular endothelial growth factor (VEGF) production. These results showed that inducing tumor cell apoptosis, modulating the immune response, and down-regulating VEGF expression may be involved in Rh2- and Rh2-O-inhibited tumor growth in H22-tumor bearing mice. [ABSTRACT FROM AUTHOR]

The aim of this study was to develop an amphipathic polyethylene glycol (PEG) derivative that was bi-terminally modified with celastrol and ginsenoside Rh2 (Celastrol-PEG-G Rh2). Such derivative was capable of forming novel, celastrol-loaded polymeric micelles (CG-M) for endo/lysosomal delivery and thereby synergistic treatment of lung cancer. Celastrol-PEG-G Rh2 with a yield of 55.6% was first synthesized and characterized. Its critical micellar concentration was 1 × 10−5 M, determined by pyrene entrapment method. CG-M had a small particle size of 121.53 ± 2.35 nm, a narrow polydispersity index of 0.214 ± 0.001 and a moderately negative zeta potential of –23.14 ± 3.15 mV. Celastrol and G Rh2 were rapidly released from CG-M under acidic and enzymatic conditions, but slowly released in normal physiological environments. In cellular studies, the internalization of celastrol and G Rh2 by human non-small cell lung cancer (A549) cells treated with CG-M was 5.8-fold and 1.8-fold higher than that of non-micelle control. Combinational therapy of celastrol and G Rh2 using CG-M exhibited synergistic anticancer activities in cell apoptosis and proliferation assays via rapid drug release within endo/lysosomes. Most importantly, the celastrol in CG-M exhibited a long elimination half-life of 445.3 ± 43.5 min and an improved area under the curve of 645060.8 ± 63640.7 ng/mL/h, that were 1.03-fold and 2.44-fold greater than those of non-micelle control, respectively. These findings suggest that CG-M is a promising vector for precisely releasing anticancer drugs within the tumor cells, and thereby exerts an improved synergistic anti-lung cancer effect. [ABSTRACT FROM AUTHOR]

Cold tumor immune microenvironment (TIME) of pancreatic cancer (PC) with minimal dendritic cell (DC) and T cell infiltration can result in insufficient immunotherapy and chemotherapy. While gemcitabine (GEM) is a first-line chemotherapeutic drug for PC, its efficacy is reduced by immunosuppression and drug resistance. Ginsenoside Rh2 (Rh2) is known to have anti-cancer and immunomodulatory properties. Combining GEM with Rh2 may thus overcome immunosuppression and induce lasting anti-tumor immunity in PC. Here, we showed that after GEM−Rh2 therapy, there was significantly greater tumor infiltration by DCs. Caspase recruitment domain-containing protein 9 (CARD9), a central adaptor protein, was strongly up-regulated DCs with GEM−Rh2 therapy and promoted anti-tumor immune responses by DCs. CARD9 was found to be a critical target for Rh2 to enhance DC function. However, GEM−Rh2 treatment did not achieve the substantial anti-PC efficacy in CARD9−/− mice as in WT mice. The adoptive transfer of WT DCs to DC-depleted PC mice treated with GEM−Rh2 elicited strong anti-tumor immune responses, although CARD9−/− DCs were less effective than WT DCs. Our results showed that GEM−Rh2 may reverse cold TIME by enhancing tumor immunogenicity and decreasing the levels of immunosuppressive factors, reactivating DCs via the CARD9-BCL10-MALT1/ NF-κB pathway. Our findings suggest a potentially feasible and safe treatment strategy for PC, with a unique mechanism of action. Thus, Rh2 activation of DCs may remodel the cold TIME and optimize GEM chemotherapy for future therapeutic use. [Display omitted] [ABSTRACT FROM AUTHOR]

Epilepsy is a chronic disease that affects a wide range of people. Furthermore, a third of patients suffering from epileptic seizures do not respond to antiepileptic drugs. In recent years, increasing attention has focused on the role of oxidative stress in acquired epilepsy, and adjuvant antiepileptic drugs to reduce oxidative stress may be a new therapeutic strategy. In this study ginsenoside Rh2 was resistant to oxidative stress induced by epileptic activity in vivo and in vitro. Using online databases, we identified forkhead box O3a (FOXO3a) overexpression in epilepsy tissue and validated this in vitro , in vivo , and in clinical tissues of patients with epilepsy. An in vitro epilepsy model revealed that the overexpression of FOXO3a led to more severe oxidative stress, while the knockdown of FOXO3a had a protective effect on SH-SY5Y cells. Moreover, our results showed that the positive effect of FOXO3a on oxidative stress was caused by the transcriptional activation of Kelch-like ECH-associated protein 1 (KEAP1), a negative regulator of nuclear factor erythroid 2–related factor 2 (NRF2). We also found that ginsenoside Rh2 can directly inhibit the activation of FOXO3a by selectively blocking CREB-binding protein (CBP)/p300-mediated FOXO3a acetylation and play a role in regulating the KEAP1–NRF2 pathway to resist oxidative stress. [Display omitted] • Ginsenoside Rh2 elicited a significant antioxidant effect and reduced neuronal apoptosis, may be used as an adjuvant treatment for epilepsy. [ABSTRACT FROM AUTHOR]

Ginsenoside Rh2 (GRh2) is a monomer isolated from red ginseng that has extensive pharmacological effects. However, whether GRh2 has a protective effect on ischaemia/reperfusion (I/R) in the myocardium has yet to be elucidated. The present study aimed to identify the anti-inflammatory and antioxidant effects of GRh2 on I/R in the myocardium and its underlying mechanism. A rat model of myocardial I/R injury was constructed by ligating the left anterior descending coronary artery, which was subsequently treated with GRh2. A total of 40 male Sprague-Dawley rats were divided into the following four groups: The sham group, the I/R group, the I/R+GRh2 (10 mg/kg) group and the I/R+GRh2 (20 mg/kg) group. Neonatal rat cardiomyocytes were also used to evaluate the protective effect of GRh2 on hypoxia/reoxygenation (H/R)-induced myocardial injury in vitro. The GRh2 pre-treatment reduced the I/R- or H/R-induced release of myocardial enzymes and the production of IL-1β, IL-18 and TNF-α. GRh2 reduced the area of myocardial infarction and the histological changes in the myocardium and improved cardiac functions. In addition, GRh2 reduced the expression levels of NOD-like receptor family pyrin domain-containing 3 (NLRP3), apoptosis-associated speck-like protein, caspase-1, malondialdehyde and reactive oxygen species and increased the expression levels of nuclear factor E2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), glutathione peroxidase and superoxide dismutase. In conclusion, the present study confirmed that GRh2 could reduce oxidative stress and inflammation in cardiomyocytes after reperfusion, and its mechanism of action may be related to its regulation of the Nrf2/HO-1/NLRP3 signalling pathway. [ABSTRACT FROM AUTHOR]

Ginsenoside Rh2 is a potential pharmacologically active metabolite of ginseng. Previously, we have reported that an octyl ester derivative of ginsenoside Rh2 (Rh2-O), has been confirmed to possess higher bioavailability and anticancer effect than Rh2 in vitro. In order to better assess the possibility that Rh2-O could be used as an anticancer compound, the underlying mechanism was investigated in this study. The present results revealed that lysosomal destabilization was involved in the early stage of cell apoptosis in HepG2 cells induced by Rh2-O. Rh2-O could induce an early lysosomal membrane permeabilization with the release of lysosomal protease cathepsins to the cytosol in HepG2 cells. The Cat B inhibitor (leu) and Cat D inhibitor (pepA) inhibited Rh2-O-induced HepG2 apoptosis as well as tBid production and Δφm depolarization, indicating that lysosomal permeabilization occurred upstream of mitochondrial dysfunction. In addition, Rh2-O induced a significant increase in the protein levels of DRAM1 and Bax (p < 0.05) in lysosomes of HepG2 cells. Knockdown of Bax partially inhibited Rh2-O-induced Cat D release from lysosomes. Thus it was concluded that Rh2-O induced apoptosis of HepG2 cells through activation of the lysosomal-mitochondrial apoptotic pathway involving the translocation of Bax to the lysosome. [ABSTRACT FROM AUTHOR]

Background: Ginseng is Chinese traditional herbal medicine, and the ginsenoside Rg3 is the main bioactive ingredient for the anti-tumor effect. However, there is no study on pharmacokinetics (PKs) of ginsenoside Rg3 and its main metabolite after oral ginsenoside Rg3 in tumor-bearing plasma. The aim of this study was to investigate the PK profiles of ginsenoside Rg3 and ginsenoside Rh2 after oral administration of pure ginsenoside Rg3 were administered, and compare the difference of the PK profiles between normal and Walker 256 tumor-bearing rats. Materials and Methods: The concentrations of two ginsenosides in plasma were determined by using a simple and rapid high-performance liquid chromatography. All the rats were divided randomly into two groups (Walker 256 tumor-bearing and normal groups). Each group received oral administration of 50 mg/kg ginsenoside Rg3. Results: The results showed that ginsenoside Rh2, possibly as a glycosylation hydrolysis product of ginsenoside Rg3, were found in plasma after oral administration of ginsenoside Rg3 to rats. Ginsenoside Rg3 had shown better absorption than ginsenoside Rh2, whether the oral administration of ginsenoside Rg3, normal rats showed better absorption than tumor-bearing rats. Discussion and Conclusion: The PKs properties of the ginsenoside Rg3 and ginsenoside Rh2 differed between tumor-bearing rats and normal rats, including area under the plasma level/time curve and concentration maximum (P < 0.05). [ABSTRACT FROM AUTHOR]

[Display omitted] • GRh2 has neuroprotective effects. • GRh2 exerts anti- Toxoplasma gondii activity via binding to TgCDPK1. • GRh2 attenuates Toxoplasma gondii -induced microglia activation. • GRh2 downregulates NLRP3 inflammasome signaling pathway. Toxoplasma gondii (T. gondii) is a neurotropic obligate intracellular parasite that can activate microglial and promote neuronal apoptosis, leading to central nervous system diseases. The NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome signaling complex plays a key role in inducing neuroinflammation. Our previous studies have found that ginsenoside Rh2 (GRh2) inhibits T. gondii infection-induced microglial activation and neuroinflammation by downregulating the Toll-like receptor 4/nuclear factor-kappa B signaling pathway. However, whether GRh2 reduces T. gondii infection-induced neuronal injury through actions on microglial NLRP3 inflammasome signaling has not yet been clarified. In this study, we employed T. gondii RH strain to establish in vitro and in vivo infection models in BV2 microglia cell line and BALB/c mice. Molecular docking, localized surface plasmon resonance assay, quantitative competitive-PCR, ELISA, western blotting, flow cytometric analysis, and immunofluorescence were performed. Our results showed that GRh2 alleviated neuropathological damage and neuronal apoptosis in cortical tissue of T. gondii -infected mice. GRh2 and CY-09 (an inhibitor of NLRP3) exhibited potent anti- T. gondii effects through binding T. gondii calcium-dependent protein kinase 1 (TgCDPK1). GRh2 decreased Iba-1 (a specific microglial marker) and NLRP3 inflammasome signaling pathway-related protein expression by binding NLRP3. Co-culture of microglia/primary cortical neurons revealed that T. gondii -induced microglial activation caused neuronal apoptosis, but GRh2 reduced this effect, consistent with the effects of CY-09. Taken together, our results show that GRh2 has a protective effect against T. gondii infection-induced neuronal injury by binding TgCDPK1 and NLRP3 to inhibit NLRP3 inflammasome signaling pathway in microglia. [ABSTRACT FROM AUTHOR]

Cancer is a global public health issue that becomes the second primary cause of death globally. Considering the side effects of radio- or chemo-therapy, natural phytochemicals are promising alternatives for therapeutic interventions to alleviate the side effects and complications. Ginsenoside Rh2 (GRh2) is the main phytochemical extracted from Panax ginseng C.A. Meyer with anticancer activity. GRh2 could induce apoptosis and autophagy of cancer cells and inhibit proliferation, metastasis, invasion, and angiogenesis in vitro and in vivo . In addition, GRh2 could be used as an adjuvant to chemotherapeutics to enhance the anticancer effect and reverse the adverse effects. Here we summarized the understanding of the molecular mechanisms underlying the anticancer effects of GRh2 and proposed future directions to promote the development and application of GRh2., Competing Interests: The author declare no conflict of interest., (© 2022 The Korean Society of Ginseng. Publishing services by Elsevier B.V.)

The interaction between ginsenoside Rh2 (G-Rh2) and calf thymus DNA (ctDNA) was investigated by spectroscopic methods including UV-vis absorption, fluorescence and circular dichroism (CD) spectroscopy, coupled with DNA melting techniques and viscosity measurements. Stern-Volmer plots at different temperatures proved that the quenching mechanism was a static quenching procedure. The thermodynamic parameters, enthalpy change (ΔH) and entropy change (ΔS) were calculated to be -22.83 KJ .mol-1and 15.11 J .mol-1 . K-1by van 't Hoff equation, suggesting that hydrophobic force might play a major role in the binding of G-Rh2 to ctDNA.Moreover, the fluorescence quenching study with potassium iodide as quencher indicated that the KSV (Stern-Volmer quenching constant) value for the bound G-Rh2 with ctDNA was lower than the free G-Rh2. The relative viscosity of ctDNA increased with the addition of G-Rh2 and also the ctDNA melting temperature increased in the presence of G-Rh2. Denatured DNA studies showed that quenching by single-stranded DNA was less than that by double-stranded DNA. The observed changes in CD spectra also demonstrated that the intensities of the positive and negative bands decreased with the addition of G-Rh2. The experimental results suggest that G-Rh2 molecules bind to ctDNA via an intercalative binding mode. [ABSTRACT FROM AUTHOR]

Allergic asthma is a chronic inflammatory disease that is regulated by coordination of T-helper type 2 cell cytokines and inflammatory signaling molecules. Ginsenoside Rh2 (G-Rh2) is an active component of ginseng with anti-inflammatory and anti-tumor effects. The aim of the present study was to determine the inhibitory effects of G-Rh2 on allergic airway inflammation in a murine model of asthma, in which mice develop the following pathophysiological features of asthma: Increased abundance of inflammatory cells; increased levels of interleukin-4 (IL-4), IL-5 and IL-13; decreased abundance of interferon gamma in the bronchoalveolar lavage fluid and lung tissue; increased total and ovalbumin (OVA)-specific immunoglobulin E (IgE) levels in the serum; increased airway hyperresponsiveness (AHR); and activation of nuclear factor kappa B (NF-κB) in lung tissue. In the asthmatic mice, administration of G-Rh2 markedly reduced peribronchiolar inflammation, recruitment of airway inflammatory cells, cytokine production, total and OVA-specific IgE levels and AHR. G-Rh2 administration inhibited NF-κB activation and p38 mitogen-activated protein kinase (MAPK) phosphorylation induced by OVA inhalation. These results suggested that G-Rh2 attenuates allergic airway inflammation by regulating NF-κB activation and p38 MAPK phosphorylation. The present study identified the molecular mechanisms of action of G-Rh2, which supported the potential use of G-Rh2 to prevent and/or treat asthma and other airway inflammatory disorders. [ABSTRACT FROM AUTHOR]

Panax ginseng is widely used as a functional food in Asia because of its bioactivities. Here, we report that ginsenoside Rh2, an extract of red Panax ginseng, suppressed growth of uterine leiomyomas (ULs) in a rat model and decreased serum hormone levels in a dose-dependent manner. Rh2 also inhibited the growth of cultured human UL cells in vitro . After Rh2 treatment, cells showed morphological changes that were consistent with apoptosis. Using ELISA, real-time RT-PCR, and Western blot methods, we found that Rh2 significantly reduced the activity of oestrogen receptor alpha (ERα) and c-Src, increased p38 MAPK activity, and reversed ERα activity mediated by PP2 and SB203580, specific inhibitors of c-Src and p38 MAPK, respectively, in UL cells. These findings provide a novel mechanism for the anti-proliferative efficacy of Rh2 that likely involves regulating ERα/Src/p38 MAPK activity. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is one of the most aggressive tumors in humans. The typical therapeutic strategies include a combination of chemotherapy, radiotherapy, and surgery, whereas the survival rate of patients is very poor. Ginsenoside Rh2 has been reported to have therapeutic effects on some tumors, but its effect on HCC has not been extensively evaluated. Here, we show that ginsenoside Rh2 can effectively inhibit the proliferation and cell survival of HCC cells in vitro and in a mouse model. Moreover, the inhibition of the tumor growth appears to result from combined effects on decreased tumor cell proliferation and cell viability. Further analyses suggest that ginsenoside Rh2 may have its anti-tumor effect through inhibition of epidermal growth factor receptor (EGFR) signaling pathway. Recombinant EGFR was given together with ginsenoside Rh2 to the tumor cells, which completely blocked the anti-tumor effect of ginsenoside Rh2. Our data also show that miR-491 is up-regulated in SMMC-7721 cells after Rh2 treatment. There is a negative correlation between EGFR and miR-491 levels in SMMC-7721 cells and miR-491 directly targeted EGFR at translational level. Our data not only reveal an anti-tumor effect of ginsenoside Rh2 but also demonstrate that this effect may function via activation and inhibition of EGFR signaling in HCC cells. The results suggest miR-491 can be a promising regulatory factor in EGFR signal transduction. [ABSTRACT FROM AUTHOR]

Ginsenosides Rh2 and Rg3 represent promising candidates for cancer prevention and therapy and have low toxicity. However, the concentrations of Rh2 and Rg3 are extremely low in the bioactive constituents (triterpene saponins) of ginseng. Despite the available heterologous biosynthesis of their aglycone (protopanaxadiol, PPD) in yeast, production of Rh2 and Rg3 by a synthetic biology approach was hindered by the absence of bioparts to glucosylate the C3 hydroxyl of PPD. In this study, two UDP-glycosyltransferases (UGTs) were cloned and identified from Panax ginseng . UGTPg45 selectively transfers a glucose moiety to the C3 hydroxyl of PPD and its ginsenosides. UGTPg29 selectively transfers a glucose moiety to the C3 glucose of Rh2 to form a 1–2-glycosidic bond. Based on the two UGTs and a yeast chassis to produce PPD, yeast cell factories were built to produce Rh2 and/or Rg3 from glucose. The turnover number ( k cat ) of UGTPg29 was more than 2500-fold that of UGTPg45, which might explain the higher Rg3 yield than that of Rh2 in the yeast cell factories. Building yeast cell factories to produce Rh2 or Rg3 from simple sugars by microbial fermentation provides an alternative approach to replace the traditional method of extracting ginsenosides from Panax plants. [ABSTRACT FROM AUTHOR]

Ginsenoside Rh2 (GRh2) has been reported to have therapeutic effects on some types of cancer, but its effect on prostatic cancer has not been extensively evaluated. Here, we show that GRh2 can substantially inhibit the growth of prostatic cancer in vivo and in vitro. Moreover, the inhibition of the tumor growth appeared to result from a combined inhibitory effect on tumor cell proliferation and tumor cell invasiveness. Further analyses suggest that GRh2 seemed to activate transforming growth factor β (TGFβ) receptor signaling in prostatic cancer cells, which subsequently inhibits cell proliferation and invasion through regulating cell-cycle controllers and (MMPs), respectively. Taken together, our data reveal an essential anti-prostatic cancer effect of GRh2 and demonstrate that this effect is through augment of TGFβ receptor signaling in the prostatic cancer cells. GRh2 thus appears to be a promising therapy for prostatic cancer. [ABSTRACT FROM AUTHOR]

Background: Nowadays, liver diseases are threatening more and more people all over the world and one of the main causes is liver fibrosis. However, there is no effective way to reverse liver fibrosis.Purpose: To investigate whether ginsenoside Rh2 (G-Rh2) can alleviate liver fibrosis and elucidate its underlying mechanism.Methods: In vivo and in vitro methods were adopted in this research. Choline-deficient, L-amino acid-defined, high-fat diet (CDAHFD) was used to feed mice to induce liver fibrosis, and HSC-T6 cells were used to establish an LPS-induced model of liver fibrosis. Through histopathological staining, hematoxylin-eosin (H&E) staining, western blot analysis, intestinal bacteria 16SrRNA sequencing, and other technical means, the research explored whether G-Rh2 possesses anti-fibrotic activity.Results: G-Rh2 could notably alleviate CDAHFD-induced liver fibrosis in mice. In particular, it could alleviate liver injury and reduce plasma lipopolysaccharide (LPS) levels. Additionally, G-Rh2 could repair intestinal injury as well as regulate intestinal microbial diversity and composition. HSC-T6 cells could be activated and autophagy could be induced further by LPS in vitro. After being treated with G-Rh2, autophagy was restrained and activation of hepatic stellate cells (HSCs) was controlled. Deeper research showed that G-Rh2 restrained the activation of HSCs via stimulating the AKT-mTOR signaling pathway, restraining autophagy.Conclusion: The results of our studies clearly suggest that G-Rh2 repairs intestinal injury, improves intestinal microbial composition, reduces plasma LPS levels, and activates the AKT-mTOR signaling pathway to restrain LPS-mediated autophagy, thus playing an important role in anti-hepatic fibrosis. G-Rh2 was found to have the potential to effectively alleviate liver fibrosis. [ABSTRACT FROM AUTHOR]

In previous experiments, ginsenoside Rh2 induced apoptosis and cell cycle arrest, which indicates a potential role for ginsenoside Rh2 in anticancer treatment. The effect of ginsenoside Rh2 on cancer is marked and ginsenoside Rh2 has been shown to inhibit pancreatic tumor migratory ability. In the present study, Transwell chambers were used in order to investigate whether ginsenoside Rh2 inhibits the migratory ability of HepG2 liver carcinoma cells. Furthermore, to analyze activator protein 1 (AP-1) transcription factor expression following Rh2 treatment, ten plasmids encoding Renilla luciferase coupled to the transcription factors were transiently transfected into the HepG2 cells and luciferase was detected by the Luciferase Reporter Assay system reagent. The results indicated that ginsenoside Rh2 inhibited HepG2 cell migratory ability. The expression levels of AP-1 transcription factors were increased in HepG2 cells following induction by phorbol 12-myristate 13-acetate, but ginsenoside Rh2 suppressed this induced AP-1 expression. AP-1 transcription factors recruit histone deacetylase (HDAC)4 and affect its transcription, thus, the expression levels of HDAC4 were also analyzed, and these were found to be increased in the Rh2 treatment group. Matrix metalloproteinase 3 (MMP3), a gene downstream of AP-1, was then investigated, and the treatment group expressed reduced levels of MMP3 gene and protein. Therefore, the inhibitory effect of ginsenoside Rh2 on the migratory ability of HepG2 may be presumed to occur by the recruitment of HDAC and the resulting inhibition of AP-1 transcription factors, in order to reduce the expression levels of MMP3 gene and protein. [ABSTRACT FROM AUTHOR]

Ginseng, one of the most widely used herbal medicines, has a wide range of therapeutic and pharmacological applications. Ginsenosides are the major bioactive ingredients of ginseng, which are responsible for various pharmacological activities of ginseng. Ginsenoside Rh2, known as an antitumour ginsenoside, exists as two different stereoisomeric forms, 20( S)-ginsenoside Rh2 [20( S)-Rh2] and 20( R)-ginsenoside Rh2 [20( R)-Rh2]. This work aimed to assess and compare skin anti-photoaging activities of 20( S)-Rh2 and 20( R)-Rh2 in UV-B-irradiated HaCat cells. 20( S)-Rh2, but not 20( R)-Rh2, was able to suppress UV-B-induced ROS production in HaCat cells. Both stereoisomeric forms could not modulate cellular survival and NO level in UV-B-irradiated HaCat cells. Both 20( S)-Rh2 and 20( R)-Rh2 exhibited suppressive effects on UV-B-induced MMP-2 activity and expression in HaCat cells. In brief, the two stereoisomers of ginsenoside Rh2, 20( S)-Rh2 and 20( R)-Rh2, possess skin anti-photoaging effects but possibly in different fashions. [ABSTRACT FROM AUTHOR]

Stress urinary incontinence (SUI) is a common disorder in middle-aged women and the elderly. Although surgical treatment of SUI has progressed, there are no effective pharmacological therapies without a side effect. We studied the effect of ginsenoside Rh2 against SUI. Here, we studied the effect of ginsenoside Rh2 on the contractile force of the urethra and blood vessels in an ex vivo organ bath assay. We further investigated the mechanisms and effects of Rh2 in cell culture and animal models. Ginsenoside Rh2 dose-dependently reduced lipopolysaccharide (LPS)-induced nitric oxide (NO) production and inducible nitric oxide synthase (iNOS) expression in RAW 264.7 cells. In the vaginal distension (VD)-induced SUI mouse model, ginsenoside Rh2 significantly reversed the VD-induced SUI physical signs and reduced blood pressure. The modulation of several SUI-related proteins, including myosin, survival motor neuron (SMN) protein, α-adrenergic receptor 1a (AdR1a), and superoxide dismutase 3 (SOD3), may play some crucial roles in the therapeutic approaches against SUI. In conclusion, the ginsenoside Rh2 may offer therapeutic potential against SUI. [ABSTRACT FROM AUTHOR]