Ginsenoside Rh2 Research Articles

Ginsenoside Rh1 Prevents Migration and Invasion through Mitochondrial ROS-Mediated Inhibition of STAT3/NF-κB Signaling in MDA-MB-231 Cells.

Breast cancer (BC) a very common cancer in women worldwide. Triple negative breast cancer (TNBC) has been shown to have a poor prognosis with a high level of tumor metastatic spread. Here, the inhibitory effects of ginsenoside-Rh1 (Rh1) on BC metastasis, and its underlying signaling pathway in TNBC were investigated. Rh1-treated MDA-MB-231 cells were analyzed for metastasis using a wound healing assay, transwell migration and invasion assay, western blotting, and qRT-PCR. Rh1 treatment significantly inhibited BC metastasis by inhibiting the both protein and mRNA levels of MMP2, MMP9, and VEGF-A. Further, Rh1-mediated inhibitory effect on BC migration was associated with mitochondrial ROS generation. Rh1 treatment significantly eliminated STAT3 phosphorylation and NF-κB transactivation to downregulate metastatic factors, such as MMP2, MMP9, and VEGF-A. In addition, Mito-TEMPO treatment reversed Rh1 effects on the activation of STAT3, NF-κB, and their transcriptional targets. Rh1 further enhanced the inhibitory effects of STAT3 or NF-κB specific inhibitor, stattic or BAY 11-7082 on MMP2, MMP9, and VEGF-A expression, respectively. In summary, our results revealed the potent anticancer effect of Rh1 on TNBC migration and invasion through mtROS-mediated inhibition of STAT3 and NF-κB signaling.

Ginsenoside Rh2 Inhibits Glycolysis through the STAT3/c-MYC Axis in Non-Small-Cell Lung Cancer.

Ginsenoside Rh2 (Rh2) is one of the pharmacologically active components of ginseng with an antitumor effect. However, its effect on non-small-cell lung cancer (NSCLC), especially on aerobic glycolysis, which plays a crucial role in the proliferation and progression of tumor cells, has not been characterized. Here, we demonstrated that Rh2 inhibited the proliferation and metastasis of NSCLC cells by promoting apoptosis and suppressing epithelial-mesenchymal transition, respectively. Notably, Rh2 exerted a glycolysis inhibition effect through regulating GLUT1, PKM2, and LDHA, which are key enzymes of the glycolysis process. Furthermore, the metabolic shift function of Rh2 was dependent on the STAT3/c-Myc axis in NSCLC. This novel regulatory role of Rh2 provides a new perspective for NSCLC treatment and highlights the potentiality of Rh2 to be used as a tumor energy blocker. The combination of Rh2 with an STAT3 or c-Myc inhibitor revealed a promising therapeutic approach for patients with NSCLC.

Ginsenoside Rh2 Suppresses Metastasis and Growth of Colon Cancer via miR-491.

Ginsenoside Rh2 is considered as a new direction for future cancer treatment because of its excellent anticancer effect. However, due to its low bioavailability, it cannot exert its significant anticancer effect when applied directly to the human body. Chitosan (CS), a nanomaterial, has been verified to be able to enhance drug efficacy via its coating for drugs. Thus, we designed this study to investigate the impact of CS-coated ginsenoside Rh2 on the metastasis and growth of colon cancer (CC). First, ginsenoside Rh2 chitosan tripolyphosphate (CS-Rh2-TPP) nanoparticles (NPs) were constructed, and MTT, transwell, scratch adhesion, and flow cytometry assays were carried out for determining the impact of CS-Rh2-TPP at various concentrations on growth, metastasis, and apoptosis of colon cancer cells (CCCs). qRT-PCR was used to detect the expression of mircoRNA-491 (miR-491) in CCCs. According to TEM-based image analysis, CS-Rh2-TPP NPs were spherical or spheroidal in even distribution, with a particle size of about 220 mm and a zeta potential of −44.58 ± 2.84 mV. Additionally, CCCs presented lower miR-491 than normal colon cells, and its relative expression in CCCs showed a stronger increase after intervention of CS-Rh2-TPP than that after intervention of ginsenoside Rh2. Moreover, CS-Rh2-TPP suppressed the activity, invasion, as well as migration of CCCs and accelerated their apoptosis more significantly than ginsenoside Rh2. According to these results, CS-Rh2-TPP is able to upregulate miR-491 in CCCs, thus suppressing the metastasis and growth of CC.

C-MYC-mediated TRIB3/P62+ aggresomes accumulation triggers paraptosis upon the combination of everolimus and ginsenoside Rh2

The mammalian target of rapamycin (mTOR) pathway is abnormally activated in lung cancer. However, the anti-lung cancer effect of mTOR inhibitors as monotherapy is modest. Here, we identified that ginsenoside Rh2, an active component of Panax ginseng C. A. Mey., enhanced the anti-cancer effect of the mTOR inhibitor everolimus both in vitro and in vivo. Moreover, ginsenoside Rh2 alleviated the hepatic fat accumulation caused by everolimus in xenograft nude mice models. The combination of everolimus and ginsenoside Rh2 (labeled Eve-Rh2) induced caspase-independent cell death and cytoplasmic vacuolation in lung cancer cells, indicating that Eve-Rh2 prevented tumor progression by triggering paraptosis. Eve-Rh2 up-regulated the expression of c-MYC in cancer cells as well as tumor tissues. The increased c-MYC mediated the accumulation of tribbles homolog 3 (TRIB3)/P62+ aggresomes and consequently triggered paraptosis, bypassing the classical c-MYC/MAX pathway. Our study offers a potential effective and safe strategy for the treatment of lung cancer. Moreover, we have identified a new mechanism of TRIB3/P62+ aggresomes-triggered paraptosis and revealed a unique function of c-MYC.

Effect of Lactic Acid Bacteria on the Pharmacokinetics and Metabolism of Ginsenosides in Mice.

This study aims to investigate the effect of lactic acid bacteria (LAB) on in vitro and in vivo metabolism and the pharmacokinetics of ginsenosides in mice. When the in vitro fermentation test of RGE with LAB was carried out, protopanaxadiol (PPD) and protopanaxadiol (PPD), which are final metabolites of ginsenosides but not contained in RGE, were greatly increased. Compound K (CK), ginsenoside Rh1 (GRh1), and GRg3 also increased by about 30%. Other ginsenosides with a sugar number of more than 2 showed a gradual decrease by fermentation with LAB for 7 days, suggesting the involvement of LAB in the deglycosylation of ginsenosides. Incubation of single ginsenoside with LAB produced GRg3, CK, and PPD with the highest formation rate and GRd, GRh2, and GF with the lower rate among PPD-type ginsenosides. Among PPT-type ginsenosides, GRh1 and PPT had the highest formation rate. The amoxicillin pretreatment (20 mg/kg/day, twice a day for 3 days) resulted in a significant decrease in the fecal recovery of CK, PPD, and PPT through the blockade of deglycosylation of ginsenosides after single oral administrations of RGE (2 g/kg) in mice. The plasma concentrations of CK, PPD, and PPT were not detectable without change in GRb1, GRb2, and GRc in this group. LAB supplementation (1 billion CFU/2 g/kg/day for 1 week) after the amoxicillin treatment in mice restored the ginsenoside metabolism and the plasma concentrations of ginsenosides to the control level. In conclusion, the alterations in the gut microbiota environment could change the ginsenoside metabolism and plasma concentrations of ginsenosides. Therefore, the supplementation of LAB with oral administrations of RGE would help increase plasma concentrations of deglycosylated ginsenosides such as CK, PPD, and PPT.

Ginsenoside 20(S)-Rh2 promotes cellular pharmacokinetics and intracellular antibacterial activity of levofloxacin against Staphylococcus aureus through drug efflux inhibition and subcellular stabilization.

Intracellular Staphylococcus aureus (S. aureus) often causes clinical failure and relapse after antibiotic treatment. We previously found that 20(S)-ginsenoside Rh2 [20(S)-Rh2] enhanced the therapeutic effect of quinolones in a mouse model of peritonitis, which we attributed to the increased concentrations of quinolones within bacteria. In this study, we investigated the enhancing effect of 20(S)-Rh2 on levofloxacin (LVF) from a perspective of intracellular bacteria. In S. aureus 25923-infected mice, coadministration of LVF (1.5 mg/kg, i.v.) and 20(S)-Rh2 (25, 50 mg/kg, i.g.) markedly increased the survival rate, and decreased intracellular bacteria counts accompanied by increased accumulation of LVF in peritoneal macrophages. In addition, 20(S)-Rh2 (1, 5, 10 μM) dose-dependently increased the uptake and accumulation of LVF in peritoneal macrophages from infected mice without drug treatment. In a model of S. aureus 25923-infected THP-1 macrophages, we showed that 20(S)-Rh2 (1, 5, 10 μM) dose-dependently enhanced the intracellular antibacterial activity of LVF. At the cellular level, 20(S)-Rh2 increased the intracellular accumulation of LVF by inhibiting P-gp and BCRP. PK-PD modeling revealed that 20(S)-Rh2 altered the properties of the cell but not LVF. At the subcellular level, 20(S)-Rh2 did not increase the distribution of LVF in lysosomes but exhibited a stronger sensitizing effect in acidic environments. Molecular dynamics (MD) simulations showed that 20(S)-Rh2 improved the stability of the DNA gyrase-LVF complex in lysosome-like acidic conditions. In conclusion, 20(S)-Rh2 promotes the cellular pharmacokinetics and intracellular antibacterial activities of LVF against S. aureus through efflux transporter inhibition and subcellular stabilization, which is beneficial for infection treatment.

(20S) Ginsenoside Rh2 Inhibits STAT3/VEGF Signaling by Targeting Annexin A2

Signal transducers and activators of transcription 3 (STAT3) acts as a transcriptional signal transducer, converting cytokine stimulation into specific gene expression. In tumor cells, aberrant activation of the tyrosine kinase pathway leads to excessive and continuous activation of STAT3, which provides further signals for tumor cell growth and surrounding angiogenesis. In this process, the tumor-associated protein Annexin A2 interacts with STAT3 and promotes Tyr705 phosphorylation and STAT3 transcriptional activation. In this study, we found that (20S) ginsenoside Rh2 (G-Rh2), a natural compound inhibitor of Annexin A2, inhibited STAT3 activity in HepG2 cells. (20S) G-Rh2 interfered with the interaction between Annexin A2 and STAT3, and inhibited Tyr705 phosphorylation and subsequent transcriptional activity. The inhibitory activity of STAT3 leaded to the negative regulation of the four VEGFs, which significantly reduced the enhanced growth and migration ability of HUVECs in co-culture system. In addition, (20S)G-Rh2 failed to inhibit STAT3 activity in cells overexpressing (20S)G-Rh2 binding-deficient Annexin A2-K301A mutant, further proving Annexin A2-mediated inhibition of STAT3 by (20S)G-Rh2. These results indicate that (20S)G-Rh2 is a potent inhibitor of STAT3, predicting the potential activity of (20S)G-Rh2 in targeted therapy applications.

Simultaneous Quantification of Four Ginsenosides in Rat Plasma and Its Application to a Comparative Pharmacokinetic Study in Normal and Depression Rats Using UHPLC-MS/MS.

A sensitive method has been developed for simultaneous determination of ginsenoside Rh1 (G-Rh1), ginsenoside Rb1 (G-Rb1), ginsenoside Rc (G-Rc), and ginsenoside Rd (G-Rd) in rat plasma of normal and depression model group after oral administration of their solutions by using Ultra-High-Performance Liquid Chromatography-Tandem Mass Spectrometry (UHPLC-QQQ-MS). The biological samples were prepared by protein precipitation. Ginsenoside Rg3 (G-Rg3) was used as an internal standard (IS). MS analysis was performed under the multiple reaction monitoring (MRM) with electron spray ionization (ESI) operated in the negative mode. The method showed good linearity over a wide concentration range (R2 > 0.999) and obtained lower limits of quantification (LLOQ) of 5 ng/mL. The whole analysis procedure could be completed in as short as 16.5 min. The intraday precisions, interday precisions, and stabilities were less than 10%. The extraction recoveries from rat plasma were exceeded 86.0%. The results indicated that there were significant differences between the two groups on pharmacokinetics parameters; the absorptions of four analytes in the depression group were higher than those in the normal group because the liver metabolism and internal environment of the model rats had been affected.

Glycogen-based pH and redox sensitive nanoparticles with ginsenoside Rh2 for effective treatment of ulcerative colitis

The purpose of this study is to construct a pH and redox sensitive nanoparticle to effectively deliver ginsenoside Rh2 for the treatment of ulcerative colitis (UC). Herein, glycogen was modified by urocanic acid and α-lipoic acid (α-LA) to obtain an amphiphilic polymer (LA-UaGly). Such polymer LA-UaGly could self-assemble to form nanoparticles (Blank NPs) in water with excellent stability, which could also successfully encapsulated ginsenoside Rh2 to form Rh2 nanoparticles (Rh2 NPs) with encapsulation efficiency of 74.36 ± 0.34%. DLS analysis indicated Rh2 NPs were spherical with a particle size of 128.9 ± 0.3 nm. As expected, Rh2 NPs exhibited typical pH and redox dual response release behaviour as well as the excellent in vivo safety. In vitro tests showed that Rh2 NPs could effectively internalize and release Rh2 into RAW264.7 cells, and protect cells from apoptosis (p < 0.05). More interestingly, Rh2 NPs exhibited strong anti-inflammatory activity via significantly inhibiting the overproduction of nitric oxide (NO) and inflammatory cytokines (TNF-α, IL-1β and IL-6) (p < 0.05). In vivo experiments suggested that Rh2 NPs significantly ameliorated the weight loss, colon length, disease activity index (DAI) score, and myeloperoxidase (MPO) activity in mice caused by dextran sulfate sodium salt (DSS) (p < 0.05). Simultaneously, pathological analysis proved that Rh2 NPs could significantly reduce histological damage and inflammatory infiltration in mice. Rh2 NPs could also effectively regulate the intestinal flora of mice by improving the species uniformity and abundance of the intestinal flora of mice and restoring the species diversity of the intestinal flora. In addition, both in vivo and in vitro experiments proved that Rh2 NPs had stronger anti-inflammatory activity than Rh2. This study provides a promising strategy for the effective treatment of UC.

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.

Anticancer Effect of Rh2, a Histone Deacetylase Inhibitor, in HepG2 Cells and HepG2 Cell-Derived Xenograft Tumors Occurs via the Inhibition of HDACs and Activation of the MAPK Signaling Pathway.

Purpose:To investigate the effect of 20(S)-ginsenoside Rh2 (Rh2) on anti HepG2 liver cancer cells and HepG2 cell-derived xenograft tumors, and explore the underlying mechanisms. Materials and Methods:The activity of total HDACs and HAT were assessed with a HDACs colorimetric kit. Expression of HDAC1, HDAC2, HDAC6, p-ERK, ERK, p-P38, P38, p-JNK and JNK proteins was tested by Western blotting.H3K9 and H3K14 proteins were also checked by immunofluorescence, changes in cell cycle distribution with flow cytometry, cell apoptosis with annexin V-FTIC/PI double staining. Activity of Renilla luciferase (HIF) was detected using the Luciferase Reporter Assay system reagent. Gene expression for CyclinD1, Bcl-2, Bax, HIF, IL-1, IL-6, IL-10 and TNF-α was tested by q-PCR. Expression levels of CD31 and Ki-67 was tested by immunohistochemical staining. Results:Total HDAC activity was decreased and total histone acetyltransferase (HAT)activity was increased in a time-dependent manner. Expression of HDAC1 and p-JNK proteins was significantly increased, expression levels of p-ERK was decreased. H3K9 and H3K14 fluorescence protein were increased. Flow cytometric analysis of the cell cycle revealed that the percentage of cells in the G0/G1 phase in the treatment group(64.35±1.36%) was significantly increased compared with the untreated group(61.61±1.23%).The apoptotic rate of the HepG2 group was 10.03±1.92%, which increased to 17.87±1.67% in the treatment group. Expression levels of the transcription factor HIF were also increased in HepG2 cells following induction by Rh2. Expression of CyclinD1 and Bcl-2 at the genetic level was significantly decreased, while expression levels of Bax, HIF, IL-1, IL-6, IL-10 and TNF-α was increased. In vivo, the expression levels of both CD31 and Ki-67 proteins were significantly down-regulated in the treatment group compared with the control group. Conclusions:The effects of Rh2 were suggested to occur through the inhibition of total HDAC activity, which subsequently induced MAPK signaling and down-regulated the expression of HIF.

Anti-Cancer Effect of Panax Ginseng and Its Metabolites: From Traditional Medicine to Modern Drug Discovery

Cancer incidence and mortality rate are growing worldwide. The effectiveness of cancer therapy depends on the degree of cancer development. Anticancer prevention, screening tests, detection of precancerous conditions or cancers at an early stage of development help to prevent the development of cancer, and in the event of cancer development, they provide the best chance for a full recovery. However, in most cases of advanced cancer, there is no method that can fully cure this disease. Recently, natural products have gained more attention in cancer therapy. Panax ginseng (PG), one of the most popular natural products, is reported to have a wide range of pharmacological activities in cancer. Therefore, the anti-cancer effects and mechanisms of PG and its metabolites (compound K, Ginsenoside Rh1, Rh2, Rh3 and F1) in five major cancers (lung cancer, breast cancer, colon cancer, prostate cancer and stomach cancer) are reviewed in this study. It is confirmed that PG and its metabolites regulated apoptosis, epithelial mesenchymal transition (EMT), angiogenesis, cell cycle arrest and multidrug resistance (MDR) in vitro and in vivo cancer models. In particular, ginsenoside Rh2 showed anticancer effects in all five major cancers. This review could improve the understanding of anticancer mechanisms of PG and its metabolites against major five cancers. Further clinical studies are needed for development anti-cancer drugs using PG and its metabolites.

Personalized bioconversion of Panax notoginseng saponins mediated by gut microbiota between two different diet-pattern healthy subjects

BackgroundPanax notoginseng saponins (PNS) as the main effective substances from P. notoginseng with low bioavailability could be bio-converted by human gut microbiota. In our previous study, PNS metabolic variations mediated by gut microbiota have been observed between high fat, high protein (HF-HP) and low fat, plant fiber-rich (LF-PF) dietary subjects. In this study, we aimed to correspondingly characterize the relationship between distinct gut microbial species and PNS metabolites.MethodsGut microbiota were collected from HF-HP and LF-PF dietary healthy adults and profiled by 16S rRNA gene sequencing. PNS were incubated with gut microbiota in vitro. A LC–MS/MS method was developed to quantify the five main metabolites yields including ginsenoside F1 (GF1), ginsenoside Rh2 (GRh2), ginsenoside compound K (GC-K), protopanaxatriol (PPT) and protopanaxadiol (PPD). The selected microbial species, Bifidobacterium adolescentis and Lactobacillus rhamnosus, were employed to metabolize PNS for the corresponding metabolites.ResultsThe five main metabolites were significantly different between the two diet groups. Compared with HF-HP group, the microbial genus Blautia, Bifidobacterium, Clostridium, Corynebacterium, Dorea, Enhydrobacter, Lactobacillus, Roseburia, Ruminococcus, SMB53, Streptococcus, Treponema and Weissella were enriched in LF-PF group, while Phascolarctobacterium and Oscillospira were relatively decreased. Furthermore, Spearman’s correlative analysis revealed gut microbials enriched in LF-PF and HF-HP groups were positively and negatively associated with the five metabolites, respectively.ConclusionsOur data showed gut microbiota diversity led to the personalized bioconversion of PNS.Graphic

Ginsenoside Rh2 inhibits renal fibrosis and renal cell apoptosis in rats with diabetic nephropathy by downregulating discoid domain receptor 1

To investigate the effect of ginsenoside Rh2 (G-Rh2) on renal fibrosis and cell apoptosis in rats with diabetic nephropathy (DN) and explore its possible mechanism. Thirty male SD rats were randomized equally into control group, DN group and ginsenoside Rh2 intervention group. In the latter two groups, rat models of DN were established by intraperitoneal injection of streptozotocin, and the rats in the control group received injection of citrate buffer. After successful modeling, the rats in ginsenoside Rh2 intervention group were given ginsenoside Rh2 (20 mg · kg-1) intragastrically on a daily basis for 12 weeks, and those in the other two groups were treated with normal saline. After the treatments, the histological changes of the kidneys of the rats were observed using HE staining and PAS staining, and renal fibrosis was assessed using Masson staining; TUNEL staining was used to observe cell apoptosis in the kidney tissue. Western blotting was performed to detect renal expressions of collagen Ⅰ, collagen Ⅲ, cleaved caspase-3, Bcl-2, and DDR1; the localization of DDR1 expression in the kidney tissue was determined using immunohistochemistry. Compared with the control rats, the rat models of DN showed obvious renal fibrosis with an increased apoptosis index in the kidneys (P < 0.01), where the expressions of collagen Ⅰ, collagen Ⅲ, cleaved caspase-3, and DDR1 were all upregulated (P < 0.01) and Bcl-2 expression was downregulated (P < 0.01). Treatment with ginsenoside Rh2 significantly reduced the severity of renal fibrosis, lowered the apoptosis index, decreased the expression levels of collagen Ⅰ, collagen Ⅲ, cleaved caspase-3, and DDR1 (P < 0.05 or P < 0.01), and increased the expression of Bcl-2 in the kidney of rats with DN (P < 0.05). Ginsenoside Rh2 inhibits renal fibrosis and renal cell apoptosis possibly in association with the down-regulation of DDR1 expression in the kidney of rat models of DN.

20 (S)-ginsenoside Rh2 inhibits colorectal cancer cell growth by suppressing the Axl signaling pathway in vitro and in vivo

BackgroundColorectal cancer (CRC) has a high morbidity and mortality worldwide. 20 (S)-ginsenoside Rh2 (G-Rh2) is a natural compound extracted from ginseng, which exhibits anticancer effects in many cancer types. In this study, we demonstrated the effect and underlying molecular mechanism of G-Rh2 in CRC cells in vitro and in vivo. MethodsCell proliferation, migration, invasion, apoptosis, cell cycle, and western blot assays were performed to evaluate the effect of G-Rh2 on CRC cells. In vitro pull-down assay was used to verify the interaction between G-Rh2 and Axl. Transfection and infection experiments were used to explore the function of Axl in CRC cells. CRC xenograft models were used to further investigate the effect of Axl knockdown and G-Rh2 on tumor growth in vivo. ResultsG-Rh2 significantly inhibited proliferation, migration, and invasion, and induced apoptosis and G0/G1 phase cell cycle arrest in CRC cell lines. G-Rh2 directly binds to Axl and inhibits the Axl signaling pathway in CRC cells. Knockdown of Axl suppressed the growth, migration and invasion ability of CRC cells in vitro and xenograft tumor growth in vivo, whereas overexpression of Axl promoted the growth, migration, and invasion ability of CRC cells. Moreover, G-Rh2 significantly suppressed CRC xenograft tumor growth by inhibiting Axl signaling with no obvious toxicity to nude mice. ConclusionOur results indicate that G-Rh2 exerts anticancer activity in vitro and in vivo by suppressing the Axl signaling pathway. G-Rh2 is a promising candidate for CRC prevention and treatment.

Ginsenoside Rg1 and ginsenoside Rh1 prevent liver injury induced by acetaminophen in mice.

With the development of technology, drugs are being developed for different purposes. Thus, the rate of drug injury considerably increased worldwide. Liver is the largest detoxification organ in the human body, but it is also the organ most vulnerable to drug damage. Ginsenoside Rg1 has been reported to have an extensive protective effect on liver injury. However, no evident results showed whether ginsenoside Rh1 could improve the injury caused by drugs. Therefore, this paper aimed to explore the protective effect in a mouse model with liver injury. Mice administered with acetaminophen (APAP) were used as the negative group, while those administered with Rg1 (10, 20, and 30mg/kg) and Rh1 (10, 20, and 30mg/kg) were used as the prevention groups. Results indicated that the treatments increased the levels of GSH and SOD remarkably and decreased that of MDA. In addition, the expression levels of GOT and GPT was remarkably reduced compared with the negative group. Inflammatory agents TNF-α, IL-6, and IL-1β were also decreased by the treatments. Meanwhile, Rg1 and Rh1 not only prevented the expression of Bax but also promoted Bcl-2 levels in mice. All results suggested that ginsenoside Rg1 and ginsenoside Rh1 exerted a preventive effect on APAP-induced liver injury in mice. PRACTICAL APPLICATIONS: With the increasing number of patients suffering from drug-induced liver injury, it is urgent to find alternative natural plant drugs to treat liver injury. This paper focuses on the protective effects of Ginsenoside Rg1 and ginsenoside Rh1 on acetaminophen (APAP) induced liver injury. From the previous studies, we found that there is no sufficient evidence to show that ginsenoside Rh1 has protective effect on liver injury. In this paper, the detection of oxidative stress indicators, liver histopathological analysis and immunoprotein analysis show that both ginsenoside Rg1 and ginsenoside Rh1 have preventive effect on liver injury caused by APAP, which provides a reference for the follow-up experimental research.

Ginsenoside Rh1 Exerts Neuroprotective Effects by Activating the PI3K/Akt Pathway in Amyloid-β Induced SH-SY5Y Cells

Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by the accumulation of β-amyloid plaques and hyperphosphorylated tau proteins in the brain. Cell signaling pathways such as PI3K/Akt are known to play an essential role in regulating cell survival, motility, transcription, metabolism, and progression of the cell cycle. Recent studies demonstrated that the disruption of these signaling pathways in neurodegenerative disorders leads to oxidative stress and cell death. Targeting these altered signaling pathways could be considered as the therapeutic approach for neurodegenerative disorders. Ginsenoside Rh1 is known to provide beneficial effects in various diseases such as cancer, diabetes, and inflammation. In this study, human neuroblastoma SH-SY5Y cells were treated with the β-amyloid oligomers alone or in combination with ginsenoside Rh1. We observed that ginsenoside Rh1 was able to attenuate β-amyloid induced oxidative stress and cell death by activating the PI3K/Akt signaling pathway. Based on these findings, we suggest that ginsenoside Rh1 might be an efficacious therapeutic agent for AD.

Retraction.

Retraction: "Ginsenoside Rh2 inhibits proliferation and migration of medulloblastoma Daoy by down-regulation of microRNA-31," by Yan Chen, Hong Shang, Shunli Zhang, Xiaohong Zhang, J Cell Biochem. 2018; 6527-6534: The above article, published online on 29 January 2018 in Wiley Online Library (https://onlinelibrary.wiley.com/doi/abs/10.1002/jcb.26716), has been retracted by agreement between the journal's Editor in Chief, Prof. Dr. Christian Behl, and Wiley Periodicals LLC. The retraction has been agreed following an investigation based on allegations raised by a third party. Several flaws and inconsistencies between results presented and experimental methods described were found, the editors consider the conclusions of this article to be invalid. The authors collaborated in the investigation initially, but were not available for a final confirmation of the retraction.

Differential antiangiogenic and anticancer activities of the active metabolites of ginsenoside Rg3

BackgroundEpimers of ginsenoside Rg3 (Rg3) have a low bioavailability and are prone to deglycosylation, which produces epimers of ginsenoside Rh2 (S–Rh2 and R–Rh2) and protopanaxadiol (S-PPD and R-PPD). The aim of this study was to compare the efficacy and potency of these molecules as anti-cancer agents. MethodsCrystal violet staining was used to study the anti-proliferatory action of the molecules on a human epithelial breast cancer cell line, MDA-MB-231, and human umbilical vein endothelial cells (HUVEC) and compare their potency. Cell death and cell cycle were studied using flow cytometry and mode of cell death was studied using live cell imaging. Anti-angiogenic effects of the drug were studied using loop formation assay. Molecular docking showed the interaction of these molecules with vascular endothelial growth factor receptor-2 (VEGFR2) and aquaporin (AQP) water channels. VEGF bioassay was used to study the interaction of Rh2 with VEGFR2, in vitro. ResultsHUVEC was the more sensitive cell line to the anti-proliferative effects of S–Rh2, S-PPD and R-PPD. The molecules induced necroptosis/necrosis in MDA-MB-231 and apoptosis in HUVEC. S–Rh2 was the most potent inhibitor of loop formation. In silico molecular docking predicted a good binding score between Rh2 or PPD and the ATP-binding pocket of VEGFR2. VEGF bioassay showed that Rh2 was an allosteric modulator of VEGFR2. In addition, SRh2 and PPD had good binding scores with AQP1 and AQP5, both of which play roles in cell migration and proliferation. ConclusionThe combination of these molecules might be responsible for the anti-cancer effects observed by Rg3.

Ginsenoside Rh1 attenuates ovalbumin-induced asthma by regulating Th1/Th2 cytokines balance.

Ginsenoside Rh1 (Rh1) has anti-inflammatory effects in asthma mice, but the underlying mechanism remains unclear. BALB/c mice were sensitized and challenged with ovalbumin (OVA) to construct asthma model. Mice received Rh1 or tiotropium bromide 0.5 h before OVA challenge. Airway morphology and airway remodeling were assessed by HE staining and Masson's trichrome staining, respectively. Th1/Th2 cytokines in serum or broncho alveolar lavage fluid (BALF) were measured by ELISA kits. Rh1 significantly alleviated the lung resistance and airway resistance, and reduced the number of total inflammation cells, eosinophils, neutrophils, and lymphocytes in BALF of the asthmatic mice. The morphological changes and collagen deposition of airway were also reduced by Rh1 in asthmatic mice. The increase of Eotaxin, IL-4, IL-5, IL-13, and IL-33 and the decrease of IL-12 and IFN-γ in both BALF and serum of OVA exposed mice were reversed by Rh1. Rh1 attenuates OVA-induced asthma in the mice model by regulating Th1/Th2 cytokines balance.