Compounds Of Ginseng Research Articles

Ginsenoside Rb1 inhibits monoiodoacetate-induced osteoarthritis in postmenopausal rats through prevention of cartilage degradation

BackgroundGinsenoside Rb1 (G-Rb1), one of the major active compounds in Panax ginseng, has already been shown to reduce inflammation in various diseases. Osteoarthritis (OA) has traditionally been considered a degenerative disease with degradation of joint articular cartilage. However, recent studies have shown the association of inflammation with OA. In the present study, we investigated whether Rb1 had an antiinflammatory effect on monoiodoacetate (MIA)-induced OA in ovariectomized rats as a model of postmenopausal arthritis. MethodsG-Rb1 at a dosage of 3 and 10 μg/kg body weight was administered every 3 days intraarticularly for a period of 4 weeks to observe antiarthritic effects. Diclofenac (10 mg/kg) served as a positive control. ResultsThe administration of Rb1 significantly ameliorated OA inflammatory symptoms and reduced serum levels of inflammatory cytokines. Furthermore, G-Rb1 administration considerably enhanced the expression of bone morphogenetic protein-2 and collagen 2A and reduced the levels of matrix metalloproteinase-13 genes, indicating a chondroprotective effect of G-Rb1. G-Rb1 also significantly reduced the expression of several inflammatory cytokines/chemokines (interferon gamma (IFN-γ), monocyte chemoattractant protein-1 (MCP-1)/CCL-2, interleukin [IL]-1β, and IL-6). Histological analysis demonstrated that G-Rb1 significantly attenuated the pathological changes in MIA-induced OA in ovariectomized rats. Safranin O and toluidine blue staining further demonstrated that G-Rb1 effectively prevented the degradation of cartilage and glycosaminoglycans, respectively. ConclusionOverall, our results suggest that G-Rb1 exerts cartilage protective effect on MIA-induced ovariectomized OA rats, by inhibiting inflammatory mediators such as IL-6, IL-1β, MCP-1/CCL-2, cyclooxygenase-2 (COX-2), and prostaglandin E2 (PGE2). These results shed a light on possible therapeutic application of G-Rb1 in OA.

Quantitative Determination of Ginsenoside Rg1 in Rat Plasma by Ultrahigh Performance Liquid Chromatography-tandem Mass Spectrometry (UHPLC-MS/MS) and its Application in a Pharmacokinetics and Bioavailability Study

Background:Ginsenoside Rg1 (Rg1) is the main active compound of ginseng herbs.Objective:The aim of this study is to develop a rapid, selective and sensitive ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method to determine the levels of Rg1 in rat plasma and investigate the pharmacokinetics and bioavailability of Rg1 in rats.Methods:Chromatographic separation was achieved on an UHPLC-MS/MS system with an UPLC BEH C18 column using an elution gradient of a mixture of acetonitrile and water (with 0.1% formic acid). The analytes were quantitatively determined by negative-mode electrospray tandem MS.Results:The linearity of the calibration curve was from 2 to 1,000 ng/mL (r ≥ 0.9956), and the lower limit of quantification was 2 ng/mL. The inter-day and intra-day precision were both lower than 12.0%, and the accuracy ranged from 90.6 to 109.7%. The recovery of the targets was higher than 87.0%, and the matrix effect at three different analyte concentrations were from 89.0 to 97.2%. The bioavailability of Rg1 was only 6.1% due to a poor oral absorption.Conclusion:This new quantitative method was found to be sensitive, rapid and selective, and was successfully used to study the pharmacokinetics of Rg1 after intravenous and oral administration in rats.

Analysis of anti-fatigue mechanism and potential targets of ginseng

Ginseng has effects in reinforcing vital energy,invigorating health effectively and relieving fatigue symptoms,and ginsenoside( GS) is the main component of its anti-fatigue effect. Totally 17 active components and 92 drug targets of ginseng compounds were screened from Traditional Chinese Medicine Systems Pharmacology; and 78 intersecting genes of diseases and drug targets were obtained based on R Language Technology. The protein-protein interaction( PPI) network was constructed by STRING 11. 0 software,and Matthews Correlation Coefficient( MCC) algorithm was used to screen core target genes. Gene ontology enrichment analysis and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis were used to analyze the major genes and their roles in regulatory networks. The results indicated that ginseng could regulate the core target genes,including AKT serine/threonine kinase( AKT1),interleukin-1β,Toll-like receptor binding molecule 1( ICAM1),mitogen-activated protein kinase 8( MAPK8),AP-1 transcription factor subunit( JUN),transducer and activator of transcription 1( STAT1) and prostaglandin peroxidase synthase 2( PTGS2). It could participate in the functions of cytokine receptor binding,cell adhesion molecule binding and tumor necrosis factor receptor superfamily binding,and also regulate the signal pathways of tumor necrosis factor,interleukin 17 and c-type lectin receptor,so as to exert an anti-fatigue effect. Based on the results of network analysis,32 four-week-old male SPFACR mice were randomly divided into control group,low-dose ginsenoside group,middle-dose ginsenoside group and high-dose ginsenoside group. The corresponding drugs were administrated for 3 weeks. The results showed that GS could significantly up-regulate the expressions of STAT1 and AKT1( P<0. 01,P<0. 05),and downregulate the expressions of PTGS2 and JUN( P<0. 01). However,there was no significant effect on MAPK8,IL-1β and ICAM1. Ginseng's anti-fatigue regulation network was constructed through network pharmacology,and the results were verified by experiments,in order to reveal the anti-fatigue mechanism of ginseng and provide scientific basis for its clinical application.

Ginseng compound K incorporated porous Chitosan/biphasic calcium phosphate composite microsphere for bone regeneration

There is a substantial for the bone graft materials in the clinical field. Porous, stable and biodegradable bone microsphere scaffold using biopolymer chitosan was studied, and biphasic calcium phosphate was added to improve mechanical and osteoconductivity properties later ginseng compound K was added for improving its medicinal properties. They were characterized using FTIR and XRD that showed the apatite crystal in the composite microsphere scaffolds were structurally similar to that of biogenic apatite crystals. Scanning electron microscopy images confirmed the presence of hydroxyapatite on the surface of the composite microspheres. In vitro results infers that the composite microspheres are biocompatible with NIH 3T3 and MG63 cells and capable of supporting growth and spreading of MG-63 cells. Further, Osteogenic markers expression was found to be higher in rat bone marrow stem cells seeded on microsphere scaffolds compared to control. The prepared biocomposite porous microsphere scaffold developed in this study can be used as an alternative for the bone regeneration or bone tissue engineering.

Development of a Validated UPLC-MS/MS Method for Analyzing Major Ginseng Saponins from Various Ginseng Species.

Ginsenosides, which contain one triterpene and one or more sugar moieties, are the major bioactive compounds of ginseng. The aim of this study was to develop and optimize a specific and reliable ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for the analysis of twelve different resources of ginseng. The six marker compounds of ginsenoside Rb1, ginsenoside Rb2, ginsenoside Rc, ginsenoside Rd, ginsenoside Re, and ginsenoside Rg1, as well as an internal standard, were separated by a reversed-phase C-18 column with a gradient elution of water and methanol-acetonitrile. The multiple-reaction monitoring (MRM) mode was used to quantify and identify twelve market products. The results demonstrated that not only is the logarithm of its partition coefficient (cLog P; octanol-water partition coefficient) one of the factors, but also the number of sugars, position of sugars, and position of the hydroxyl groups are involved in the complicated separation factors for the analytes in the analytical system. If the amount of ginsenoside Rb1 was higher than 40 mg/g, then the species might be Panax quinquefolius, based on the results of the marker ginsenoside contents of various varieties. In summary, this study provides a rapid and precise analytical method for identifying the various ginsenosides from different species, geographic environments, and cultivation cultures.

Effects of pulsed electric field (PEF) treatment on physicochemical properties of Panax ginseng

Abstract Effects of pulsed electric field (PEF) technology on physicochemical properties of raw Panax ginseng roots were investigated in this study. PEF treatment was conducted with different electric field strength (0.5, 1.5, and 2.5 kV/cm) and pulse width of 25 μs. Ginseng cell and vacuole membranes were significantly affected by PEF treatment at field strengths >1.5 kV/cm. Changes in membrane systems due to PEF treatment were verified by increased ion leaching and increased cell membrane disintegration (conductivity disintegration index Z value). Observation by electron microscopy revealed vacuole destruction and plasma membrane separation following PEF treatment. Texture profile analysis showed a significant decrease in hardness (by 44%) and chewiness (by 45%) at 2.5 kV/cm. PEF treatment had little effect on proximate composition and crude saponin content of ginseng roots. However, total phenolic content (by 11%) and antioxidant activity (by 21.4% for DPPH and 3.64% for ABTS) were significantly increased. Industrial relevance Raw ginseng is normally steamed and dried to make white ginseng and red ginseng. However, using these methods is time consuming and requires much energy. Pulsed electric field (PEF) can induce the changes in physicochemical properties of ginseng with less energy for a short period of time. By using this technology, we can obtain ginseng products with high cell permeability and high antioxidant ability by tailoring the microstructure. This potentially increases the extraction of bioactive compounds in ginseng and significantly enhances the mass transfer during subsequent processing, thereby improving the efficiency of the whole process. These results could be used as basic study for the production of high-quality ginseng products using non-thermal technologies.

Ginsenoside Rc Is a New Selective UGT1A9 Inhibitor in Human Liver Microsomes and Recombinant Human UGT Isoforms.

Ginseng is known to have inhibitory effects on UGT1A9 activity. However, little is known about the inhibitory effects of ginsenosides, the major active compounds in ginseng, on UGT1A9 activity. In vitro investigation of UGT1A9 inhibition by ginsenosides was carried out using human liver microsomes (HLMs). Among 10 ginsenosides, ginsenoside Rc was the strongest inhibitor of UGT1A9-mediated mycophenolic acid glucuronidase activity. Further inhibition kinetic studies using HLMs suggested that ginsenoside Rc competitively and noncompetitively inhibited UGT1A9-mediated propofol and mycophenolic acid glucuronidation activities, with K i values of 2.83 and 3.31 μM, respectively. Next, to investigate whether the inhibitory effect of ginsenoside Rc is specific to the UGT1A9 isoform, we studied the inhibitory potency of ginsenoside Rc on nine human uridine diphospho-glucuronosyltransferase (UGT) activities using recombinant human UGT isoforms. Ginsenoside Rc exhibited a 12.9-fold selectivity (which was similar to niflumic acid at 12.5-fold) for UGT1A9 inhibition. Ginsenoside Rc at 50 μM also inhibited none of the other UGT isoform-specific activities above 12.0%, except for UGT1A9 (>91.5%) in HLMs, indicating that ginsenoside Rc might be used as a selective UGT1A9 inhibitor in reaction phenotyping studies of new chemical entities. Considering lower plasma concentrations (0.01 μM) of ginsenoside Rc in healthy subjects and no induction potential on UGT isoforms, ginsenoside Rc does not cause pharmacokinetic drug interactions with other coadministered drugs metabolized by UGT1A9. SIGNIFICANCE STATEMENT: Ginsenoside Rc selectively inhibited UGT1A9-mediated propofol and mycophenolic acid glucuronidation activities in human liver microsomes and recombinant uridine diphospho-glucuronosyltransferase (UGT) isoforms. It exhibited a 12.9-fold selectivity for UGT1A9 inhibition. Therefore, ginsenoside Rc might be used as a selective UGT1A9 inhibitor in reaction phenotyping studies of new chemical entities, such as niflumic acid.

Ginsenoside Rd reverses cisplatin resistance in non-small-cell lung cancer A549 cells by downregulating the nuclear factor erythroid 2-related factor 2 pathway.

Clinical drug resistance to platinum-based chemotherapy is considered a major impediment in the successful treatment of non-small-cell lung cancer (NSCLC). The nuclear factor erythroid 2-related factor 2 (NRF2) signaling pathway regulates the oxidative stress response, and in many cancer types, the high constitutive expression of NRF2 leads to proliferation and chemoresistance. Ginsenoside Rd (GS-Rd) is the main active component of ginsenosides. Here, GS-Rd was found to inhibit the proliferation of A549 lung cancer cells and induce G0/G1 phase arrest. We established cisplatin (DDP)-resistant A549 cell lines (A549/DDP). The half maximal inhibitory concentrations of DDP, gemcitabine, and adriamycin were much higher in A549/DDP cells than in A549 cells. The A549/DDP cell lines developed multidrug resistance, accompanied by activation of multidrug resistance protein 1 and multidrug resistance-associated protein 1, as well as NRF2 and its target genes. Treatment with GS-Rd inhibited the NRF2 pathway and significantly sensitized A549/DDP cells to therapeutic drugs. In addition, NRF2 knockdown attenuated the synergistic effects of GS-Rd in both A549 and A54/DDP cells. Taken together, these data show that NRF2 plays an important role in acquired drug resistance in NSCLC, and GS-Rd may ameliorate this chemoresistance by downregulating the NRF2 pathway. This study demonstrates that the NRF2 pathway may serve as a therapeutic target in NSCLC, and ginseng compounds may be effective for the treatment of this disease.

Transcriptome profiling of poly(I:C)-induced RAW 264.7 mouse macrophages in response to panaxadiol

Panaxadiol is an active compound in steamed ginseng that possesses anti-cancer properties. Nonetheless, the effect of panaxadiol on inflammation remains unclear. Double-stranded RNA (dsRNA) acts as a molecular mimic associated with viral infection. It is recognized by Toll-like receptor-3 (TLR3), and it induces pro-inflammatory cytokines production of immune cells-like macrophages. Synthetic dsRNA polyriboinosinic polyribocytidylic acid [Poly(I:C)] is structurally similar to double-stranded RNA, which is used to simulate dsRNA in inducing immune response. In this study, we used an RNA-Seq based approach to analyze changes in mRNA level of poly (I:C)-induced RAW264.7 treated by panaxadiol. First, our data suggested that 20 μM and 40 μM panaxadiol may reduce poly(I:C)-induced RAW264.7 cell viability, while the concertation of 10 μM panaxadiol was enough to inhibit the cell production of TNF-α and IL-6. Next, 10 μM panaxadiol was applied to investigate the transcriptome profile change of Poly(I:C)-induced RAW264.7 cells. Transcriptome profile showed that inflammatory related genes (such as Cxcl2, Csf3, Ptgs2, Acod1, Lif and Il1b) could be downregulated by panaxadiol, which was confirmed by real-time PCR. Moreover, Gene Ontology enrichment analysis showed that downregulated genes were associated with immune responses, while many upregulated genes were related to DNA replication. In addition, KEGG enrichment showed changes of pathways like NF-kappa B signaling pathway and DNA replication after treatment with panaxadiol. To sum up, our results suggested that panaxadiol may inhibit inflammatory associated genes in macrophages induced by poly(I:C). Considering its anti-virus effects, panaxadiol could be used to treat a variety of virus related diseases.

Metabolomic understanding of intrinsic physiology in Panax ginseng during whole growing seasons

BackgroundPanax ginseng Meyer has widely been used as a traditional herbal medicine because of its diverse health benefits. Amounts of ginseng compounds, mainly ginsenosides, vary according to seasons, varieties, geographical regions, and age of ginseng plants. However, no study has comprehensively determined perturbations of various metabolites in ginseng plants including roots and leaves as they grow. MethodsNuclear magnetic resonance (1H NMR)–based metabolomics was applied to better understand the metabolic physiology of ginseng plants and their association with climate through global profiling of ginseng metabolites in roots and leaves during whole growing periods. ResultsThe results revealed that all metabolites including carbohydrates, amino acids, organic acids, and ginsenosides in ginseng roots and leaves were clearly dependent on growing seasons from March to October. In particular, ginsenosides, arginine, sterols, fatty acids, and uracil diphosphate glucose–sugars were markedly synthesized from March until May, together with accelerated sucrose catabolism, possibly associated with climatic changes such as sun exposure time and rainfall. ConclusionThis study highlights the intrinsic metabolic characteristics of ginseng plants and their associations with climate changes during their growth. It provides important information not only for better understanding of the metabolic phenotype of ginseng but also for quality improvement of ginseng through modification of cultivation.

American ginseng microbial metabolites attenuate DSS-induced colitis and abdominal pain

Inflammatory bowel disease (IBD) is a significant public health problem in the United States. Abdominal pain is a major complaint among individuals with IBD. Successful IBD management not only controls enteric inflammation, but also reduces abdominal discomfort. Recently, increased attention has been focused on alternative strategies for IBD management. HPLC/Q-TOF-MS analysis was employed to evaluate the intestinal microbiome's biotransformation of parent American ginseng compounds into their metabolites. Using a DSS mouse model, the effects of American ginseng microbial metabolites on chemically induced colitis was investigated with disease activity index and histological assessment. Expressions of inflammatory cytokines were determined using real-time PCR and ELISA. Abdominal pain was evaluated using the von Frey filament test. After the gut microbiome's biotransformation, the major metabolites were found to be the compound K and ginsenoside Rg3. Compared with the DSS animal group, American ginseng treatment significantly attenuated experimental colitis, as supported by the histological assessment. The enteric microbiome-derived metabolites of ginseng significantly attenuated the abdominal pain. American ginseng treatment significantly reduced gut inflammation, consistent with pro-inflammatory cytokine level changes. The gut microbial metabolite compound K showed significant anti-inflammatory effects even at low concentrations, compared to its parent ginsenoside Rb1. American ginseng intestinal microbial metabolites significantly reduced chemically-induced colitis and abdominal pain, as mediated by the inhibition of pro-inflammatory cytokine expression. Intestinal microbial metabolism plays a critical role in American ginseng mediated colitis management.

Ginsenoside Rg1 protects against acetaminophen-induced liver injury via activating Nrf2 signaling pathway in vivo and in vitro

Acetaminophen (APAP) is a worldwide used drug for treating fever and pain. However, APAP overdose is the leading cause of drug-induced liver injury. The purpose of the current study is to evaluate the hepatoprotective effect of ginsenoside Rg1 (Rg1), the main pharmacologically active compounds of Panax ginseng, against APAP-induced acute liver injury, and further to elucidate the involvement of Nrf2 signaling pathway by in vivo and in vitro experiments. Male C57BL/6 mice were treated with Rg1 for 3 days before injection of APAP. Serum and liver tissue samples were collected 6 h later. The results indicated that Rg1 significantly attenuated APAP-induced hepatotoxicity and oxidative stress in a dose-dependent manner. Rg1 effectively enhanced antioxidant and detoxification capacity, which is largely dependent on up-regulating Nrf2 nuclear translocation, reducing Keap1 protein expression and up-regulating Nrf2 target genes including GCLC, GCLM, HO-1, NQO1, Ugt1a1, Ugt1a6, Ugt2b1, Sult2a1, Mrp2, Mrp3 and Mrp4. Furthermore, Rg1 repressed the activities of Cyp2e1, Cyp3a11, Cyp1a2, which are important enzymes in the formation of APAP toxic metabolite N-acetyl-p-benzoquinone imine. However, the changes in transporters and enzymes, as well as ameliorative liver histology induced by Rg1 were abrogated by Nrf2 antagonist all-transretinoic acid in vivo and Nrf2 siRNA in vitro. In conclusion, Rg1 produced hepatoprotective effects against APAP-induced acute liver injury via Nrf2 signaling pathway. Rg1 might be an effective approach for the prevention against acute liver injury.

Study on the Structure of Ginseng Glycopeptides with Anti-Inflammatory and Analgesic Activity.

Panax ginseng is well known for its medicinal functions. As a class of important compound of ginseng, ginsenoside is widely studied around the world. In addition, ginseng glycopeptides also showed good biological activity, but researches in this field are rarely reported. In this study, ginseng glycopeptides (Gg) were first prepared from Panax ginseng by reflux extracted with 85% ethanol and the following purification with Sephadex G-15 column. Then, the inflammatory pain models induced by carrageenan and the rat pain models induced by Faure Marin were established for research on mechanism of analgesic activities. It is showed that Gg had an obvious inhibiting effect on inflammation and a significant reduction on the Malondialdehyde (MDA) of inflammatory foot tissue. And there were significant differences between moderate to high dose of Gg and model group in Interleukin 1β (IL-1β), Interleukin 2 (IL-2), Interleukin 4 (IL-4), Tumor necrosis factor α (TNF-α) and Histamine. The two models can be preliminarily determined that the analgesic effect of Gg may be peripheral, which mechanism may be related to the dynamic balance between proinflammatory cytokines (TNF-α, IL-1β) and anti-inflammatory cytokines (IL-2, IL-4, and Interleukin 10 (IL-10)). A series of methods were used to study Gg in physical-chemical properties and linking mode of glycoside. The high-resolution mass spectrometry was used for identification of the structure of Gg. Moreover, the structure of 20 major Gg were investigated and identified. The structural analysis of Gg was benefit for the next study on structure-activity relationship.

Rg1 inhibits high glucose-induced mesenchymal activation and fibrosis via regulating miR-2113/RP11-982M15.8/Zeb1 pathway

Recent study has showed that Ginsenoside Rg1, the mian active compound of Panax ginseng, could ameliorate oxidative stress and myocardial apoptosis in diabetes mellitus. However, the roles and mechanisms of Rg1 in proliferative diabetic retinopathy (PDR) are still unclear. In the present study, we aimed to investigate the effects of Rg1 on mesenchymal activation of high-glucose (HG) cultured müller cells. High glucose conditions up-regulate MMP-2, MMP-9 and down-regulate TIMP-2, and promote mesenchymal activation in Müller cells. And Rg1 inhibits the HG-induced mesenchymal activation and HG-increased MMP-2 and MMP-9 and HG-decreased TIMP-2 in Müller cells. HG up-regulates Zeb1 and lncRNA RP11-982M15.8, and down-regulates miR-2113, and Rg1 inhibits these effects of HG. Both inhibition of miR-2113 and over-expression of RP11-982M15.8 significantly restored the HG induced mesenchymal activasion. Taken together, our findings suggested that Rg1 inhibited HG-induced mesenchymal activation and fibrosis via regulating miR-2113/RP11-982M15.8/Zeb1 pathway.

Ginsenoside Rg3 Decreases NHE1 Expression via Inhibiting EGF-EGFR-ERK1/2-HIF-1 Pathway in Hepatocellular Carcinoma: A Novel Antitumor Mechanism.

Na /H exchanger 1 (NHE1) plays a vital role in the oncogenesis and development of hepatocellular carcinoma (HCC) and has been regarded as a promising target for the treatment of HCC. Ginsenoside Rg3 (Rg3), a bioactive ginseng compound, is suggested to possess pleiotropic antitumor effects on HCC. However, the underlying mechanisms of Rg3 suppressing HCC remain unclear. In the present study, we uncovered a novel antitumor mechanism of Rg3 on HCC by decreasing NHE1 expression through in vivo and in vitro studies. Mechanistically, we demonstrated that epidermal growth factor (EGF) could dramatically upregulate NHE1 expression, while increasing the phosphorylated extracellular signal-regulated protein kinase (ERK1/2) level and hypoxia-inducible factor 1 alpha (HIF-1 expression. In the presence of ERK1/2-specific inhibitor PD98059, EGF stimulated HIF-1 and NHE1 expression was obviously blocked in addition, the presence of HIF-1 -specific inhibitor 2-methoxyestradiol (2-MeOE2) blocked EGF stimulated NHE1 expression. Moreover, results from in vivo and in vitro studies indicate that Rg3 treatment markedly decreased the expression of EGF, EGF receptor (EGFR), phosphorylated ERK1/2 and HIF-1 . Conclusively, these findings suggested that NHE1 was stimulated by EGF, and Rg3 could decrease NHE1 expression by integrally inhibiting EGF-EGFR-ERK1/2-HIF- signal axis in HCC. Together, our evidence indicated that Rg3 was an effective multi-targets antitumor agent for the treatment of HCC.

Ginsenoside Rg1 attenuates adjuvant-induced arthritis in rats via modulation of PPAR-γ/NF-κB signal pathway.

Ginsenoside Rg1, the main active compound in Panax ginseng, has already been shown to have anti-inflammatory effects. However, the protective effects of Rg1 on rheumatoid arthritis (RA) remain unclear. The aim of the present study was to investigate the effects and mechanisms of Rg1 on adjuvant-induced arthritis (AIA) in rats. AIA rats were given Rg1 at doses of 5, 10, and 20 mg/kg intraperitoneally for 14 days to observe the anti-arthritic effects. The results showed that Rg1 significantly alleviated joint swelling and injuries. Rg1 can also significantly reduce the level of TNF-α and IL-6, increase PPAR-γ protein expression, inhibit IκBα phosphorylation and NF-κB nuclear translocation in the inflammatory joints of AIA rats and RAW264.7 cells stimulated by lipopolysaccharide (LPS). The results indicate that Rg1 has therapeutic effects on AIA rats, and the mechanism might be associated with its anti-inflammatory effects by up-regulating PPAR-γ and subsequent inhibition of NF-κB signal pathway.

Effects of ginsenoside Rg1-loaded alginate-chitosan microspheres on human bone marrow stromal cells.

The ginsenoside Rg1 is the most abundant compound in ginseng. Recent studies showed that Rg1 had neuroprotective effects on neuronal cells. The present study was to prepare Rg1-loaded alginate-chitosan microspheres and research the effects of microspheres on human bone marrow (BM) stromal cells (hBMSC). The alginate-chitosan microspheres were prepared by mechanical emulsification technique in combination with ion (Ca2+) and chitosan solidification. Subsequently, the microspheres were employed to load Rg1 ginseng extracts. The microspheres had a smooth surface and were spherical in shape. The average diameter of the microspheres was 3.95 µm. The loading efficiency was approximately 2.12%. The purity of isolated hBMSC was over 98.8%. Rg1-loaded microspheres could promote hBMSC proliferation and differentiation. Meanwhile, Rg1-loaded microspheres could also suppress hBMSC apoptosis induced by hypoxia-reoxygenation. In conclusion, these loaded microspheres may be used in the research of neuroprotective effects of Rg1.

Ginsenoside Rg3 promotes inflammation resolution through M2 macrophage polarization

BackgroundGinsenosides have been reported to have many health benefits, including anti-inflammatory effects, and the resolution of inflammation is now considered to be an active process driven by M2-type macrophages. In order to determine whether ginsenosides modulate macrophage phenotypes to reduce inflammation, 11 ginsenosides were studied with respect to macrophage polarization and the resolution of inflammation. MethodsMouse peritoneal macrophages were polarized into M1 or M2 phenotypes. Reverse transcription-polymerase chain reaction, Western blotting, and measurement of nitric oxide (NO) and prostaglandin E2 levels were performed in vitro and in a zymosan-induced peritonitis C57BL/6 mouse model. ResultsGinsenoside Rg3 was identified as a proresolving ginseng compound based on the induction of M2 macrophage polarization. Ginsenoside Rg3 not only induced the expression of arginase-1 (a representative M2 marker gene), but also suppressed M1 marker genes, such as inducible NO synthase, and NO levels. The proresolving activity of ginsenoside Rg3 was also observed in vivo in a zymosan-induced peritonitis model. Ginsenoside Rg3 accelerated the resolution process when administered at peak inflammatory response into the peritoneal cavity. ConclusionThese results suggest that ginsenoside Rg3 induces the M2 polarization of macrophages and accelerates the resolution of inflammation. This finding opens a new avenue in ginseng pharmacology.

Ginseng on Cancer: Potential Role in Modulating Inflammation-Mediated Angiogenesis.

Angiogenesis is a regulated process integral to many physiological and pathological situations, including carcinogenesis and tumor growth. The majority of the angiogenic processes are related to inflammation. The interplay is not only important in the case of pathogen entry but also influential in chronic inflammatory diseases, tumor growth and tissue regeneration. Modulating the interaction between inflammation and angiogenesis could be an important target for cancer treatment and wound healing alike. Ginseng has a wide range of pharmacological effects, including anti-inflammatory and angiogenesis-modulating activities. This paper presents the recent research progresses on the inhibition of angiogenesis by ginseng and its active constituents, with a particular focus on processes mediated by inflammation. The modulatory role of ginseng compounds in inflammation-mediated angiogenesis involving hypoxia and microRNAs are also discussed. With the potential to modulate the angiogenesis at the transcriptional, translational and protein signaling level via various different mechanisms, ginseng could prove to be effective in cancer therapeutics.

Enhancing Saccharomyces cerevisiae reactive oxygen species and ethanol stress tolerance for high-level production of protopanoxadiol

Protopanaxadiol (PPD) is an active compound in Panax ginseng. Recently, an optimized PPD synthesis pathway contained a ROS releasing step (a P450-type PPD synthase, PPDS) was introduced into Saccharomyces cerevisiae. Here reported a synergistic effect of PPDS-CPR (CPR, cytochrome P450 reductase) uncoupling and ethanol stress on ROS releasing, which reduced cells viability. To build a robust strain, a cell wall integrity associated gene SSD1 was high-expressed to improve ethanol tolerance, and ROS level decreased for 24.7%. Then, regulating the expression of an oxidative stress regulation gene YBP1 decreased 75.2% of ROS releasing, and improved cells viability from 71.3±1.3% to 88.3±1.4% at 84h. Increased cells viability enables yeast to produce more PPD through feeding additional ethanol. In 5L fermenter, PPD production of W3a-ssPy reached to 4.25±0.18g/L (19.48±0.28mg/L/OD600), which is the highest yield reported so far. This work makes the industrial production of PPD possible by microbial fermentation.