Ginseng Saponins Research Articles

Ginsenoside Rg1 prevents early diabetic retinopathy via reducing retinal ganglion cell layer and inner nuclear layer cell apoptosis in db/db mice.

BackgroundDiabetic retinopathy (DR), a diabetic vascular complication, is prone to developing into blindness. Ginsenoside Rg1 (GRg1), a major saponin in ginseng, exerts high anti-apoptotic activity.MethodsThis study aimed to explore the protective effects of GRg1 against diabetes-induced retinal damage. Measurements of blood glucose, blood lipids and vascular permeability were performed, as well as assessments of pathological changes, and the retinal thickness of each layer. Retinal cell apoptosis related protein expression levels were measured by immunofluorescence and western blot assays.ResultsOur data demonstrated that GRg1 effectively reduced blood glucose and triglyceride levels and maintained normal retinal permeability and physiological structure. GRg1 maintained the thickness of the ganglion cell layer (GCL) and the inner nuclear layer (INL) by reducing cell apoptosis.ConclusionsThese data strongly indicate that GRg1 prevents diabetic retinal changes by decreasing GCL and INL cell apoptosis. GRg1 may be a promising drug for early DR treatment.

A Combination of Korean Red Ginseng Extract and Glycyrrhiza glabra L. Extract Enhances Their Individual Anti-Obesity Properties in 3T3-L1 Adipocytes and C57BL/6J Obese Mice.

Anti-obesity activities of Korean red ginseng saponin fraction (RGS) and/or Glycyrrhiza glabra L. extract (GG) were investigated in 3T3-L1 adipocytes and high-fat diet-induced C57BL/6J obese mice. RGS and GG extracts were mixed at a mass ratio of 3:1 (SG31), 1:1 (SG11), or 1:3 (SG13). SG31 showed the highest anti-obesity activity among the three different mass ratios of RGS and GG extracts. SG31 showed higher inhibition efficiency on triglyceride (TG) accumulation than either single extract in 3T3-L1 adipocytes and without any cytotoxicity. It also decreases the expression of adipogenic and lipogenic genes such as C/EBPα and SREBP-1c (sterol regulatory element-binding protein 1c). In the obese induced mouse model, SG31 significantly reduced white adipose tissue weight and body weight, attenuated dyslipidemia, and decreased serum TG levels. In some indices, the activity of SG31 was even higher compared with Garcinia Cambogia water extract, a positive control. The possible mechanism by which SG31 causes the above results was by activating the AMP-activated protein kinase (AMPK) pathway and stimulating the secretion of adiponectin in adipose tissue to regulate energy metabolism balance, inhibit TG formation, and promote β-oxidation of fatty acids. Therefore, SG31 may have efficacy as an anti-obesity functional food or raw material if the results can be confirmed in human studies.

A Solution with Ginseng Saponins and Selenium as Vaccine Diluent to Increase Th1/Th2 Immune Responses in Mice.

Pseudorabies is an important infectious disease of swine, and immunization using attenuated pseudorabies virus (aPrV) vaccine is a routine practice to control this disease in swine herds. This study was to evaluate a saline solution containing ginseng stem-leaf saponins (GSLS) and sodium selenite (Se) as a vaccine adjuvant for its enhancement of immune response to aPrV vaccine. The results showed that aPrV vaccine diluted with saline containing GSLS-Se (aP-GSe) induced significantly higher immune responses than that of the vaccine diluted with saline alone (aP-S). The aP-GSe promoted higher production of gB-specific IgG, IgG1, and IgG2a, neutralizing antibody titers, secretion of Th1-type (IFN-γ, IL-2, IL-12), and Th2-type (IL-4, IL-6, IL-10) cytokines, and upregulated the T-bet/GATA-3 mRNA expression when compared to aP-S. In addition, cytolytic activity of NK cells, lymphocyte proliferation, and CD4+/CD8+ ratio was also significantly increased by aP-GSe. More importantly, aP-GSe conferred a much higher resistance of mice to a field virulent pseudorabies virus (fPrV) challenge. As the present study was conducted in mice, further study is required to evaluate the aP-GSe to improve the vaccination against PrV in swine.

Promotion of compound K production in Saccharomyces cerevisiae by glycerol

BackgroundGinsenoside compound K (CK), one of the primary active metabolites of protopanaxadiol-type ginsenosides, is produced by the intestinal flora that degrade ginseng saponins and exhibits diverse biological properties such as anticancer, anti-inflammatory, and anti-allergic properties. However, it is less abundant in plants. Therefore, enabling its commercialization by construction of a Saccharomyces cerevisiae cell factory is of considerable significance.ResultsWe induced overexpression of PGM2, UGP1, and UGT1 genes in WLT-MVA5, and obtained a strain that produces ginsenoside CK. The production of CK at 96 h was 263.94 ± 2.36 mg/L, and the conversion rate from protopanaxadiol (PPD) to ginsenoside CK was 64.23 ± 0.41%. Additionally, it was observed that the addition of glycerol was beneficial to the synthesis of CK. When 20% glucose (C mol) in the YPD medium was replaced by the same C mol glycerol, CK production increased to 384.52 ± 15.23 mg/L, which was 45.68% higher than that in YPD medium, and the PPD conversion rate increased to 77.37 ± 3.37% as well. As we previously observed that ethanol is beneficial to the production of PPD, ethanol and glycerol were fed simultaneously in the 5-L bioreactor fed fermentation, and the CK levels reached 1.70 ± 0.16 g/L.ConclusionsIn this study, we constructed an S. cerevisiae cell factory that efficiently produced ginsenoside CK. Glycerol effectively increased the glycosylation efficiency of PPD to ginsenoside CK, guiding higher carbon flow to the synthesis of ginsenosides and effectively improving CK production. CK production attained in a 5-L bioreactor was 1.7 g/L after simultaneous feeding of glycerol and ethanol.

Ginsenoside Rd attenuates ACTH-induced corticosterone secretion by blocking the MC2R-cAMP/PKA/CREB pathway in Y1 mouse adrenocortical cells

BackgroundHigher levels of glucocorticoids (GCs), and impaired regulation of the hypothalamic-pituitary-adrenal (HPA) axis may cause or exacerbate the occurrence of metabolic and psychiatric disorders. It has been reported that ginseng saponin extract (GSE) has an inhibitory effect on the hyperactivity of the HPA axis induced by stresses and increased corticosterone level induced by intraperitoneal injection of adrenocorticotrophic hormone (ACTH) in mice. However, the molecular mechanisms by which GSE and its active ginsenosides inhibit corticosterone secretion remain elusive. Main methodsY1 mouse adrenocortical cells were treated with ACTH for up to 60 min to establish a cell model of corticosterone secretion. After treatment with different concentrations of GSE or ginsenoside monomers for 24 h prior to the addition of ACTH, analyses of cAMP content, PKA activity, and the levels of steroidogenesis regulators, melanocortin-2 receptor (MC2R), and melanocortin-2 receptor accessory protein (MRAP) in ACTH-induced Y1 cells were performed. ResultsWe demonstrated that GSE inhibits ACTH-stimulated corticosterone production in Y1 cells by inhibiting factors critical for steroid synthesis. Ginsenoside Rd, an active ingredient of GSE, inhibits corticosterone secretion in the cells and impedes ACTH-induced corticosterone biosynthesis through down-regulation of proteins in the cAMP/PKA/CREB signaling pathway. In addition, Western blot and qPCR analyses showed that ginsenoside Rd attenuated the induction of MC2R and MRAP by ACTH. ConclusionOur findings indicate that ginsenoside Rd inhibits ACTH-induced corticosterone production through blockading the MC2R-cAMP/PKA/CREB pathway in adrenocortical cells. Overall, this mechanism may represent an important therapeutic option for the treatment of stress-related disorders, further supporting the pharmacological benefits of ginseng.

Stem-leaves of Panax as a rich and sustainable source of less-polar ginsenosides: comparison of ginsenosides from Panax ginseng, American ginseng and Panax notoginseng prepared by heating and acid treatment

BackgroundGinsenosides, which have strong biological activities, can be divided into polar or less-polar ginsenosides. MethodsThis study evaluated the phytochemical diversity of the saponins in Panax ginseng (PG) root, American ginseng (AG) root, and Panax notoginseng (NG) root; the stem-leaves from Panax ginseng (SPG) root, American ginseng (SAG) root, and Panax notoginseng (SNG) root as well as the saponins obtained following heating and acidification [transformed Panax ginseng (TPG), transformed American ginseng (TAG), transformed Panax notoginseng (TNG), transformed stem-leaves from Panax ginseng (TSPG), transformed stem-leaves from American ginseng (TSAG), and transformed stem-leaves from Panax notoginseng (TSNG)]. The diversity was determined through the simultaneous quantification of the 16 major ginsenosides. ResultsThe content of ginsenosides in NG was found to be higher than those in AG and PG, and the content in SPG was greater than those in SNG and SAG. After transformation, the contents of polar ginsenosides in the raw saponins decreased, and contents of less-polar compounds increased. TNG had the highest levels of ginsenosides, which is consistent with the transformation of ginseng root. The contents of saponins in the stem-leaves were higher than those in the roots. The transformation rate of SNG was higher than those of the other samples, and the loss ratios of total ginsenosides from NG (6%) and SNG (4%) were the lowest among the tested materials. In addition to the conversion temperature, time, and pH, the crude protein content also affects the conversion to rare saponins. The proteins in Panax notoginseng allowed the highest conversion rate. ConclusionThus, the industrial preparation of less-polar ginsenosides from SNG is more efficient and cheaper.

Increase in Protective Effect of Panax vietnamensis by Heat Processing on Cisplatin-Induced Kidney Cell Toxicity.

Cisplatin is a platinum-based anticancer agent used for treating a wide range of solid cancers. One of the side effects of this drug is its severe nephrotoxicity, limiting the safe dose of cisplatin. Therefore, many natural products have been studied and applied to attenuate the toxicity of this compound. In this study, we found that steamed Vietnamese ginseng (Panax vietnamensis) could significantly reduce the kidney damage of cisplatin in an in vitro model using porcine proximal tubular LLC-PK1 kidney cells. From processed ginseng under optimized conditions (120 °C, 12 h), we isolated seven compounds (20(R,S)-ginsenoside Rh2, 20(R,S)-ginsenoside Rg3, ginsenoside Rk1, ginsenoside-Rg5, and ocotillol genin) that showed kidney-protective potential against cisplatin toxicity. By comparing the 50% recovery concentration (RC50), the R form of ginsenoside, Rh2 and Rg3, had RC50 values of 6.67 ± 0.42 µM and 8.39 ± 0.3 µM, respectively, while the S forms of ginsenoside, Rh2 and Rg3, and Rk1, had weaker protective effects, with RC50 ranging from 46.15 to 88.4 µM. G-Rg5 and ocotillol, the typical saponin of Vietnamese ginseng, had the highest RC50 (180.83 ± 33.27; 226.19 ± 66.16, respectively). Our results suggest that processed Vietnamese gingseng (PVG), as well as those compounds, has the potential to improve kidney damage due to cisplatin toxicity.

Correlative analysis of agronomic traits and quality of Panax ginseng saponins cultivation in farmland

Cultivated ginseng in the farmland would become the mainly planting mode of Panax ginseng. However,there are relatively few cultivation ginseng varieties for farmland in China. Correlative analysis of qualitity and agronomic traits of P. ginseng cultivation in the farmland could provide a reference for the selection of excellent germplasm and new variety breeding of P. ginseng. In this study,the main index of saponin and agronomic traits of 4-6 years' samples were analyzed by UPLC and measured. The results show that there was significant difference in agronomic indexes of Damaya. The coefficient of variation of the root length( CV = 41. 97%) and fresh weight( CV = 31. 81%) were maximum,and the coefficient of variation of the stems thickness( 16. 72%) and root thickness were minimum. There was a significant correlation between yield and root thickness( P<0. 05). There was significant difference in drug yield of different harvest years( P<0. 05),and the yield of 6-years was 31. 52%-39. 69% higher than 4-years. However,there wasn't significant difference in total ginsenosides between 4 and 6 years old P. ginseng,but there was significant difference in ginseng Rg2,Rc and Rb2( P<0. 05),and the ginsenoside contents of different harvesting years were accorded with the criterion standards of 2015 Chinese Pharmacopoeia. There was no significant correlation between the saponin and the agronomic trait,while there was positive correlation with root thickness( P < 0. 05). Therefore,the stem diameter was positive correlation with yield of P. ginseng. Selection of the stem thickness of seedlings is beneficial to the increase of the yield and breeding of P. ginseng.

20(R)-Ginsenoside Rg3 Influences Cancer Stem Cell Properties and the Epithelial-Mesenchymal Transition in Colorectal Cancer via the SNAIL Signaling Axis.

BackgroundCancer stem cells (CSCs) have been proposed as central drivers of cancer relapse in many cancers. In the present study, we investigated the inhibitory effect of 20(R)-Ginsenoside Rg3 (Rg3R), a major active component of ginseng saponin, on CSC-like cells and the Epithelial-Mesenchymal Transition (EMT) in colorectal cancer (CRC).MethodsThe effects of ginsenoside Rg3R on the colony-forming, migration, invasion, and wound-healing abilities of CRC cells were determined in HT29 and SW620 cell lines in vitro. Further, ginsenoside Rg3R was given intraperitoneally at 5mg/kg of mouse body weight to check its effect on the metastasis of CRC cells in vivo.ResultsGinsenoside Rg3R significantly inhibited CSC properties, but did not affect cell proliferation. Moreover, ginsenoside Rg3R treatment significantly inhibited the motility of CRC cells based on migration, invasion, and wound-healing assays. The inhibitory effects of ginsenoside Rg3R on CRC are potentially mediated by significant down-regulation of the expression of stemness genes and EMT markers in CRC cells in a SNAIL-dependent manner. Furthermore, ginsenoside Rg3R treatment decreased both the number and size of tumor nodules in the liver, lung, and kidney tissues in a metastasis mouse model.ConclusionThese findings highlighted the potential use of ginsenoside Rg3R in clinical applications for colorectal cancer treatment.

Purification of ginseng rare sapogenins 25-OH-PPT and its hypoglycemic, antiinflammatory and lipid-lowering mechanisms

BackgroundPanax ginseng Meyer has been used as a nourishing edible herb in East Asia for thousands of years. 25-OH-PPT was first discovered as a natural rare triterpenoid saponin in ginseng stems and leaves by our group. Research found that it showed strong inhibitory effects on α-glucosidase and protein tyrosine phosphatase 1B, and protected cardiocytes (H9c2) through PI3K/Akt pathway. MethodsIn the research, in order to optimize the 25-OH-PPT enrichment process, optimal macroporous resins and optimal purification conditions were studied. Meanwhile, the hypoglycemic effect and mechanism of 25-OH-PPT were evaluated by using STZ to establish insulin-dependent diabetic mice and the spontaneous type 2 diabetes DB/DB mice. Results and ConclusionResearch found that 25-OH-PPT can reduce blood glucose and enhance glucose tolerance in STZ model mice. It increases insulin sensitivity by upregulating GLUT4 and AMPK in skeletal muscle, and activating insulin signaling pathways. In DB/DB mice, 25-OH-PPT achieves hypoglycemic effects mainly by activating the insulin signaling pathway. Meanwhile, through the influence of liver inflammatory factors and lipids in serum, it can be seen that 25-OH-PPT has obvious anti-inflammatory and lipid-lowering effects. These results provide new insights into the study of ginseng as a functional food.

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.

Early IgG Response to Foot and Mouth Disease Vaccine Formulated with a Vegetable Oil Adjuvant.

The present study evaluated soybean oil (SO) containing vitamin E (VE) and ginseng saponins (GS) (SO-VE-GS) for their adjuvant effect on foot-and-mouth disease (FMD) vaccine. Since mineral oil ISA 206 is a common adjuvant used in the FMD vaccine, it was used as a control adjuvant in this study. VE and GS were found to have a synergistic adjuvant effect. When mice were immunized with the FMD vaccine emulsified in SO with VE and GS, significantly higher serum IgG, IgG1, and IgG2a were found than VE and GS used alone. SO-VE-GS and ISA 206 behaved differently in adjuvant activities. When mice were immunized with the FMD vaccine adjuvanted with SO-VE-GS, significantly higher and earlier production of serum IgG was found than that adjuvanted with ISA 206. Although both adjuvants significantly increased the number of bone marrow plasma cells, a stimulation index of lymphocytes (SI) as well as the production of IL-4 and IL-6, SO-VE-GS promoted significantly higher SI and the ratio of CD4+/CD8+ T cells with production of increased IFN-γ and decreased TGF-β1 as compared with the ISA 206 group. The data suggested that SO-VE-GS activated Th1/Th2 immune responses. Transcriptome analysis of splenocytes showed that differentially expressed genes (DEGs), immune-related gene ontology (GO) terms, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were significantly enriched in the SO-VE-GS group. Therefore, the potent adjuvant effect of SO-VE-GS on the FMD vaccine may be attributed to the immune-related gene profile expressed in lymphocytes. Due to its plant origin and due to being much cheaper than imported mineral oil ISA 206, SO-VE-GS deserves further study in relation to vaccines used in food animals.

A Review of the Different Methods Applied in Ginsenoside Extraction From Panax ginseng and Panax quinquefolius Roots

Ginseng saponins, also called ginsenosides, are the main active ingredients of Panax ginseng and Panax quinquefolius and are often used as qualitative and quantitative markers in the regulation of ginseng products. Various methods have been used to extract the major ginsenosides, such as ginsenosides Rb1, Rb2, Rc, Rd, and Rf from P. ginseng and P. quinquefolius. The objective of this paper is to review the studies regarding the influence of different extraction systems on ginsenoside amount and pattern in P. ginseng and P. quinquefolius roots. Although traditional extraction methods, Soxhlet and heat reflux extractions, have many disadvantages, including long extraction times and low extraction efficiency, they are the most widely used methods for ginseng saponin extraction. The amount and pattern of ginsenosides found in P. ginseng and P. quinquefolius roots differ depending on the method of extraction. In particular, the total ginsenoside amount and extraction efficiency can be significantly increased with the use of advanced extraction techniques that apply the conditions of high temperature and/or high pressure, such as pressurized liquid extraction, high-pressure microwave-assisted extraction, supercritical fluid extraction, and pulsed electric field extraction. Among several advanced extraction procedures, ultrahigh-pressure extraction is thought to offer the most advanced and efficient technology in that it requires only a few minutes for ginseng saponin extraction.

Enhanced Production of Protopanaxatriol from Ginsenoside Re and Rg1 Using a Recombinant Bacterial β-glucosidase

20(S)-protopanaxatriol (PPTA), an aglycone of ginseng saponins, is rarely found and is present in a limited amount; it exhibits various pharmaceutical activities, including memory improvement, and anti-diabetic and anti-cancer effects. An enzymatic method was developed to improve 20(S)-protopanaxatriol aglycone [20(S)-PPTA] production using recombinant β-glucosidase (BgpA) cloned from Terrabacter ginsenosidimutans Gsoil 3082T. The optimal hydrolytic activity was obtained at pH 7.0 and 37°C. The enzyme could hydrolyze the rutinoside and glucose moieties at the C6 and C20 positions, respectively, of ginsenosides Re and Rg1 to produce 20(S)-PPTA through the formation of ginsenoside F1 as an intermediate. For gram-scale production, the enzyme reaction was performed in a 10-L fermenter for 48 h at a substrate concentration of 10 mg/mL. Finally, 5.45 g 20(S)-PPTA was produced from 36 g PPT type ginsenoside mixture with 95% purity by chromatography. This study thus reveals an industrial application of a minor component, 20(S)-PPTA.

AKT1-targeted proapoptotic activity of compound K in human breast cancer cells

BackgroundBreast cancer is a severe disease and the second leading cause of cancer death in women worldwide. To surmount this, various diagnosis and treatment options for breast cancer have been developed. One of the most effective strategies for cancer treatment is to induce apoptosis using naturally occurring compounds. Compound K (CK) is a ginseng saponin metabolite generated by human intestinal bacteria. CK has been studied for its cardioprotective, antiinflammatory, and liver-protective effects; however, the role of CK in breast cancer is not fully understood. MethodsTo investigate the anticancer effects of CK in SKBR3 and MDA-MB-231 cells, cell viability assays and flow cytometry analysis were used. In addition, the direct targets of CK anticancer activity were identified using immunoblotting analysis and overexpression experiments. Invasion, migration, and clonogenic assays were carried out to determine the effects of CK on cancer metastasis. ResultsCK-induced cell apoptosis in SKBR3 cells as determined through 3-(4-5-dimethylthiazol-2-yl)-2-5-diphenyltetrazolium bromide assays, propidium iodide (PI) and annexin V staining, and morphological changes. CK increased the cleaved forms of caspase-7, caspase-8, and caspase-9, whereas the expression of Bcl-2 was reduced by CK. In assays probing the cell survival pathway, CK activated only AKT1 and not AKT2. Moreover, CK inhibited breast cancer cell invasion, migration, and colony formation. Through regulation of AKT1 activity, CK exerts anticancer effects by inducing apoptosis. ConclusionOur results suggest that CK could be used as a therapeutic compound for breast cancer.

Efficient production of polysaccharide by Chaetomium globosum CGMCC 6882 through co-culture with host plant Gynostemma pentaphyllum.

Endophytic fungus, as a new kind of microbial resources and separated from plants, has attracted increasing attention due to its ability to synthesize the same or similar bioactive secondary metabolites as the host plants. Nevertheless, the effects of the symbiotic relationship between microorganisms and elicitors existed in host plant on metabolite production are not adequately understood. In the present work, the impacts of elicitors (ginseng saponin and puerarin) and symbiotic microorganisms on endophytic fungus Chaetomium globosum CGMCC 6882 synthesizing polysaccharide were evaluated. Results show that the polysaccharide titers increased from 2.36 to 3.88g/L and 3.67g/L with the addition of 16μg/L ginseng saponin and puerarin, respectively. Moreover, the maximum polysaccharide titer reached 4.55g/L when C. globosum CGMCC 6882 was co-cultured with UV-irradiated G. pentaphyllum. This work brings a significant contribution to the research and interpretation of the relationship between endophytic fungus and its host plant.

Chemical Structures and Pharmacological Profiles of Ginseng Saponins.

Ginseng is a group of cosmopolitan plants with more than a dozen species belonging to the genus Panax in the family Araliaceae that has a long history of use in traditional Chinese medicine (TCM). Among the bioactive constituents extracted from ginseng, ginseng saponins are a group of natural steroid glycosides and triterpene saponins found exclusively throughout the plant. Studies have shown that these ginseng saponins play a significant role in exerting multiple therapeutic effects. This review covers their chemical structure and classification, as well as their pharmacological activities, including their regulatory effects on immunomodulation, their anticancer effects, and their functions in the central nervous and cardiovascular systems. The general benefits of ginseng saponins for boosting physical vitality and improving quality of life are also discussed. The review concludes with fruitful directions for future research in the use of ginseng saponins as effective therapeutic agents.

Preliminary study on response and its mechanism of ginsenoside biosynthesis in Panax ginseng to water regulation

The study is aimed to explore the effect of soil moisture content on ginsenoside biosynthesis and explain its mechanism from the perspectives of antioxidant enzyme system and gene expression of key enzymes in the pathway of ginsenoside synthesis. In the study,two years old Panax ginseng was used as the experimental material and three moisture gradient,40% of saturated water content( W1),60%( W2),80%( W3) were set up. The content of 11 monomeric saponins were determined by HPLC. With GAPDH as a reference gene,six key enzymes( HMGR,SS,β-AS,CYP716 A47,CYP716 A52 v2,CYP716 A53 v2) in ginseng saponin synthesis pathway expression were analyzed by fluorescent quantitative PCR and the activities of superoxide dismutase( SOD),peroxidase( POD),catalase( CAT) activity and MDA content were also determined. With the increase of soil water,the content of ginseng saponin and biomass showed an increasing trend. PPD( Rb1,Rc,Rb2,Rd,Rh2,Rb3,Rg3),PPT( Rg1,Re,Rf) ginsenoside,Ro and total ginsenoside reached the maximum value on August 30,were 9.92,5.48,0.63 mg·g-1,respectively. During the whole regulation period,the antioxidant activity of W3 was greater than that of W1,and the MDA content was less than that of W1. At W3,expression levels of β-AS,CYP716 A47 and CYP716 A53 v2 showed an increasing trend,while HMGR and SS genes showed relatively stable expression levels under various water conditions. According to the correlation analysis,HMGR and SS genes in the W3 treatment group were significantly positively correlated with PPD,PPT ginsenoside and Ro,CYP716 A52 v2 gene was significantly positively correlated with Ro,and CYP716 A47 gene was significantly positively correlated with PPD ginsenoside. There was a significant positive correlation between β-AS gene and PPD ginsenoside in W1 and W2 treatment. Therefore,W3 is the optimum moisture content,ginseng total saponins and monomer saponin content is the highest,the gene closely correlation with content of saponins and more conducive to the accumulation of ginsenosides.

Neuroprotective Effects of Red Ginseng Saponins in Scopolamine-Treated Rats and Activity Screening Based on Pharmacokinetics.

Ginseng has been used to alleviate age-related dementia and memory deterioration for thousands of years. This study investigated the protective effect of red ginseng saponins against scopolamine-induced cerebral injury. Meanwhile, pharmacokinetics of ginsenosides in normal and scopolamine-treated rats were compared. After scopolamine injection, glutathione, catalase and superoxide dismutase levels were significantly decreased when compared with control group. Compared with SA group, pretreatment of rats with red ginseng saponins could increase glutathione, catalase and superoxide dismutase level. Treatment with red ginseng saponins significantly decreased malondialdehyde level. In the pharmacokinetic analysis, a pattern recognition analysis method was used to investigate the pharmacokinetics of the absorbed compounds in blood. The pharmacokinetic parameters of Rg1, Rg2, Rh3, Rg5 and Rk1 in model group had higher area under the curve (AUC), mean residence time (MRT) and peak plasma concentration (Cmax) values; area under the curve (AUC) values and peak plasma concentration (Cmax) of model group was significantly different from that of normal group (p < 0.05). The Cmax value of Rk3, Rh1, Rh2 and Rh4 in model group was higher than normal group, but their AUC values were not significantly different. There was no significantly difference in time at Cmax (Tmax), AUC and Cmax values of Rb1, Rb2 Re, Rc, Rd and Rf between the model and normal group. 16 ginsenosides were grouped into three separate clusters according to principal component analysis (PCA) score plot based on pharmacokinetic data. The results suggested red ginseng saponins have significant protective effect against scopolamine-induced memory deficit and scopolamine-induced rats could lead to the changes of pharmacokinetic behaviors of ginsenosides.

Ginsenoside F1 promotes angiogenesis by activating the IGF-1/IGF1R pathway

Ischemic stroke is one of the most lethal and highly disabling diseases that seriously affects the human health and quality of life. A therapeutic angiogenic strategy has been proposed to alleviate ischemia-induced injury by promoting angiogenesis and improving cerebrovascular function in the ischemic regions. The insulin-like growth factor 1 (IGF-1)/insulin-like growth factor 1 receptor (IGF1R) axis is crucial for cerebral angiogenesis and neurogenesis. However, effective drugs that prevent cerebral ischemic injury by inducing cerebral angiogenesis via activation of the IGF1R pathway are lacking. Here, we screened a pro-angiogenic agent ginsenoside F1 (GF1), a ginseng saponin isolated from a traditional Chinese medicine that was widely used in ischemic stroke treatment. It promoted the proliferation, mobility and tube formation of human umbilical vein endothelial cells and human brain microvascular endothelial cells, as well as pericytes recruitment to the endothelial tubes. GF1 stimulated vessel sprouting in the rat arterial ring and facilitated neovascularization in chicken embryo chorioallantoic membrane (CAM). In the in vivo experiments, GF1 rescued the axitinib-induced vascular defect in zebrafish. It also increased the microvessel density (MVD) and improved focal cerebral blood perfusion in the rat middle cerebral artery occlusion (MCAO) model. Mechanism studies revealed that GF1-induced angiogenesis depended on IGF1R activation mediated by the autocrine IGF-1 loop in endothelial cells. Based on our findings, GF1-induced activation of the IGF-1/IGF1R pathway to promote angiogenesis is an effective approach to alleviate cerebral ischemia, and GF1 is a potential agent that improves cerebrovascular function and promotes recovery from ischemic stroke.