Ginsenoside F2 Research Articles

Effect of citric acid and heat treatment on the content of less-polar ginsenosides in flower buds of Panax ginseng

Ginseng flower bud (GFB), as an inexpensive part of Panax ginseng, attracted significant attention as a beneficial functional food with medicinal potentials due to its high content of ginsenosides. A few studies focused on the utilization of heat treatment and citric acid treatment to process ginseng flowers, converting its polar ginsenosides into rare ginsenosides to improve its biological activities. Thus, in this study, we compared the changes of ginsenosides in GFB after citric acid and heat treatment by HPLC method. The results revealed that less-polar ginsenoside, Rg6 and F4, increased to 1.01 and 0.27% by heat treatment, respectively. Further, ginsenoside F2 increased to 1.13% with 1 M citric acid treatment. Furthermore, based on the combination of these two processing methods for the first time, the conversion rate of less-polar ginsenosides surged to 80%. The content of ginsenoside Rg3(s) and Rg5 increased to 1.509 and 1.871%, respectively, by simultaneous heat and citric acid treatment. Therefore, a processing approach that simultaneously performs heat and citric acid treatments has been proposed, and this considerably inexpensive and convenient processing method could be applied to the processing of GFBs and produce less-polar ginsenosides.

Ginsenoside F1 Attenuates Eosinophilic Inflammation in Chronic Rhinosinusitis by Promoting NK Cell Function

BackgroundGinsenosides have beneficial effects on several airway inflammatory disorders primarily through glucocorticosteroid-like anti-inflammatory activity. Among inflammatory cells, eosinophils play a major pathogenic role in conferring a risk of severe refractory diseases including chronic rhinosinusitis (CRS). However, the role of ginsenosides in reducing eosinophilic inflammation and CRS pathogenesis is unexplored. MethodsWe investigated the therapeutic efficacy and underlying mechanism of ginsenoside F1 (G-F1) in comparison with those of dexamethasone, a representative glucocorticosteroid, in a murine model of CRS. The effects of G-F1 or dexamethasone on sinonasal abnormalities and infiltration of eosinophils and mast cells were evaluated by histological analyses. The changes in inflammatory cytokine levels in sinonasal tissues, macrophages, and NK cells were assessed by qPCR, ELISA, and immunohistochemistry. ResultsWe found that G-F1 significantly attenuated eosinophilic inflammation, mast cell infiltration, epithelial hyperplasia, and mucosal thickening in the sinonasal mucosa of CRS mice. Moreover, G-F1 reduced the expression of IL-4 and IL-13, as well as hematopoietic prostaglandin D synthase required for prostaglandin D2 production. This therapeutic efficacy was associated with increased NK cell function, without suppression of macrophage inflammatory responses. In comparison, dexamethasone potently suppressed macrophage activation. NK cell depletion nullified the therapeutic effects of G-F1, but not dexamethasone, in CRS mice, supporting a causal link between G-F1 and NK cell activity. ConclusionOur results suggest that potentiating NK cell activity, for example with G-F1, is a promising strategy for resolving eosinophilic inflammation in CRS.

Ginsenoside F2 induces cellular toxicity to glioblastoma through the impairment of mitochondrial function

BackgroundGlioblastoma (GBM) is the most aggressive tumor residing within the central nervous system, with extremely poor prognosis. Although the cytotoxic effects of ginsenoside F2 (GF2) on GBM were previously suggested, the precise anti-GBM mechanism of GF2 remains unclear. The aim of this study was to explore the anti-cancer molecular mechanism of GF2 toward human GBM. MethodsGF2-driven cellular toxicity was confirmed in two different GBM cells, U373 and Hs683. To test mitochondrial impairment driven by GF2, we examined the mitochondrial membrane potential, OCR, and ATP production. An intracellular redox imbalance was identified by measuring the relative ratio of reduced glutathione to oxidized glutathione (GSH/GSSG), glutaredoxin (GLRX) mRNA expression, intracellular NAD+ level, and AMPK phosphorylation status. ResultsGF2 increased the percentage of cleaved caspase 3-positive cells and γH2AX signal intensities, confirming that GF2 shows the cytotoxicity against GBM. GO enrichment analysis suggested that the mitochondrial function could be negatively influenced by GF2. GF2 reduced the mitochondrial membrane potential, basal mitochondrial respiratory rate, and ATP production capacity. Our results showed that GF2 downregulated the relative GSH/GSSG, intracellular NAD+ level, and GLRX expression, suggesting that GF2 may alter the intracellular redox balance that led to mitochondrial impairment. ConclusionGF2 reduces mitochondrial membrane potential, inhibits cellular oxygen consumption, activates AMPK signaling, and induces cell death. Our study examined the potential vulnerability of mitochondrial activity in GBM, and this may hold therapeutic promise.

Rapid identification of cytochrome P450 inductive constituents of Shenmai injection by combined pregnane X receptor reporter gene assay and LC-TOF-MS analysis

Ethnopharmacological relevanceIdentifying the inductive constituents of cytochrome P450 (CYP) enzymes is important in characterizing the safety of ethnopharmacological herbal preparations. Aim of the studyThis study provides a rapid and accurate method for screening CYP inducers in Shenmai injection (SMI), a traditional Chinese medicine. Materials and methodsWe combined a pregnane X receptor (PXR) reporter gene assay and liquid chromatography time-of-flight mass spectrometry (LC-TOF-MS) analysis to screen ethanol and aqueous extracts of SMI for CYP-inducing constituents. ResultsThe ethanol extract exhibited stronger PXR activity than the aqueous extract. Of the 29 chemical compounds identified, 7 compounds with high relative concentrations in the ethanol extract were further evaluated for PXR activity. The highest activity was exhibited by methyl ophiopogonanone B and ginsenoside F2, indicating that they are CYP inducers. ConclusionsThe identification method applied in this study was rapid and accurate and is suitable for screening CYP inducers in herbal preparations.

Mixture of enzyme-processed Panax ginseng and Gastrodia elata extract prevents UVB-induced decrease of procollagen type 1 and increase of MMP-1 and IL-6 in human dermal fibroblasts.

According to the previously described anti-photoaging effect of the enzyme-processed Panax ginseng extract and Gastrodia elata extract, we hypothesized that the combination of the two extracts would have superior effect to protect human skin from UVB radiation. Besides, the mixture of active components isolated from herbal extracts, ginsenoside F2, and α-gastrodin was investigated on the photo-protective capability. The expression of aging-related markers including matrix metalloproteinase-1 (MMP-1), interleukin-6 (IL-6), and procollagen type 1 was evaluated using ELISA kits. It was reported that the herbal extract at a Panax ginseng extract to Gastrodia elata extract ratio of 1:10 (w/w) and the compound mixture with equal proportion of ginsenoside F2 and α-gastrodin exhibited significant inhibition of MMP-1 and IL-6 production, and marked upregulation of procollagen type 1 formation. Thus, the combination of either the enzyme-processed herbal extracts or their active components would enhance the properties of prevention and treatment of UVB-induced skin damage.

Differences in Intestinal Metabolism of Ginseng Between Normal and Immunosuppressed Rats.

Ginseng is usually consumed as a dietary supplement for health care in the normal state or prescribed as a herbal medicine in pathologic conditions. Although metabolic studies of ginseng are commonly performed on healthy organisms, the metabolic characteristics in pathologic organisms remain unexplored. This study aimed to uncover the difference in intestinal metabolism of ginseng between normal and cyclophosphamide-induced immunosuppressed rats and further discuss the potential mechanisms involved. Twelve Sprague-Dawley rats (6-8weeks old) were randomly divided into two groups: the normal group (NG) and immunosuppressed group (ISG). Rats in the NG and ISG groups were intraperitoneally administered normal saline and cyclophosphamide injections (40mg/kg) on the 1st, 2nd, 3rd and 10th days; on the 12th day, all rats were intragastrically administered ginseng water extract (900mg/kg). The difference in intestinal metabolism of ginseng was compared using an ultra-high-performance liquid chromatography coupled with quadruple time-of-flight mass spectrometry-based metabolomics approach, and the diversities of gut microbiota were analyzed by 16S rRNA gene sequencing between the two groups. The intestinal metabolomic characteristics of ginseng were significantly different between the normal and immunosuppressed rats, with the ginsenoside F2 (F2), 20S-ginsenoside Rg3 (20(S)-Rg3), pseudo-ginsenoside Rt5 (Pseudo-Rt5), ginsenoside Rd (Rd), ginsenoside Rh1 (Rh1), 20S-ginsenoside Rg1 (20(S)-Rg1), ginsenoside compound K (CK), ginsenoside Rg2 (Rg2) and 20S-panaxatriol (S-PPT) more abundant in immunosuppressed ones (P < 0.05). Additionally, the composition of gut microbiota was remarkably altered in the two groups, with some specific bacterial communities such as Bacteroides spp., Eubacterium spp. and Lachnospiraceae_UCG-010 spp. increased and Bifidobacterium spp. decreased in immunosuppressed rats compared with normal ones. The intestinal metabolism of ginseng in immunosuppressed rats was significantly different from that in normal ones, which might be partly attributed to the changes in the intensity of specific gut bacteria. The outcomes of this study could provide scientific data for rationalization of ginseng use as both a dietary supplement and herbal medicine.

Protective effects of SGB121, ginsenoside F1-enriched ginseng extract, on scopolamine-induced cytotoxicity and memory impairments

• Ginsenoside F1 was determined as the representative constituent of SGB121. • SGB121 reversed scopolamine-induced neurotoxicity in SH-SY5Y cells. • SGB121 significantly recovered scopolamine-induced cognitive deficits in ICR mice. • SGB121-induced memory improvements were mediated by ERK/CREB/BDNF signaling pathway. Ginsenosides have been reported to improve memory impairments. However, the effects of metabolized minor ginsenosides on neuronal damage and cognitive function remain unclear. We investigated the effects of SGB121, ginsenoside F1 enriched ginseng extract, on scopolamine-induced cytotoxicity and cognitive deficits in vitro and in vivo , respectively. We observed that SGB121 reversed the scopolamine-induced apoptosis; mitochondrial membrane potential reduction; and dephosphorylation of Akt, glycogen synthase kinase-3beta (GSK3β), and extracellular signal-regulated kinases (ERK) in SH-SY5Y cells. Oral SGB121 administration in ICR-mice once-daily for 7 days significantly recovered scopolamine-induced memory impairment analyzed using Y-maze test and passive avoidance task. In mouse hippocampi, SGB121 restored scopolamine-induced decrease in ERK and cAMP response element-binding protein (CREB) phosphorylation and brain-derived neurotrophic factor (BDNF) expression. Furthermore, SGB121 decreased acetylcholinesterase expression both in SH-SY5Y cells and in mouse hippocampi. SGB121 demonstrated protective effects against neurotoxicity and memory impairments, suggesting its potential as oral therapeutics in neurodegenerative diseases.

SGL 121 Attenuates Nonalcoholic Fatty Liver Disease through Adjusting Lipid Metabolism Through AMPK Signaling Pathway.

A ginsenoside F2-enhanced mixture (SGL 121) increases the content of ginsenoside F2 by biotransformation. In the present study, we investigated the effect of SGL 121 on nonalcoholic fatty liver disease (NAFLD) in vitro and in vivo. High-fat, high-carbohydrate-diet (HFHC)-fed mice were administered SGL 121 for 12 weeks to assess its effect on improving NAFLD. In HepG2 cells, SGL 121 acted as an antioxidant, a hepatoprotectant, and had an anti-lipogenic effect. In NAFLD mice, SGL 121 significantly improved body fat mass; levels of hepatic triglyceride (TG), hepatic malondialdehyde (MDA), serum total cholesterol (TC), high-density lipoprotein (HDL), and low-density lipoprotein (LDL); and activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST). In HepG2 cells, induced by oxidative stress, SGL 121 increased cytoprotection, inhibited reactive oxygen species (ROS) production, and increased antioxidant enzyme activity. SGL 121 activated the Nrf2/HO-1 signaling pathway and improved lipid accumulation induced by free fatty acids (FFA). Sterol regulatory element-binding protein-1 (SREBP-1) and fatty acid synthase (FAS) expression was significantly reduced in NAFLD-induced liver and HepG2 cells treated with SGL 121. Moreover, SGL 121 activated adenosine monophosphate-activated protein kinase (AMPK), which plays an important role in the regulation of lipid metabolism. The effect of SGL 121 on the improvement of NAFLD seems to be related to its antioxidant effects and activation of AMPK. In conclusion, SGL 121 can be potentially used for the treatment of NAFLD.

Changes of Ginsenoside Composition in the Creation of Black Ginseng Leaf.

Ginseng is an increasingly popular ingredient in supplements for healthcare products and traditional medicine. Heat-processed ginsengs, such as red ginseng or black ginseng, are regarded as more valuable for medicinal use when compared to white ginseng due to some unique less polar ginsenosides that are produced during heat-treatment. Although ginseng leaf contains abundant ginsenosides, attention has mostly focused on ginseng root; relatively few publications have focused on ginseng leaf. Raw ginseng leaf was steamed nine times to make black ginseng leaf using a process that is similar to that used to produce black ginseng root. Sixteen ginsenosides were analyzed during each steaming while using high-performance liquid chromatography (HPLC). The contents of ginsenosides Rd and Re decreased and the less polar ginsenosides (F2, Rg3, Rk2, Rk3, Rh3, Rh4, and protopanaxatriol) enriched during steam treatment. After nine cycles of steaming, the contents of the less polar ginsenosides F2, Rg3, and Rk2 increased by 12.9-fold, 8.6-fold, and 2.6-fold, respectively. Further, we found that the polar protopanaxadiol (PPD) -type ginsenosides are more likely to be converted from ginsenoside Rg3 to ginsenosides Rk1 and Rg5 via dehydration from Rg3, and from ginsenoside Rh2 to ginsenosides Rk2 and Rh3 through losing an H2O molecule than to be completely degraded to the aglycones PPD during the heat process. This study suggests that ginseng leaves can be used to produce less polar ginsenosides through heat processes, such as steaming.

Comparative analysis of metabolite profiles from Panax herbs in specific tissues and cultivation conditions reveals the strategy of accumulation

Panax ginseng is one of the most valuable medicinal plants in the world, and wild-forest (WG) and artificial-forest (AG) ginseng are very popular in the ginseng market, with ginsenosides constituting a majority of the bioactives. Research on the biochemical and physiological patterns of metabolic accumulation in different tissues of ginseng cultivated under various conditions is relatively scarce. We profiled metabolites using GC/MS and LC/MS to explore the bioactive component changes and interrelationships that occur in 7 tissues of WG and AG. In total, 149 primary metabolites and 46 secondary compounds were found in aboveground and belowground tissues. Metabolite changes associated with primary and secondary biochemistry were observed, and the levels of ginsenoside F2 and other compounds showed a significant correlation by statistical analysis in ginseng under both cultivation methods, as observed for secondary compounds and C and N metabolites. In addition, the number of secondary components was higher in the aboveground parts than in the belowground parts, showing a different pattern, and the same accumulation pattern of compounds involved in C and N metabolism was observed in individual plant tissues, but the high rate of photosynthesis and energy metabolism in WG provided energy for the biosynthesis of secondary compounds. Furthermore, artificial neural network models explained the variation in the secondary compounds very well via the combination of several different metabolites from WG and AG. Finally, C and N metabolism plays a key role in secondary compound biosynthesis in specific tissues and cultivation conditions and highlights large-scale metabolite patterns in WG and AG.

Ginsenoside F2 attenuates chronic-binge ethanol-induced liver injury by increasing regulatory T cells and decreasing Th17 cells

BackgroundRecently, beneficial roles of ginsenoside F2 (GF2), a minor constituent of Panax ginseng, have been demonstrated in diverse inflammatory diseases. However, its roles in alcoholic liver inflammation and injury have not been clearly understood. Here, we investigated the underlying mechanism by which GF2 ameliorated alcoholic liver injury. MethodsTo induce alcoholic liver injury, C57BL/6J wild type (WT) or interleukin (IL)-10 knockout (KO) mice were orally administered with ethanol (3 g/kg) or ethanol-containing GF2 (50 mg/kg) for 2 wk. Liver injury and infiltration of macrophages and neutrophils were evaluated by serum biochemistry and immunohistochemistry, respectively. The changes of hepatic immune cells were assessed by flow cytometry and polymerase chain reaction analysis. In vitro differentiation of naïve T cells was performed. ResultsGF2 treatment significantly attenuated alcoholic liver injury, in which infiltrations of inflammatory macrophages and neutrophils were decreased. Moreover, the frequencies of Foxp3+ regulatory T cells (Tregs) increased but IL-17–producing T (Th17) cells decreased in GF2-treated mice compared to controls. Furthermore, the mRNA expression of IL-10 and Foxp3 was significantly increased, whereas IL-17 mRNA expression was suppressed in GF2-treated mice. However, these beneficial roles of GF2 were not observed in GF2-treated IL-10 KO mice, suggesting a critical role of IL-10. Similarly, GF2 treatment suppressed differentiation of naïve T cells into Th17 cells by inhibiting RORγt expression and stimulating Foxp3 expression. ConclusionThe present study suggests that GF2 treatment attenuates alcoholic liver injury by increasing IL-10 expression and Tregs and decreasing IL-17 expression and Th17 cells.

Transformation of Major Ginsenosides into Minor Ginsenosides in Ginseng by Pickling in Salted Rice Malt Paste

Increasing the content of minor ginsenosides in ginseng enhances its pharmaceutical activities. For this study, minor ginsenosides F2 and CK were produced in ginseng by pickling in a salted rice malt paste fermented using Aspergillus kawachii. The A. kawachii excluded β-glucosidase in the culture broth with 125 mU/mL after 16 d cultivation, and hydrolyzed major ginsenoside Rb1 to generate F2 and CK on the pathway Rb1→Rd→F2→CK. Steamed rice was fermented by A. kawachii with 14% NaCl to produce a salted rice malt paste as a pickle bed with 165 mU/mL of β-glucosidase. Fresh 1-year-old and 6-year-old ginseng, which had Rb1 and Rd but which had neither F2 nor CK, were pickled in the salted rice malt paste for 28d. The extract showed production of F2 and CK, and changed the ratio of Rb1, Rd2, F2, and CK in ginseng

Optimization of UDP-glucose supply module and production of ginsenoside F1 in Saccharomyces cerevisiae

Ginsenoside F1 is a rare ginsenoside in medicinal plants such as Panax ginseng,P. notogingseng and P. quinquefolius. It has strong pharmacological activities of anti-tumor,anti-oxidation and anti-aging. In order to directly produce ginsenoside F1 by using inexpensive raw materials such as glucose,we integrated the codon-optimized P.ginseng dammarenediol-Ⅱ synthase(Syn Pg DDS),P.ginseng protopanaxadiol synthase(Syn Pg PPDS),P. ginseng protopanaxatriol synthase(Syn Pg PPTS) genes and Arabidopsis thaliana cytochrome P450 reductase(At CPR1) gene into triterpene chassis strain BY-T3. The transformant BY-PPT can produce protopanaxatriol. Then we integrated the Sacchromyces cerevisiae phosphoglucomutase 1(PGM1),phosphoglucomutase 2(PGM2) and UDP-glucose pyrophosphorylase 1(UGP1) genes into chassis strain BY-PPT. The UDP-glucose supply module increased UDP-glucose production by 8. 65 times and eventually reached to 44. 30 mg·L-1 while confirmed in the transformant BY-PPT-GM. Next,we integrated the UDPglucosyltransferase Pg3-29 gene which can catalyze protopanaxatriol to produce ginsenoside F1 into chassis strain BY-PPT-GM. The transformant BY-F1 produced a small amount of ginsenoside F1 which was measured as 0. 5 mg·L-1. After the fermentation process was optimized,the titer of ginsenoside F1 could be increased by 900 times to 450. 5 mg·L-1. The high-efficiency UDP-glucose supply module in this study can provide reference for the construction of cell factories for production of saponin,and provide an important basis for further obtaining high-yield ginsenoside yeast cells.

Minor ginsenoside F1 improves memory in APP/PS1 mice

Ginseng has been shown to produce a cognitive improvement effect. The key molecular components in ginseng that produce pharmacological effects are ginsenosides. Previous studies reported a memory improvement effect of a few major ginsenosides. However, the identity of specific minor ginsenosides mediating such function remains unknown. Here, we report that a minor ginsenoside F1 improves memory function in APPswe/PSEN1dE9 (APP/PS1) double-transgenic Alzheimer’s disease (AD) model mice. After 8-wk oral administration of F1 jelly, we observed that spatial working memory, but not context-dependent fear memory, was restored in AD mice. To search for a possible underlying molecular and cellular mechanism, we investigated the effect of F1 on Aβ plaque. We observed F1 administration reduced the Aβ plaque area and density in the cortex, but not in the hippocampus of AD mice. Next, we tested for the effect of F1 on the expression level of key molecules involved in learning and memory. Results from Western blot assay revealed that an abnormally reduced level of a phosphorylated form of CREB in the hippocampus of AD mice was restored to a normal level by F1 administration. Moreover, in the same animals, BDNF level was augmented in the cortex. Our results, therefore, suggest that minor ginsenoside F1 constitutes a promising target to develop therapeutic agents for AD.

Dose-dependent exposure profile and metabolic characterization of notoginsenoside R1 in rat plasma by ultra-fast liquid chromatography-electrospray ionization-tandem mass spectrometry.

Notoginsenoside R1 (NGR1 ), a diagnostic protopanaxatriol-type (ppt-type) saponin in Panax notoginseng, possesses potent biological activities including antithrombotic, anti-inflammatory, neuron protection and improvement of microcirculation, yet its pharmacokinetics and metabolic characterization as an individual compound remain unclear. The aim of this study was to investigate the exposure profile of NGR1 in rats after oral and intravenous administration and to explore the metabolic characterization of NGR1 . A simple and sensitive ultra-fast liquid chromatographic-tandem mass spectrometric method was developed and validated for the quantitative determination of NGR1 and its major metabolites, and for characterization of its metabolic profile in rat plasma. The blood samples were precipitated with methanol, quantified in a negative multiple reaction monitoring mode and analyzed within 6.0 min. Validation parameters (linearity, precision and accuracy, recovery and matrix effect, stability) were within acceptable ranges. After oral administration, NGR1 exhibited dose-independent exposure behaviors with t1/2 over 8.0 h and oral bioavailability of 0.25-0.29%. A total of seven metabolites were characterized, including two pairs of epimers, 20(R)-notoginsenoside R2 /20(S)-notoginsenoside R2 and 20(R)-ginsenoside Rh1 /20(S)-ginsenoside Rh1 , with the 20(R) form of saponins identified for the first time in rat plasma. Five deglycometabolites were quantitatively determined, among which 20(S)-notoginsenoside R2 , ginsenoside Rg1 , ginsenoside F1 and protopanaxatriol displayed relatively high exploration, which may partly explain the pharmacodynamic diversity of ginsenosides after oral dose.

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.

Effects of gut microbiota on the pharmacokinetics of protopanaxadiol ginsenosides Rd, Rg3, F2, and compound K in healthy volunteers treated orally with red ginseng

BackgroundIt is well recognized that gut microbiota is involved in the biotransformation of ginsenosides by converting the polar ginsenosides to nonpolar bioactive ginsenosides. However, the roles of the gut microbiota on the pharmacokinetics of ginsenosides in humans have not yet been fully elucidated. MethodsRed ginseng (RG) or fermented red ginseng was orally administered to 34 healthy Korean volunteers, and the serum concentrations of the ginsenosides were determined using liquid chromatography–tandem mass spectrometry. In addition, the fecal ginsenoside Rd– and compound K (CK)–forming activities were measured. Then, the correlations between the pharmacokinetic profiles of the ginsenosides and the fecal ginsenoside–metabolizing activities were investigated. ResultsFor the RG group, the area under the serum concentration–time curve values of ginsenosides Rd, F2, Rg3, and CK were 8.20 ± 11.95 ng·h/mL, 4.54 ± 3.70 ng·h/mL, 36.40 ± 19.68 ng·h/mL, and 40.30 ± 29.83 ng·h/mL, respectively. For the fermented red ginseng group, the the area under curve from zero to infinity (AUC∞) values of ginsenosides Rd, F2, Rg3, and CK were 187.90 ± 95.87 ng·h/mL, 30.24 ± 41.87 ng·h/mL, 28.68 ± 14.27 ng·h/mL, and 137.01 ± 96.16 ng·h/mL, respectively. The fecal CK-forming activities of the healthy volunteers were generally proportional to their ginsenoside Rd–forming activities. The area under the serum concentration–time curve value of CK exhibited an obvious positive correlation (r = 0.566, p < 0.01) with the fecal CK-forming activity. ConclusionThe gut microbiota may play an important role in the bioavailability of the nonpolar RG ginsenosides by affecting the biotransformation of the ginsenosides.

하우스에서 재배된 새싹인삼의 재배시기별 생육, 유효성분 및 물성의 변화

Background: The ginseng ginsenosides, which have various physiological activities, are known to be more abundant in the leaves than in the roots, and the consumers" interest in ginseng sprout as a functional vegetable has been increasing. Methods and Results: The aim of this study was to investigate the effects of growth period on growth properties, active ingredients and rheology of ginseng sprouts cultivated in a non-heated greenhouse equipped with a shade net for 60 days, starting from the end of May to the middle of July. The chlorophyll content of the leaves decreased, but their length and width increased with increasing cultivation days. In particular, growth increased significantly until 40 days, but only slightly after 50 days. The stem length did not increase greatly from the 20 th to the 30 th day of cultivation, but increased significantly from the 30 th to the 40 th day, and then further increased gradually. The weight of the leaves, stems, and roots increased slightly, but not change significantly. After 40 days of cultivation, the total ginsenoside content increased by 1.07 times in the leaves and decreased by 0.80 times in the roots with increasing cultivation days. The leaf contents of ginsenosides Rg₁, Re, Rb₁, Rc, F₃ and F₄ increased with increasing cultivation days. The rheological properties of ginseng sprout showed the greatest influence on stem hardening with increasing cultivation days. Conclusions: Therefore, based on the growth characteristics, active ingredients and physical properties, 40 days after sowing was considered to be an appropriate harvesting time for ginseng sprouts.

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.

Ginsenoside F4 inhibits platelet aggregation and thrombus formation by dephosphorylation of IP3RI and VASP

Ginsenoside F4 inhibits platelet aggregation and thrombus formation by dephosphorylation of IP₃RI and VASP