Ginseng Polysaccharide Research Articles

Studies on the mechanism of Panax Ginseng in the treatment of deficiency of vital energy dementia rats based on urine metabolomics

Panax Ginseng (PG) has been used to strengthen memory and physique for thousands of years, because its main components ginsenosides (GS) and ginseng polysaccharides (GP) play a major role, but its mechanism is not clear. In this study, a rat model of dementia with vital energy deficiency (DED) was established through intraperitoneal injection with D-galactose and AlCl3 and combined with exhaustive swimming. Pharmacological studies and the urine metabolomics based on ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) were employed for evaluation the efficacy of PG and exploring this treatment mechanism. Through urine metabolic profiling, it can be seen that DED rats after PG administration are close to normal group (NG) rats, and PG can regulate the in vivo status of DED rats which tend to NG. The results of behavioral, biochemical indicators and immunohistochemistry further verified the above results, and the mechanism of action of each component is refined. Ultimately, we believe that the mechanism of PG in the treatment of DED is that ginsenosides (GS) intervenes in phenylalanine tryptophan and tyrosine metabolism, stimulates dopamine production, inhibits Aβ deposition and neuroinflammation; and that ginseng polysaccharides (GP) provides energy to strengthen the TCA cycle and improve immune capacity.

Red ginseng polysaccharide alleviates cytotoxicity and promotes anti-inflammatory activity of ginsenosides

Although Ginsenosides are a major physiological component of red ginseng (RG), some isolated ginsenosides are known to have cytotoxic activity. This study was intended to reduce cytotoxicity and promote anti-inflammatory activity of ginsenosides by mixing the crude ginsenosides (RG-CG) and polysaccharides (RG-CP). RG-CG-CM, fractionated from RG-CG, not only had higher anti-inflammatory activity than that of RG-CG at 100 μg/mL, but also showed increased cytotoxicity, while RG-CP-4P and RG-CP-8P, fractionated from RG-CP, showed no anti-inflammatory activity and cytotoxicity. To reduce the cytotoxicity without affecting the high anti-inflammatory activity of RG-CG-CM, RG-CG-CM and RG-CP-4P were mixed in a ratio of 2:8. The anti-inflammatory activity was significantly increased at a concentration of 75 μg/mL, while no cytotoxicity was observed. A combination of RG-CP and RG-CG effectively reduced the cytotoxicity and enhanced the anti-inflammatory activity of RG-CG, specifically RG-CG-CM fraction, providing scope for its industrial application.

Strategies for Remodeling the Tumor Microenvironment Using Active Ingredients of Ginseng-A Promising Approach for Cancer Therapy.

The tumor microenvironment (TME) plays a key role in promoting the initiation and progression of tumors, leading to chemoradiotherapy resistance and immunotherapy failure. Targeting of the TME is a novel anti-tumor therapeutic approach and is currently a focus of anti-tumor research. Panax ginseng C. A. Meyer (ginseng), an ingredient of well-known traditional Asia medicines, exerts beneficial anti-tumor effects and can regulate the TME. Here, we present a systematic review that describes the current status of research efforts to elucidate the functions and mechanisms of ginseng active components (including ginsenosides and ginseng polysaccharides) for achieving TME regulation. Ginsenosides have variety effects on TME, such as Rg3, Rd and Rk3 can inhibit tumor angiogenesis; Rg3, Rh2 and M4 can regulate the function of immune cells; Rg3, Rd and Rg5 can restrain the stemness of cancer stem cells. Ginseng polysaccharides (such as red ginseng acidic polysaccharides and polysaccharides extracted from ginseng berry and ginseng leaves) can regulate TME mainly by stimulating immune cells. In addition, we propose a potential mechanistic link between ginseng-associated restoration of gut microbiota and the tumor immune microenvironment. Finally, we describe recent advances for improving ginseng efficacy, including the development of a nano-drug delivery system. Taken together, this review provides novel perspectives on potential applications for ginseng active ingredients as anti-cancer adjuvants that achieve anti-cancer effects by reshaping the tumor microenvironment.

Extraction, Structural Characterization, and Anti-Hepatocellular Carcinoma Activity of Polysaccharides From Panax ginseng Meyer.

Polysaccharides are the main active ingredients of ginseng. To extract the most effective polysaccharides against hepatocellular carcinoma (HCC), we isolated and characterized the polysaccharides from the mountain cultivated ginseng (MCG) and compared their composition and cytotoxic effect with cultivated ginseng (CG) polysaccharide against HepG2 cell lines for the first time. MCG polysaccharides and CG polysaccharides were fractionated into two fractions such as MTPS-1, MTPS-2 and CTPS-1, CTPS-2 by salting out, respectively. Compared to CG, MCG possessed appreciable cytotoxic effect against HepG2 cells among that MTPS-1 possess fortified effect. Then, MTPS-1 was selected for further isolation process and seven acidic polysaccharides (MCGP-1–MCGP-7) were obtained using ethanol precipitation, ion-exchange, and gel permeation chromatography techniques. Structural characteristics of the polysaccharides (MCGP-1–MCGP-7) were done by adapting methylation/GC-MS and NMR analysis. Overall, MCGP-3 polysaccharide was found to possess significant cytotoxic effect against HepG2 cells with the IC50 value.

Identifying Suitable Supplements to Improve Piglet Survival during Farrowing and Lactation.

Simple SummaryThe death of piglets during birth and prior to weaning is a concern for welfare and affects the profitability of production systems. Four distinct parameters can be identified as having a direct impact on the survival of piglets to weaning. These parameters are stillbirth rate, birth weight and weight variation, daily gain and weaning weight, and colostrum and milk quality. These four parameters were found to benefit from different supplements provided to the sow around the time of farrowing (giving birth). For example, stillbirth could be reduced by supplements in late pregnancy, including forms of arginine, alpha-tocopherol-selenium, uridine, and Saccharomyces cerevisiae yeast culture, whereas average daily weight gain and weaning weight of the piglets were closely related to supplements which improved colostrum and milk quality. Therefore, an effective supplement plan to improve piglet survival must consider the circumstances of the individual system and target one or more of the highlighted parameters. It is unlikely that any one supplement will successfully target all four parameters discussed.Piglet mortality during parturition and prior to weaning is an ongoing economic and welfare issue. This review collates the current literature describing the effects of specific dietary supplements on key parameters affecting piglet survival. Four distinct parameters were identified as having a direct impact on the survival of piglets to weaning: stillbirth rate, birth weight and weight variation, daily gain and weaning weight, and colostrum and milk quality. In the primary stage, relevant literature from the past 5 years was reviewed, followed by a secondary review of literature older than 5 years. The focal parameters benefitted from different supplements. For example, stillbirth may be reduced by supplements in late gestation, including forms of arginine, alpha-tocopherol-selenium, uridine, and Saccharomyces cerevisiae yeast culture, whereas average daily gain and weaning weight were related closely to supplements which improved colostrum and milk quality, most commonly fats and fatty acids in the form of n-3 polyunsaturated fatty acids, soybean oil, and fish oil, and polysaccharides, such as ginseng polysaccharide. Therefore, an effective supplement plan for piglet mortality reduction must consider the circumstances of the individual system and target one or more of the highlighted parameters.

Polysaccharides Extracted From Panax Ginseng C.A. Mey Enhance Complement Component 4 Biosynthesis in Human Hepatocytes.

Panax ginseng C.A. Mey (ginseng) is a classic medicinal plant which is well known for enhancing immune capacity. Polysaccharides are one of the main active components of ginseng. We isolated water-soluble ginseng polysaccharides (WGP) and analyzed the physicochemical properties of WGP including molecular weight, monosaccharide composition, and structural characteristics. WGP had minimal effect on the growth of hepatocytes. Interestingly, WGP significantly increased the mRNA and protein levels of complement component 4 (C4), one of the core components of the complement system. Promoter reporter gene assays revealed that WGP significantly enhanced activity of the C4 gene promoter. Deletion analyses determined that the E-box1 and Sp1 regions play key roles in WGP-induced C4 transcription. Taken together, our results suggest that WGP promotes C4 biosynthesis through upregulation of transcription. These results provide new explanation for the intrinsic mechanism by which ginseng boosts human immune capacity.

Characterisation, Chain Conformation and Antifatigue Effect of Steamed Ginseng Polysaccharides With Different Molecular Weight.

Two polysaccharides were obtained from steamed ginseng via ultrafiltration, and their physical–chemical properties, solution properties and antifatigue activities were studied. WSGP-S3 and WSGP-G3 were acid heteropolysaccharides with the molecular weights of 2.03 × 104 and 4.86 × 104, respectively. They were composed of different molar ratios of the monosaccharides Rha, GlcA, GalA, Glc, Gal, and Ara. The results of size-exclusion chromatography–multiangle laser light scattering analysis, Conge red staining and Circular dichroism spectroscopy revealed that WSGP-S3 exhibited a random conformation of branched clusters in solution. By contrast, WSGP-G3 exhibited an ordered conformation, including helix-like conformations in aqueous solution. Antifatigue activity tests proved that WSGP-S3 markedly prolonged the exhaustive swimming time of fatigued mice; increased liver and muscle glycogen levels and superoxide dismutase, catalase, glutathione peroxidase activities and decreased blood lactic acid, nitrogen and malondialdehyde levels compared with the control treatment. Moreover, it enhanced spleen cell proliferation in fatigued mice. By contrast, WSGP-G3 had no significant effect on fatigued mice. The results showed that WSGP-S3 might have a major contribution to the antifatigue effects of steamed ginseng polysaccharides and could be a potential anti-fatigue polysaccharide.

Insight Into Polysaccharides From Panax ginseng C. A. Meyer in Improving Intestinal Inflammation: Modulating Intestinal Microbiota and Autophagy.

Polysaccharides from Panax ginseng C. A. Meyer (P. ginseng) are the main active component of P. ginseng and exhibit significant intestinal anti-inflammatory activity. However, the therapeutic mechanism of the ginseng polysaccharide is unclear, and this hinders the application for medicine or functional food. In this study, a polysaccharide was isolated from P. ginseng (GP). The primary structure and morphology of the GP were studied by HPLC, FT-IR spectroscopy, and scanning electron microscopy (SEM). Further, its intestinal anti-inflammatory activity and its mechanism of function were evaluated in experimental systems using DSS-induced rats, fecal microbiota transplantation (FMT), and LPS-stimulated HT-29 cells. Results showed that GP modulated the structure of gut microbiota and restored mTOR-dependent autophagic dysfunction. Consequently, active autophagy suppressed inflammation through the inhibition of NF-κB, oxidative stress, and the release of cytokines. Therefore, our research provides a rationale for future investigations into the relationship between microbiota and autophagy and revealed the therapeutic potential of GP for inflammatory bowel disease.

Clinical potentials of ginseng polysaccharide for treating gestational diabetes mellitus.

Gestational diabetes mellitus (GDM) is the most common glucose metabolism complication or cause of potential impaired glucose tolerance that can occur either before or during pregnancy and lactation. The prevalence of GDM and its related complications in young women is increasing, and this condition may cause serious outcomes and health hazards to the foetus. However, traditional oral hypoglycaemic drugs have potential safety hazards; therefore, it is urgent to develop new, safe, effective, and easily administered agents and remedies. Ginseng polysaccharide (GPS), which is isolated from Panax (P.) ginseng C. A. Meyer, exhibits notably promising biological activities and effects; specifically, it has been shown to lower blood glucose with mild, safe, and nontoxic characteristics, and it can also improve human bodily functions. Hence, we hypothesise that GPS might be used as an additional therapy and candidate agent for treating GDM. This review innovatively summarizes the available reports and evidence from basic studies to analyze the potential for and feasibility of using GPS as a new therapeutic agent for treating GDM. Additionally, for the first time, this review provides a rationale for the use of GPS. Our summarized results show that GPS may be developed as a novel antidiabetic drug and a remedy for use in preventing and treating GDM, with great application prospects.

Ginseng polysaccharides alter the gut microbiota and kynurenine/tryptophan ratio, potentiating the antitumour effect of antiprogrammed cell death 1/programmed cell death ligand 1 (anti-PD-1/PD-L1) immunotherapy

ObjectiveProgrammed death 1 and its ligand 1 (PD-1/PD-L1) immunotherapy is promising for late-stage lung cancer treatment, however, the response rate needs to be improved. Gut microbiota plays a crucial role...

In vitro Assessment of Polysaccharides Immunoregulatory Effects on CD3+CD56+ NKT-like Cells

Aims: Polysaccharides have shown efficacy in a broad range of applications, especially in immune regulation. However, there are only few effective methods available to evaluate and compare the immunoregulatory properties of the different polysaccharides in vitro. To screen stringently and extend the fields of application of polysaccharide-based treatments, a novel in vitro method, based on the use of cord blood-derived CD3+CD56+ NKT-like cells, was developed in this study.
 Methodology: Four injectable polysaccharides used in clinics, including Lentinan (LNT), Bacillus Calmette-Guerin polysaccharide nucleic acids (BCG-PSN), ginseng polysaccharides (GPS), and Shengfu polysaccharides (SFPS), which all might benefit cancer therapy, were further validated by testing their effect on cell proliferation and cytotoxicity in vitro. This new evaluation system could discriminate the effects of the four polysaccharides.
 Results: Cells treated for 4 days with either of the four polysaccharides were fewer than untreated cells. Upon 7-day treatments, plant- or bacteria-derived BCG-PSN, GPS, and SFPS induced higher level of IFN-, proportion of cells with a CD3+CD56+ phenotype, and cytolytic activity toward A549 cells, compared to controls. However, fungus-derived LNT yielded lower IFN-, proportion of CD3+CD56+ cells, and cytolytic activity than control conditions.Additionally, all four polysaccharides, in decreasing order GPS, SFPS, BCG-PSN, and LNT, induced significantly higher concentrations of TNF-α compared to control, with respectively.
 Conclusion:Cord blood-derived CD3+CD56+ NKT-like cells may represent a powerful tool to screen and evaluate the immunoregulatory potential of biological or chemical compounds for clinical developments and applications.

The Synergistic Effects of Polysaccharides and Ginsenosides From American Ginseng (Panax quinquefolius L.) Ameliorating Cyclophosphamide-Induced Intestinal Immune Disorders and Gut Barrier Dysfunctions Based on Microbiome-Metabolomics Analysis.

Cyclophosphamide (CTX), used in cancer chemotherapy, a high dose of which would cause immunosuppressive effect and intestinal mucosa damage. American ginseng (Panax quinquefolius L.) has a long history of functional food use for immunological disorder, colitis, cancer, and so on. This study aimed to illustrate the underlying mechanism of American ginseng’s immunomodulatory effect in CTX-induced mice. In this study, all groups of American ginseng (American ginseng polysaccharide [AGP], American ginseng ginsenoside [AGG], co-treated with American ginseng polysaccharide and ginsenoside [AGP_AGG]) have relieve the immune disorder by reversing the lymphocyte subsets ratio in spleen and peripheral blood, as well as stimulating CD4+T cells and IgA-secreting cells in small intestine. These three treatment groups, especially AGP_AGG co-treated group recovered the intestine morphology that up-regulated villus height (VH)/crypt depth (CD) ratio, areas of mucins expression, quantity of goblet cells, and expression of tight junction proteins (ZO-1, occludin). Importantly, the microbiome-metabolomics analysis was applied in this study to illustrate the possible immuno-modulating mechanism. The synergistic effect of polysaccharides and ginsenosides (AGP_AGG group) restored the gut microbiota composition and increased various beneficial mucosa-associated bacterial taxa Clostridiales, Bifidobacterium, and Lachnospiraceae, while decreased harmful bacteria Escherichia-Shigella and Peptococcaceae. Also, AGP_AGG group altered various fecal metabolites such as uric acid, xanthurenic acid, acylcarnitine, 9,10-DHOME, 13-HDoHE, LysoPE15:0, LysoPC 16:0, LysoPI 18:0, and so on, that associated with immunometabolism or protective effect of gut barrier. These results suggest AG, particularly co-treated of polysaccharide and ginsenoside may be used as immunostimulants targeting microbiome-metabolomics axis to prevent CTX-induced side effects in cancer patients.

Co-production of polysaccharides, ginsenosides and succinic acid from Panax ginseng residue: A typical industrial herbal waste

Co-production of polysaccharides, ginsenosides and succinic acid was achieved from Panax ginseng residue (PGR) in this study. Physico-chemical separation was first applied to recover the released polysaccharides and ginsenoside. Enzymatic hydrolysis was then conducted to covert the left PGR into mono-sugars which was following transformed into succinic acid by constructing a succinic acid-producing strain of Escherichia coli—ZW333. Results indicated that the yields of polysaccharides and ginsenosides increased according to the increase of deconstruction content of PGR. A total sugar yield reached 52 g/L at 10% PGR loading and increased to 94.33 g/L following fed-batch enzymatic hydrolysis. Finally, 56.28 g/L succinic acid was produced. In total, 18 g ginseng polysaccharides, 230 mg ginsenosides and 39 g succinic acid were produced from 100 g PGR. Accordingly, the total economic output could reach RMB 80,149 from 1 t PGR, illustrating the great value increasement of PGR by this industrially possible process.

Transdermal nanotherapeutics: Panax quinquefolium polysaccharide nanoparticles attenuate UVB-induced skin cancer

Ultraviolet (UV) radiation is known to cause an imbalance of the endogenous antioxidant system leading to an increase in skin cancer. Panax quinquefolium (American ginseng) polysaccharides (GPS) can inhibit such an imbalance due to its anti-oxidative and anti-inflammatory properties. The aim of this study was to investigate the therapeutic effects of topical formulations containing GPS nanoparticles (NPs) to inhibit UVB induced oxidative damage and skin cancer. Photoaging was conducted under UVB irradiation with a dose of 300 mJ/cm2 on SKH1 hairless mice. The treatment groups (n = 5) were as follows: sham control, native GPS, GPS NPs and fluorescent labeled GPS NPs. To compare the photoprotective performance, the topical formulations were applied before and after UVB induction (pre-treatment and post-treatment), followed by sacrificing the animals. Then, skin and blood samples were collected, and inflammatory cytokines production was measured using ELISA. Compared to the sham control, GPS NPs pre-treated mice skin and blood samples exhibited a significant lowering in all cytokine production. In addition, skin histology analysis showed that pre-treatment of GPS NPs prevented epidermal damage and proliferation. The results support that topical formulation containing GPS NPs can inhibit UVB induced oxidative damage and skin cancer.

Endoplasmic Reticulum Stress-Activated PERK-eIF2α-ATF4 Signaling Pathway is Involved in the Ameliorative Effects of Ginseng Polysaccharides against Cisplatin-Induced Nephrotoxicity in Mice.

Although previous studies have reported that saponins (ginsenosides, the major active and most representative ingredients in Panax ginseng C.A. Meyer) exerted a good ameliorative effect on cisplatin (CP)-induced acute kidney injury in animal models, little attention has been paid to a large number of polysaccharides isolated and purified from ginseng. This work aimed to investigate the protective effect and the possible molecular mechanism of ginseng polysaccharide (WGP) on CP-induced kidney toxicology in mice. The results from biomarker analysis including serum creatinine (CRE) and blood urea nitrogen (BUN) confirmed the protective effect of WGP at 200 and 400 mg/kg on CP-induced renal-toxicology. We found that WGP reduces the apoptosis of kidney cells by inhibiting endoplasmic reticulum (ER) stress caused by CP, which is manifested by increased phosphorylation of PERK. In addition, the apoptosis-associated with caspase 3 activation in renal cells induced by CP was inhibited after administration of WGP, and the phosphorylation levels of PI3K and AKT were also reduced significantly. We also demonstrated that after exposure to CP, the unfolded protein response signaling pathway PERK-eIF2α-ATF4 axis was significantly activated, manifested by increased phosphorylation of eIF2α and increased expression of ATF4 and CHOP. Interestingly, the WGP administration improves this situation. Furthermore, the supplement of WGP inhibited the overexpression of nuclear factor-kappa B p65 (NF-κB p65) and tumor necrosis factor-α (TNF-α) caused by CP exposure. In short, for the first time, our findings indicated that WGP could effectively prevent CP-induced ER stress, inflammation, and apoptosis in renal cells, in part, by regulating the PI3K/AKT and PERK-eIF2α-ATF4 signaling pathways.

Novel analysis procedure for red ginseng polysaccharides by matrix-assisted laser desorption/ionization time-of-flight/time-of-flight mass spectrometry

BackgroundRed ginseng polysaccharides (RGPs) have been acknowledged for their outstanding immunomodulation and anti-tumor activities. However, their studies are still limited by the complexity of their structural features, the absence of purification and enrichment methods, and the rarity of the analytical instruments that apply to the analysis of such macromolecules. Thus, this study is an attempt to establish a new mass spectrometry (MS)-based analysis procedure for RGPs. MethodsSaponin pre-excluded powder of RG (RG-SPEP, 10 mg) was treated with 200 μL of distilled water and centrifuged for 5 h at 1000 rpm and 85 °C. Ethanol-based precipitation and centrifugation were applied to obtain RGPs from the heated extracts. Further, endo-carbohydrase treatments were performed to produce specific saccharide fragments. Solid-phase extraction (SPE) processes were implemented to purify and enrich the enzyme-treated RGPs, while matrix-assisted laser desorption/ionization time-of-flight/time-of-flight (MALDI-TOF/TOF) MS was employed for the partial structural analysis of the obtained RGPs. ResultsUtilizing cellulase, porous graphitized carbon (PGC), hydrophilic interaction chromatography (HILIC), and MALDI-TOF/TOF MS, the neutral and acidic RGPs were qualitatively analyzed. Hexn and Hexn−18 (cellulose analogs) were determined to be novel neutral RGPs. Additionally, the [Unknown + Hexn] species were also determined as new acidic RGPs. Furthermore, HexAn (H) was determined as another form of the acidic RGPs. ConclusionCompared to the previous methods of analysis, these unprecedented applications of HILIC-SPE and MALDI-TOF/TOF MS to analyze RGPs proved to be fairly effective for fractionating and detecting neutral and acidic components. This new procedure exhibits great potential as a specific tool for searching and determining various polysaccharides in many herbal medicines.

Panax quinquefolius (North American Ginseng) Polysaccharides as Immunomodulators: Current Research Status and Future Directions.

Panax quinquefolius (North American ginseng, NAG) is a popular medicinal plant used widely in traditional medicine. NAG products are currently available in various forms such as roots, extracts, nutraceuticals, dietary supplements, energy drinks, etc. NAG polysaccharides are recognized as one of the major bioactive ingredients. However, most NAG reviews are focused on ginsenosides with little information on polysaccharides. NAG polysaccharides have demonstrated a therapeutic activity in numerous studies, in which many of the bioactivities involve regulation of the immune response. The purpose of this review is to summarize the structural features and the immunomodulatory properties of crude, partially purified, and pure polysaccharides isolated from NAG. Receptors of the innate immune system that potentially bind to NAG polysaccharides and the respective signal transduction pathways initiated by these compounds are discussed. Major challenges, recent innovations, and future directions in NAG polysaccharide research are also summarized.

Ginseng polysaccharide inhibits MDA-MB-231 cell proliferation by activating the inflammatory response.

Ginseng polysaccharide (GPS) is known for its efficacy in cancer therapy; however, its regulatory mechanism in breast cancer (BC) remains unclear. To analyze the effect of GPS on BC cell proliferation, cell proliferation rate calculations, western blotting, plasmid transfections, electrophoretic mobility shift assays and chromatin immunoprecipitation assays were performed. GPS treatment in the culture cell medium inhibited cell proliferation in the BC cell line MDA-MB-231. In addition, the E-cadherin level was enhanced while the vimentin level was suppressed following GPS treatment (both P<0.05). Furthermore, the levels of apoptotic markers, including cleaved-Caspase-3 and p53, and inflammatory response markers, including plasminogen activator inhibitor and TNF-α, were induced by GPS treatment in MDA-MB-231 cells (all P<0.05). These results indicated that GPS supplementation activated the inflammatory response and apoptosis in BC cells. GPS treatment activated the phosphorylation levels of c-Jun N-terminal kinase, Akt and NF-κB. In MDA-MB-231 cells, GPS resulted in the accumulation of the NF-κB components p65, p50 and Ikaros family zing finger protein 1 (IKZF1; all, P<0.05). Chromatin immunoprecipitation and electrophoretic mobility shift assays indicated that p65 bound to the IKZF1 promoter. The overexpression of IKZF1 or p65 inhibited MDA-MB-231 cell proliferation (P<0.05), indicating that GPS treatment may inhibit BC cell proliferation by the activation of IKZF1. Taken together, these results suggested that GPS significantly inhibited BC cell proliferation via the control of the biological processes, including the activation of p65-IKZF1 signaling and apoptosis. The data indicated a novel mechanism for further understanding of cancer cell proliferation.

Enhanced uronic acid content, antioxidant, and anti‐inflammatory activities of polysaccharides from ginseng fermented by Saccharomyces cerevisiae GIW‐1

In this study, Panax ginseng was fermented using Saccharomyces cerevisiae GIW-1. The crude ginseng polysaccharides were extracted and purified by DEAE-Sepharose Fast Flow, and the monosaccharide analysis was performed by GC/MS. In addition, the in vitro antioxidant and the anti-inflammatory activities in mice of polysaccharides were determined. Results showed that the uronic acid content of fermented polysaccharide was significantly increased than nonfermented ginseng, showing that the acid polysaccharide was increased after fermentation. And the ginseng polysaccharides between fermented and nonfermented showed different physiological activity after fermentation. Results of the in vitro antioxidant assay showed ginseng polysaccharides after S. cerevisiae GIW-1 fermentation were found to possess higher capacity on scavenging hydroxyl and superoxide anion free radicals. Furthermore, fermented ginseng polysaccharides attenuated increases of liver index and the level of serum AST, and some inflammatory-related factors including TNF-α, IL-1β, and IL-6 in lipopolysaccharide (LPS)-induced mice. Practical applications Microorganism as one of the important tools of biological method has been considered as a more effective and economical way to convert and synthesize natural compounds with more biologically activities. In this paper, we analyze the ginseng polysaccharides after fermented by S. cerevisiae GIW-1. Result showed that fermented ginseng polysaccharides existed superior potency than nonfermented ginseng polysaccharides on antioxidant and anti-inflammatory activities. Moreover, the content of uronic acid in fermented ginseng polysaccharides have increased. These data maybe provide new insight into the natural antioxidants and impetus the development of ginseng in food industry with improving added value of ginseng products.

Dextran sulfate sodium-induced colitis and ginseng intervention altered oral pharmacokinetics of cyclosporine A in rats

Ethnopharmacological relevanceApplication of cyclosporine A (CsA) as a rescue treatment in acute severe ulcerative colitis (UC) is limited by its narrow therapeutic window and great interpatient variability. As a substrate of cytochrome P450 3A enzyme (CYP3A) and P-glycoprotein (P-gp), the oral pharmacokinetics of CsA is susceptible to disease status and concomitant medications. Combined treatment with ginseng, a famous medicinal herb frequently prescribed for ameliorating abnormal immune response in many diseases including UC, showed immunologic safety in CsA-based immunosuppression. Aim of the studySince the therapeutic levels of CsA can be achieved within 24 h, this study first assessed the impact of acute colitis and ginseng intervention on the single oral dose pharmacokinetics of CsA and explored the underlying mechanisms in dextran sulfate sodium (DSS)-induced colitis rats and Caco-2 cells. Materials and methodsRats received drinking water (normal group), 5% DSS (UC group), or 5% DSS plus daily oral ginseng extract (GS+UC group). On day 7, GS+UC group only received an oral dose of CsA (5 mg/kg), while animals of normal or UC group received an oral, intravenous (1.25 mg/kg), or intraperitoneal dose of CsA (1.25 mg/kg), respectively. Blood, liver/intestine tissues and fecal samples were collected for determining CsA and main hydroxylated metabolite HO-CsA or measuring hepatic/intestinal CYP3A activity. Caco-2 cells were incubated with gut microbial culture supernatant (CS) of different groups or ginseng (decoction or polysaccharides), and then CYP3A, P-gp and tight junction (TJ) proteins were determined. ResultsOral CsA exhibited enhanced absorption, systemic exposure and tissue accumulation, and lower fecal excretion, while intravenous or intraperitoneal CsA showed lower systemic exposure and enhanced distribution, in colitis rats. Diminished intestinal and hepatic P-gp expression well explained the changes with DSS-induced colitis. Moreover, blood exposures of HO-CsA in both normal and colitis after oral dosing were significantly higher than intravenous/intraperitoneal dosing, supporting the dominant role of intestinal first-pass metabolism. Interestingly, colitis reduced CYP3A expression in intestine and liver but only potentiated intestinal CYP3A activity, causing higher oral systemic exposure of HO-CsA. Oral ginseng mitigated colitis-induced down-regulation of CYP3A and P-gp expression, facilitated HO-CsA production, biliary excretion and colonic sequestration of CsA, while not affected CsA oral systemic exposure. In Caco-2 cells, gut microbial CS from both colitis and GS+UC group diminished P-gp function, while ginseng polysaccharides directly affected ZO-1 distribution and suppressed TJ proteins expression, explaining unaltered oral CsA systemic exposure. ConclusionsDSS-induced colitis significantly altered oral CsA disposition through regulating intestinal and hepatic P-gp and CYP3A. One-week ginseng treatment enhanced colonic accumulation while not altered the systemic exposure of CsA after single oral dosing, indicating pharmacokinetic compatibility between the two medications.