Discrimination of white ginseng origins using multivariate statistical analysis of data sets – Uncorrected Proof

Abstract: Background: White ginseng (Panax ginseng Meyer) is commonly distributed as a health food in food markets. However, there is no practical method for distinguishing Korean white ginseng (KWG) from Chinese white ginseng (CWG), except for relying on the traceability system in the market.Methods: Ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry combined with orthogonal partial least squares discrimination analysis (OPLS-DA) was employed to discriminate between KWG and CWG.Results: The origins of white ginsengs in two test sets (1.0 μL and 0.2 μL injections) could be successfully discriminated by the OPLS-DA analysis. From OPLS-DA S-plots, KWG exhibited tentative markers derived from ginsenoside Rf and notoginsenoside R3 isomer, whereas CWG exhibited tentative markers derived from ginsenoside Ro and chikusetsusaponin Iva.Conclusion: Results suggest that ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry coupled with OPLS-DA is an efficient tool for identifying the difference between the geographical origins of white ginsengs.

Effect of a soluble prebiotic fiber, NUTRIOSE®, on the absorption of ginsenoside Rd in ginseng orally-administered rats – Accepted Manuscript

Abstract: In order to understand the effect of dietary components on the absorption of ginsenosides and their metabolites into the blood, we studied the pharmacokinetics of the ginseng extract and its main constituent ginsenoside Rb1 in rats with or without pretreatment with a prebiotic fiber, NUTRIOSE®, by liquid chromatography tandem mass spectrometry (LC–MS/MS). When ginsenoside Rb1 was incubated with rat feces, its main metabolite was ginsenoside Rd. When the intestinal microbiota of rat feces were cultured in vitro, their ginsenoside Rd-forming activities were significantly induced by NUTRIOSE®. When ginsenoside Rb1 was orally administered to rats, the maximum plasma concentration (Cmax) and area under the plasma drug concentration time curve (AUC) for the main metabolite, ginsenoside Rd, was 72.4 ± 31.6 ng/mL and 663.9 ± 285.3 μg·h/mL, respectively. When the ginseng extract (2,000 mg/kg) was orally administered, Cmax and AUC for ginsenoside Rd were 906.5 ± 330.2 ng/mL and 11,377.3 ± 4,470.2 μg·h/mL, respectively. When ginseng extract was orally administered to rats fed NUTRIOSE® containing diets (2.5%, 5%, or 10%), Cmax and AUC were increased in the NUTRIOSE® receiving groups in a dose-dependent manner. These findings reveal that intestinal microflora promote metabolic conversion of ginsenoside Rb1 and ginseng extract to ginsenoside Rd and promote its absorption into the blood in rats. Its conversion may be induced by prebiotic diets such as NUTRIOSE®.

Effects of Korean Red Ginseng (Panax ginseng), urushiol (Rhus vernicifera Stokes), and probiotics (Lactobacillus rhamnosus R0011 and Lactobacillus acidophilus R0052) on the gut-liver axis of alcoholic liver disease – Accepted Manuscript

Abstract: The roles of immune reaction and toll-like receptor-4 (TLR-4) have been widely established in the pathogenesis of alcoholic liver disease (ALD). We evaluated the biologic efficacy of Korean Red Ginseng (KRG), urushiol, and probiotics (Lactobacillus rhamnosus R0011 and Lactobacillus acidophilus R0052) in mouse models of ALD. Sixty C57BL/6 mice were equally divided into 6 feeding groups for 10 weeks: normal diet, alcohol, control, alcohol+KRG, alcohol+urushiol, and alcohol+probiotics. Alcohol was administered via a Lieber–DeCarli liquid diet with 10% alcohol. TLR-4 expression, pro-inflammatory cytokines, and histology as well as the results of liver function tests were evaluated and compared. No between-group differences were observed with regard to liver function. TLR-4 levels were significantly lower in the KRG, urushiol, and probiotics groups than in the alcohol group (0.37±0.06, 0.39±0.12, and 0.33±0.07, respectively vs. 0.88±0.31 ng/ml, p

Antiviral activity of ginsenosides against coxsackievirus B3, enterovirus 71, and human rhinovirus 3 – Accepted Manuscript

Abstract: Background: Ginsenosides are the major components responsible for the biochemical and pharmacological actions of ginseng, and have been shown to have various biological activities. In this study, we investigate the antiviral activities of seven ginsenosides (PT type: Re, Rf, and Rg2; PD type: Rb1, Rb2, Rc, and Rd) against coxsackievirus B3 (CVB3), enterovirus 71 (EV71), and human rhinovirus 3 (HRV3).Methods: Assays of antiviral activity and cytotoxicity were evaluated by the SRB method using cytopathic effect (CPE) reduction assay.Results: Antiviral assays demonstrated that, of the seven ginsenosides, the PT type ginsenosides (Re, Rf, and Rg2) possess significant antiviral activities against CVB3 and HRV3 at a concentration of 100 μg/mL. Among the PT type ginsenosides, only ginsenoside Rg2 showed significant anti-EV71 activity with no cytotoxicity to cells at 100 μg/mL. The PD type ginsenosides (Rb1, Rb2, Rc, and Rd), on the other hand, did not show any significant antiviral activity against CVB3, EV71, and HRV3, and exhibited cytotoxic effects to virus-infected cells. Notably, the antiviral efficacies of PT type ginsenosides were comparable to those of ribavirin, a commonly used antiviral drug.Conclusion: Collectively, our findings suggest that the ginsenosides Re, Rf, and Rg2 have the potential to be effective in the treatment of CVB3, EV71, and HRV3 infection.

Plant regeneration of Korean wild ginseng (Panax ginseng Meyer) mutant lines induced by γ-irradiation (60Co) of adventitious roots – Accepted Manuscript

Abstract: We established an efficient in vitro protocol for somatic embryogenesis and plantlet conversion of Korean wild ginseng (Panax ginseng Meyer). Wild-type and mutant adventitious roots derived from the ginseng produced calli on Murashige and Skoog (MS) medium supplemented with 0.5 mg/L 2,4-dichlorophenoxyacetic acid (2,4-D) and 0.3 mg/L kinetin; 53.3% of the explants formed callus. Embryogenic callus proliferation and somatic embryo induction occurred on MS medium containing 0.5 mg/L 2,4-D. The induced somatic embryos further developed to maturity on MS medium with 5 mg/L gibberellic acid (GA3) and 85% of them germinated. The germinated embryos were developed to shoots and elongated on MS medium with 5 mg/L GA3. The shoots developed into plants with well-developed taproots on 1/3 strength Schenk and Hildebrandt (SH) basal medium supplemented with 0.25 mg/L 1-naphthaleneacetic acid (NAA). When the plants transferred to soil, about 30% of the regenerated plants developed into normal plants.

AMP-activated protein kinase: An emerging target for ginseng

Abstract: The adenosine monophosphate (AMP)-activated protein kinase (AMPK) is a key sensor of cellular energy. Once activated, it switches on catabolic pathways generating adenosine triphosphate (ATP), while switching off biosynthetic pathways consuming ATP. Pharmacological activation of AMPK by metformin holds a therapeutic potential to reverse metabolic abnormalities such as type 2 diabetes and nonalcoholic fatty liver disease. In addition, altered metabolism of tumor cells is widely recognized and AMPK is a potential target for cancer prevention and/or treatment. Panax ginseng is known to be useful for treatment and/or prevention of cancer and metabolic diseases including diabetes, hyperlipidemia, and obesity. In this review, we discuss the ginseng extracts and ginsenosides that activate AMPK, we clarify the various mechanisms by which they achieve this, and we discuss the evidence that shows that ginseng or ginsenosides might be useful in the treatment and/or prevention of metabolic diseases and cancer.

Protective effect of ginsenoside Re on acute gastric mucosal lesion induced by compound 48/80

Abstract: The protective effect of ginsenoside Re, isolated from ginseng berry, against acute gastric mucosal lesions was examined in rats with a single intraperitoneal injection of compound 48/80 (C48/80). Ginsenoside Re (20 mg/kg or 100 mg/kg) was orally administered 0.5 h prior to C48/80 treatment. Ginsenoside Re dose-dependently prevented gastric mucosal lesion development 3 h after C48/80 treatment. Increases in the activities of myeloperoxidase (MPO; an index of neutrophil infiltration) and xanthine oxidase (XO) and the content of thiobarbituric acid reactive substances (TBARS; an index of lipid peroxidation) and decreases in the contents of hexosamine (a marker of gastric mucus) and adherent mucus, which occurred in gastric mucosal tissues after C48/80 treatment, were significantly attenuated by ginsenoside Re. The elevation of Bax expression and the decrease in Bcl2 expression after C48/80 treatment were also attenuated by ginsenoside Re. Ginsenoside Re significantly attenuated all these changes 3 h after C48/80 treatment. These results indicate that orally administered ginsenoside Re protects against C48/80-induced acute gastric mucosal lesions in rats, possibly through its stimulatory action on gastric mucus synthesis and secretion, its inhibitory action on neutrophil infiltration, and enhanced lipid peroxidation in the gastric mucosal tissue.

Influence of Panax ginseng on obesity and gut microbiota in obese middle-aged Korean women

Abstract: Background: Gut microbiota is regarded as one of the major factors involved in the control of body weight. The antiobesity effects of ginseng and its main constituents have been demonstrated, but the effects on gut microbiota are still unknown.Methods: To investigate the effect of ginseng on gut microbiota, 10 obese middle-aged Korean women took Panax ginseng extracts for 8 wk and assessment of body composition parameters, metabolic biomarkers, and gut microbiota composition was performed using 16S rRNA gene-based pyrosequencing at baseline and at 8 wk. Significant changes were observed in body weight and body mass index; however, slight changes were observed in gut microbiota. We divided the participants into two groups, the effective and the ineffective weight loss groups, depending on weight loss effect, in order to determine whether the antiobesity effect was influenced by the composition of gut microbiota, and the composition of gut microbiota was compared between the two groups.Results: Prior to ginseng intake, significant differences of gut microbiota were observed between both at phyla and genera and the gut microbiota of the effective and ineffective weight loss groups was segregated on a principal coordinate analysis plot.Conclusion: Results of this study indicate that ginseng exerted a weight loss effect and slight effects on gut microbiota in all participants. In addition, its antiobesity effects differed depending on the composition of gut microbiota prior to ginseng intake.

Free-fatty-acid-regulating effects of fermented red ginseng are mediated by hormones and by the autonomic nervous system

Abstract: Background: Understanding what causes changes in the flux of free fatty acids (FFA) is important to elucidate the etiology of metabolic syndrome. The first aim of this study was to test whether or not hormones and the autonomic nervous system influence blood FFA levels. A secondary aim was to test by means of a multiple group path analysis whether the consumption of fermented red ginseng (FRG; Panax ginseng) would influence those causal relationships.Methods: Ninety-three postmenopausal women (age 50–73 yr) were randomly divided into two groups. One group (44 women; age, 58.4 ± 5.9 yr; body mass index, 23.6 ± 2.5 kg/m2) was supplied placebo capsules and the other group (49 women, age 58.4 ± 5.5 yr; body mass index, 22.9 ± 2.4 kg/m2) was supplied FRG capsules. Both prior to and after the study (2 wk), blood samples were collected from the participants and several blood variables were measured and analyzed.Results: Squared multiple correlations of FFA were 0.699 in the placebo group and 0.707 in the FRG group. The unstandardized estimate of estradiol (E2) for FFA was 0.824 in both groups.Conclusion: The path coefficients of cortisol and the branchial pulse for FFA were significantly different between the FRG group and the placebo group.

Evidence of genome duplication revealed by sequence analysis of multi-loci expressed sequence tag–simple sequence repeat bands in Panax ginseng Meyer

Abstract: Background: Panax ginseng, the most famous medicinal herb, has a highly duplicated genome structure. However, the genome duplication of P. ginseng has not been characterized at the sequence level. Multiple band patterns have been consistently observed during the development of DNA markers using unique sequences in P. ginseng.Methods: We compared the sequences of multiple bands derived from unique expressed sequence tag-simple sequence repeat (EST-SSR) markers to investigate the sequence level genome duplication.Results: Reamplification and sequencing of the individual bands revealed that, for each marker, two bands around the expected size were genuine amplicons derived from two paralogous loci. In each case, one of the two bands was polymorphic, showing different allelic forms among nine ginseng cultivars, whereas the other band was usually monomorphic. Sequences derived from the two loci showed a high similarity, including the same primer-binding site, but each locus could be distinguished based on SSR number variations and additional single nucleotide polymorphisms (SNPs) or InDels. A locus-specific marker designed from the SNP site between the paralogous loci produced a single band that also showed clear polymorphism among ginseng cultivars.Conclusion: Our data imply that the recent genome duplication has resulted in two highly similar paralogous regions in the ginseng genome. The two paralogous sequences could be differentiated by large SSR number variations and one or two additional SNPs or InDels in every 100 bp of genic region, which can serve as a reliable identifier for each locus.