Ginsenoside Absorption Rate and Extent Enhancement of Black Ginseng (CJ EnerG) over Red Ginseng in Healthy Adults

Yoo, Saebyul; Park, Bom I.; Kim, Do Hyun; Lee, Soo Young; Lee, Jun Young; Shim, Wang Seob; Seo, Yong Ki; Kang, Kimoon; Lee, Kyung Tae; Yim, Sung Vin; Soung, Do Y.; Kim, Bo Hyung

doi:10.3390/pharmaceutics13040487

Cited by 22 publications

(18 citation statements)

References 30 publications

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“…Kim et al [ 72 ] reported that the plasma AUCs of GRd, GRg3, GF2, and CK were correlated with the intake amount of these ginsenosides in humans. Additionally, plasma concentrations of GRg3 after the oral intake of black ginseng, which contains a higher amount of GRg3 than RGE, were significantly higher than that after oral intake of RGE in human [ 73 ]. Contrary to the case of GRg3, GRh1 and GRh2 was not detected in the plasma from mice supplemented with LAB.…”

Section: Discussionmentioning

confidence: 99%

Effect of Lactic Acid Bacteria on the Pharmacokinetics and Metabolism of Ginsenosides in Mice

et al. 2021

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This study aims to investigate the effect of lactic acid bacteria (LAB) on in vitro and in vivo metabolism and the pharmacokinetics of ginsenosides in mice. When the in vitro fermentation test of RGE with LAB was carried out, protopanaxadiol (PPD) and protopanaxadiol (PPD), which are final metabolites of ginsenosides but not contained in RGE, were greatly increased. Compound K (CK), ginsenoside Rh1 (GRh1), and GRg3 also increased by about 30%. Other ginsenosides with a sugar number of more than 2 showed a gradual decrease by fermentation with LAB for 7 days, suggesting the involvement of LAB in the deglycosylation of ginsenosides. Incubation of single ginsenoside with LAB produced GRg3, CK, and PPD with the highest formation rate and GRd, GRh2, and GF with the lower rate among PPD-type ginsenosides. Among PPT-type ginsenosides, GRh1 and PPT had the highest formation rate. The amoxicillin pretreatment (20 mg/kg/day, twice a day for 3 days) resulted in a significant decrease in the fecal recovery of CK, PPD, and PPT through the blockade of deglycosylation of ginsenosides after single oral administrations of RGE (2 g/kg) in mice. The plasma concentrations of CK, PPD, and PPT were not detectable without change in GRb1, GRb2, and GRc in this group. LAB supplementation (1 billion CFU/2 g/kg/day for 1 week) after the amoxicillin treatment in mice restored the ginsenoside metabolism and the plasma concentrations of ginsenosides to the control level. In conclusion, the alterations in the gut microbiota environment could change the ginsenoside metabolism and plasma concentrations of ginsenosides. Therefore, the supplementation of LAB with oral administrations of RGE would help increase plasma concentrations of deglycosylated ginsenosides such as CK, PPD, and PPT.

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Section: Discussionmentioning

confidence: 99%

Effect of Lactic Acid Bacteria on the Pharmacokinetics and Metabolism of Ginsenosides in Mice

et al. 2021

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“…The maximal concentration of Rg5 in the blood of human subjects taking ginseng orally at a dose of 9 g was 2−10 nM [44]. Ginsenoside Rg5 protected neuronal cells from glutamate−induced apoptosis in an in vitro Huntington's disease assay at a concentration of 1000 nM [32] and exhibited a neuroprotective effect in heat stress−induced apoptosis at concentrations of 26−52 μM in experiments with murine hippocampal neuronal HT22 cells, but was toxic at concentrations of 78−104 μM [33].…”

Section: Discussionmentioning

confidence: 99%

“…Numerous in vitro studies on isolated cells have been conducted to uncover the molecular mechanisms of action of ginseng extracts and isolated ginsenosides (Supplemental Table S1 in Supplement 1). However, the concentrations of ginsenosides and the extracts used in these studies [32][33][34][35][36][37][38][39][40][41][42][43] were incompatibly higher than those detected in pharmacokinetic (PK) studies in humans [44,45] and animals orally administrated with ginseng preparations at the highest therapeutic doses [46][47][48][49][50][51] (Supplemental Table S2 in Supplement 1).…”

Section: Introductionmentioning

confidence: 85%

“…As an example, ginsenoside Rg5, the major ginsenoside of Red Ginseng, was tested in vitro (Supplemental Table S2 in Supplement 1) mainly in the concentration range from 20 to 100 μM, while the maximal concentration of Rg5 was 2-10 nM (about 2000-fold lower) in the blood of human subjects taking ginseng orally at a dose of 9 g [44] (Supplemental Table S2 in Supplement 1). The maximal concentration of Rg5 was only 81 nM, [48] (20-3300-fold lower) in the blood of dogs after orally administered ginseng at a dose of 5 g (corresponding human dose: 39 g).…”

Section: Introductionmentioning

confidence: 99%

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Network Pharmacology of Red Ginseng (Part I): Effects of Ginsenoside Rg5 at Physiological and Sub-Physiological Concentrations

Panossian¹,

Abdelfatah

Efferth

2021

Pharmaceuticals

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Numerous in vitro studies on isolated cells have been conducted to uncover the molecular mechanisms of action of Panax ginseng Meyer root extracts and purified ginsenosides. However, the concentrations of ginsenosides and the extracts used in these studies were much higher than those detected in pharmacokinetic studies in humans and animals orally administered with ginseng preparations at therapeutic doses. Our study aimed to assess: (a) the effects of ginsenoside Rg5, the major “rare” ginsenoside of Red Ginseng, on gene expression in the murine neuronal cell line HT22 in a wide range of concentrations, from 10−4 to 10−18 M, and (b) the effects of differentially expressed genes on cellular and physiological functions in organismal disorders and diseases. Gene expression profiling was performed by transcriptome-wide mRNA microarray analyses in HT22 cells after treatment with ginsenoside Rg5. Ginsenoside Rg5 exhibits soft-acting effects on gene expression of neuronal cells in a wide range of physiological concentrations and strong reversal impact at high (toxic) concentration: significant up- or downregulation of expression of about 300 genes at concentrations from 10−6 M to 10−18 M, and dramatically increased both the number of differentially expressed target genes (up to 1670) and the extent of their expression (fold changes compared to unexposed cells) at a toxic concentration of 10−4 M. Network pharmacology analyses of genes’ expression profiles using ingenuity pathway analysis (IPA) software showed that at low physiological concentrations, ginsenoside Rg5 has the potential to activate the biosynthesis of cholesterol and to exhibit predictable effects in senescence, neuroinflammation, apoptosis, and immune response, suggesting soft-acting, beneficial effects on organismal death, movement disorders, and cancer.

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“…As a matter of fact, the blood cells and tissues are continuously exposed to varying concentrations of ginsenosides after oral administration of ginseng in the daily therapeutic doses of 0.6-9.0 g [10,29,30]. They range from maximal detected concentrations of 35 ng/ml to the limit of detection 0.5 ng/ml and less within 12-48 h after oral intake [29]. A recent study demonstrated that ginsenoside Rg5 exhibits soft-acting effects in a wide range of physiological and sub-physiological concentrations from 1 μM to 1 aM.…”

Section: Introductionmentioning

confidence: 99%

Network Pharmacology of Ginseng (Part II): The Differential Effects of Red Ginseng and Ginsenoside Rg5 in Cancer and Heart Diseases as Determined by Transcriptomics

Panossian¹,

Abdelfatah²,

Efferth³

2021

Preprint

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Panax ginseng C.A.Mey. is an adaptogenic plant traditionally used to enhance mental and physical capacities in cases of weakness, exhaustion, tiredness, loss of concentration, and during recovery. According to ancient records, Red Ginseng root preparations enhance longevity with long-term intake. Recent pharmacokinetic studies of ginsenosides in humans and our in vitro study in neuronal cells suggest that ginsenosides are effective when their level in blood is shallow - at concentrations from 10-6 to 10-18 M. In the present study, we compared the effects of Red Ginseng root preparation HRG80TM(HRG) at concentrations from 0.01 to 10,000 ng/ml with effects of White Ginseng (WG) and purified ginsenosides Rb1, Rg3, Rg5 and Rk1 on gene expression of isolated hippocampal neurons. The aim of this study was to predict the effects of differently expressed genes on cellular and physiological functions in organismal disorders and diseases. Gene expression profiling was performed by transcriptome-wide mRNA microarray analyses in murine HT22 cells after treatment with ginseng preparations. Ingenuity pathway downstream/upstream analysis (IPA) was performed with datasets of significantly up-or downregulated genes, and expected effects on cellular function and disease were identified by IPA software. Ginsenosides Rb1, Rg3, Rg5, and Rk1 have substantially various effects on gene expression profiles (signatures) and are different from signatures of HRG and WG. Furthermore, the signature of HRG is changed significantly with dilution from 10000 to 0.01 ng/ml. Network pharmacological analyses of gene expression profiles showed that HRG exhibits predictable positive effects in neuroinflammation, senescence, apoptosis, and immune response, suggesting beneficial soft-acting effects in cancer, gastrointestinal, and endocrine systems diseases and disorders in a wide range of low concentrations in blood.

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Ginsenoside Absorption Rate and Extent Enhancement of Black Ginseng (CJ EnerG) over Red Ginseng in Healthy Adults

Cited by 22 publications

References 30 publications

Effect of Lactic Acid Bacteria on the Pharmacokinetics and Metabolism of Ginsenosides in Mice

Effect of Lactic Acid Bacteria on the Pharmacokinetics and Metabolism of Ginsenosides in Mice

Network Pharmacology of Red Ginseng (Part I): Effects of Ginsenoside Rg5 at Physiological and Sub-Physiological Concentrations

Network Pharmacology of Ginseng (Part II): The Differential Effects of Red Ginseng and Ginsenoside Rg5 in Cancer and Heart Diseases as Determined by Transcriptomics

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