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

Kim, Jeon-Kyung; Choi, Min Sun; Jeung, Woonhee; Ra, Jehyeon; Yoo, Hye Hyun; Kim, Dong-Hyun

doi:10.1016/j.jgr.2019.05.012

Cited by 33 publications

(34 citation statements)

References 42 publications

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“…In addition, many constituents of orally administered RG and fRG are not easily absorbed from the intestine into the blood [16]. Therefore, these constituents contact with gut microbiota in the gastrointestinal tract and are metabolized to easily absorbable compounds such as compound K. When RG and fRG are orally administered in humans and mice, the ginsenosides most highly absorbed into the blood were Rd followed by protopanaxatriol and compound K [27,29], Supplement Table S6. In the present study, we found that oral administration of ginsenoside Rd and protopanaxatriol significantly suppressed the IS-or EC-induced depression-like behaviors, NF-κB activation, and NF-κB + /Iba1 + cell population in the hippocampus of mice, while the BDNF expression and CREB phosphorylation increased.…”

Section: Discussionmentioning

confidence: 99%

Bifidobacteria-Fermented Red Ginseng and Its Constituents Ginsenoside Rd and Protopanaxatriol Alleviate Anxiety/Depression in Mice by the Amelioration of Gut Dysbiosis

et al. 2020

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Gut dysbiosis is closely connected with the outbreak of psychiatric disorders with colitis. Bifidobacteria-fermented red ginseng (fRG) increases the absorption of ginsenoside Rd and protopanxatriol into the blood in volunteers and mice. fRG and Rd alleviates 2,4,6-trinitrobenzenesulfonic acid-induced colitis in mice. Therefore, to understand the gut microbiota-mediated mechanism of fRG against anxiety/depression, we examined the effects of red ginseng (RG), fRG, ginsenoside Rd, and protopanaxatriol on the occurrence of anxiety/depression, colitis, and gut dysbiosis in mice. Mice with anxiety/depression were prepared by being exposed to two stressors, immobilization stress (IS) or Escherichia coli (EC). Treatment with RG and fRG significantly mitigated the stress-induced anxiety/depression-like behaviors in elevated plus maze, light-dark transition, forced swimming (FST), and tail suspension tasks (TST) and reduced corticosterone levels in the blood. Their treatments also suppressed the stress-induced NF-κB activation and NF-κB+/Iba1+ cell population in the hippocampus, while the brain-derived neurotrophic factor (BDNF) expression and BDNF+/NeuN+ cell population were increased. Furthermore, treatment with RG or fRG suppressed the stress-induced colitis: they suppressed myeloperoxidase activity, NF-κB activation, and NF-κB+/CD11c+ cell population in the colon. In particular, fRG suppressed the EC-induced depression-like behaviors in FST and TST and colitis more strongly than RG. fRG treatment also significantly alleviated the EC-induced NF-κB+/Iba1+ cell population and EC-suppressed BDNF+/NeuN+ cell population in the hippocampus more strongly than RG. RG and fRG alleviated EC-induced gut dysbiosis: they increased Bacteroidetes population and decreased Proteobacteria population. Rd and protopanaxatriol also alleviated EC-induced anxiety/depression and colitis. In conclusion, fRG and its constituents Rd and protopanaxatriol mitigated anxiety/depression and colitis by regulating NF-κB-mediated BDNF expression and gut dysbiosis.

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Section: Discussionmentioning

confidence: 99%

Bifidobacteria-Fermented Red Ginseng and Its Constituents Ginsenoside Rd and Protopanaxatriol Alleviate Anxiety/Depression in Mice by the Amelioration of Gut Dysbiosis

et al. 2020

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“…Rg1, CK, ginsenoside Rg3, and protopanaxtriol [32,33]. The contents of these ginsenosides except ginsenoside Rg3 absorbed into the blood are significantly higher in the fRG-treated volunteers and mice than in the RG-treated volunteers and mice.…”

Section: The Role Of Gut-microbiota-mediated Metabolism In the Mediatmentioning

confidence: 92%

“…The biological activities of ginsenosides Rb1 and Re, such as anti-inflammatory and anti-allergic activities, are attenuated in mice by oral gavage of antibiotics [30,31]. When RG extract is orally administered in humans and mice, ginsenoside Rd is the most highly detected, followed by ginsenoside Rg3, ginsenoside Rg1, and protopanaxatriol [32,33]. However, when bifidobacteria-fermented red ginseng (fRG) is orally administered, ginsenoside Rd is the most highly detected, followed by ginsenoside Rg1, CK, ginsenoside Rg3, and protopanaxtriol [32,33].…”

Section: The Role Of Gut-microbiota-mediated Metabolism In the Mediatmentioning

confidence: 99%

“…When RG extract is orally administered in humans and mice, ginsenoside Rd is the most highly detected, followed by ginsenoside Rg3, ginsenoside Rg1, and protopanaxatriol [32,33]. However, when bifidobacteria-fermented red ginseng (fRG) is orally administered, ginsenoside Rd is the most highly detected, followed by ginsenoside Rg1, CK, ginsenoside Rg3, and protopanaxtriol [32,33]. The contents of these ginsenosides except ginsenoside Rg3 absorbed into the blood are significantly higher in the fRG-treated volunteers and mice than in the RG-treated volunteers and mice.…”

Section: The Role Of Gut-microbiota-mediated Metabolism In the Mediatmentioning

confidence: 99%

“…This is controversial. Nevertheless, of parental ginsenosides and their metabolites, CK, ginsenosides Rh1, Rh2 and protopanaxatriol, which are hydrophobic metabolites of ginsenosides by gut microbiota, exhibit the most potent biological effects compared to those of parental compounds [31][32][33][35][36][37][38][39][40]. These results suggest that when ginseng extracts are orally administered, their hydrophilic constituents are metabolized by gut microbiota and their metabolites absorbable into the blood can express pharmacological effects: the pharmacological activities of ginseng extracts may be dependent on the absorbable metabolites produced by gut microbiota.…”

Section: The Role Of Gut-microbiota-mediated Metabolism In the Mediatmentioning

confidence: 99%

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Effects of Red and Fermented Ginseng and Ginsenosides on Allergic Disorders

Han

Kim

2020

Biomolecules

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Both white ginseng (WG, dried root of Panax sp.) and red ginseng (RG, steamed and dried root of Panax sp.) are reported to exhibit a variety of pharmacological effects such as anticancer, antidiabetic, and neuroprotective activities. These ginsengs contain hydrophilic sugar-conjugated ginsenosides and polysaccharides as the bioactive constituents. When taken orally, their hydrophilic constituents are metabolized into hydrophobic ginsenosides compound K, Rh1, and Rh2 that are absorbable into the blood. These metabolites exhibit the pharmacological effects more strongly than hydrophilic parental constituents. To enforce these metabolites, fermented WG and RG are developed. Moreover, natural products including ginseng are frequently used for the treatment of allergic disorders. Therefore, this review introduces the current knowledge related to the effectiveness of ginseng on allergic disorders including asthma, allergic rhinitis, atopic dermatitis, and pruritus. We discuss how ginseng, its constituents, and its metabolites regulate allergy-related immune responses. We also describe how ginseng controls allergic disorders.

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Neuroprotection and mechanisms of ginsenosides in nervous system diseases: Progress and perspectives

Zhou,

Tan,

Zhang

et al. 2024

IUBMB Life

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Ginsenosides are the primary component discernible from ginseng, including Rb1, Rb2, Rd, Rg1, Rg2, and compound K, and so forth. They have been shown to have multiple pharmacological activities. In recent years, more and more studies have been devoted to the neuroprotection of various ginsenosides against neurological diseases and their potential mechanisms. This paper comprehensively summarizes and reviews the neuroprotective effects of various ginsenosides on neurological diseases, especially acute and chronic neurodegenerative diseases, and their mechanisms, as well as their potential therapeutic applications to promote neuroprotection in disease prevention, treatment, and prognosis. Briefly, ginsenosides exert effective neuroprotective effects on neurological conditions, including stroke, Alzheimer's disease, Parkinson's disease, and brain/spinal cord injuries through a variety of molecular mechanisms, including anti‐inflammatory, antioxidant, and anti‐apoptotic. Among them, some signaling pathways play important roles in related processes, such as PI3K/Akt, TLR4/NF‐κB, ROS/TXNIP/NLRP3, HO‐1/Nrf2, Wnt/β‐catenin, and Ca2+ pathway. In conclusion, the present study reviews the research progress on the neuroprotective effects of ginsenosides in the last decade, with the aim of furnishing essential theoretical underpinning and effective references for further research and exploration of the multiple medicinal values of Chinese herbal medicines and their small molecule compounds, including ginseng and panax ginseng. Because there is less evidence in the existing clinical studies, future research should be focused on clinical trials in order to truly reflect the clinical value of various ginsenosides for the benefit of patients.

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

Cited by 33 publications

References 42 publications

Bifidobacteria-Fermented Red Ginseng and Its Constituents Ginsenoside Rd and Protopanaxatriol Alleviate Anxiety/Depression in Mice by the Amelioration of Gut Dysbiosis

Bifidobacteria-Fermented Red Ginseng and Its Constituents Ginsenoside Rd and Protopanaxatriol Alleviate Anxiety/Depression in Mice by the Amelioration of Gut Dysbiosis

Effects of Red and Fermented Ginseng and Ginsenosides on Allergic Disorders

Neuroprotection and mechanisms of ginsenosides in nervous system diseases: Progress and perspectives

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