A 26-week 20(S)-ginsenoside Rg3 oral toxicity study in Beagle dogs

Gao, Yonglin; Wang, Guangfei; Wang, Tong; Li, Guisheng; Lin, Jian; Sun, Liqin; Wu, Xuran; Sun, Xilin; Wang, Hongbo; Li, Chunmei; Tian, Jingwei; Zhu, Jing; Wang, Kezhou; Cho, Susan

doi:10.1016/j.yrtph.2019.104522

Cited by 14 publications

(9 citation statements)

References 33 publications

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“…The only adverse finding was the increased but reversible kidney weight in dogs that received 60 mg/kg SRg3. The NOAEL in this study was found to be 20 mg/kg [ 112 ], the human equivalent dose of which is approximately 11 mg/kg. In healthy humans receiving intramuscular injections of 10–60 mg/kg SRg3 as a single dose or 30 mg/kg once every two days for 15 days the drug was well tolerated with no detectable sign or symptoms of toxicity [ 110 ].…”

Section: Safety Of Rg3mentioning

confidence: 96%

Anti-Angiogenic Properties of Ginsenoside Rg3

et al. 2020

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Ginsenoside Rg3 (Rg3) is a member of the ginsenoside family of chemicals extracted from Panax ginseng. Like other ginsenosides, Rg3 has two epimers: 20(S)-ginsenoside Rg3 (SRg3) and 20(R)-ginsenoside Rg3 (RRg3). Rg3 is an intriguing molecule due to its anti-cancer properties. One facet of the anti-cancer properties of Rg3 is the anti-angiogenic action. This review describes the controversies on the effects and effective dose range of Rg3, summarizes the evidence on the efficacy of Rg3 on angiogenesis, and raises the possibility that Rg3 is a prodrug.

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Section: Safety Of Rg3mentioning

confidence: 96%

Anti-Angiogenic Properties of Ginsenoside Rg3

et al. 2020

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“…Rg3, one of the enriched ginsenosides in BGE, has been reported to be relatively safe for oral consumption through several toxicity studies; LD50 of 20(S)-Rg3 was determined to be > 800 mg/kg in SD rats and > 1600 mg/kg in mice, and NOAEL in SD rats was 180 mg/kg [42]. In another study using beagle dogs, NOAEL of 20(S)-Rg3 was detected to be 20 mg/kg BW after oral administration for 26 weeks [23]. Regarding Rg5, 30-day repeated intraperitoneal administration of 20 mg/ kg into mice did not cause any significant deviations from normal ranges in all clinical and pathological parameters examined in the study [18].…”

Section: Discussionmentioning

confidence: 99%

“…Ginseng has been generally acknowledged as safe based on its clinical use in traditional medicine and the results of toxicity studies [19][20][21]. Among the processed ginseng products, safety of red ginseng has been well investigated, establishing essential toxicity parameters including LD50 and NOAEL in model systems [22][23][24][25][26]. On the contrary, safety information on black ginseng has been limited despite its growing popularity in commercial markets, raising safety concerns; only one study reported acute oral toxicity for single oral administration of black ginseng [27], but to date the toxicity profile associated with its repetitive use has not been available.…”

mentioning

confidence: 99%

Efficacy and safety evaluation of black ginseng (Panax ginseng C.A. Mey.) extract (CJ EnerG): broad spectrum cytotoxic activity in human cancer cell lines and 28-day repeated oral toxicity study in Sprague-Dawley rats

Park

Kim

Han

et al. 2022

BMC Complement Med Ther

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Background Ginseng (Panax ginseng C.A. Mey.) has been used as a valuable ingredient in traditional medicine for thousands of years mostly in Asian countries due to its therapeutic effects in various diseases. Among the processed ginseng products, black ginseng is produced by a repeated steaming and drying process of ginseng roots and has been known for its superior efficacy based on high accumulation of minor ginsenosides as recently discovered. Despite its popularity and increasing use, the toxicity information on black ginseng still remained largely lacking, raising safety concerns. This study was therefore carried out to determine the repeated oral toxicity of black ginseng extract (BGE; CJ EnerG) with evaluation of cytotoxic activity as validation of its pharmacological activity for toxicity testing. Methods Prior to the toxicity test, we examined the cytotoxicity of BGE in six cancer cell lines derived from distinct human tissues in comparison with red ginseng extract (RGE), ginsenosides Rg5 and 20(S)-Rg3, and then assessed 28-day repeated oral toxicity in Sprague-Dawley (SD) rats using daily administration of up to 2000 mg/kg BGE. Results BGE showed higher cytotoxicity than RGE in all the cell lines used in this study. Interestingly, the efficacy of BGE closely resembled the cytotoxic pattern of Rg5, suggesting Rg5 as the main effector in the cytotoxic activity of BGE. During the toxicity study, BGE-treated groups showed no noticeable abnormality in clinical signs, body weight gain, food and water consumption and urinalysis. Furthermore, hematological, serum biochemical and histopathological analyses did not find any BGE-related toxicity. Conclusion Our findings demonstrated that BGE has broad-spectrum in vitro cytotoxic activity, and that NOAEL of BGE in SD rats is > 2000 mg/kg, providing the essential safety information for human consumption.

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“…Gao et al conducted an acute toxicity study on GRg3 by oral administration, in which the median lethal dose (LD 50 ) is 800 mg/kg for rats and 1600 mg/kg for mice. In a longer term (26 week) oral administration of the GRg3 study, the no-observed-adverse-effect level (NOAEL) is 20 mg/kg for dogs and 180 mg/kg for rats. , GRg3 is mainly distributed to the liver and gastrointestinal tract and eliminated via urine after oral administration in rats . Ginsenoside Rh2 is a metabolite of GRg3.…”

Section: Introductionmentioning

confidence: 99%

“…In a longer term (26 week) oral administration of the GRg3 study, the no-observed-adverse-effect level (NOAEL) is 20 mg/kg for dogs and 180 mg/kg for rats. 26,27 GRg3 is mainly distributed to the liver and gastrointestinal tract and eliminated via urine after oral administration in rats. 28 Ginsenoside Rh2 is a metabolite of GRg3.…”

Section: ■ Introductionmentioning

confidence: 99%

Ginsenoside Rg3 Alleviates Complete Freund’s Adjuvant-Induced Rheumatoid Arthritis in Mice by Regulating CD4⁺CD25⁺Foxp3⁺Treg Cells

Wang

Song

Yang

et al. 2020

J. Agric. Food Chem.

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Ginsenoside Rg3 (GRg3) is one of the major bioactive ingredients of ginseng, which is not only used as a herbal medicine but also used as a functional food to support body functions. In this study, the beneficial effects of GRg3 on rheumatoid arthritis (RA) mice was evaluated from anti-inflammatory and immunosuppressive aspects. The footpad swelling rate, pathological changes of the ankle joint, and levels of tumor necrosis factor α, interleukin 6, interleukin 10, and tumor necrosis factor β were used to assess the anti-inflammatory effect of GRg3 on RA mice. Flow cytometric analysis of CD4 + CD25 + Foxp3 + Treg cell percentage and metabolomic analysis based on gas chromatography−tandem mass spectrometry were used to assess the immunosuppressive effect and underlying mechanisms. GRg3 exhibited anti-inflammatory and immunosuppressive effects on RA mice. The potential mechanisms were related to regulate the pathways of oxidative phosphorylation and enhance the function of CD4 + CD25 + Foxp3 + Treg cells to maintain peripheral immune tolerance of RA mice. These findings can provide a preliminary experimental basis to exploit GRg3 as a functional food or an effective complementary for the adjuvant therapy of RA.

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A 26-week 20(S)-ginsenoside Rg3 oral toxicity study in Beagle dogs

Cited by 14 publications

References 33 publications

Anti-Angiogenic Properties of Ginsenoside Rg3

Anti-Angiogenic Properties of Ginsenoside Rg3

Efficacy and safety evaluation of black ginseng (Panax ginseng C.A. Mey.) extract (CJ EnerG): broad spectrum cytotoxic activity in human cancer cell lines and 28-day repeated oral toxicity study in Sprague-Dawley rats

Ginsenoside Rg3 Alleviates Complete Freund’s Adjuvant-Induced Rheumatoid Arthritis in Mice by Regulating CD4⁺CD25⁺Foxp3⁺Treg Cells

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A 26-week 20(S)-ginsenoside Rg3 oral toxicity study in Beagle dogs

Cited by 14 publications

References 33 publications

Anti-Angiogenic Properties of Ginsenoside Rg3

Anti-Angiogenic Properties of Ginsenoside Rg3

Efficacy and safety evaluation of black ginseng (Panax ginseng C.A. Mey.) extract (CJ EnerG): broad spectrum cytotoxic activity in human cancer cell lines and 28-day repeated oral toxicity study in Sprague-Dawley rats

Ginsenoside Rg3 Alleviates Complete Freund’s Adjuvant-Induced Rheumatoid Arthritis in Mice by Regulating CD4+CD25+Foxp3+Treg Cells

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Ginsenoside Rg3 Alleviates Complete Freund’s Adjuvant-Induced Rheumatoid Arthritis in Mice by Regulating CD4⁺CD25⁺Foxp3⁺Treg Cells