Cytoprotective Effect of 20(<i>S</i>)-Rg3 on Benzo[<i>a</i>]pyrene-Induced DNA Damage

Poon, Po Ying; Kwok, Hoi‐Hin; Yue, Patrick; Yang, M. S.; Mak, Nai Ki; Wong, Chris K C; Wong, Ricky N S

doi:10.1124/dmd.111.039503

Cited by 33 publications

(45 citation statements)

References 35 publications

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“…Rb1 was demonstrated to promote Nrf2 nuclear translocation in endothelial cells, lung tissue, and renal tissues after mouse intestinal ischemia–reperfusion, as well as in the skeletal muscle of aged rats following a major small intestinal resection . In addition, Rg3 was found to stimulate nuclear translocation of Nrf2 in rat hepatocyte‐derived H4IIE cells and neonatal human dermal fibroblasts . Moreover, Rg1 induced Nrf2 translocation in human umbilical vein endothelial cells (HUVECs), hepatic stellate cells (HSCs), and the liver tissues of CCl4‐induced hepatic fibrosis rats .…”

Section: Cellular Stress Response Mechanisms Regulated By Ginsenosidesmentioning

confidence: 95%

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Cellular stress response mechanisms as therapeutic targets of ginsenosides

2017

Medicinal Research Reviews

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Ginseng, one of the most widely used traditional herbal medicines and dietary supplements, has historically been recognized as a tonic herb and adaptogen that can enhance the body's tolerance to various adversities. Ginsenosides are a diverse group of steroidal saponins that comprise the major secondary metabolites of ginseng and are responsible for its multiple pharmacological effects. Emerging evidence suggests that hormetic phytochemicals produced by environmentally stressed plants can activate the moderate cellular stress response mechanisms at a subtoxic level in humans, which may enhance tolerance against severe dysfunction or disease. In this review, we initially describe the role of ginsenosides in the chemical defense of plants from the genus Panax suffering from biotic and abiotic stress. Next, we summarize the diverse evolutionarily conserved cellular stress response pathways regulated by ginsenosides and the subsequent stress tolerance against various dysfunctions or diseases. Finally, the structure-activity relationship involved in the effect of ginsenosides is also analyzed. The evidence presented in this review implicates that ginseng as "the King of all herbs" could be regarded as a well-characterized example of the critical role of cellular stress response mechanisms in understanding the health benefits provided by herbal medicines from an evolutionary and ecological perspective.

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Section: Cellular Stress Response Mechanisms Regulated By Ginsenosidesmentioning

confidence: 95%

“…To date, several ginsenosides, including Rb1, Rg3, Rg1, Rd, Rh1, and 20( S )‐protopanaxatriol, were found to activate the Nrf2 pathway, whereas Rg3 was also shown to inhibit the Nrf2 pathway (Fig. ).…”

Section: Cellular Stress Response Mechanisms Regulated By Ginsenosidesmentioning

confidence: 99%

Cellular stress response mechanisms as therapeutic targets of ginsenosides

2017

Medicinal Research Reviews

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“…Rg3 has been reported to exert various biological activities, including antiinflammatory, antiallergy, antitumor, and vascular relaxation [6–8]. Recently, work with Rg3 has been focused on the major stereoisomer 20(S)-Rg3, that is, converted from protopanaxadiol-type ginsenosides Rb1, Rb2, Rc, and Rd [26]. We demonstrated for the first time that 20(S)-Rg3, not Rg1 and Re, is an active ingredient responsible for the GSTA2 induction for hepatoprotection by Korean red ginseng [4].…”

Section: Discussionmentioning

confidence: 99%

The Amelioration of N-Acetyl-p-Benzoquinone Imine Toxicity by Ginsenoside Rg3: The Role of Nrf2-Mediated Detoxification and Mrp1/Mrp3 Transports

Gum

Cho

2013

Oxidative Medicine and Cellular Longevity

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Previously, we found that Korean red ginseng suppressed acetaminophen (APAP)-induced hepatotoxicity via alteration of its metabolic profile involving GSTA2 induction and that ginsenoside Rg3 was a major component of this gene induction. In the present study, therefore, we assessed the protective effect of Rg3 against N-acetyl-p-benzoquinone imine (NAPQI), a toxic metabolic intermediate of APAP. Excess NAPQI resulted in GSH depletion with increases in the ALT and AST activities in H4IIE cells. Rg3 pretreatment reversed GSH depletion by NAPQI. Rg3 resulted in increased mRNA levels of the catalytic and modulatory subunit of glutamate cysteine ligase (GCL), the rate-limiting steps in GSH synthesis and subsequently increased GSH content. Rg3 increased levels of nuclear Nrf2, an essential transcriptional factor of these genes. The knockdown or knockout of the Nrf2 gene abrogated the inductions of mRNA and protein by Rg3. Abolishment of the reversal of GSH depletion by Rg3 against NAPQI was observed in Nrf2-deficient cells. Rg3 induced multidrug resistance-associated protein (Mrp) 1 and Mrp3 mRNA levels, but not in Nrf2-deficient cells. Taken together, these results demonstrate that Rg3 is efficacious in protecting hepatocytes against NAPQI insult, due to GSH repletion and coordinated gene regulations of GSH synthesis and Mrp family genes by Nrf2.

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“…Wild PG exerts its hepatoprotective effect by attenuating the increased serum AST and ALT levels from benzo[a]pyrene-induced hepatic injury [69]. Specifically, ginsenoside Rg3 prevents benzo[a]pyrene-induced DNA damage [70]; ginsenosides CK, O, and Mc1 inhibit benzo[a]pyrene-induced mutagenicity, and ginsenosides CK and Mc1 reduce the frequency of chromosome aberration induced by benzo[a]pyrene [71]. These findings suggest that ginseng containing the ginsenosides Rg3 and CK may attenuate benzo[a]pyrene-induced hepatitis by suppressing benzo[a]pyrene-induced mutagenicity through the inhibition of ROS production.…”

Section: Multiple Efficacies For Hepatic Injuriesmentioning

confidence: 99%

Ginseng for Liver Injury: Friend or Foe?

Kim

2016

Medicines

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Panax sp., including Panax ginseng Meyer, Panax quiquifolius L., or Panax notoginseng (Burk.) FH Chen, have been used as functional foods or for traditional Chinese medicine for diabetes, inflammation, stress, aging, hepatic injury, and cancer. In recent decades, a number of both in vitro and in vivo experiments as well as human studies have been conducted to investigate the efficacy and safety of various types of ginseng samples and their components. Of these, the hepatoprotective and hepatotoxic effects of ginseng and their ginsenosides and polysaccharides are reviewed and summarized.

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Cytoprotective Effect of 20(S)-Rg3 on Benzo[a]pyrene-Induced DNA Damage

Cited by 33 publications

References 35 publications

Cellular stress response mechanisms as therapeutic targets of ginsenosides

Cellular stress response mechanisms as therapeutic targets of ginsenosides

The Amelioration of N-Acetyl-p-Benzoquinone Imine Toxicity by Ginsenoside Rg3: The Role of Nrf2-Mediated Detoxification and Mrp1/Mrp3 Transports

Ginseng for Liver Injury: Friend or Foe?

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