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Korean red ginseng prevents APAP‐induced hepatotoxicity and mortality through metabolic regulation: The role of ginsenoside Rg3, a protopanaxadiol
Author(s) -
Cho Min Kyung,
Kim Sang Geon,
Gum Sang
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.lb593
Subject(s) - ginseng , acetaminophen , pharmacology , hepatoprotection , protopanaxadiol , cyp2e1 , antioxidant , ginsenoside , pi3k/akt/mtor pathway , chemistry , medicine , apoptosis , metabolism , glutathione , biochemistry , enzyme , cytochrome p450 , alternative medicine , pathology
Inappropriate use of acetaminophen (APAP) can lead to significant morbidity and mortality secondary to hepatic necrosis. We determined the beneficial effect and molecular mechanism of Korean red ginseng (KRG) on the APAP‐mediated hepatotoxicity and identified a major component of KRG for protection. Pretreatment with high doses of KRG for 1 week significantly reduced mortality at the LD50 of APAP. APAP increased AST and ALT activities, which was abrogated by low doses of KRG for 5 weeks. KRG also delayed APAP metabolism in plasma through CYP2E1 inhibition. These protective effects of KRG were consistent with the results from histopathological examinations. KRG induced antioxidant/phase 2 gene battery in rat liver and H4IIE. Exposure of KRG increased the nuclear Nrf2 and C/EBPβ, which are important transcriptional factors for those genes including GSTA2. These effects were downstream of multiple cellular signaling, including PI3K, JNK or PKA. Rg3 but not Rb1, Rc and Rg1 significantly increased those gene expressions. Rg3 resulted in the transcriptional activation of GSTA2 through Nrf2 and C/EBP downstream of the cellular signaling. These results demonstrate that KRG is efficacious in protection from APAP‐induced hepatotoxicity and mortality and that Rg3 is a major component of KRG for the hepatoprotection, implying that Rg3 should be considered to be a potential hepatoprotective agent.