Sang Mi Park1, Jong Rok Lee1, Sae Kwang Ku1, Il Je Cho1, Sung Hui Byun1, Sang Chan Kim1, Sook Jahr Park2, Young Woo Kim3. 1. Medical Research Center for Globalization of Herbal Formulation, College of Oriental Medicine, Daegu Haany University, Gyeongsan, Gyeongsangbuk-do, 712-715, South Korea. 2. Medical Research Center for Globalization of Herbal Formulation, College of Oriental Medicine, Daegu Haany University, Gyeongsan, Gyeongsangbuk-do, 712-715, South Korea. haany@dhu.ac.kr. 3. Medical Research Center for Globalization of Herbal Formulation, College of Oriental Medicine, Daegu Haany University, Gyeongsan, Gyeongsangbuk-do, 712-715, South Korea. ywkim@dhu.ac.kr.
Abstract
PURPOSE: Liver is the major site of biotransformation for exogenous toxins, in having a defense system against oxidative stress as well as cytochrome P450 system. Isoliquiritigenin (isoLQ) is an active component present in Glycyrrhizae radix and has been shown to have various biological activities. This study investigated the effect of isoLQ as a liver protectant against oxidative stress, both in vivo and in vitro, and also its molecular mechanisms. METHODS: We used tert-butylhydroperoxide-induced hepatocyte damage model and cadmium (Cd)-stimulated liver toxicity animal model, which are assessed by immunoblot and flow cytometry as well as plasma and histopathological parameters. RESULTS: In HepG2 cells, pretreatment of 10 and 30 µM isoLQ significantly inhibited the induction of apoptosis and mitochondrial damage, and production of reactive oxygen species. Moreover, isoLQ induced the activation of nuclear factor erythroid 2-related factor-2 (Nrf2), as indicated by an increase in its nuclear translocation and antioxidant response element-luciferase activity. IsoLQ also induced the expression of Nrf2 target phase II enzymes, such as heme oxygenase-1, glutamate-cysteine ligase catalytic subunit and NAD(P)H:quinone oxidoreductase 1. IsoLQ also induced phosphorylation of extracellular stimuli-regulated kinase (ERK), and its activation of Nrf2 was mediated with ERK-dependent phosphorylation of Nrf2, as determined by its chemical inhibitor. In rats, oral treatment of 5 and 20 mg/kg isoLQ prevented Cd-induced acute hepatic damage, as assessed by plasma parameters and semiquantative histology, such as the modified HAI grading scores and the degenerative regions in hepatic parenchyma. CONCLUSION: These findings are considered as scientific evidence that isoLQ in licorice has the function of being a hepatic protectant against oxidative damages through ERK-mediated Nrf2 activation.
PURPOSE: Liver is the major site of biotransformation for exogenous toxins, in having a defense system against oxidative stress as well as cytochrome P450 system. Isoliquiritigenin (isoLQ) is an active component present in Glycyrrhizae radix and has been shown to have various biological activities. This study investigated the effect of isoLQ as a liver protectant against oxidative stress, both in vivo and in vitro, and also its molecular mechanisms. METHODS: We used tert-butylhydroperoxide-induced hepatocyte damage model and cadmium (Cd)-stimulated liver toxicity animal model, which are assessed by immunoblot and flow cytometry as well as plasma and histopathological parameters. RESULTS: In HepG2 cells, pretreatment of 10 and 30 µM isoLQ significantly inhibited the induction of apoptosis and mitochondrial damage, and production of reactive oxygen species. Moreover, isoLQ induced the activation of nuclear factor erythroid 2-related factor-2 (Nrf2), as indicated by an increase in its nuclear translocation and antioxidant response element-luciferase activity. IsoLQ also induced the expression of Nrf2 target phase II enzymes, such as heme oxygenase-1, glutamate-cysteine ligase catalytic subunit and NAD(P)H:quinone oxidoreductase 1. IsoLQ also induced phosphorylation of extracellular stimuli-regulated kinase (ERK), and its activation of Nrf2 was mediated with ERK-dependent phosphorylation of Nrf2, as determined by its chemical inhibitor. In rats, oral treatment of 5 and 20 mg/kg isoLQ prevented Cd-induced acute hepatic damage, as assessed by plasma parameters and semiquantative histology, such as the modified HAI grading scores and the degenerative regions in hepatic parenchyma. CONCLUSION: These findings are considered as scientific evidence that isoLQ in licorice has the function of being a hepatic protectant against oxidative damages through ERK-mediated Nrf2 activation.
Authors: K Ishak; A Baptista; L Bianchi; F Callea; J De Groote; F Gudat; H Denk; V Desmet; G Korb; R N MacSween Journal: J Hepatol Date: 1995-06 Impact factor: 25.083
Authors: Sang Mi Park; Sung Woo Kim; Eun Hye Jung; Hae Li Ko; Chae Kwang Im; Jong Rok Lee; Sung Hui Byun; Sae Kwang Ku; Sang Chan Kim; Chung A Park; Kwang Joong Kim; Il Je Cho Journal: Evid Based Complement Alternat Med Date: 2018-11-06 Impact factor: 2.629