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Published Online: 10 February 2017

Antcin H Protects Against Acute Liver Injury Through Disruption of the Interaction of c-Jun-N-Terminal Kinase with Mitochondria

Publication: Antioxidants & Redox Signaling
Volume 26, Issue Number 5

Abstract

Aim: Antrodia Camphorate (AC) is a mushroom that is widely used in Asian countries to prevent and treat various diseases, including liver diseases. However, the active ingredients that contribute to the biological functions remain elusive. The purpose of the present study is to test the hepatoprotective effect of Antcin H, a major triterpenoid chemical isolated from AC, in murine models of acute liver injury.
Results: We found that Antcin H pretreatment protected against liver injury in both acetaminophen (APAP) and galactosamine/tumor necrosis factor (TNF)α models. More importantly, Antcin H also offered a significant protection against acetaminophen-induced liver injury when it was given 1 h after acetaminophen. The protection was verified in primary mouse hepatocytes. Antcin H prevented sustained c-Jun-N-terminal kinase (JNK) activation in both models. We excluded an effect of Antcin H on acetaminophen metabolism and TNF receptor signaling and excluded a direct effect as a free radical scavenger or JNK inhibitor. Since the sustained JNK activation through its interaction with mitochondrial Sab, leading to increased mitochondrial reactive oxygen species (ROS), is pivotal in both models, we examined the effect of Antcin H on p-JNK binding to mitochondria and impairment of mitochondrial respiration. Antcin H inhibited the direct effect of p-JNK on isolated mitochondrial function and binding to isolated mitochondria.
Innovation and Conclusion: Our study has identified Antcin H as a novel active ingredient that contributes to the hepatoprotective effect of AC, and Antcin H protects against liver injury through disruption of the binding of p-JNK to Sab, which interferes with the ROS-dependent self-sustaining activation of MAPK cascade. Antioxid. Redox Signal. 26, 207–220.

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Information & Authors

Information

Published In

cover image Antioxidants & Redox Signaling
Antioxidants & Redox Signaling
Volume 26Issue Number 5February 10, 2017
Pages: 207 - 220
PubMed: 27596680

History

Published in print: February 10, 2017
Published online: 10 February 2017
Published ahead of print: 11 October 2016
Published ahead of production: 5 September 2016
Accepted: 5 September 2016
Revision received: 11 August 2016
Received: 14 July 2016

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Yazhen Huo
Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, China.
USC Research Center for Liver Disease, Keck School of Medicine, University of Southern California, Los Angeles, California.
Sanda Win
USC Research Center for Liver Disease, Keck School of Medicine, University of Southern California, Los Angeles, California.
Tin Aung Than
USC Research Center for Liver Disease, Keck School of Medicine, University of Southern California, Los Angeles, California.
Shutao Yin
Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, China.
Min Ye
State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, China.
Hongbo Hu
Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, China.
Neil Kaplowitz
USC Research Center for Liver Disease, Keck School of Medicine, University of Southern California, Los Angeles, California.

Notes

Address correspondence to:Prof. Hongbo HuBeijing Advanced Innovation Center for Food Nutrition and Human HealthCollege of Food Science and Nutritional EngineeringChina Agricultural UniversityNo. 17 Qinghua East RoadHaidian DistrictBeijing 100083China
E-mail: [email protected]
Dr. Neil KaplowitzUSC Research Center for Liver DiseaseKeck School of MedicineUniversity of Southern California2011 Zonal Avenue, HMR101Los Angeles, CA 90033E-mail: [email protected]

Author Disclosure Statement

No competing financial interests exist.

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