Author(s): Huo Y, , Win S, Than TA, Yin S,
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Abstract AIM: Antrodia Camphorate is a mushroom which 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 Antrodia Camphorate, in murine models of acute liver injury. RESULTS: We found that Antcin H pretreatment protected against liver injury in both acetaminophen and galactosamine/TNFα models. More importantly, Antcin H also offered a significant protection against acetaminophen-induced liver injury when it was given one hour after acetaminophen. The protection was verified in primary mouse hepatocytes. Antcin H prevented sustained 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 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 Antrodia Camphorate and Antcin H protects against liver injury through disruption of the binding of p-JNK to Sab which interferes the ROS-dependent self-sustaining activation of MAPK cascade.
This article was published in Antioxid Redox Signal
and referenced in Journal of Bioprocessing & Biotechniques