Am J Cardiovasc Dis 2013;3(4):227-238
Original Article
Gambogic acid suppresses pressure overload cardiac hypertrophy in rats
Shouting Liu, Canguo Zhao, Changshan Yang, Xiaofen Li, Hongbiao Huang, Ningning Liu, Shujue Li, Xuejun Wang, Jinbao
Liu
Protein Modification and Degradation Laboratory, Department of Pathophysiology, Guangzhou Medical University,
Guangdong 510182, China; The Cardiovascular Institute, The Second Affiliated Hospital, Guangzhou Medical University,
Guangzhou, Guangdong 510260, China; Guangdong Provincial Key Lab of Urology, Department of Urology, Minimally
Invasive Surgery Center, The First Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong 510230,
China; Division of Basic Biomedical Sciences, Sanford School of Medicine of The University of South Dakota, Vermillion,
South Dakota 57069, USA. Equal contributors.
Received October 15, 2013; Accepted October 25, 2013; Epub November 1, 2013; Published November 15, 2013
Abstract: Cardiac hypertrophy is a common response of the heart to a variety of cardiovascular stimuli. Pathological
cardiac hypertrophy eventually leads to heart failure. Gambogic acid (GA) is a main active ingredient isolated from the
gamboge resin of Garcinia hanburyi trees and has potent anti-tumor and anti-inflammatory effects that are associated with
inhibition of the NF-κB pathway. We and others recently reported that GA can significantly inhibit the function of the
proteasome with much less toxicity than conventional proteasome inhibitors. The increasing lines of evidence indicate that
the inhibition of the proteasome can promote the regression of cardiac hypertrophy induced by pressure overload through
the blockade of the NF-κB pathway. In the present study, we examined the effect of GA on pressure overload or
isoproterenol infusion induced cardiac hypertrophy and fibrosis, and changes in myocardial NF-κB signaling. We observed
that the heart weight/body weight ratio, the size of cardiomyocytes, interstitial fibrosis, and the reactivation of fetal genes (α-
SK-actin and BNP mRNA) were markedly increased by abdominal aorta constriction (AAC) or isoproterenol infusion (ISO),
all of which were effectively inhibited by GA treatment. Furthermore, GA treatment abolished proteasome chymotrypsin-like
activity increases induced by AAC or ISO, led to increased myocardial IκB protein, decreased NF-κB p65 subunit levels in
the nuclear fraction, decreased NF-κB DNA-binding activity, and reduced IL2 levels in the myocardium of rats subject to
AAC or ISO. In conclusion, GA treatment can suppress cardiac hypertrophy and fibrosis induced by pressure overload or
isoproterenol possibly through the inhibition of the proteasome and the NF-κB pathway, suggesting that GA treatment may
provide a new strategy to treat cardiac hypertrophy. (AJCD1310005).
Keywords: Gambogic acid, cardiac hypertrophy, pressure overload, isoproterenol, proteasome, NF-κB
Address correspondence to: Dr. Jinbao Liu, Protein Modification and Degradation Laboratory, Department of
Pathophysiology, Guangzhou Medical Univer-sity, Guangzhou, Guangdong 510182, P. R. China; Tel: +8620-81340720; Fax:
+8620-81340542; E-mail: jliu@gzhmc.edu.cn; Dr. Xuejun Wang, Division of Basic Biomedical Sciences, Sanford School of
Medicine of the University of South Dakota, Vermilli-on, SD 57069, USA. E-mail: XuejunWang@usd.edu
Original Article
Gambogic acid suppresses pressure overload cardiac hypertrophy in rats
Shouting Liu, Canguo Zhao, Changshan Yang, Xiaofen Li, Hongbiao Huang, Ningning Liu, Shujue Li, Xuejun Wang, Jinbao
Liu
Protein Modification and Degradation Laboratory, Department of Pathophysiology, Guangzhou Medical University,
Guangdong 510182, China; The Cardiovascular Institute, The Second Affiliated Hospital, Guangzhou Medical University,
Guangzhou, Guangdong 510260, China; Guangdong Provincial Key Lab of Urology, Department of Urology, Minimally
Invasive Surgery Center, The First Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong 510230,
China; Division of Basic Biomedical Sciences, Sanford School of Medicine of The University of South Dakota, Vermillion,
South Dakota 57069, USA. Equal contributors.
Received October 15, 2013; Accepted October 25, 2013; Epub November 1, 2013; Published November 15, 2013
Abstract: Cardiac hypertrophy is a common response of the heart to a variety of cardiovascular stimuli. Pathological
cardiac hypertrophy eventually leads to heart failure. Gambogic acid (GA) is a main active ingredient isolated from the
gamboge resin of Garcinia hanburyi trees and has potent anti-tumor and anti-inflammatory effects that are associated with
inhibition of the NF-κB pathway. We and others recently reported that GA can significantly inhibit the function of the
proteasome with much less toxicity than conventional proteasome inhibitors. The increasing lines of evidence indicate that
the inhibition of the proteasome can promote the regression of cardiac hypertrophy induced by pressure overload through
the blockade of the NF-κB pathway. In the present study, we examined the effect of GA on pressure overload or
isoproterenol infusion induced cardiac hypertrophy and fibrosis, and changes in myocardial NF-κB signaling. We observed
that the heart weight/body weight ratio, the size of cardiomyocytes, interstitial fibrosis, and the reactivation of fetal genes (α-
SK-actin and BNP mRNA) were markedly increased by abdominal aorta constriction (AAC) or isoproterenol infusion (ISO),
all of which were effectively inhibited by GA treatment. Furthermore, GA treatment abolished proteasome chymotrypsin-like
activity increases induced by AAC or ISO, led to increased myocardial IκB protein, decreased NF-κB p65 subunit levels in
the nuclear fraction, decreased NF-κB DNA-binding activity, and reduced IL2 levels in the myocardium of rats subject to
AAC or ISO. In conclusion, GA treatment can suppress cardiac hypertrophy and fibrosis induced by pressure overload or
isoproterenol possibly through the inhibition of the proteasome and the NF-κB pathway, suggesting that GA treatment may
provide a new strategy to treat cardiac hypertrophy. (AJCD1310005).
Keywords: Gambogic acid, cardiac hypertrophy, pressure overload, isoproterenol, proteasome, NF-κB
Address correspondence to: Dr. Jinbao Liu, Protein Modification and Degradation Laboratory, Department of
Pathophysiology, Guangzhou Medical Univer-sity, Guangzhou, Guangdong 510182, P. R. China; Tel: +8620-81340720; Fax:
+8620-81340542; E-mail: jliu@gzhmc.edu.cn; Dr. Xuejun Wang, Division of Basic Biomedical Sciences, Sanford School of
Medicine of the University of South Dakota, Vermilli-on, SD 57069, USA. E-mail: XuejunWang@usd.edu
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