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Int. J. Mol. Sci. 2017, 18(7), 1482; doi:10.3390/ijms18071482

Hepatoprotective Role of Hydrangea macrophylla against Sodium Arsenite-Induced Mitochondrial-Dependent Oxidative Stress via the Inhibition of MAPK/Caspase-3 Pathways

1
College of Veterinary Medicine and Biosafety Research Institute, Chonbuk National University, Iksan 54596, Korea
2
Department of Pharmacology and Toxicology, Sylhet Agricultural University, Sylhet 3100, Bangladesh
3
Department of Crop Science and Biotechnology, Chonbuk National University, Jeonju 54896, Korea
*
Author to whom correspondence should be addressed.
Received: 26 May 2017 / Revised: 30 June 2017 / Accepted: 5 July 2017 / Published: 10 July 2017
(This article belongs to the Special Issue Biological Activity of Natural Secondary Metabolite Products)
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Abstract

Sodium arsenite (NaAsO2) has been recognized as a worldwide health concern. Hydrangea macrophylla (HM) is used as traditional Chinese medicine possessing antioxidant activities. The study was performed to investigate the therapeutic role and underlying molecular mechanism of HM on NaAsO2-induced toxicity in human liver cancer (HepG2) cells and liver in mice. The hepatoprotective role of HM in HepG2 cells was assessed by using 3-(4,5-dimethylthiazol-2-Yl)-2,5-diphenyltetrazolium bromide (MTT), reactive oxygen species (ROS), and lactate dehydrogenase (LDH) assays. Histopathology, lipid peroxidation, serum biochemistry, quantitative real-time polymerase chain reaction (qPCR) and Western blot analyses were performed to determine the protective role of HM against NaAsO2 intoxication in liver tissue. In this study, we found that co-treatment with HM significantly attenuated the NaAsO2-induced cell viability loss, intracellular ROS, and LDH release in HepG2 cells in a dose-dependent manner. Hepatic histopathology, lipid peroxidation, and the serum biochemical parameters alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were notably improved by HM. HM effectively downregulated the both gene and protein expression level of the mitogen-activated protein kinase (MAPK) cascade. Moreover, HM well-regulated the Bcl-2-associated X protein (Bax)/B-cell lymphoma-2 (Bcl-2) ratio, remarkably suppressed the release of cytochrome c, and blocked the expression of the post-apoptotic transcription factor caspase-3. Therefore, our study provides new insights into the hepatoprotective role of HM through its reduction in apoptosis, which likely involves in the modulation of MAPK/caspase-3 signaling pathways. View Full-Text
Keywords: hepatoprotection; Hydrangea macrophylla; NaAsO2; mitogen-activated protein kinase (MAPK); caspase-3 hepatoprotection; Hydrangea macrophylla; NaAsO2; mitogen-activated protein kinase (MAPK); caspase-3
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MDPI and ACS Style

Akanda, M.R.; Tae, H.-J.; Kim, I.-S.; Ahn, D.; Tian, W.; Islam, A.; Nam, H.-H.; Choo, B.-K.; Park, B.-Y. Hepatoprotective Role of Hydrangea macrophylla against Sodium Arsenite-Induced Mitochondrial-Dependent Oxidative Stress via the Inhibition of MAPK/Caspase-3 Pathways. Int. J. Mol. Sci. 2017, 18, 1482.

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