Senkyunolides reduce hydrogen peroxide-induced oxidative damage in human liver HepG2 cells via induction of heme oxygenase-1 |
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| Authors: | Hongyi Qi Shiu On Siu Yan Chen Yifan Han Ivan K. Chu Yao Tong Allan S.Y. Lau Jianhui Rong |
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| Affiliation: | 1. School of Chinese Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, 10 Sassoon Road, Pokfulam, Hong Kong;2. Department of Chemistry, The University of Hong Kong, 21 Sassoon Road, Pokfulam, Hong Kong;3. Department of Surgery, The University of Hong Kong, 21 Sassoon Road, Pokfulam, Hong Kong;4. Department of Applied Biology and Chemical Technology, Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong;5. Molecular Chinese Medicine Lab, Li Ka Shing Faculty of Medicine, The University of Hong Kong, 10 Sassoon Road, Pokfulam, Hong Kong;1. School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, People’s Republic of China;2. Institute of Innovative Medicine Ingredients of Southwest Specialty Medicinal Materials, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, People’s Republic of China;1. School of Medicine, Nantong University, Nantong 226001, China;2. School of Pharmacy, Nantong University, Nantong 226001, China;3. Department of Neurochemistry, Institute for Nautical Medicine, Nantong University, 19 Qixiu Road, Nantong 226001, China;1. Department of Blood Transfusion, The Third Affiliated Hospital of Sun Yat-sen University, No. 600 Tianhe Road, 510630 Guangzhou, PR China;2. Department of Hematology, The Third Affiliated Hospital of Sun Yat-sen University, No. 600 Tianhe Road, 510630 Guangzhou, PR China;3. Department of Cardiology, The Third Affiliated Hospital of Southern Medical University, No. 183 Zhongshan Road West, 510630 Guangzhou, PR China |
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| Abstract: | Rhizoma Chuanxiong is widely used as folk medicine to treat the diseases caused by oxidative stress and inflammation. To delineate the underlying molecular mechanisms, we recently found that Rhizoma Chuanxiong extract significantly induced heme oxygenase-1 (HO-1), an enzyme that degrades intracellular heme into three bioactive products: biliverdin, carbon monoxide and free iron. The anti-inflammatory, antiapoptotic and antiproliferative actions of these products highlight HO-1 as a key endogenous antioxidant and cytoprotective gene. This study was designed to further characterize HO-1 induction of Rhizoma Chuanxiong through bioactivity-guided fractionation. All isolated fractions were assayed for HO-1 induction in human HepG2 cell line at mRNA and protein levels. Based on chromatographic profiling, nuclear magnetic resonance (NMR) and mass spectrometric analysis, the active compounds were identified as senkyunolide-H and its stereoisomer senkyunolide-I. Both senkyunolide isomers inhibited the formation of reactive oxygen species and lipid peroxidation and enhanced the cellular resistance to hydrogen peroxide-induced oxidative damage. Notably, heme oxygenase inhibitor tin protoporphyrin IX (SnPP) significantly suppressed the antioxidant activity of senkyunolide stereoisomers. Thus, this study demonstrated that senkyunolide-H and -I attenuated oxidative damage via activation of HO-1 pathway. |
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