Induction of heme oxygenase-1 by traditional Chinese medicine formulation ISF-1 and its ingredients as a cytoprotective mechanism against oxidative stress.
Traditional medicines are clinically used to treat post-stroke disorders in China. In search of alternative medicines for post-stroke rehabilitation, we recently identified the heme oxygenase-1 (HO-1) pathway as a key mechanism underlying the biological activities of the ischemic stroke formulation ISF-1. This study was designed to further investigate ISF-1 for HO-1 induction in cultured human cells and corresponding cytoprotective effects against oxidative injury. A rat stroke model induced by middle cerebral artery occlusion was employed to verify the activity of ISF-1 in vivo. It was found that HO-1 expression was induced by ISF-1 in a dose- and time-dependent manner. Four ingredients from ISF-1 were identified to be responsible for HO-1 induction. The appropriate combinations of these active ingredients or purified compounds resulted in synergistic induction of HO-1 expression. A minimal HO-1-inducing formulation was prepared and showed significant cytoprotection against H2O2-induced oxidative stress. Collectively, the herbal formulation ISF-1 was capable of inducing HO-1 expression, in vitro and in vivo, offering a potential mechanism for post-stroke rehabilitation. This study may shed light on the development of mechanism-defined therapies based on traditional herbal remedies.
Rong
Jianhui
J
Molecular Chinese Medicine Laboratory, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, People's Republic of China. jrong@hku.hk
Cheung
Cynthie Yim-Hing
CY
Lau
Allan Sik-Yin
AS
Shen
Jiangang
J
Tam
Paul Kwong-Hang
PK
Cheng
Yung-Chi
YC
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001921:Brain / Q000187:drug effects / Q000201:enzymology; D002460:Cell Line; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D004790:Enzyme Induction / Q000187:drug effects; D006418:Heme / Q000378:metabolism; D006419:Heme Oxygenase (Decyclizing) / Q000096:biosynthesis; D051547:Heme Oxygenase-1 / Q000096:biosynthesis*; D006706:Homeostasis; D006801:Humans; D006861:Hydrogen Peroxide / Q000633:toxicity; D007501:Iron / Q000378:metabolism; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects*; D008517:Phytotherapy; D051381:Rats; D017207:Rats, Sprague-Dawley; D020521:Stroke / Q000188:drug therapy / Q000201:enzymology
D000975:Antioxidants; D004365:Drugs, Chinese Herbal; C524130:ISF-1 decoction; D006418:Heme; D006861:Hydrogen Peroxide; D007501:Iron; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1; C491523:Hmox1 protein, rat