Rong Jianhui, Cheung Cynthie Yim-Hing, Lau Allan Sik-Yin, Shen Jiangang, Tam Paul Kwong-Hang, Cheng Yung-Chi
Molecular Chinese Medicine Laboratory, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, People's Republic of China.
Int J Mol Med. 2008 Apr;21(4):405-11.
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.
在中国，传统药物临床上用于治疗中风后疾病。为了寻找中风后康复的替代药物，我们最近确定血红素加氧酶-1（HO-1）途径是缺血性中风制剂ISF-1生物活性的关键机制。本研究旨在进一步研究ISF-1在培养的人细胞中诱导HO-1的作用以及对氧化损伤的相应细胞保护作用。采用大脑中动脉闭塞诱导的大鼠中风模型来验证ISF-1在体内的活性。发现ISF-1以剂量和时间依赖性方式诱导HO-1表达。已确定ISF-1中的四种成分负责诱导HO-1。这些活性成分或纯化化合物的适当组合导致HO-1表达的协同诱导。制备了一种最小的HO-1诱导制剂，其对H2O2诱导的氧化应激具有显著的细胞保护作用。总体而言，草药制剂ISF-1能够在体外和体内诱导HO-1表达，为中风后康复提供了一种潜在机制。本研究可能为基于传统草药的机制明确的疗法的开发提供启示。
