title: Cerebral vasodilator properties of Danshen and Gegen: a study of their combined efficacy and mechanisms of actions.
abstract: Danshen and Gegen are two commonly used Chinese herbal medicines for treatment of cardiovascular diseases. The aim of the present study was to elucidate the combination effects of these two herbs on cerebral vascular tone and their underlying mechanisms of actions. Basilar artery rings were obtained from rats and precontracted with U46619. Cumulative administrations of aqueous extracts of Danshen, Gegen, or the two herbs combined (DG; ratio 7:3) produced concentration-dependent relaxation of the artery rings. Statistical analysis on these findings produced a combination index (CI) of 1.041 at ED50, which indicates the two herbs produced additive vasodilator effects when used as a combined decoction. Removal of the endothelium had no effect on the vasodilator properties of Danshen, Gegen, and DG. However, their maximum effects (Imax) were significantly blunted by a KATP channel inhibitor glibenclamide, a non-selective K(+) channel inhibitor tetraethylammonium (TEA), and by a combination of K(+) channel inhibitors (glibenclamide+TEA+iberiotoxin+4-aminopyridine+barium chloride). In addition, Danshen, Gegen, and DG produced augmentation of KATP currents and inhibited Ca(2+) influx in vascular smooth muscle cells isolated from rat basilar arteries. Furthermore, these agents inhibited CaCl2-induced contraction in the artery rings. In conclusion, the present study showed that Danshen and Gegen produced additive vasodilator effects on rat cerebral basilar arteries. These effects were independent of endothelium-derived relaxant factors (EDRF), but required the opening of KATP channels and inhibition of Ca(2+) influx in the vascular smooth muscle cells. It is suspected that the cerebral vasodilator effects of Danshen and Gegen produced either on their own or in combination, can help patients with obstructive cerebrovascular diseases.
authors.affiliation: School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong Special Administrative Region.
authors.forename: Y
authors.initials: Y
authors.lastname: Deng
authors.affiliation: School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong Special Administrative Region.
authors.forename: E S K
authors.initials: ES
authors.lastname: Ng
authors.affiliation: School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong Special Administrative Region.
authors.forename: Y W
authors.initials: YW
authors.lastname: Kwan
authors.affiliation: Institute of Chinese Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong Special Administrative Region; State Key Laboratory of Phytochemistry and Plant Resources in West China, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong Special Administrative Region.
authors.forename: C B S
authors.initials: CB
authors.lastname: Lau
authors.affiliation: Institute of Chinese Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong Special Administrative Region; State Key Laboratory of Phytochemistry and Plant Resources in West China, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong Special Administrative Region.
authors.forename: D W S
authors.initials: DW
authors.lastname: Cheung
authors.affiliation: Institute of Chinese Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong Special Administrative Region; State Key Laboratory of Phytochemistry and Plant Resources in West China, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong Special Administrative Region.
authors.forename: J C M
authors.initials: JC
authors.lastname: Koon
authors.affiliation: School of Pharmacy, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong Special Administrative Region.
authors.forename: Z
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: School of Pharmacy, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong Special Administrative Region.
authors.forename: Z
authors.initials: Z
authors.lastname: Zuo
authors.affiliation: Institute of Chinese Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong Special Administrative Region; State Key Laboratory of Phytochemistry and Plant Resources in West China, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong Special Administrative Region.
authors.forename: P C
authors.initials: PC
authors.lastname: Leung
authors.affiliation: School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong Special Administrative Region; Institute of Chinese Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong Special Administrative Region; State Key Laboratory of Phytochemistry and Plant Resources in West China, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong Special Administrative Region.
authors.forename: K P
authors.initials: KP
authors.lastname: Fung
authors.affiliation: School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong Special Administrative Region. Electronic address: francisLam@cuhk.edu.hk.
authors.forename: F F Y
authors.initials: FF
authors.lastname: Lam
mesh_terms: D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000818:Animals; D001488:Basilar Artery / Q000187:drug effects*; D015220:Calcium Channels / Q000187:drug effects; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000187:drug effects; D054086:KATP Channels / Q000187:drug effects; D018613:Microscopy, Confocal; D029908:Pueraria; D051381:Rats; D027561:Salvia miltiorrhiza; D014664:Vasodilation / Q000187:drug effects*
chemical_list: D015220:Calcium Channels; C568783:Danshen-Gegen; D004365:Drugs, Chinese Herbal; D054086:KATP Channels; C028972:dan-shen root extract; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid
keywords: Basilar artery; Combination index; Danshen; Gegen; Stroke; Vasodilatation