An Investigation of the Vascular Effects of Sai-luo-tong (SLT), a Standardised Chinese Herbal Formula, for Vascular Dementia

摘要

Background: Vascular dementia (VaD) is recognised as a global health issue and causes significant distress to patients and carers, as well as substantial economic burden to the social problem and healthcare system. Sailuotong (SLT), a standardised three herbs formulation consisting of Panax ginseng, Ginkgo biloba and Crocus sativus, has been shown to increase cerebral blood flow and improve memory and cognitive functions in both animal and clinical studies. However, the direct vasodilatory effect of SLT has not been demonstrated. In this study, we hypothesised that SLT can induce vasodilatation in rat isolated arteries via an endothelium-dependent mechanism. The aims of this study were to investigate the direct vasodilatory effect of SLT extract and identify the underlying mechanism(s) using rat isolated tail artery. The vasodiltatory effect of SLT on rat isolated basilar artery was also evaluated. Methods: Male, 250-300g Wistar Kyoto (WKY) rat basilar and tail arteries were isolated for isometric tension measurement using a wire myography system. SLT and its individual components-induced vasodilatations were assessed in phenylephrine (PE, 1 muM)-preconstricted tail artery or potassium chloride (KCl, 40 mM)-pre-constricted basilar artery with or without pre-incubation of various pharmacological inhibitors. The effects of SLT on PE, KCl and calcium chloride (CaCl2)-induced vasoconstriction were also evaluated using rat isolated tail artery. Results: SLT (0.1-5000 mug/mL) induced vasodilatation in the rat isolated tail artery in a concentration dependent manner. The SLT-induced vasodilatation was not significantly suppressed by pre-incubation of N-nitro-L-arginine methyl ester (L-NAME; 20 muM), an endothelial nitric oxide synthese (eNOS) inhibitor. A similar L-NAME-insensitivevasodilatations were also observed with Ginkgo biloba (0.1-5000 mug/mL) and Crocus sativus (0.1-5000 mug/mL). Pre-incubation of K+ channel blockers, including TEA (tetraethyl-ammonium, 1 mM), glibenclamide (3 muM), and clotrimazole (5 muM) had no effect to SLT-induced relaxation. In contraction experiments, SLT (500, 1000 and 5000 mug/mL) attenuated agonist (PE, 0.001-10 muM)- and high K+ (KCl 10-80 mM)-induced contraction in the rat tail artery. In Ca2+-free solution, SLT (500, 1000 and 5000 mug/mL) markedly suppressed Ca2+-induced (0.1-3 mM) vasoconstriction in both PE (1 muM)-and KCl (80 mM)-stimulated tail arteries. In rat isolated basilar artery SLT (0.1-5000 mug/mL) caused a marked relaxation at 5000 mug/mL. The SLT-induced relaxation was not affected by pre-incubation of L-NAME (20 muM). Conclusion: Putting these together, our results suggested that SLT induces relaxation of rat isolated tail arterial rings through an endothelium-independent pathway, involving blockade of extracellular Ca2+ influx.