In the present study, an aqueous extract comprising Danshen and Gegen in the ratio of 7:3 (DG) was investigated for its anti-hypertension in vivo and vasodilative activities ex vivo. The anti-hypertensive effect of DG was investigated in spontaneously hypertensive rat (SHR) by measuring systolic blood pressure (SBP) using tail-cuff method. DG was found to ameliorate the SBP in a dose-dependent manner. The vasodilative mechanism of DG was studied by using isolated blood vessels and organ bath or myograph. The endothelium, potassium channel and calcium channel dependency was found in different type of vessels.
In the present study, we aimed at investigating the anti-oxidative effects of DG post-treatment on ischemic-reperfusion (I/R) injuries and its underlying mechanisms. Also, the anti-inflammatory activity of DG and underlying mechanisms involved with regards to its molecular basis of action were studied. Our results showed that DG significantly improved rat heart function after I/R challenge and suppressed the release of enzymes by damaged heart muscles in a dose-dependent manner. DG also significantly inhibited the death of cardiomyocytes, H9c2 cells, with a hypoxia-reperfusion (H/R) challenge. Moreover, the results suggested the inhibitory effects of DG on the production of inflammatory mediators through the inhibition of the NFB pathway.
DG have significantly reduced the carotid intimal-media thickening (IMT) in patients in our previous clinical study. The same result (reduction of IMT in carotid artery) was demonstrated in a balloon-injury rat model. The mechanisms on IMT reduction was then investigated by its key anti-atherosclerotic processes on both vascular smooth muscle cell (vSMC) and endothelial cells. The results showed that DG could inhibit the proliferation and migration of vSMCs and inhibit the adhesion by suppressing the expression of cell adhesion molecules and inflammatory mediators in endothelium.
The collaborative studies with Prof. Qinshi Zhao and Prof. Handong Sun of Kunming Institute of Botany on the biological activities of Erigerontis Herba have been started since 2009. In this study, the vasodilator effects of Erigerontis Herba water extract and Erigerontis Herba polyphenol were investigated using rat isolated aorta rings. The involvement of endothelium in the vasorelaxation was studied by comparing response of endothelium-intact and endothelium-denuded aorta rings which precontracted with U46619. These findings suggested that the vasodilatory activities of EH were endothelium-independent, mediated by decreasing the influx of Ca2+ by calcium channel inhibition and increasing the influx of K+ by opening of a KATP channel.
The pre-clinical part of the project aims at evaluating the vasodilatory and angiogenic response in ischemia soft tissue to DG using an animal chronic limb ischemia model. In summary, our results demonstrated positive dose-dependent vasodilatory response to DG via an endothelium-independent mechanism that involved inwardly rectifying K+ channels and Ca2+ channels. We also demonstrated significant improvement in blood perfusion and micro-vessel density in the ischemic limb and positive effects in functional limb recovery. The clinical trial study was designed as a prospective-randomized, double-blind, placebo-controlled trial (RCT). Carotid artery intima-media thickness (IMT), maximal walking distances (MWD) and pain-free walking distances (PFWD) were evaluated after 24 weeks’ treatment. In summary, DG can improve the patient’s vascular function, increase MWD and improve the daily walking ability of patients.