Centre for Cancer and Inflammation Research, School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tong, Kowloon, Hong Kong, China.
Phytomedicine. 2010 Nov;17(13):1006-15. doi: 10.1016/j.phymed.2010.06.012. Epub 2010 Aug 17.
Ginseng is the most popular herb used for treatment of ischemic heart diseases in Chinese community; ginsenosides are considered to be the major active ingredients. However, whether ginsenosides can enhance the coronary artery flow of ischemic heart and, if so, by what mechanisms they do this, remains unclear.
Isolated rat hearts with ischemia/reperfusion injury in Langendorff system were employed for examining the effect of total ginsenosides (TGS) on coronary perfusion flow (CPF). In addition, human aortic endothelial cells (HAECs) were used for mechanistic study. Levels of various vasodilative molecules, intracellular calcium concentration (Ca²+), and expressions and activation of proteins involving regulation of nitric oxide (NO) signaling pathways in heart tissues and HAECs were determined.
TGS dose-dependently and significantly increased CPF and improved systolic and diastolic function of the ischemia/reperfused rat heart, while inhibitors of NO synthase (NOS), soluble guanylate cyclase (sGC), heme oxygenase (HO), cyclooxygenase (COX), and potassium channel abolished the vasodilation effect of TGS. Positive control verapamil was effective only in increasing CPF. TGS elevated levels of NO and 6-keto-prostaglandin F₁α, a stable hydrolytic product of prostacyclin I₂ (PGI₂), in both coronary effluents and supernatants of HAECs culturing medium, and augmented Ca²+ in HAECs. TGS significantly up-regulated expression of phosphoinositide 3-kinase (PI3K) and phosphorylations of Akt and endothelial NOS (eNOS) as well.
TGS significantly increased CPF of ischemia/reperfused rat hearts through elevation of NO production via activation of PI3K/Akt-eNOS signaling. In addition, PGI₂, EDHF and CO pathways also partially participated in vasodilation induced by TGS.
人参是华人社区治疗缺血性心脏病最常用的草药，被认为是主要的活性成分。然而，人参皂苷是否能增加缺血性心脏病患者的冠状动脉血流，如果可以，其作用机制是什么，目前还不清楚。
采用 Langendorff 系统分离的大鼠缺血/再灌注损伤心脏模型，观察总人参皂苷（TGS）对冠状动脉灌注流量（CPF）的影响。此外，还用人主动脉内皮细胞（HAEC）进行了机制研究。测定心脏组织和 HAEC 中各种血管舒张分子、细胞内钙浓度(Ca²+)、涉及一氧化氮（NO）信号通路调节的蛋白表达和激活水平。
TGS 呈剂量依赖性显著增加 CPF，改善缺血/再灌注大鼠心脏的收缩和舒张功能，而一氧化氮合酶（NOS）、可溶性鸟苷酸环化酶（sGC）、血红素加氧酶（HO）、环氧化酶（COX）和钾通道抑制剂则消除了 TGS 的血管舒张作用。阳性对照维拉帕米仅能有效增加 CPF。TGS 增加了冠状动脉流出液和 HAEC 培养上清液中 NO 和 6-酮-前列腺素 F₁α（PGI₂ 的稳定水解产物）的水平，并增加了 HAEC 的 Ca²+。TGS 还显著上调了磷酸肌醇 3-激酶（PI3K）和蛋白激酶 B（Akt）及内皮型一氧化氮合酶（eNOS）的磷酸化水平。
TGS 通过激活 PI3K/Akt-eNOS 信号通路显著增加缺血/再灌注大鼠心脏的 CPF，从而增加 NO 的产生。此外，PGI₂、EDHF 和 CO 途径也部分参与了 TGS 诱导的血管舒张。
