The Cardiovascular Effect Of Dendranthema Morifolium Ramat. And Its Active Compositions

The flower of Dendranthema morifolium Ramat. (DM) has been widely used in China. It was appointed to traditional medicine and healthy food by State Ministry of Health of China. The previous study showed the water extract of DM (0.25 g/L to 1.0g/L) increased coronary flow and ventricular contractility, decreased heart rate (HR) in isolated rat heart and intact dog heart in dose dependent manner. Furthermore, water extract of DM attenuated ST-segment reduction induced by electrically stimulation to paraventricular nuclei and decrease of contractile function and coronary flow (CF) of isolated rat heart subjected to by ischemia/reperfusion. It also increased CF in isolated heart of rat with high plasma cholesterol. Clinical study demonstrated that DM had beneficial effect on coronary heart disease, reduced the onset times of angina and improves the change of cardiogram caused by ischemia.However, because of limitation of technology, the previous studies had not elucidated the direct cardiovascular effect and underlying mechanism. For example, it has not been determined that what are the active compositions or active parts of DM for the cardiovascular action. Moreover, the biotransformation of the extract from DM was also not investigated when the drug was orally administrated.Therefore, the first aim of the present study was to observe the global effect of total extract from DM on cardiovascular system. The second aim was to determine the active parts or active components specific to cardiovascular system. The third aim was to investigate the main components in plasma after DM was orally administrated. The fourth aim was to clarify the vesorelaxation and the mechanism of DM extract and the main component of DM in plasma. The last aim was to study the structure-activity relationship of flavonoids, including main flavonoids (luteolin-7-O-B-D-glucoside and apigenin-7-O-B-D-glucoside) from DM and main transformational products (luteolin and apigenin) of DM in vasorelaxation and antioxidation.1. Cardiovascular Effect of Total Extract from Dendranthema morifolium Ramat.OBJECTIVE: To verify the effect of Dendranthema morifolium Ramat. (DM) on cardiovascular system.METHODS: The Langendorff technique was applied to determine the effects of DM on left ventricular developed pressure (LVDP), and maximal rate of rise/fall of ventricular pressure (+dP/dtmax), heart rate (HR) and coronary flow (CF) in isolated perfused rat hearts. Ischemia/reperfusion was induced by ligation of the left anterior descending artery for 30min followed by 30min reperfusion in isolated rat heart. The superoxide dismutase (SOD) activity and malondiadehyde (MDA) content of heart were measured. The cell contraction and intracellular calcium transient in enzymatically isolated ventricular myocytes were determined by the video tracking system and spectrofluorometry, respectively. The vasorelaxation effect of DM was evaluated by measuring the tension of rat thoracic aorta precontracted by phenylephrine (PE) (10-6mol/L) or KC1 (60mmol/L).RESULTS: (1) DM (0.25-1.0g/L) dose-dependently increased LVDP, P/dtmax and CF in the isolated rat hearts; (2) DM (0.5g/L) significantly attenuated the inhibitory effects inducedby ischemia/reperfusion on LVDP, P/dtmax, CF and LVDPxHR, meanwhile increased the content of SOD and decreased the content of MDA in the myocardium; (3) DM (0.25~1.0g/L) also dose-dependently increased +dL/dtmax, -dL/dtmax and dL, but had no effect on the end-diastolic length in the isolated myocytes; (4) During anoxia, [Ca2+]i transient, L/dtmax and dL of cell contraction were decreased, and during reoxygenation they went back but did not returned to the pre-anoxia level. DM (0.5g/L) attenuated the effect of anoxia and rexoxygenation on [Ca2+]i transient and cell contraction; (5) DM caused concentration-dependent relaxation of aorta rings precontracted with phenylephrine and high level of K+.CONCLUSION: DM attenuated the inhibitory effects on contractility and intracellular calcium induced by ischemia/anoxia and reperfusion/...