Studies Of Reinioside's Anti-atherosclerosis Mechanism

Chapter One Pharmacodynamics Studies of total triterpenoidsaponins of Polygala aureocaudaBACKGROUNDDyslipidemia includes the high level of TC or TG, and low level ofHDL-C. Clinic studies demonstrate that cholesterol-lowing therapies reducethe incidence of cardiovascular diseases.Among the medicines using to regulate lipids at present, chemicaldrugs are mostly aimed at one target. Comparing to chemical drugs,traditional Chinese herbals are mainly aimed at multi-targets and playmulti-activities.Pharmacological experiments have validated that total triterpenoidsaponins of Polygala aureocauda (TTS) have anti-inflammation, anti-oxidize, reducing blood lipids. In this experiment, We investigated the effectsof TTS on the levels ofTG. TC and LDL-C directed by Guide of New DrugsResearch. METHODSThe levels of TG, TC and LDL-C were measured by means of auto-biochemical analytical instrument; the figures such asηb,ηp and HCT inhigh shear rate and the indexes such asηr, AI were determined by intelligentblood viscosity apparatus. The distribution of lipid plaque were observed byeyes.RESULTS1. TTS can reduce the level of TG,TC,LDL-C in hyperlipemia ratsand have little effect on the level of HDL-C.2. TTS can significantly bring down blood viscosity and HCT and haslittle effect onηr and AI.3. TTS can reduce pathological changes in intima of aortic arch. lipidplaque in the treatment group is much smaller than the control one.CONCLUSIONS1. TTS can reduce the level of TG, TC, LDL-C and significantly bringdown blood viscosity in hyperlipidemic rats.2. TTS can ease pathological changes in intima of aortic arch. Chapter Two Reinioside C reduces the level of MMP-9 andsICAM-1 in acute coronary syndromeBACKGRORNDRecent studys show that proteolystic enzyme plays an important rolein acute coronary syndrome. The plasma level of matrix metalloproteinase-9(MMP-9) is high in the patients with acute coronary syndrome. Intercellularadhesion molecule-1 (sICAM-1) also plays an important role in acutecoronary syndrome. Studys also show that MMP-9 and ICAM-1 are relatedto the stability of atherosclerotic plaques. Pharmacological experiments havevalidated that reinioside C has the effects of anti-inflammation, but itsmechanism remains unknown. There is no report that RC can affect thesecretion of MMP-9 and sICAM-1. So this clinical study was made to explorethe effects of RC on the patients with acute coronary syndrome.OBJECTIVETo explore the relationship between inflammatory response and acutesyndrome and protective effect of RC on the patients with acute coronarysyndrome. METHODSThe subjects were divided into three groups: patients with acutemyocardial infarction, patients with unstable angina pectoris and controlledgroup(group C). Patients with acute myocardial infarction were divided intosub-group reinioside C (group A₁) and sub-group non- reinioside C (groupB₁); Patients with unstable angina pectoris were also divided into sub-groupreinioside C (group A₂) and sub-group non-reinioside C (group B₂); Matrixmetalproteinase-9(MMP-9) and soluble intercellular adhesion molecule-1(sICAM-1) were measured using sandwich enzyme immunoassarvRESULTSSerum level were significantly high in all patients with acute coronarysyndrome compared with control group; Serum MMP-9 and slCAM-1 levelin acute myocardial infarction group were the highest in all groups.After RCtreatment Serum MMP-9 and slCAM-1 level were significantly lowcompared with that before RC treatment, and also significantly low comparedwith that non-RC treatmentCONCLUSIONRC may have cardiovascular protective effect on patients with acutecoronary syndrome by reducing serum MMP-9 and sICAM-1 level. Chapter Three Anti-inflammation Mechanism Studies ofReinioside CBACKGROUNDPolygala aureocauda Dunn. (Polygalaceae), which distributes mainly inHunan, Fujian, Guangdong and Guangxi provinces, is used as a tonic for thetreatment of anti-inflammation, hepatitis, hypercholesterolemia and injury infolk medicine. It was reported that triterpenoid saponins and xanthones werethe dominating constituents. Reinioside C was the most part among totaltriterpenoid saponins. Pharmacological experiments have validated that totaltriterpenoid saponins have effect of anti-inflammation, reducing blood lipid.However which single triterpenoid saponin is the main active compounds andhow does its functions remain unclear.METHODSTNF-αand sICAM-1 induced by ox-LDL in monocytes were interferedby RC and the contents of TNF-αand sICAM-1 were determined by meansof ELISA. The levels of ADMA were measured by HPLC; and the adhesion of the monocytes to endothelial cells was observed by advanced microscope;and the NF-κB DNA-binding activity was determined by EMSARESULTSOx-LDL can increase the expression of ADMA in monocytes. RC cansignificantly low the content of TNF-α, sICAM-1 and ADMA in monocyteswhich were induced by ox-LDL and these actions are dose dependent. RCalso can decrease the adhesion of the monocytes to endothelial cells.CONCLUSIONS1. Ox-LDL can induce the increased expression of ADMA in monocytes.RC can decrease expression through inhibiting the activity of NF-κB.2. RC can reduce the contents of TNF-α, sICAM-1 and the adhesion ofthe monocytes to endothelial cells induced by ox-LDL. Those inhibitionswere related to the decreasing content of ADMA.