Study On Anti - Platelet And Inflammatory Response Of Huoxue Jiedu Herbal Medicine

Platelet activation plays a crucial role in the development of acute coronary syndromes (ACS) and contributes to cardiovascular events. In addition, it also involves in the disruption of atherosclerotic plaques. Atherosclerosis is a chronic inflammatory process, and inflammation is an important component of ACS. According to the theory of traditional Chinese medicine, platelet activation and thrombosis can be regarded as blood stasis. Therefore, a series of therapies for activating blood circulation have been used on cardiovascular diseases, showing favorable effects. However, the inflammatory reactions and tissue necrosis occurred during the development of the diseases cannot be attributed to the pathogenesis of blood stasis. The characteristics of these pathological changes are similar to the traditional Chinese medicine’s theory——blood stasis may lead to toxin production. On the background of this theory, our research team hypothesized that transformation of toxin from blood-stasis and the combination of toxin and stasis remains throughout the whole process of the cardiovascular disease and may result in cardiovascular events. In order to verify the reliability of the hypothesis, we explored the antiplatelet and anti-inflammation effect of activating blood circulation and detoxifying Chinese medicine from the following three aspects:systematic review, clinical research and animal experiment to confirm the etiology and pathogenesis of coronary heart disease with blood stasis and toxin.Part 1 Traditional Chinese Medicine for Activating Blood Circulation and Detoxifying in Unstable Angina Pectoris:A Systematic Review Objective:To evaluate the effectiveness and safety of traditional Chinese medicine for activating blood circulation and detoxifying (ABCD) in patients with unstable angina pectoris (UAP).Methods:We performed an electronic literature search of six medical databases for relevant articles published up to January 2015. Randomized controlled trials (RCTs) comparing ABCD Chinese medicine alone or in combination with conventional drugs and conventional drugs or other Chinese medicines alone were included. A meta-analysis was performed for the following outcome measures:reduction of angina symptoms (RAS), electrocardiogram (ECG) improvement, blood lipid levels, inflammatory factor levels, and plasma fibrinogen (FIB) levels.Results:11 moderate-to-low-quality studies involving 686 patients were included. The evidence indicated that ABCD Chinese medicine exhibited superior effectiveness in relieving angina symptoms compared with conventional drugs [relative risk (RR),1.23; 95% confidence interval (CI),1.05-1.44]; however, ECG improvement was not significant (RR,1.21; 95%CI, 0.91-1.62). Moreover, ABCD Chinese medicine exhibited superior anti-inflammatory, anticoagulant, and lipid-lowering effects compared with other medicines.Conclusion:The systematic review suggest that ABCD Chinese medicine had beneficial effects for the treatment of UAP although there were some methodological limitations of the included studies.Part 2 Activating blood circulation and detoxifying Chinese medicine in unstable angina patients after percutaneous coronary intervention—open label randomized trialObjective:To observe the effects of activating blood circulation and detoxifying Chinese medicine on inflammatory reaction and platelet activation in patients with unstable angina pectoris (UAP) on a background of standard treatment.Methods:We enrolled 154 diagnosed UAP patients in six clinical research centers and the patients were randomly assigned in a 1:1 ratio to the ABCD Chinese medicine group and the activating blood circulation (ABC) Chinese medicine group. The ABC group received the Guanxindanshen Drop pills (ten grain, three times per day for one month) in addition to standard medication; while the ABCD group was treated with Guanxindanshen Drop Pills and Andrographis tablet (two pills, three times per day for one month) based on the standard medication. The serum levels of the hs-CRP、TNFa、IL-6、TM、sCD40L of UAP patients before and after one-month treatment were determined. Moreover, the sores of angina pectoris, blood stasis syndrome and TCM symptoms were also examined.Results:The gender, age, history of disease and medication history of the two groups were consistent and comparable. After one month treatment, a significant reduction in serum hs-CRP level of ABCD group from baseline was observed, and the ABCD group demonstrated a significantly greater reduction than ABC group (P<0.05). Moreover, treatment with ABCD group with also demonstrated superior performance in comparison to the ABC group with respect to blood stasis syndrome scores, angina pectoris scores and TCM symptoms scores.Conclusion:Combination treatment of Guanxindanshen Drop pills and Andrographis tablet on the background of standard treatment not only improved the angina and blood stasis symptoms, but also had favorable anti-inflammatory and anti-thrombosis effects.Part 3 Antiplatelet and anti-inflammatory effects of activating blood circulation and detoxifying Chinese medicine in rats with coronary microembolizationObjective:To evaluate the antiplatelet and anti-inflammatory effects of a combination of activating blood circulation and detoxifying Chinese medicine in a rat model of coronary microembolization (CME).Methods:Ninety male rats were allocated randomly to six groups (sham, CME model, ligustrazine, berberine, ligustrazine+berberine, and clopidogrel). Drugs were given daily by gavage for two weeks to all groups. Twelve hours after the last treatment, coronary microembolization was induced by the internal left ventricular injection of sodium laurate while obstructing the ascending aorta. To evaluate the cardioprotective effect of treatment with ligustrazine and berberine, we measured hemodynamics and the serum level of creatine kinase MB (CK-MB). The infiltration of inflammatory cells was evaluated with hematoxylin-eosin staining. Micronecrotic foci were identified with Heidenhain staining and the microthrombotic condition was evaluated with Carstairs staining. The possible underlying mechanism was explored by examining platelet activation; plasma ET-1 and vWF; serum TNFa, IL-1β, ICAM-1, RANTES, and the corresponding expression of these proteins in heart tissue.Results:Pretreatment with the combination of ligustrazine (27 mg/kg/d) and berberine (90 mg/kg/d) significantly improved cardiac function, and decreased myocardial necrosis, inflammatory cell infiltration, microthrombosis and serum CK-MB levels in CME rats. In addition, this combination significantly decreased plasma ET-1 levels and von Willebrand factor, inhibited ADP-induced platelet activation, and reduced TNFa, IL-1βp, ICAM-1 and RANTES levels in serum and heart tissues. The protective effects of this combination were more prominent than those of ligustrazine or berberine alone, but comparable to those of a positive control clopidogrel (6.75 mg/kg/d).Conclusion:Coronary microembolization resulted in cardiac dysfunction in rats. The combination of ligustrazine and berberine significantly improved cardiac function in rat CME model via a mechanism involving antiplatelet and anti-inflammatory effects.