The Therapeutic Effect and Mechanism of Qishen Yiqi Dripping Pills on Cardiovascular and Cerebrovascular Diseases and Diabetic Complications.

The alterations in vascular homeostasis are deeply involved in the development of numerous diseases, such as coronary heart disease, stroke, and diabetic complications. Changes in blood flow and endothelial permeability caused by vascular dysfunction are the common mechanisms for these three types of diseases. The disorders of glucose and lipid metabolism can bring changes in the energy production patterns in endothelium and surrounding cells which may consequently cause energy metabolic disorders, oxidative stress, and inflammatory responses. Traditional Chinese medicine (TCM) follows the principle of the "treatment by the syndrome differentiation." TCM considers coronary heart disease, stroke, and diabetes complications all as the type of Qi-deficiency and blood stasis syndrome, which mainly occurs in the vascular system. Therefore, the common pathogenesis of these three types of diseases suggests that the treatment strategy by TCM should be in a close manner and referred to as "treating different diseases by the same treatment." Qishen Yiqi dripping pill is a modern Chinese herbal medicine that has been widely used for the treatment of patients with coronary heart disease characterized as Qi-deficiency and blood stasis in China. Recently, many clinical reports have demonstrated the potential therapeutic effects of Qishen Yiqi dripping pills on ischemic stroke and diabetic nephropathy. Based on these reports, we will summarize the clinical applications of Qishen Yiqi dripping pills on coronary heart disease, ischemic stroke, and diabetic nephropathy, including the involved mechanisms discussed in various research works.

Compound Danshen Dripping Pill inhibits high altitude-induced hypoxic damage by suppressing oxidative stress and inflammatory responses.

CONTEXT: Previous studies indicate that compound Danshen Dripping Pill (CDDP) improves the adaptation to high-altitude exposure. However, its mechanism of action is not clear. OBJECTIVE: To explore the protective effect of CDDP on hypobaric hypoxia (HH) and its possible mechanism. MATERIALS AND METHODS: A meta-analysis of 1051 human volunteers was performed to evaluate the effectiveness of CDDP at high altitudes. Male Sprague-Dawley rats were randomized into 5 groups (n = 6): control at normal pressure, model, CDDP-170 mg/kg, CDDP-340 mg/kg and acetazolamide groups. HH was simulated at an altitude of 5500 m for 24 h. Animal blood was collected for arterial blood-gas analysis and cytokines detection and their organs were harvested for pathological examination. Expression levels of AQP1, NF-κB and Nrf2 were determined by immunohistochemical staining. RESULTS: The meta-analysis data indicated that the ratio between the combined RR of the total effective rate and the 95% CI was 0.23 (0.06, 0.91), the SMD and 95% CI of SO2 was 0.37 (0.12, 0.62). Pre-treatment of CDDP protected rats from HH-induced pulmonary edoema and heart injury, left-shifted oxygen-dissociation curve and decreased P50 (30.25 ± 3.72 vs. 37.23 ± 4.30). Mechanistically, CDDP alleviated HH-reinforced ROS by improving SOD and GPX1 while inhibiting pro-inflammatory cytokines and NF-κB expression. CDDP also decreased HH-evoked D-dimer, erythrocyte aggregation and blood hemorheology, promoting AQP1 and Nrf2 expression. DISCUSSION AND CONCLUSIONS: Pre-treatment with CDDP could prevent HH-induced tissue damage, oxidative stress and inflammatory response. Suppressed NF-κB and up-regulated Nrf2 might play significant roles in the mechanism of CDDP.

Compound Danshen Dripping Pill inhibits doxorubicin or isoproterenol-induced cardiotoxicity.

Heart failure (HF) is the advanced heart disease with high morbidity and mortality. Compound DanShen Dripping Pill (CDDP) is a widely used Traditional Chinese Medicine for cardiovascular disease treatment. Herein, we investigated if CDDP can protect mice against doxorubicin (DOX) or isoprenaline (ISO)-induced HF. After 3 days feeding of normal chow containing CDDP, mice were started DOX or ISO treatment for 4 weeks or 18 days. At the end of treatment, mice were conducted electrocardiogram and echocardiographic test. Blood and heart samples were determined biochemical parameters, myocardial structure and expression of the related molecules. CDDP normalized DOX/ISO-induced heart weight changes, HF parameters and fibrogenesis. The DOX/ISO-impaired left ventricular ejection fraction and fractional shortening were restored by CDDP. Mechanistically, CDDP blocked DOX/ISO-inhibited expression of antioxidant enzymes and DOX/ISO-induced expression of pro-fibrotic molecules, inflammation and cell apoptosis. Additional DOX/ISO-impaired targets in cardiac function but protected by CDDP were identified by RNAseq, qRT-PCR and Western blot. In addition, CDDP protected cardiomyocytes against oxygen-glucose deprivation-induced injuries. Taken together, our study shows that CDDP can protect against myocardial injuries in different models, suggesting its potential application for HF treatment.

Elucidating direct kinase targets of compound Danshen dropping pills employing archived data and prediction models.

Research on direct targets of traditional Chinese medicine (TCM) is the key to study the mechanism and material basis of it, but there is still no effective methods at present. We took Compound Danshen dropping pills (CDDP) as a study case to establish a strategy to identify significant direct targets of TCM. As a result, thirty potential active kinase targets of CDDP were identified. Nine of them had potential dose-dependent effects. In addition, the direct inhibitory effect of CDDP on three kinases, AURKB, MET and PIM1 were observed both on biochemical level and cellular level, which could not only shed light on the mechanisms of action involved in CDDP, but also suggesting the potency of drug repositioning of CDDP. Our results indicated that the research strategy including both in silico models and experimental validation that we built, were relatively efficient and reliable for direct targets identification for TCM prescription, which will help elucidating the mechanisms of TCM and promoting the modernization of TCM.