Boli Zhang

Identifying roles of "Jun-Chen-Zuo-Shi" component herbs of QiShenYiQi formula in treating acute myocardial ischemia by network pharmacology.

BackgroundThe role of “Jun-Chen-Zuo-Shi” (also known as “sovereign-minister-assistant-courier”) component herbs of Chinese medicine is not fully understood. This study aims to test the “Jun-Chen-Zuo-Shi” rule with the QiShenYiQi formula (QSYQ) on treating acute myocardial ischemia (AMI) by a network pharmacology approach.MethodsAn Acute Myocardial Ischemia (AMI) specific Organism Disturbed Network (AMI-ODN), was constructed by integrating data of disease-associated genes, protein-protein interaction and microarray experiments. A network-based index, Network Recovery Index for Organism Disturbed Network (NRI-ODN), was developed to measure the therapeutic efficacy of QSYQ and its ingredients, i.e., the ability to recover disturbed AMI network model back to normal state.ResultsThe whole formula of QSYQ got a NRI-ODN score of 864.48, which outperformed all individual herbs. Additionally, the primary component herbs, Radix Astragalus membranaceus and Radix Salvia miltiorrrhiza showed NRI-DON score of 680.27 and 734.31 respectively, which meant a better performance to recover disturbed AMI network than the supplementary component herbs, Panax notoginseng and Dalbergia sissoo did (545.76 and 584.88, respectively).ConclusionAMI-ODN model and NRI-ODN identified the possible roles of “Jun-Chen-Zuo-Shi” component herbs of QSYQ in treating AMI at molecular network and pathway level.

QI-SHEN-YI-QI accelerates angiogenesis after myocardial infarction in rats

Abstract The present study aimed to evaluate the possible cardioprotective effects of QI-SHEN-YI-QI(QSYQ) through stimulating angiogenesis in vivo . QSYQ significantly reduced infarct size of heart, and increased density of vessel during seven days in ischemic rats with LAD ligation. The mRNA and protein levels of VEGF and bFGF were both increased in QSYQ treatment group. The mRNA level of PDGF-B was also increased. Our study demonstrated that therapeutical angiogenesis of QSYQ may lead to neovascularization and confer myocardial protective effects.

Administration of Danhong Injection to diabetic db/db mice inhibits the development of diabetic retinopathy and nephropathy

Danhong Injection (DHI), a Chinese medicine for treatment of patients with coronary heart disease, inhibits primary abdominal aortic aneurysms in apoE deficient (apoE−/−) mice. Formation of microaneurysms plays an important role in the development of diabetic retinopathy and nephropathy. It remains unknown if DHI can reduce these diabetic complications. In this study, diabetic db/db mice in two groups were injected with saline and DHI, respectively, for 14 weeks. Blood and tissue samples were collected to determine serum glucose, lipids and tissue structure. DHI reduced diabetes-induced body weight gain, serum cholesterol and glucose levels. In retinas, DHI blocked the shrink of whole retina and retinal sub-layers by inhibiting expression of caspase 3, matrix metalloproteinase 2 (MMP-2) and MMP-9, accumulation of carbohydrate macromolecules and formation of acellular capillaries. DHI improved renal functions by inhibiting mesangial matrix expansion, expression of vascular endothelial growth factor A, fibronectin and advanced glycation end products in kidneys. Mechanistically, DHI induced expression of glucokinase, AMPKα/phosphorylated AMPKα, insulin receptor substrate 1, fibroblast growth factor 21 and peroxisome proliferator-activated γ. Expression of genes responsible for energy expenditure was also activated by DHI. Therefore, DHI inhibits diabetic retinopathy and nephropathy by ameliorating glucose metabolism and demonstrates a potential application in clinics.

Danhong injection attenuates cardiac injury induced by ischemic and reperfused neuronal cells through regulating arginine vasopressin expression and secretion.

Ischemic stroke is associated with cardiac myocyte vulnerability through some unknown mechanisms. Arginine vasopressin (AVP) may exert considerable function in the relationship of brain damage and heart failure. Danhong injection (DHI) can protect both stroke and heart failure patients with good efficacy in clinics. The aim of this study is to investigate the mechanism of DHI in heart and brain co-protection effects to determine whether AVP plays key role in this course. In the present study, we found that both the supernatant from oxygen-glucose deprivation (OGD) and reperfused primary rat neuronal cells (PRNCs) and AVP treatment caused significant reduction in cell viability and mitochondrial activity in primary rat cardiac myocytes (RCMs). Besides, DHI had the same protective effects with conivaptan, a dual vasopressin V1A and V2 receptor antagonist, in reducing the RCM damage induced by overdose AVP. DHI significantly decreased the injury of both PRNCs and RCMs. Meanwhile, the AVP level was elevated dramatically in OGD and reperfusion PRNCs, and DHI was able to decrease the AVP expression in the injured PRNCs. Therefore, our present results suggested that OGD and reperfusion PRNCs might induce myocyte injury by elevating the AVP expression in PRNCs. The ability of DHI to reinstate AVP level may be one of the mechanisms of its brain and heart co-protection effects.

A critical courier role of volatile oils from Dalbergia odorifera for cardiac protection in vivo by QiShenYiQi

Component-based Chinese medicine (CCM) is derived from traditional Chinese medicine but produced with modern pharmaceutical standard and clearer clinical indications. However, it still faces challenges of defining individual component contribution in the complex formula. Using QiShenYiQi (QSYQ) as a model CCM, we investigated the role of Dalbergia odorifera (DO), an herbal component, in preventing myocardial damage. We showed that in vitro, QSYQ exerted considerable protective activities on cardiomyocytes from H2O2-induced mitochondrial dysfunction with or without DO. However, in isolated rat hearts, myocardial protection by QSYQ was significantly weakened without DO. In everted gut sac model, DO significantly enhanced absorption of the major QSYQ ingredients in different regions of rat intestine. Finally, in in vivo mouse model of doxorubicin (DOX)-induced myocardial damage, only QSYQ, but not QiShenYiQi without DO (QSYQ-DO), exerted a full protection. Taken together, our results showed that instead of directly contributing to the myocardial protection, Dalbergia odorifera facilitates the major active ingredients absorption and increases their efficacy, eventually enhancing the in vivo potency of QSYQ. These findings may shed new lights on our understanding of the prescription compatibility theory, as well as the impacts of “courier herbs” in component-based Chinese medicine.