The traditional Chinese medicines treat chronic heart failure and their main bioactive constituents and mechanisms

Chronic heart failure (CHF) is a severe public health problem with increasing morbidity and mortality, any treatment targeting a single session is insufficient to tackle this. CHF is characterized by reduced cardiac output resulting from neurohumoral dysregulation and cardiac remodeling, which might be related to oxidative stress, inflammation, endoplasmic reticulum stress, apoptosis, autophagy, mitochondrial function, and angiogenesis. These molecular mechanisms interact with each other through crosstalk. Historically, Chinese medicinal herbs have been widely applied in the treatment of CHF, and therapeutic effects of Chinese medicinal herbs and their ingredients have been scientifically confirmed over the past decades. Traditional Chinese medicine (TCM) with multiple components can confront the different pathogenesis of CHF through multiple targets. This review analyzes commonly used TCM patent drugs and TCM decoctions that are applicable to different stages of CHF based on clinical trials. Diverse bioactive ingredients in Chinese medicinal herbs have been found to treat CHF via multiple molecular mechanisms. This review comprehensively covers the key works on the effects and underlying mechanisms of TCM, herbal ingredients and synergistic effects of constituent compatibility in treating CHF, providing additional ideas to address this threat.

Advance of novel target strategies participating in myocardial ischemia reperfusion injury / 中国药科大学学报

@#Worldwide morbidity and mortality of acute myocardial infarction (AMI) and related heart failure are still high.While effective early reperfusion of the criminal coronary artery after a confirmed AMI is the typical and effective treatment at present, collateral myocardial ischemia reperfusion injury (MIRI) and pertinent cardio-protection are still challenging to address and have inadequately understood mechanisms.One important reason might be that AMI is multifactorial, causing cardiomyocyte death via multiple mechanisms, as well as affecting other cell types, including platelets, fibroblasts, endothelial and smooth muscle cells, and immune cells.Many cardioprotective strategies act through common end-effectors and may be suboptimal in patients with comorbidities.Therefore, unveiling the related multitarget strategies participating in triggering and resisting the pathobiology of MIRI is a promising and valuable frontier.The review specifically focuses on the recent MIRI advances that are supported by multitarget strategies and new targets under development in order to bring the rational combination of multitarget therapies up to date, as well as to identify findings that may facilitate the new drug of novel targets.

Study on anti-inflammatory effect of taurolithocholic acid based on network pharmacology and its mechanism / 中国药理学通报

Aim To explore the anti-inflammatory effect of taurolithocholic acid (TLCA) through network pharmacology-based analyses, to verify with in vitro macrophage study and to reveal the possible mechanisms. Methods The potential targets of TLCA were acquired from public database, and then the protein-protein interaction (PPI) networks against inflammation were constructed and visualized by using Cytoscape. Gene ontology (GO) analyses and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment were performed. The binding activity of TLCA and its target (TGR5) was evaluated through molecular docking analysis. Lastly, the results of the network analysis were confirmed by lipopolysaccharide and interferon-γ induced RAW264.7 cells. Results There were 87 anti-inflammatory potential targets were screened. GO analysis revealed gene functions were mainly involved in regulation of inflammatory response, membrane raft and protein tyrosine kinase. The results of KEGG pathway analysis suggested that PI3K-Akt signaling pathway, human cytomegalovirus infection might be the critical pathways of TLCA against inflammation. The results of in vitro experiments showed that TLCA decreased the LPS and IFN-γ induced inflammatory response in RAW 264.7 macrophages. Furthermore, the expression of TGR5 protein increased after TLCA treatment. Conclusions The potential therapeutic targets of TLCA against inflammation are revealed through network pharmacology analysis. Our results indicate that TLCA might regulate key inflammatory markers through the membrane receptor TGR5.

Research Progress on Pharmacological Mechanism of Danhong Injection in Treatment of Cardiovascular and Cerebrovascular Diseases / 中国实验方剂学杂志

Cardiovascular and cerebrovascular diseases are one of the major diseases endangering human health， and its morbidity and mortality are still in the rising stage in our country. Traditional Chinese medicine （TCM） injections play an important role in the prevention and treatment of cardiovascular and cerebrovascular diseases due to their advantages of rapid onset， remarkable curative effect， and convenient use. Among them， Danhong injection （DHI）， a Chinese medicine injection for promoting blood circulation and removing blood stasis， is widely used in the clinical treatment of cardio-cerebrovascular diseases. DHI is composed of Salviae Miltiorrhizae Radix et Rhizoma （Danshen in Chinese） and Carthami Flos （Honghua in Chinese）， and mainly contains phenolic acids， tanshinones and flavonoids. A large number of studies have shown that DHI has a significant effect in the treatment of ischemic cardio-cerebrovascular diseases， is a representative drug of co-therapy of brain and heart of TCM， its pharmacological effects related to many aspects such as anti-inflammatory， anti-oxidation， anti-coagulation. At the same time， Other studies have also explained the protective effects of DHI on cardiovascular and cerebrovascular diseases through the overall regulation and intervention of multiple targets and pathways. However， DHI has a wide range of clinical applications， there are still many unknown pharmacological effects to be further explored. Therefore， this article summarizes the current researches on the chemical components of DHI， the multi-target and multi-path pharmacological mechanisms of DHI in the treatment of cardiovascular and cerebrovascular diseases， and introduces the latest pharmacological research progress， so as to provide theoretical guidance for clinical rational drug use and subsequent in-depth research.

Action Mechanisms of Zhongjing's Antidepressant Prescriptions： A Review / 中国实验方剂学杂志

Depression is a threat to human health due to high incidence， recurrence， and disability rates. At present， the complex etiology and pathogenesis of depression are still unclear， and such hypotheses as monoamine neurotransmitters and their receptor abnormality， hyperactivity of hypothalamic-pituitary-adrenal （HPA） axis， inflammation， and neuron damage and remodeling have been put forward. Anti-depressants developed based on the pathogenesis have a certain effect， but there also exist some problems like low cure rate， poor compliance， relapse after discontinuation， and obvious side effects. According to Zhongjing's theory， depression falls into the categories of depression syndrome， visceral agitation， insomnia， and lily disease， and it is mainly located in the liver， involving the spleen， heart， and kidney. The pathogenesis mainly lies in qi stagnation and zang-fu organ dysfunction. Attention should be focused on regulating qi and relieving depression. Zhongjing's antidepressant prescriptions have exhibited good clinical efficacy in the treatment of depression， reflecting the multi-pathway action advantages of Chinese herbs. Based on the pathogenesis of depression and domestic and foreign literature on the intervention of depression with Zhongjing's prescriptions available in the past 20 years， this paper summarized the mechanisms of Zhongjing's prescriptions against depression from the experimental and clinical research aspects， in order to provide reference for clinical treatment of depression with Zhongjing's prescriptions.

DL0410, a candidate for anti-Alzheimer disease with multiple targets in multiple pathways / 中国药理学与毒理学杂志

OBJECTIVE To find a promising candidate for anti- Alzheimer disease (AD) with multiple targets in multiple pathways. METHODS A series of classifiers were constructed for predicting the active compounds against 51 key targets toward Alzheimer disease (AD) using the multitarget-quantitative structure- activity relationships (mt- QSAR) method. While drug screening assays were established to evaluate the predicted active molecules. In addition, various cellular models and animal models related with AD were set up to further study the effects of the active compounds. RESULTS A system for the discovery of Multitarget-Directed Ligands against AD was set up and applied, the predicted active compounds were validated by the drug screening assays, and several active compounds with multiple targets were discovered. Among them, DL0410 exerted high activity on H3R, α7nAChR, AChE and ERα, also displayed the most significant effect in improving the ability of memory and learning in several AD animal models. The study on its action mechanisms showed that it's effect may partially through increasing neurotransmitter, inhibiting oxidative emergency, inhibiting the expression of APP, and promoting long- term potentiation. Besides, DL0410 is of more safety than the first- line clinical medicines. CONCLUSION DL0410 is a promising candidate for further development for AD treatment.

Experimental study on shadowing effect of multi static human targets respiration detection with UWB bio-radar / 医疗卫生装备

Objective To study the shadowing effect when using UWB bio-radar to detect multiple static human targets to solve the problem in multi-target detection.Methods With simulated breathing apparatus as detection targets,the UWB bioradar multi static targets respiration detection experiment was designed,and the influences of distance and angle between targets and its respiratory frequency and amplitude on the shadowing effect were studied.Result The shadowing effect was mainly affected by the relative position of the multiple targets,while the respiratory frequency and amplitude of the target had less influence on it.Conclusion When multi static human targets are detected the shadowing effect does exist,and the effect mainly derives from the block of electromagnetic wave by the front target,while the change of respiratory parameters of the front target has little influence on the effect.

Advances in the pharmacological activities and mechanisms of diosgenin / 中国天然药物

Diosgenin, a well-known steroid sapogenin derived from plants, has been used as a starting material for production of steroidal hormones. The present review will summarize published literature concerning pharmacological potential of diosgenin, and the underlying mechanisms of actions. Diosgenin has shown a vast range of pharmacological activities in preclinical studies. It exhibits anticancer, cardiovascular protective, anti-diabetes, neuroprotective, immunomodulatory, estrogenic, and skin protective effects, mainly by inducing apoptosis, suppressing malignant transformation, decreasing oxidative stress, preventing inflammatory events, promoting cellular differentiation/proliferation, and regulating T-cell immune response, etc. It interferes with cell death pathways and their regulators to induce apoptosis. Diosgenin antagonizes tumor metastasis by modulating epithelial-mesenchymal transition and actin cytoskeleton to change cellular motility, suppressing degradation of matrix barrier, and inhibiting angiogenesis. Additionally, diosgenin improves antioxidant status and inhibits lipid peroxidation. Its anti-inflammatory activity is through inhibiting production of pro-inflammatory cytokines, enzymes and adhesion molecules. Furthermore, diosgenin drives cellular growth/differentiation through the estrogen receptor (ER) cascade and transcriptional factor PPARγ. In summary, these mechanistic studies provide a basis for further development of this compound for pharmacotherapy of various diseases.

Research progress in characterizing multiple-target mechanisms of novel anti-Alzheimer's dimers / 中国药理学通报

Alzheimer's disease ( AD ) is a complex disease caused by environmental and genetic factors. Therefore, one-drug-multiple-target compounds represent the most promising pharmacological approaches to preventing and treating this dis-ease. We have previously designed and synthesized bis( n)-Cog-nitin, novel anti-Alzheimer's dimers derived from tacrine. Bis ( n)-Cognitin have been proven to act on multiple important AD targets, including acetylcholinesterase, β-secretase, N-methyl-D-aspartic acid receptor and neuronal nitric oxide synthase, con-currently. Moreover, Bis(n)-Cognitin could inhibit β-amyloid-induced neurotoxicity, decrease glutamate-induced excitotoxici-ty, reduce oxidative stress, improve learning and memory, and protect against neuronal apoptosis in various in vitro and in vivo models, suggesting that bis ( n )-Cognitin are potential anti-AD drug candidates.