peoniflorin and Cardiovascular-Diseases

The monoterpene glycoside paeoniflorin (PF) is the principal active constituent of the traditional Chinese herbal medicines, Radix Paeoniae Alba and Radix Paeoniae Rubra, which have been used for millennia to treat cardiovascular diseases (eg, hypertension, bleeding, and atherosclerosis) and neurological ailments (eg, headaches, vertigo, dementia, and pain). Recent evidence has revealed that PF exerts inhibitory effects on inflammation, fibrosis, and apoptosis by targeting several intracellular signaling cascades. In this review, we address the current knowledge about the pharmacokinetic properties of PF and its molecular mechanisms of action. We also present results from recent preclinical studies supporting the utility of PF for the treatment of pain, cerebral ischemic injury, and neurodegenerative diseases, such as Alzheimer's and Parkinson's diseases. Moreover, new evidence suggests a general protective role of PF in heart attack, diabetic kidney, and atherosclerosis. Mechanistically, PF exerts multiple anti-inflammatory actions by targeting toll-like receptor-mediated signaling in both parenchymal and immune cells (in particular, macrophages and dendritic cells). A better understanding of the molecular actions of PF may lead to the expansion of its therapeutic uses.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Cardiovascular Diseases; Drugs, Chinese Herbal; Glucosides; Humans; Kidney Diseases; Monoterpenes; Nervous System Diseases

To investigate the synergistic effects of Chuanxiong-Chishao herb-pair (CCHP) on promoting angiogenesis in silico and in vivo.. The mechanisms of action of an herb-pair, Chuanxiong-Chishao, were investigated using the network pharmacological and pharmacodynamic strategies involving computational drug target prediction and network analysis, and experimental validation. A set of network pharmacology methods were created to study the herbs in the context of targets and diseases networks, including prediction of target profiles and pharmacological actions of main active compounds in Chuanxiong and Chishao. Furthermore, the therapeutic effects and putative molecular mechanisms of Chuanxiong-Chishao actions were experimentally validated in a chemical-induced vascular insuffificiency model of transgenic zebrafifish in vivo. The mRNA expression of the predicted targets were further analyzed by real-time polymerase chain reaction (RT-PCR).. The computational prediction results found that the compounds in Chuanxiong have antithrombotic, antihypertensive, antiarrhythmic, and antiatherosclerotic activities, which were closely related to protecting against hypoxic-ischemic encephalopathy, ischemic stroke, myocardial infarction and heart failure. In addition, compounds in Chishao were found to participate in anti-inflflammatory effect and analgesics. Particularly, estrogen receptor α (ESRα) and hypoxia-inducible factor 1-α (HIF-1α) were the most important potential protein targets in the predicted results. In vivo experimental validation showed that post-treatment of tetramethylpyrazine hydrochloride (TMP•HCl) and paeoniflorin (PF) promoted the regeneration of new blood vessels in zebrafifish involving up-regulating ESRα mRNA expression. Co-treatment of TMP•HCl and PF could enhance the vessel sprouting in chemical-induced vascular insuffificiency zebrafifish at the optimal compatibility proportion of PF 10 μmol/L with TMP•HCl 1 μmol/L.. The network pharmacological strategies combining drug target prediction and network analysis identified some putative targets of CCHP. Moreover, the transgenic zebrafifish experiments demonstrated that the Chuanxiong-Chishao combination synergistically promoted angiogenic activity, probably involving ESRα signaling pathway.

Topics: Animals; Cardiovascular Diseases; Drug Synergism; Drugs, Chinese Herbal; Embryo, Nonmammalian; Estrogen Receptor alpha; Gene Expression Regulation; Glucosides; Ligands; Monoterpenes; Neovascularization, Physiologic; Pyrazines; Reproducibility of Results; Zebrafish