Salvianolic acid A improve mitochondrial respiration and cardiac function via inhibiting apoptosis pathway through CRYAB in diabetic cardiomyopathy.

Salvianolic acid A (SAA) is a traditional Chinese medicine that has a good therapeutic effect on cardiovascular disease. However, the underlying mechanisms by which SAA improves mitochondrial respiration and cardiac function in diabetic cardiomyopathy (DCM) remain unknown. This study aims to elucidate whether SAA had any cardiovascular protection on the pathophysiology of DCM and explored the potential mechanisms. Diabetes was induced in rats by 30 mg/kg of streptozotocin (STZ) treatment. After a week of stability, 5 mg/kg isoprenaline (ISO) was injected into the rats subcutaneously. 3 mg/kg SAA was orally administered for six weeks and 150 mg/kg Metformin was selected as a positive group. At the end of this period, cardiac function was assessed by ultrasound, electrocardiogram, and relevant cardiac injury biomarkers testing. Treatment with SAA improved cardiac function, glucose, and lipid levels, mitochondrial respiration, and suppressed myocardial inflammation and apoptosis. Furthermore, SAA treatment inhibits the apoptosis pathway through CRYAB in diabetic cardiomyopathy rats. As a result, this study not only provides new insights into the mechanism of SAA against DCM but also provides new therapeutic ideas for the discovery of anti-DCM compounds in the clinic.

Dan-Shen-Yin Granules Prevent Hypoxia-Induced Pulmonary Hypertension via STAT3/HIF-1α/VEGF and FAK/AKT Signaling Pathways.

Traditional Chinese medicine (TCM) plays an important role in the treatment of complex diseases, especially cardiovascular diseases. However, it is hard to identify their modes of action on account of their multiple components. The present study aims to evaluate the effects of Dan-Shen-Yin (DSY) granules on hypoxia-induced pulmonary hypertension (HPH), and then to decipher the molecular mechanisms of DSY. Systematic pharmacology was employed to identify the targets of DSY on HPH. Furthermore, core genes were identified by constructing a protein-protein interaction (PPI) network and analyzed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes (KEGG) analysis. Related genes and pathways were verified using a hypoxia-induced mouse model and hypoxia-treated pulmonary artery cells. Based on network pharmacology, 147 potential targets of DSY on HPH were found, constructing a PPI network, and 13 hub genes were predicted. The results showed that the effect of DSY may be closely associated with AKT serine/threonine kinase 1 (AKT1), signal transducer and activator of transcription 3 (STAT3), and HIF-1 signaling pathways, as well as biological processes such as cell proliferation. Consistent with network pharmacology analysis, experiments in vivo demonstrated that DSY could prevent the development of HPH in a hypoxia-induced mouse model and alleviate pulmonary vascular remodeling. In addition, inhibition of STAT3/HIF-1α/VEGF and FAK/AKT signaling pathways might serve as mechanisms. Taken together, the network pharmacology analysis suggested that DSY exhibited therapeutic effects through multiple targets in the treatment of HPH. The inferences were initially confirmed by subsequent in vivo and in vitro studies. This study provides a novel perspective for studying the relevance of TCM and disease processes and illustrates the advantage of this approach and the multitargeted anti-HPH effect of DSY.

Salvianolic acid A attenuates vascular remodeling in a pulmonary arterial hypertension rat model.

AIM: The current therapeutic approaches have a limited effect on the dysregulated pulmonary vascular remodeling, which is characteristic of pulmonary arterial hypertension (PAH). In this study we examined whether salvianolic acid A (SAA) extracted from the traditional Chinese medicine 'Dan Shen' attenuated vascular remodeling in a PAH rat model, and elucidated the underlying mechanisms. METHODS: PAH was induced in rats by injecting a single dose of monocrotaline (MCT 60 mg/kg, sc). The rats were orally treated with either SAA (0.3, 1, 3 mg·kg(-1)·d(-1)) or a positive control bosentan (30 mg·kg(-1)·d(-1)) for 4 weeks. Echocardiography and hemodynamic measurements were performed on d 28. Then the hearts and lungs were harvested, the organ indices and pulmonary artery wall thickness were calculated, and biochemical and histochemical analysis were conducted. The levels of apoptotic and signaling proteins in the lungs were measured using immunoblotting. RESULTS: Treatment with SAA or bosentan effectively ameliorated MCT-induced pulmonary artery remodeling, pulmonary hemodynamic abnormalities and the subsequent increases of right ventricular systolic pressure (RVSP). Furthermore, the treatments significantly attenuated MCT-induced hypertrophic damage of myocardium, parenchymal injury and collagen deposition in the lungs. Moreover, the treatments attenuated MCT-induced apoptosis and fibrosis in the lungs. The treatments partially restored MCT-induced reductions of bone morphogenetic protein type II receptor (BMPRII) and phosphorylated Smad1/5 in the lungs. CONCLUSION: SAA ameliorates the pulmonary arterial remodeling in MCT-induced PAH rats most likely via activating the BMPRII-Smad pathway and inhibiting apoptosis. Thus, SAA may have therapeutic potential for the patients at high risk of PAH.

The Potential of Traditional Chinese Medicine in the Treatment and Modulation of Pain.

Pain is an unpleasant sensory and emotional experience associated with various diseases. Extensive research has been conducted to find appropriate methods of relieving pain and improving the quality of life. However, the most commonly used pain-relieving agents such as opioid therapeutics are often associated with harmful side effects; moreover, users are prone to become addicted to these agents and may develop tolerance. Often, nonopioid therapeutics is only marginally effective, thus leading to a significant unmet medical need. Scientists have studied herbal medicines, finding more than 800 kinds of traditional Chinese medicine (TCM) to be effective in relieving pain while also creating several monomeric compounds to develop novel analgesic drugs. In this review, we summarize the representative TCM currently available for the treatment and modulation of pain. Ten different natural products, mainly herbs, used in Chinese medicine to relieve pain are discussed in light of the theories of TCM and modern pharmacology. We hope that this review will provide valuable information for future studies on the potential of TCM in alleviating pain.

Inhibitory effects of Brazilin on the vascular smooth muscle cell proliferation and migration induced by PDGF-BB.

Abnormal vascular smooth muscle cell (VSMC) proliferation and migration contribute to the pathogenesis of vascular diseases including atherosclerosis and restenosis. Brazilin isolated from the heartwood of Caesalpinia sappan L. has been reported to exhibit various biological activities, such as anti-platelet aggregation, anti-inflammation, vasorelaxation and pro-apoptosis. However, the functional effects of Brazilin on VSMCs remain unexplored. The present study investigated the potential effects of Brazilin on platelet-derived growth factor (PDGF)-BB induced VSMC proliferation and migration as well as the underlying mechanism of action. VSMC proliferation and migration were measured by Crystal Violet Staining, wound-healing and Boyden chamber assays, respectively. Cell cycle was analyzed by flow cytometry. Enzymatic action of matrix metalloproteinase-9 (MMP-9) was carried out by gelatin zymography. Expression of adhesion molecules, cell cycle regulatory proteins, the phosphorylated levels of PDGF receptor ß (PDGF-Rß), Src, extracellular signal regulated kinase (ERK) and Akt were tested by immunoblotting. The present study demonstrated that pretreatment with Brazilin dose-dependently inhibited PDGF-BB stimulated VSMC proliferation and migration, which were associated with a cell-cycle arrest at G0/G1 phase, a reduction in the adhesion molecule expression and MMP-9 activation in VSMCs. Furthermore, the increase in PDGF-Rß, Src, ERK1/2 and Akt phosphorylation induced by PDGF-BB were suppressed by Brazilin. These findings indicate that Brazilin inhibits PDGF-BB induced VSMC proliferation and migration, and the inhibitory effects of Brazilin may be associated with the blockade of PDGF-Rß - ERK1/2 and Akt signaling pathways. In conclusion, the present study implicates that Brazilin may be useful as an anti-proliferative agent for the treatment of vascular diseases.

Rho kinase inhibition activity of pinocembrin in rat aortic rings contracted by angiotensin II.

AIM: To investigate the effects of pinocembrin on angiotensin II (Ang II)-induced vascular contraction, and to explore its molecular mechanism of actions. METHODS: The isometric vascular tone was measured in rat thoracic aortic rings with denuded endothelium. Phosphorylation level of myosin phosphatase target unit 1 (MYPT1), and protein levels of Rho kinase 1 (ROCK1, ROKß or p160ROCK) and angiotensin II type-1 receptor (AT1R) were determined by Western blot analysis. RESULTS: Pinocembrin produced a relaxant effect on endothelium-denuded aortic rings contracted by Ang II (100 nmol·L(-1)) in a dose-dependent manner. In endothelium-denuded aortic rings stimulated by Ang II, pretreatment with pinocembrin (25 and 100 µmol·L(-1)) for 20 min significantly attenuated MYPT1 phosphorylation and ROCK1 protein levels. Meanwhile, the protein level of AT1R in response to Ang II was not affected by pinocembrin in rat aortic rings. CONCLUSION: These findings indicate that pinocembrin inhibits vasoconstriction induced by Ang II in rat endothelium-denuded aortic rings, and the mechanism at least in part, is due to the blockade of the RhoA/ROCK pathway.

[Advance in study on pharmacological effect of Eucommiae Folium].

Eucommia ulmoides is a valuable traditional Chinese medicine, whose cortexes have long been used as medi cines. Due to the scarcity of its resources, people began using its leaves instead of cortexes in medicines. Eucommiae Folium and its leaves have many pharmacological effects and thereby being clinically applied as genuine traditional Chinese medicines. Modern pharmological studies have showed that Eucommiae Folium leaves have such effects as blood pressure reduction, blood lipid regulation, cardiovascular protection, anti-obesity, anti-inflammation, anti-virus, enhancement of immunologic function, resistance against senility and anti-fatigue. In clinic, Eucommiae Folium is mainly used to treat hypertention and obstetrical and gynecological disease. The essay summarizes the latest advance in domestic and foreign studie on pharmacological effeets and clinical applications of Eucommiae Folium leaves, and thus providing reference for studies on new drugs of Eucommiae Folium leave.