Intervention effect of Chuanxiong-Chishao herb pair on circRNA/lncRNA expression profile in a myocardial infarction-atherosclerosis model / 中国中药杂志

This study aimed to explore the intervention effect of Chuanxiong-Chishao herb pair(CX-CS) on a myocardial infarction-atherosclerosis(MI-AS) mouse model and investigate its effect on the expression profile of circular RNAs(circRNAs)/long non-coding RNAs(lncRNAs) in ischemic myocardium and aorta. Sixty male ApoE~(-/-) mice were randomly assigned to a model group, high-, medium-, and low-dose CX-CS groups(7.8, 3.9, and 1.95 g·kg~(-1)), and a positive drug group(metoprolol 26 mg·kg~(-1) and simvastatin 5.2 mg·kg~(-1)), with 12 mice in each group. Male C57BL/6J mice were assigned to the sham group. The mice in the model group and the groups with drug intervention were fed on a high-fat diet for 10 weeks, followed by anterior descending coronary artery ligation. After that, the mice were fed on a high-fat diet for another two weeks to induce the MI-AS model. The mice in the sham group received normal feed, followed by sham surgery without coronary artery ligation. Mice in the groups with drug intervention received CX-CS or positive drug by gavage for four weeks from the 9th week of high-fat feeding, and those in the model group and the sham group received an equal volume of normal saline. Whole transcriptome sequencing was performed on the heart and aorta tissues of the medium-dose CX-CS group, the model group, and the sham group after administration. The results showed that the medium-and high-dose CX-CS groups showed improved cardiac function and reduced myocardial fibrosis area, and the medium-dose CX-CS group showed significantly reduced plaque area. CX-CS treatment could reverse the expression of circRNA＿07227 and circRNA＿11464 in the aorta of AS model and circRNA expression(such as circRNA＿11505) in the heart of the MI model. Differentially expressed circRNAs between the CX-CS-treated mice and the model mice were mainly enriched in lipid synthesis, lipid metabolism, lipid transport, inflammation, and angiogenesis in the aorta, and in angiogenesis, blood pressure regulation, and other processes in the heart. CX-CS treatment could reverse the expression of lncRNAs such as ENSMUST00000162209 in the aorta of the AS model and TCONS＿00002123 in the heart of the MI model. Differentially expressed lncRNAs between the CX-CS-treated mice and model mice were mainly enriched in lipid metabolism, angiogenesis, autophagy, apoptosis, and iron death in the aorta, and in angiogenesis, autophagy, and iron death in the heart. In summary, CX-CS can regulate the expression of a variety of circRNAs and lncRNAs, and its intervention mechanism in coronary heart disease may be related to the regulation of angiogenesis and inflammation in ischemic myocardium, as well as lipid metabolism, lipid transport, inflammation, angiogenesis in AS aorta.

Effects of components in stasis-resolving and collateral-dredging Chinese herbal medicines on angiogenesis and inflammatory response of human umbilical vein endothelial cells induced by VEGF / 中国中药杂志

The present study investigated the mechanism of components in stasis-resolving and collateral-dredging Chinese herbal medicines, including scutellarin(Scu), paeonol(Pae), and hydroxy safflower yellow A(HSYA), in the treatment of psoriasis by regulating angiogenesis and inflammation. The human umbilical vein endothelial cells(HUVECs) cultured in vitro were divided into a normal group, a model group, a VEGFR tyrosine kinase inhibitor Ⅱ(VRI) group, and Scu, Pae, and HSYA groups with low, me-dium, and high doses. Cell viability was detected by the CCK-8 assay. Cell migration was detected by wound healing assay. Tube formation assay was used to measure the tube formation ability. Western blot was used to detect the protein expression of the VEGFR2/Akt/ERK1/2 signaling pathway. The secretion levels of inflammatory cytokines IFN-γ, IL-1β, IL-6, and TNF-α were detected by ELISA. The results showed that compared with the model group, all the Scu, Pae, and HSYA groups could reduce cell viability, inhibit cell migration and tube formation(P<0.05, P<0.01), and down-regulated the protein expression of VEGFR2, p-VEGFR2, Akt, p-Akt, ERK1/2, and p-ERK1/2. Scu and Pae could down-regulate VEGFR2 expression(P<0.05, P<0.01), while other groups only showed a downward trend. Scu and Pae significantly reduced IFN-γ and IL-6 levels(P<0.01), and HSYA significantly reduced the levels of IFN-γ, IL-1β, and IL-6(P<0.01). Scu, Pae, and HSYA had no significant effect on TNF-α. The results suggested that Scu, Pae, and HSYA may exert a therapeutic role in psoriasis-related angiogenesis and inflammation by inhibiting VEGFR2/Akt/ERK1/2 signaling pathway and inhibiting the secretion of IFN-γ, IL-1β, and IL-6.

Correlation of Platelet and Coagulation Function with Blood Stasis Syndrome in Coronary Heart Disease: A Systematic Review and Meta-Analysis / 中国结合医学杂志

OBJECTIVE@#To investigate the correlation of platelet and coagulation function with blood stasis syndrome (BSS) in coronary heart disease (CHD).@*METHODS@#The protocol for this meta-analysis was registered on PROSPERO (CRD42019129452). PubMed, Excerpta Medica Database (Embase), the Cochrane Library, and China National Knowledge Infrastructure (CNKI) were searched from inception to 1st June, 2020. Trials were considered eligible if they enrolled BSS and non-BSS (NBSS) patients with CHD and provided information on platelet and coagulation function. The platelet function, coagulation function, and fibrinolytic activity were compared between the BSS and NBSS groups. Forest plots were generated to show the SMDs or ESs with corresponding 95% CIs for each study. Subgroup analysis and sensitivity analysis were performed to explore potential sources of heterogeneity.@*RESULTS@#The systematic search identified 1,583 articles. Thirty trials involving 10,323 patients were included in the meta-analysis. The results showed that mean platelet volume, platelet distribution width, platelet aggregation rate, platelet P selectin, fibrinogen, plasminogen activator inhibitor-1 (PAI-1), thromboxane B2 (TXB2), 6-keto-prostaglandin F1alpha (6-keto-PGF1 α), and TXB2/6-keto-PGF1 α were higher in the BSS group than in the NBSS group (P<0.05 or P<0.01). Activated partial thromboplastin time was lower in the BSS group than in the NBSS group in the acute phase of CHD (P<0.01). The R and K values in thromboelastography and tissue plasminogen activator (t-PA) and t-PA/PAI-1 were lower in the BSS group than in the NBSS group (all P<0.01). No difference was found in the results of platelet count, plateletcrit, maximum amplitude, von Willebrand factor, prothrombin time, thrombin time, international normalized ratio, etc. between groups.@*CONCLUSIONS@#Increased platelet function, hypercoagulability, and decreased fibrinolytic activity were found among CHD patients with BSS.

Effect of Ginkgo biloba extract (EGb50) on mitochondrial function in SH-SY5Y cells after hypoxia/reoxygenation injury / 中国中药杂志

Ischemic cerebrovascular disease and cerebral ischemia/reperfusion injury threaten the health of human being. We studied the protective effect of Ginkgo biloba extract 50 (EGb50) on the mitochondrial function in SH-SY5Y cells after hypoxia/reoxygenation (H/R) injury and explored its mechanisms, so as to provide new ideas for studies on the treatment for ischemic cerebrovascular disease. We established the H/R injury model in SH-SY5Y cells after administrating EGb50. Subsequently, the mitochondrial membrane potential and the concentration of intracellular Ca²⁺ were measured by flow cytometer. The levels of optic atrophy1 (Opa1) and dynamin-like protein 1 (Drp1) were evaluated by immunofluorescence and western blot. The results showed that the mitochondrial membrane potential was decreased and the level of intracellular Ca²⁺ was increased after H/R injury. Moreover, the expression of mitochondrial fusion protein Opa1 was decreased, while the expression of mitochondrial fission protein Drp1 was increased. However, EGb50 significantly increased the mitochondrial membrane potential and suppressed the level of intracellular Ca²⁺. In addition, EGb50 increased the expression of Opa1 and decreased the expression of Drp1. The results demonstrated that EGb50 has a neuroprotective effect on SH-SY5Y cells after H/R injury, and could improve the energy metabolism and mitochondrial function. The underlying mechanisms may be associated with the regulation of mitochondrial fusion and fission, which provided data support for the treatment of ischemic cerebrovascular disease with EGb50.

Paeoniflorin Promotes Angiogenesis in A Vascular Insufficiency Model of Zebrafish in vivo and in Human Umbilical Vein Endothelial Cells in vitro / 中国结合医学杂志

<p><b>OBJECTIVE</b>To investigate the pro-angiogenic effects of paeoniflorin (PF) in a vascular insufficiency model of zebrafish and in human umbilical vein endothelial cells (HUVECs).</p><p><b>METHODS</b>In vivo, the pro-angiogenic effects of PF were tested in a vascular insufficiency model in the Tg(fli-1:EGFP)y1 transgenic zebrafish. The 24 h post fertilization (hpf) embryos were pretreated with vascular endothelial growth factor (VEGF) receptor tyrosine kinase inhibitor II (VRI) for 3 h to establish the vascular insufficiency model and then post-treated with PF for 24 h. The formation of intersegmental vessels (ISVs) was observed with a fluorescence microscope. The mRNA expression of fms-like tyrosine kinase-1 (flt-1), kinase insert domain receptor (kdr), kinase insert domain receptor like (kdrl) and von Willebrand factor (vWF) were analyzed by real-time polymerase chain reaction (PCR). In vitro, the pro-angiogenic effects of PF were observed in HUVECs in which cell proliferation, migration and tube formation were assessed.</p><p><b>RESULTS</b>PF (6.25-100 μmol/L) could rescue VRI-induced blood vessel loss in zebrafish and PF (25-100 μmol/L), thereby restoring the mRNA expressions of flt-1, kdr, kdrl and vWF, which were down-regulated by VRI treatment. In addition, PF (0.001-0.03 μmol/L) could promote the proliferation of HUVECs while PF stimulated HUVECs migration at 1.0-10 μmol/L and tube formation at 0.3 μmol/L.</p><p><b>CONCLUSION</b>PF could promote angiogenesis in a vascular insufficiency model of zebrafish in vivo and in HUVECs in vitro.</p>

Synergistic effects of Chuanxiong-Chishao herb-pair on promoting angiogenesis at network pharmacological and pharmacodynamic levels / 中国结合医学杂志

<p><b>OBJECTIVE</b>To investigate the synergistic effects of Chuanxiong-Chishao herb-pair (CCHP) on promoting angiogenesis in silico and in vivo.</p><p><b>METHODS</b>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).</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSIONS</b>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.</p>

Ginkgo preparations of Chinese medicine and treatment of diabetes: mechanisms and clinical applications / 中国中药杂志

Ginkgo is one of the most successful cases of botanical drugs developed by modern science and technology during the past fifty years all over the world. At present ginkgo has been applied to the prevention and treatment of cardiovascular disease widely, and has good clinical efficacy. Type 2 diabetes has been proved to be the risk equivalents of cardiovascular disease, therefore it has an important scientific significance for looking for more effective drugs of prevention and control of diabetes. To seek more efficient and safe drug from the plant medicine which has the function of regulate blood sugar and improve insulin resistance becomes a hotspot at home and abroad. Basic and clinical studies have shown the ginkgo preparations of Chinese medicine have certain regulation effect on blood sugar and insulin resistance. In this paper, we review the mechanisms and clinical applications of ginkgo preparations on diabetes and its applications during the past 10 years.