YiQiFuMai (YQFM) powder injection has been reported to be used in cardiovascular and nervous system diseases with marked efficacy. However, as a treatment against diseases characterized by hypoxia, lassitude, and asthenia, the effects and underlying mechanisms of YQFM in neuronal mitochondrial function and dynamics have not been fully elucidated. Here, we demonstrated that YQFM inhibited mitochondrial apoptosis and activation of dynamin-related protein 1 (Drp1) in cerebral ischemia-injured rats, producing a significant improvement in cerebral infarction and neurological score. YQFM also attenuated oxidative stress-induced mitochondrial dysfunction and apoptosis through increasing ATP level and mitochondria membrane potential (Δψm), inhibiting ROS production, and regulating Bcl-2 family protein levels in primary cultured neurons. Moreover, YQFM inhibited excessive mitochondrial fission, Drp1 phosphorylation, and translocation from cytoplasm to mitochondria induced by oxidative stress. We provided the first evidence that YQFM inhibited the activation, association, and translocation of PKCδ and Drp1 upon oxidative stress. Taken together, we demonstrate that YQFM ameliorates ischemic stroke-induced neuronal apoptosis through inhibiting mitochondrial dysfunction and PKCδ/Drp1-mediated excessive mitochondrial fission. These findings not only put new insights into the unique neuroprotective properties of YQFM associated with the regulation of mitochondrial function but also expand our understanding of the underlying mechanisms of ischemic stroke.

Circular RNAs (circRNAs) are a class of endogenous noncoding RNAs that regulate gene expression in eukaryotes. Recently, exosomes from cardiomyocytes (CMs) have been found to facilitate cell proliferation and survival by transporting various bioactive molecules, including circRNA. However, the functions of exosomal circRNAs are not clear. The present research is aimed at determining whether circHIPK3 released from hypoxia-pretreated CMs is transferred into cardiac microvascular endothelial cells (CMVECs) by exosomes and becomes functionally active in the CMVECs under oxidative stress conditions.

Cardiac stem cells (CSCs) have emerged as one of the most promising stem cells for cardiac protection. Recently, exosomes from bone marrow-derived mesenchymal stem cells (BMSCs) have been found to facilitate cell proliferation and survival by transporting various bioactive molecules, including microRNAs (miRs). In this study, we found that BMSC-derived exosomes (BMSC-exos) significantly decreased apoptosis rates and reactive oxygen species (ROS) production in CSCs after oxidative stress injury. Moreover, a stronger effect was induced by exosomes collected from BMSCs cultured under hypoxic conditions (Hypoxic-exos) than those collected from BMSCs cultured under normal conditions (Nor-exos). We also observed greater miR-214 enrichment in Hypoxic-exos than in Nor-exos. In addition, a miR-214 inhibitor or mimics added to modulate miR-214 levels in BMSC-exos revealed that exosomes from miR-214-depleted BMSCs partially reversed the effects of hypoxia-induced exosomes on oxidative damage in CSCs. These data further confirmed that miR-214 is the main effector molecule in BMSC-exos that protects CSCs from oxidative damage. miR-214 mimic and inhibitor transfection assays verified that CaMKII is a target gene of miR-214 in CSCs, with exosome-pretreated CSCs exhibiting increased miR-214 levels but decreased CaMKII levels. Therefore, the miR-214/CaMKII axis regulates oxidative stress-related injury in CSCs, such as apoptosis, calcium homeostasis disequilibrium, and excessive ROS accumulation. Collectively, these findings suggest that BMSCs release miR-214-containing exosomes to suppress oxidative stress injury in CSCs through CaMKII silencing.

Exosomes play critical roles in mediating cell-to-cell communication by delivering noncoding RNAs (including miRNAs, lncRNAs, and circRNAs). Our previous study found that cardiomyocytes (CMs) subjected to hypoxia released circHIPK3-rich exosomes to regulate oxidative stress damage in cardiac endothelial cells. However, the role of exosomes in regulating angiogenesis after myocardial infarction (MI) remains unknown. The aim of this study was to establish the effects of exosomes derived from hypoxia-induced CMs on the migration and angiogenic tube formation of cardiac endothelial cells. Here, we reported that hypoxic exosomes (HPC-exos) can effectively reduce the infarct area and promote angiogenesis in the border surrounding the infarcted area. HPC-exos can also promote cardiac endothelial cell migration, proliferation, and tube formation in vitro. However, these effects were weakened after silencing circHIPK3 in hypoxia-induced CMs. We further verified that silencing and overexpressing circHIPK3 changed cardiac endothelial cell proliferation, migration, and tube formation in vitro by regulating the miR-29a expression. In addition, exosomal circHIPK3 derived from hypoxia-induced CMs first led to increased VEGFA expression by inhibiting miR-29a activity and then promoted accelerated cell cycle progression and proliferation in cardiac endothelial cells. Overexpression of miR-29a mimicked the effect of silencing circHIPK3 on cardiac endothelial cell activity in vitro. Thus, our study provides a novel mechanism by which exosomal circRNAs are involved in the communication between CMs and cardiac endothelial cells.

Radix Salviae miltiorrhizae, danshen root (danshen), is one of the widely used Chinese herbal medicines in clinics, containing rich phenolic compounds. Salvianolic acid is the main active compound responsible for the pharmacologic effects of danshen. Here, we aimed to evaluate the effects of salvianolic acid on cardioprotection through promoting angiogenesis in experimental myocardial infarction. Studies of salvianolic acid in animal models of myocardial infarction were obtained from 6 databases until April 2016. The outcome measures were vascular endothelium growth factor (VEGF), blood vessel density (BVD), and myocardial infarct size. All the data were analyzed using Rev-Man 5.3 software. Ultimately, 14 studies were identified involving 226 animals. The quality score of studies ranged from 3 to 6. The meta-analysis of six studies showed significant effects of salvianolic acid on increasing VEGF expression compared with the control group (P < 0.01). The meta-analysis of the two salvianolic acid A studies and three salvianolic acid B studies showed significantly improving BVD compared with the control group (P < 0.01). The meta-analysis of five studies showed significant effects of salvianolic acid for decreasing myocardial infarct size compared with the control group (P < 0.01). In conclusion, these findings demonstrated that salvianolic acid can exert cardioprotection through promoting angiogenesis in animal models of myocardial infarction.

Astragalus membranaceus (AM) is a traditional Chinese medicine, which possesses a variety of biological activities in the cardiovascular systems. We conducted a clinical and preclinical systematic review of 28 randomized clinical control studies with 2522 participants and 16 animal studies with 634 animals to evaluate the efficacy, safety, and possible mechanisms of AM for viral myocarditis (VM). The search strategies were performed in 7 databases from inception to January 2020. Application of the Cochrane Collaboration's tool 7-item checklist, SYRCLE's tool 10-item checklist, and Rev-Man 5.3 software to analyze the risk of bias of studies and data. The results show the score of clinical study quality ranged from 3 to 7 points with an average of 3.32, and the score of animal study quality ranged from 2 to 5 points with an average of 3. In clinical study, AM significantly reduced serum myocardial enzymes and cardiac troponin I levels and improved the clinical treatment efficiency in VM patients compared with the control group (P < 0.05). There was no significant difference in the incidence of adverse reactions (P > 0.05). Significant increase of the survival rate and decrease of the cardiac cardiology score, cardiac enzymes, and cardiac troponin I were compared with the placebo group in animal studies (P < 0.05). The possible mechanisms of AM are largely through antivirus and antivirus receptors, anti-inflammatory, antioxidation, antiapoptotic, antifibrosis, and reducing cardiac calcium load. In conclusion, the findings suggested that AM is a cardioprotection candidate drug for VM.

Ginseng is an important herbal drug that has been used worldwide for many years. Ginsenoside Rb1 (G-Rb1), the major pharmacological extract from ginseng, possesses a variety of biological activities in the cardiovascular systems. Here, we conducted a preclinical systematic review to investigate the efficacy of G-Rb1 for animal models of myocardial ischemia/reperfusion injury and its possible mechanisms. Ten studies involving 211 animals were identified by searching 6 databases from inception to May 2017. The methodological quality was assessed by using the CAMARADES 10-item checklist. All the data were analyzed using RevMan 5.3 software. As a result, the score of study quality ranged from 3 to 7 points. Meta-analyses showed that G-Rb1 can significantly decrease the myocardial infarct size and cardiac enzymes (including lactate dehydrogenase, creatine kinase, and creatine kinase-MB) when compared with control group (P < 0.01). Significant decrease in cardiac troponin T and improvement in the degree of ST-segment depression were reported in one study (P < 0.05). Additionally, the possible mechanisms of G-Rb1 for myocardial infarction are antioxidant, anti-inflammatory, antiapoptosis, promoting angiogenesis and improving the circulation. Thus, G-Rb1 is a potential cardioprotective candidate for further clinical trials of myocardial infarction.