Salvianolic Acid A Protects Neonatal Cardiomyocytes Against Hypoxia/Reoxygenation-Induced Injury by Preserving Mitochondrial Function and Activating Akt/GSK-3ß Signals.

OBJECTIVE: To investigate the effects of salvianolic acid A (SAA) on cardiomyocyte apoptosis and mitochondrial dysfunction in response to hypoxia/reoxygenation (H/R) injury and to determine whether the Akt signaling pathway might play a role. METHODS: An in vitro model of H/R injury was used to study outcomes on primary cultured neonatal rat cardiomyocytes. The cardiomyocytes were treated with 12.5, 25, 50 µg/mL SAA at the beginning of hypoxia and reoxygenation, respectively. Adenosine triphospate (ATP) and reactive oxygen species (ROS) levels were assayed. Cell apoptosis was evaluated by flow cytometry and the expression of cleaved-caspase 3, Bax and Bcl-2 were detected by Western blotting. The effects of SAA on mitochondrial dysfunction were examined by determining the mitochondrial membrane potential (△Ψm) and mitochondrial permeability transition pore (mPTP), followed by the phosphorylation of Akt (p-Akt) and GSK-3ß (p-GSK-3ß), which were measured by Western blotting. RESULTS: SAA significantly preserved ATP levels and reduced ROS production. Importantly, SAA markedly reduced the number of apoptotic cells and decreased cleaved-caspase 3 expression levels, while also reducing the ratio of Bax/Bcl-2. Furthermore, SAA prevented the loss of △Ψm and inhibited the activation of mPTP. Western blotting experiments further revealed that SAA significantly increased the expression of p-Akt and p-GSK-3ß, and the increase in p-GSK-3ß expression was attenuated after inhibition of the Akt signaling pathway with LY294002. CONCLUSION: SAA has a protective effect on cardiomyocyte H/R injury; the underlying mechanism may be related to the preservation of mitochondrial function and the activation of the Akt/GSK-3ß signaling pathway.

Promoting blood circulation for removing blood stasis therapy for acute intracerebral hemorrhage: a systematic review and meta-analysis.

AIM: To conduct a systematic review and meta-analysis to assess the current evidence available regarding the promoting blood circulation and removing blood stasis (PBCRBS) therapy for Chinese patients with acute intracerebral hemorrhage (ICH). METHODS: Six databases were searched from their inception to November 2013. The studies assessed in ≥ 4 domains with 'yes' were selected for detailed assessment and meta-analysis. The herbal compositions for PBCRBS therapy for acute ICH patients were also assessed. RESULTS: From the 6 databases, 292 studies claimed randomized-controlled clinical trials (RCTs). Nine studies with 798 individuals were assessed in ≥ 4 domains with 'yes' by using the Cochrane RoB tool. Meta-analysis showed that PBCRBS monotherapy and adjuvant therapy for acute ICH could improve the neurological function deficit, reduce the volume of hematoma and perihematomal edema, and lower the mortality rate and dependency. Moreover, there were fewer adverse effects when compared with Western conventional medication controls. Xueshuantong Injection and Fufang Danshen Injection, Buyang Huanwu Decoction and Liangxue Tongyu formula, and three herbs (danshen root, sanqi and leech) were the most commonly used Chinese herbal patent injections, herbal prescriptions and single herbs, respectively. CONCLUSION: Despite the apparently positive findings, it is premature to conclude that there is sufficient efficacy and safety of PBCRBS for ICH because of the high clinical heterogeneity of the included studies and small number of trials in the meta-analysis. Further large sample-sizes and rigorously designed RCTs are needed.

Rhubarb root and rhizome-based Chinese herbal prescriptions for acute ischemic stroke: a systematic review and meta-analysis.

BACKGROUND: Traditional Chinese Medicine has been using in stroke victims for thousands of years, and the rhubarb root and rhizome (RRR)-based Chinese herbal prescription is one of the principle treatments for stroke. The objective of this study is to systematically assess the clinical efficacy and safety of RRR-based prescriptions for acute ischemic stroke. METHODS: A systematic literature search in six databases was performed to identify randomized controlled trials (RCTs), which compared RRR-based prescriptions with western conventional medicine (WCM) for acute ischemic stroke. The methodological quality of RCTs was assessed independently based on the 12 criteria recommended by the Cochrane Back Review Group. RESULTS: A total of 968 participants were included in 12 eligible studies. All trials were deemed to have high a risk of bias. RRR-based prescriptions have a significant effect on the improvement of the clinical efficacy rate (n=10), Barthel Index scores (n=5), National Institutes of Health Stroke Scale scores (n=2), Glasgow Coma Scale scores (n=1), and neurological deficit scores (n=5) when compared with WCM controls (p<0.05 or p<0.01). Six trials reported that there were no adverse events, while no mention of adverse effect monitoring was reported in the other 6 studies. CONCLUSIONS: Despite the apparently positive findings, it is premature to recommend the routine use of RRR-based prescriptions for acute ischemic stroke because methodological flaws undermine the strength of our findings. However, this work identifies an area, which is worthy of improvement and development for further research. Larger sample-sizes and rigorously designed RCTs are required in the future.

A possible role of myristoylated alanine-rich C kinase substrate in endocytic pathway of Alzheimer's disease.

It is believed that amyloid-beta peptide (Abeta) plays a central role in the pathogenesis of Alzheimer's disease (AD). Thus, the process of amyloid precursor protein (APP) cleavage is a key event and has raised much attention in the field of AD research. It is proposed that APP, beta- and gamma-secretases are all located on the lipid raft, and the meeting of them is an indispensable step for Abeta generation. Endocytosis can lead to clustering of APP, beta- and gamma-secretases from separate smaller lipid rafts into a larger one. On the other hand, for myristoylated alanine-rich C kinase substrate (MARCKS), phosphorylation by protein kinase C (PKC) or interaction with Ca(2+) can lead to its release from membrane into cytoplasm. This process induces the release of actins and phosphatidylinositol 4, 5-bisphosphate (PIP2), which are important factors for endocytosis. Thus, the present review proposes that MARCKS may be implicated in Abeta generation, by modulating free PIP2 level and actin movement, causing endocytosis.

[Studies on the chemical constituents of Rumex crispus].

OBJECTIVE: To study the chemical constituents of Rumex crispus. METHODS: Compounds were isolated and purified repeatedly by silica gel, Sephadex gel and ODS C18 column chromatographies, and structure identifications of compounds were carried out by physical, chemical methods and spectral data. RESULTS: Fifteen compounds were obtained from the petroleum ether and ethyl acetate fractions of R. crispus, and were identified as beta-sitosterol(1), hexadecanoic acid(2), hexadecanoic-2,3-dihydroxy propyleste(3), chrysophanol(4), physcion(5), emodin(6), chrysophanol-8-O-beta-D-glucopyranoside(7), physcion-8-O-beta-D-glucopyranoside(8), emodin-8O-beta-D-glucopyranoside(9), gallic acid(10), (+)-catechin(11), kaempferol(12), quercetin(13), kaempferol-3-O-alpha-L-rhamnopyranoside(14), quercetin-3-O-alpha-L-rhamnopyranoside(15). CONCLUSION: Compounds 3,8-12,14 and 15 are obtained from R. crispus for the first time.

[Study on the anti-apopotosis induced by hypoxia/hypoglycemia and reoxygenation of panax notoginseng saponins in cultured rat hippocampal neurons].

OBJECTIVE: To study the inhibitory effects of Panax Notoginseng Saponins(PNS) on apoptosis induced by hypoxia/hypoglycemia and reoxygenation in cultured rat hippocampal neurons. METHOD: Apoptosis were measured by flow cytometry, intracellular free calcium concentration([Ca2+]i) was measured with confocal laser scanning microscopy, morphological changes and neuronal necrosis were observed with fluorescence microscope, and meanwhile the leakage of lactic dehydrogenase(LDH) was measured. RESULT: Hypoxia/hypoglycemia cultures for 5 hours and reoxygenation induced neuronal apoptosis and necrosis, and significantly increased neuronal [Ca2+]i and the leakage of LDH. The effects were increased with the extending time of reoxygenation. PNS has could significantly decrease the percentage of neuronal apoptosis and necrosis, and reduce neuronal [Ca2+]i and the leakage of LDH. CONCLUSION: PNS has inhibitory effect on neuronal apoptosis. This effect might be related to its effect of decreasing intracellular free calcium concentration.