乳香有效成分治疗冠心病的作用机制研究进展

乳香Olibanum为活血止痛之常用药,是胸痹心痛方剂中的常用药材。现代研究表明乳香在冠心病的治疗中具有较大的开发前景,其主要活性成分为萜类和挥发油等。通过查阅近年来国内外有关乳香有效成分治疗冠心病的相关文献,综述了乳香单味药材及其有效成分治疗冠心病的作用机制与药效作用的研究进展,列举了含乳香复方的临床应用,并总结了乳香的不良反应,为乳香治疗冠心病的临床应用提供依据与参考。     

Use of multiplexed tandem PCR to estimate the prevalence and intensity of Theileria orientalis infections in cattle

This study employed a semi-quantitative, multiplexed tandem PCR (MT-PCR) to assess the prevalence and infection intensity of four genotypes (buffeli, chitose, ikeda and type 5) of Theileria orientalis in cattle in Australia. Genomic DNA samples from blood samples (n = 448) collected from 27 to 32 dairy cows from each of 15 dairy herds with a history of recent theileriosis outbreaks (Group 1), and from blood samples available from 24 cows with or without oriental theileriosis (Group 2) were tested using MT-PCR. Results revealed that all four genotypes were present in Group 1 cattle; genotype buffeli had the highest prevalence (80.5%), followed by genotypes ikeda (71.4%), chitose (38.6%) and type 5 (20.3%). Genotype ikeda had the highest average infection intensity in the cattle (relating to 55,277 DNA copies), followed by buffeli, chitose and type 5 (6354–51,648 copies). For Group 2, results indicated that genotype ikeda had a significantly higher average intensity of infection than buffeli in symptomatic cattle (P < 0.001), and symptomatic cattle had a higher intensity of ikeda than asymptomatic cattle (P = 0.004). Future studies should assess the utility of the present MT-PCR assay as a diagnostic and epidemiological tool in other parts of Australasia and the world.     

Potential advantages of a combination of Chinese Medicine and bone marrow mesenchymal stem cell transplantation for removing blood stasis and stimulating neogenesis during ischemic stroke treatment

Combined treatment of ischemic stroke with Chinese medicine and exogenous bone marrow mesenchymal stem cell (BMSC) transplantation may improve the removal of blood stasis and stimulation of neogenesis.Chinese medicines that remove blood stasis not only promote blood circulation but also calm the endopathic wind,remove heat,resolve phlegm,remove toxic substances and strengthen body resistance.The medicinal targeting effect of Chinese medicine can promote the homing of BMSCs,and the synergistic therapeutic effects of drugs can contribute to BMSC differentiation.As such,exogenous BMSC transplantation has potential advantages for neogenesis.Chinese medicines and exogenous BMSCs provide complementary functions for the removal of blood stasis and stimulation of neogenesis.Therefore,a combination of Chinese medicine and transplantation of exogenous BMSCs may be particularly suited to ischemic stroke treatment.     

Nobiletin and its derivatives overcome multidrug resistance (MDR) in cancer: total synthesis and discovery of potent MDR reversal agents

Our recent studies demonstrated that the natural product nobiletin (NOB) served as a promising multidrug resistance (MDR) reversal agent and improved the effectiveness of cancer chemotherapy in vitro. However, low aqueous solubility and difficulty in total synthesis limited its application as a therapeutic agent. To tackle these challenges, NOB was synthesized in a high yield by a concise route of six steps and fourteen derivatives were synthesized with remarkable solubility and efficacy. All the compounds showed improved sensitivity to paclitaxel (PTX) in P-glycoprotein (P-gp) overexpressing MDR cancer cells. Among them, compound 29d exhibited water solubility 280-fold higher than NOB. A drug-resistance A549/T xenograft model showed that 29d, at a dose of 50 mg/kg co-administered with PTX (15 mg/kg), inhibited tumor growth more effective than NOB and remarkably increased PTX concentration in the tumors via P-gp inhibition. Moreover, Western blot experiments revealed that 29d inhibited expression of NRF2, phosphorylated ERK and AKT in MDR cancer cells, thus implying 29d of multiple mechanisms to reverse MDR in lung cancer.     

Anti-obesity effects of seaweeds of Jeju Island on the differentiation of 3T3-L1 preadipocytes and obese mice fed a high-fat diet

The seaweeds were collected from the coast of Jeju Island, South Korea. We investigated ethanol extracts from seaweed as potential antiobesity agents by testing their effect on adipogenic differentiation in 3T3-L1 cells. Among the red algae extracts tested, the Plocamium telfairiae extract (PTE) showed the highest inhibitory effect on lipogenesis in adipocytes and, thus, was selected as a potential antiobesity agent. PTE treatment significantly decreased the expression of the adipogenic-specific proteins peroxisome proliferator-activated receptor-γ, CCAAT/enhancer-binding protein-α, sterol regulatory element-binding protein 1, and fatty acid-binding protein 4 compared with that in the untreated 3T3-L1 cells. PTE also inhibited high-fat diet (HFD)-induced obesity in male C57BL/6 mice. Oral administration of PTE significantly reduced the body weight, fatty liver, amount of white adipose tissue, and levels of triglyceride and glucose in the tested animals. Taken together, these data demonstrate that PTE can be developed as a therapeutic agent for obesity.     

Targeted LOWering of Central Blood Pressure in patients with hypertension: Baseline recruitment,rationale and design of a randomized controlled trial (The LOW CBP study)

BackgroundHigh blood pressure (BP) is the most common modifiable cause of death from cardiovascular disease. Lowering BP with medication improves patient outcomes, but even in populations with normal upper arm (brachial) BP there remains considerable residual risk for cardiovascular disease and this may be due to persistently elevated central BP. There has never been a trial to determine the value of targeted central BP lowering among patients with hypertension, and this was the aim of this study.MethodsThis is a multi-centre, randomized, open-label, blinded endpoint trial among 308 patients treated for uncomplicated hypertension with controlled brachial BP (< 140/90 mmHg) but elevated central BP (≥ 0.5SD above age- and sex-specific normal values). Baseline recruitment has been completed. Participants were randomized to intervention with spironolactone (25 mg/d) or usual care and are being followed over 24 months, with the primary outcome being left ventricular mass index (using cardiac magnetic resonance imaging). Brachial and central BP will be measured in the clinic, at home over 7-days and by 24-h ambulatory monitoring. Aortic stiffness will be assessed by carotid-to-femoral pulse wave velocity. Primary (intention to treat) analysis will determine the role of central versus brachial BP for predicting changes in left ventricular mass index.ConclusionsCompared with control, intervention is expected to significantly lower left ventricular mass index, and this effect is expected to be independently correlated with central BP lowering. These findings would support the concept of central BP as an important therapeutic target in hypertension management. Results are expected in 2018.     

Flavonoids derived from liquorice suppress murine macrophage activation by up-regulating heme oxygenase-1 independent of Nrf2 activation

Liquiritigenin (LQG), isoliquiritin (ILQ) and isoliquiritigenin (ILG) are flavonoids derived from liquorice and all possess a similar chemical structural backbone. In the current study, we found that ILQ and ILG had suppressive effects on lipopolysaccharide (LPS)-induced inflammatory responses in murine macrophage by suppressing the iNOS and COX-2 proteins and mRNA expression. A mechanistic study indicated that the effect was associated with an induction of antioxidant and detoxification enzymes, including UGT1A1, NQO1, and heme oxygenase-1 (HO-1) mRNA expression. The regulator of these enzymes, nuclear factor-erythroid 2-related factor 2 (Nrf2), which plays a critical role in LPS-induced inflammatory responses, could be activated by ILQ and ILG. Additionally, ILQ and ILG promoted Nrf2 signaling activation by inhibiting the Kelch-like ECH-associated protein 1 (Keap1) and increasing Nrf2 translocation, inducing the expression of these antioxidant enzymes. We further found that ILQ and ILG induced HO-1 expression independent of Nrf2 expression. With respect to the effect of these compounds on NF-κB signaling, ILG was found to markedly inhibit IκBα degradation and phosphorylation, while LQG and ILQ had no significant effects. These results indicate that there are correlations between the anti-inflammatory responses and the chemical structural properties of these flavonoids.     

Protective effect of platycodin D on liver injury in alloxan-induced diabetic mice via regulation of Treg/Th17 balance

Platycodin D is a major pharmacological constituent of Platycodi Radix with immunomodulatory activity. The present study was designed to investigate how platycodin D (PLD) reveals liver injury in diabetic mice and its mechanism. Fifty mice were divided into five groups randomly: control group, model group, rosiglitazone (ROG, 10 mg/kg) group, PLD (50 mg/kg) group, and PLD (100 mg/kg) group. Diabetes was induced with the injection of alloxan monohydrate (150 mg/kg) subcutaneously, and animals with blood glucose level of ≥ 250 mg/dl were considered as diabetic mice. After the first day of diabetes induction, the treatments were performed for 8 weeks. Then the animals were anaesthetized, and blood and liver samples were also collected for further assay. PLD significantly decreased the serum levels of glucose, insulin, interleukin-6 (IL-6), interleukin-1β, tumor necrosis factor-α (TNF-α), and interleukin (IL)-17A and increased IL-10 level in serum. PLD effectively downregulated aspartate transaminase (AST), alanine aminotransferase (ALT), total cholesterol (TC), and triglycerides (TG) in liver. PLD also attenuated liver histological change. In addition, PLD significantly attenuated IL-17A and IL-10 levels in vitro, flow cytometry (FCM) studies also showed that PLD remarkably inhibited Th17 cells and significantly increased Treg cells in liver tissues and spleen cells. Western blot demonstrated PLD inhibited the phosphorylation of JAK and STAT-3 and the expression of RORγt and increased the expression of Foxp3. The findings showed that PLD exerts beneficial effects on alloxan-induced liver injury in mice.