Functional mechanism of tracheal relaxation,antiasthmatic, and toxicological studies of 6-hydroxyflavone

Previously, we described tracheal rat rings relaxation by several flavonoids, being 6-hydroxyflavone (6-HOF) the most active derivative of the series. Thus, its mechanism of action was determined in an ex vivo tracheal rat ring bioassay. The anti-asthmatic effect was assayed in in vivo OVAlbumin (OVA)-sensitized guinea pigs. Finally, the toxicological profile of 6-HOF was studied based on Organization of Economic Cooperation and Development guidelines with modifications. 6-HOF–induced relaxation appears to be related with receptor-operated calcium channel and voltage-operated calcium channel blockade as the main mechanism of action, and also through the production of relaxant second messengers NO and cGMP. Molecular docking supports that 6-HOF acts as calcium channel blocker and by activation of nitric oxide synthase. In addition, the in vivo anti-asthmatic experiments demonstrate the dose-dependent significant anti-allergic effect of 6-HOF induced by OVA, with best activity at 50 /kg. Finally, toxicological studies determined a LD50 > 2,000 mg/kg and, after 28 day of treatment with 6-HOF (50 mg/kg) by intragastric route, mice did not exhibit evidence of any significant toxicity. In conclusion, experiments showed that 6-HOF exerts significant relaxant activity through calcium channel blockade, and possibly, by NO/cGMP-system stimulation on rat trachea, which interferes with the contraction mechanism of smooth muscle cells in the airways. In addition, the flavonoid shows potential anti-asthmatic properties in an anti-allergic pathway. Furthermore, because the pharmacological and safety evidence, we propose this flavonoid as lead for the development of a novel therapeutic agent for the treatment of asthma and related respiratory diseases.     

釉基质蛋白对人牙周膜细胞群骨钙素的影响

目的研究人牙周膜细胞群(human periodontal ligament cell populations,hPDLPs)在釉基质蛋白(em-dogain,EMD)诱导下骨钙素(osteocalcin,OCN)表达的改变。方法组织块法分离培养人牙周膜细胞,实验组用含100 mg/L EMD的培养液诱导6 d,对照组不经EMD诱导培养。免疫细胞化学和实时定量聚合酶链反应(polymer-ase chain reaction,PCR)检测成牙骨质细胞矿化相关蛋白OCN的表达。结果免疫细胞化学结果显示,实验组和对照组hPDLPs细胞胞浆均可见黄色或棕黄色颗粒,OCN表达呈阳性;实验组hPDLPs的OCN检测平均光密度值为0.172 43±0.014 85,对照组为0.167 01±0.017 03,组间差异无统计学意义(t=0.757,P=0.459);实时定量PCR检测结果显示,实验组骨钙素相对表达量是对照组的1.13倍。结论 EMD对hPDLPs的OCN表达无明显影响。     

糖尿病对大鼠骨组织白细胞介素-6及血清C反应蛋白水平的影响

目的探讨糖尿病对大鼠骨组织白细胞介素-6（interleukin-6,IL-6）表达和血清C反应蛋白（Creactiveprotein,CRP）水平的影响。方法48只sD大鼠随机分为糖尿病组38只和正常组10只。第24周时,2组大鼠检测血糖以及血清胆固醇、甘油三酯,免疫散射比浊法检测血清CRP浓度,取大鼠股骨及颌骨制作石蜡切片,免疫组织化学法检测大鼠骨组织中IL-6的表达情况。结果正常组和糖尿病组大鼠骨组织IL-6平均积分光密度值分别为16.42±4.25和18,78±2．14;正常组血糖、胆固醇、甘油三酯、C反应蛋白浓度分别为（3．910±0．396）mmol／L、（4．935±0．343）mmol／L、（2．137±0．092）mmol／L、（0．858±0.096）mg／L,糖尿病组血糖、胆固醇、甘油三酯、C反应蛋白浓度分别为（12．418±1．302）mmol／L．（5．041±0．336）mmolfL、（2．197±0．120）mmol／L、（5.948±0．860）mg／L。糖尿病组大鼠骨组织IL-6（t=0．642）表达以及胆固醇水平（t=0．850）与正常组比较差异无统计学意义（P〉0.05）;血糖（t=30．818）、甘油三酯（t=3．276）和C反应蛋白（t=30．751）与正常组比较,差异有统计学意义（P〈0.05）。结论糖尿病致体内多种炎症因子高表达,对于炎症类疾病的发展是一个危险信号。