贝母提取物对异丙肾上腺素诱导心肌H9c2细胞肥大的干预作用

目的: 研究贝母提取物(FE)对异丙肾上腺素(Iso)诱导H9c2 心肌细胞肥大(CH)的干预作用。方法: 采用体外培养心肌H9c2 细胞,MTT法测定心肌H9c2细胞存活率; 细胞分4组(n=10):对照组、2 μmol/L Iso (模型)组、2 μmol/L Iso+FE 400 μg/L 组、2 μmol/LIso+FE 1 000 μg/L 组;相差显微镜观察细胞形态及测定心肌细胞直径;二辛可酸法检测细胞总蛋白;钙-4 试剂检测细胞内钙离子浓度。结果: Iso 组心肌H9c2细胞直径、总蛋白量及[Ca²⁺]i均显著高于对照组(P＜0.01);400 μg/ml 和1 000 μg/ml FE各组心肌H9c2细胞直径、总蛋白量及细胞[Ca²⁺]i均显著低于Iso组 (P＜0.05 或P＜0.01)。结论: FE对Iso诱导H9c2 CH有干预作用,可能与抑制钙信号通路激活有关。     

Design,synthesis and biological evaluation of 8-(2-amino-1-hydroxyethyl)-6-hydroxy-1,4-benzoxazine-3(4H)-one derivatives as potent β2-adrenoceptor agonists

A series of β₂-adrenoceptor agonists with an 8-(2-amino-1-hydroxyethyl)-6-hydroxy-1,4-benzoxazine-3(4H)-one moiety is presented. The stimulatory effects of the compounds on human β₂-adrenoceptor and β₁-adrenoceptor were characterized by a cell-based assay. Their smooth muscle relaxant activities were tested on isolated guinea pig trachea. Most of the compounds were found to be potent and selective agonists of the β₂-adrenoceptor. One of the compounds, (R)-18c, possessed a strong β₂-adrenoceptor agonistic effect with an EC₅₀ value of 24 pM. It produced a full and potent airway smooth muscle relaxant effect same as olodaterol. Its onset of action was 3.5 min and its duration of action was more than 12 h in an in vitro guinea pig trachea model of bronchodilation. These results suggest that (R)-18c is a potential candidate for long-acting β₂-AR agonists.     

Analysis of maslinic acid and gallic acid compounds as xanthine oxidase inhibitors in isoprenaline administered myocardial necrotic rats

ObjectiveThis research designed to analyze the in vivo and in silico ameliorative action of maslinic acid (MA) and gallic acid (GA) on reactive oxygen species generating enzyme xanthine oxidase (XO) in isoprenaline or isoproterenol (ISO) induced myocardial infarcted rats.MethodsAlbino Wistar rats were categorized into four groups with eight rats in each group. A dose of 15 mg/kg of MA and GA were pretreated to each MA and GA groups for seven days. A dose of 85 mg/kg of ISO administered to the ISO group along with MA and GA groups except normal group on two consecutive days of pretreatment. All animals sacrificed and the heart tissues were collected for the analysis of XO. The in silico molecular docking analysis of the compounds MA and GA with XO was analyzed by using Gold 3.0.1 software.ResultsXO enzyme levels were significantly increased in the heart homogenate of ISO administered rats when compared to normal rats. Pretreatment of MA and GA to ISO treated rats significantly brought XO enzyme to the near normal levels which indicate the protective action of MA and GA against myocardial necrosis. The in vivo results were further supported by the in silico molecular docking study which revealed the inhibition of XO enzyme by the formation of enzyme and ligand complex with the compounds MA and GA.ConclusionMA and GA compounds manifested the ameliorative effect against ISO administrated myocardial necrosis by inhibiting the free radical generating enzyme XO which is evidenced by both in vivo and in silico studies.