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Leonurine: From Gynecologic Medicine to Pleiotropic Agent 被引量:11
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作者 LI Yun-yun LIN yi-kong +5 位作者 LIU Xin-hua WANG Li YU Min LI Da-jin zhu yi-zhun DU Mei-rong 《Chinese Journal of Integrative Medicine》 SCIE CAS CSCD 2020年第2期152-160,共9页
Leonurus japonicus Houtt,a Chinese traditional herbal medicine,has been widely used to cure gynecological diseases,such as incomplete abortion and menoxenia.Leonurine,a major active alkaloid compound only be found in ... Leonurus japonicus Houtt,a Chinese traditional herbal medicine,has been widely used to cure gynecological diseases,such as incomplete abortion and menoxenia.Leonurine,a major active alkaloid compound only be found in Leonurus japonicus Houtt,has been successfully extracted and purified.Recent evidence has shown that leonurine can regulate a variety of pathologic processes including oxidative stress,inflammation,fibrosis,apoptosis,and multiple metabolic disorders.Here,we have reviewed the pharmacological actions and biological functions of leonurine,with a focus on the role of leonurine in the amelioration of various pathological processes.Insights into the related signaling pathways and molecular mechanisms have strengthened our understanding on the function of leonurine in the alleviation of multiple pathological states.Our summary of the existing researches should help direct future research into the basic science and clinical applications in related diseases. 展开更多
关键词 LEONURINE Leonurus japonicus Houtt Chinese medicine oxidative stress inflammation FIBROSIS clinical application
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益母草碱在大鼠急性内毒素性葡萄膜炎模型中的保护作用 被引量:9
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作者 熊佳伟 顾纪锋 +4 位作者 石碗如 吴甦潜 麦尔哈巴.肖开提 朱依谆 莫晓芬 《复旦学报(医学版)》 CAS CSCD 北大核心 2018年第3期291-296,329,共7页
目的建立SD大鼠急性内毒素性葡萄膜炎(endotoxin induced uveitis,EIU)模型,研究益母草碱(leonurine,SCM-198)是否对脂多糖(lipopolysaccharide,LPS)所致眼部结构、功能损伤具有保护作用,并探讨其作用机制。方法体重180~200 g正常雄性S... 目的建立SD大鼠急性内毒素性葡萄膜炎(endotoxin induced uveitis,EIU)模型,研究益母草碱(leonurine,SCM-198)是否对脂多糖(lipopolysaccharide,LPS)所致眼部结构、功能损伤具有保护作用,并探讨其作用机制。方法体重180~200 g正常雄性SD大鼠36只,随机分为3组。实验组:又分为4个亚组,分别以每日每千克体重10、20、40、80 mg的SCM-198生理盐水溶液灌胃,共21天;阴性对照组:每日以0.9%Na Cl溶液10 m L/kg体重灌胃;阳性对照组:以每日每千克体重0.5 mg的地塞米松(dexamethasone,DEX)磷酸钠生理盐水溶液灌胃。组间饲养无差异,每7天测体重。第18天灌胃后,全部大鼠全麻并充分暗适应后行全视网膜电图(electroretinogram,ERG)检测;第21天灌胃后以1 g/L的伤寒沙门氏菌(S.typhi)LPS生理盐水溶液0.1 m L于全部大鼠左足底注射造模,造模后24 h行全麻下ERG检测,裂隙灯下行双眼炎症评分,取左眼房水-80℃冻存后处死动物,取右侧眼球固定后石蜡包埋切片,HE染色,光学显微镜下观察,免疫组织化学(immunohistochemistry,IHC)染色检测肿瘤坏死因子-α(tumour necrosis factor-α,TNF-α)、细胞间黏附分子-1(intercellular cell adhesion molecule-1,ICAM-1)表达水平;对留取的房水样本用BCA法测定蛋白浓度,Western blot检测房水TNF-α、白细胞介素-1β(interleukin-1β,IL-1β)、IL-6、ICAM-1水平;以SPSS 19.0软件处理所得数据,综合分析SCM-198对EIU模型大鼠的保护作用。结果实验组、阴性对照组第21天时体重均显著高于阳性对照组(P<0.05)。实验组裂隙灯下炎症评分低于阴性对照组、高于阳性对照组;实验组病理切片炎症程度介于阴性对照组和阳性对照组之间;SCM-198 20 mgkg-1d-1组造模后0.01 cd下ERG a波波幅显著低于造模前(P<0.05),亦低于其他组造模后;SCM-198 10 mgkg-1d-1组房水TNF-α、IL-6和IL-1β表达低于其他各组。结论 SCM-198灌胃对EIU模型大鼠具有抗炎保护作用,且常规剂量下� 展开更多
关键词 益母草碱 炎症 急性内毒素性葡萄膜炎 TLR4 NF-ΚB SD大鼠
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益母草碱对压力超负荷心肌肥厚大鼠的作用及机制研究 被引量:6
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作者 丁晓丽 袁青青 +3 位作者 薛丁嘉 杨福明 朱依谆 钱海兵 《中国中药杂志》 CAS CSCD 北大核心 2022年第2期461-468,共8页
探讨益母草碱(leonurine,Leo)对腹主动脉缩窄(abdominal aortic constriction,AAC)致大鼠压力负荷型心肌肥厚的作用及作用机制。AAC方法建立压力超负荷大鼠心肌肥大模型,经益母草碱高、低剂量组(30、15 mg·kg^(-1))及阳性对照药氯... 探讨益母草碱(leonurine,Leo)对腹主动脉缩窄(abdominal aortic constriction,AAC)致大鼠压力负荷型心肌肥厚的作用及作用机制。AAC方法建立压力超负荷大鼠心肌肥大模型,经益母草碱高、低剂量组(30、15 mg·kg^(-1))及阳性对照药氯沙坦钾片组(losartan,5 mg·kg^(-1))干预27 d后,采用血流动力学方法评价心功能,并记录左室收缩压(left ventricular systolic pressure,LVSP)、左心室舒张末压(left ventricular end-diastolic pressure,LVEDP)、左心室内压最大上升和下降速率(maximum increase and decrease in left ventricular pressure,±dp/dt_(max));采用心脏质量指数(heart weight index,HWI)和左室质量指数(left ventricular mass index,LVWI)测定左心室肥大程度;苏木精-伊红(HE)染色检测心肌组织变化和心肌细胞直径(the size of myocardial cell diameter,MD);ELISA法检测心肌组织中血管紧张素Ⅱ(AngⅡ)、血管紧张素Ⅱ1型受体(AT1R)含量;比色法检测心肌组织中Ca^(2+)水平;Western blot法检测磷脂酶C(PLC)、肌醇三磷酸(IP3)、AngⅡ、AT1R蛋白的表达;实时荧光定量PCR(real-time quantitative PCR,qRT-PCR)法检测β-肌球蛋白重链(β-MHC)、心房利钠因子(ANF)、AngⅡ、AT1R蛋白的表达。与模型组比较,益母草碱组可降低模型组大鼠LVSP、LVEDP、HWI、LVWI、MD的值,升高左心室±dp/dt_(max);改善心肌组织病理形态,减少心肌细胞的肥大、水肿及炎症细胞的浸润;降低心肌组织AngⅡ、AT1R和Ca^(2+)含量,降低心肌组织中PLC、IP3、AngⅡ、AT1R蛋白水平以及β-MHC、ANF、AngⅡ、AT1R、c-fos、c-myc mRNA表达。益母草碱可抑制AAC诱导的心肌肥大,其作用可能与肾素-血管紧张素(RAS)系统有关。 展开更多
关键词 益母草碱 心肌肥厚 RAS系统 AngⅡ AT1R
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益母草碱抑制血管紧张素Ⅱ诱导心肌成纤维细胞增殖的作用与机制 被引量:5
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作者 薛丁嘉 李雪斐 +2 位作者 丁晓丽 朱依谆 钱海兵 《中国新药与临床杂志》 CAS CSCD 北大核心 2022年第5期301-306,共6页
目的探究益母草碱对血管紧张素Ⅱ(AngⅡ)诱导的心肌成纤维细胞(CFs)增殖的作用及机制。方法选用大鼠心肌成纤维细胞株作为实验对象,将其分为正常对照组、模型组、益母草碱组、雷帕霉素组。正常对照组仅用新鲜培养基培养,其余组均加入终... 目的探究益母草碱对血管紧张素Ⅱ(AngⅡ)诱导的心肌成纤维细胞(CFs)增殖的作用及机制。方法选用大鼠心肌成纤维细胞株作为实验对象,将其分为正常对照组、模型组、益母草碱组、雷帕霉素组。正常对照组仅用新鲜培养基培养,其余组均加入终浓度为1×10^(-7)mol·L^(-1)的AngⅡ诱导CFs增殖;益母草碱组给予1×10^(-6)mol·L^(-1)益母草碱,雷帕霉素组给予1×10^(-7)mol·L^(-1)雷帕霉素。免疫荧光显微镜观测各组的自噬水平,CCK-8法检测CFs增殖活力,ELISA法检测Ⅰ型胶原(ColⅠ)和Ⅲ型胶原(ColⅢ)的含量,real-time PCR法检测各组微管相关蛋白1轻链3(LC3)、自噬蛋白1(Beclin1)、磷脂酰肌醇3激酶(PI3K)、蛋白激酶B(Akt)、哺乳动物雷帕霉素靶蛋白(mTOR)mRNA的表达,Western blot法检测各组LC3-Ⅱ、Beclin1、PI3K、Akt、mTOR蛋白的表达。结果与正常对照组相比,模型组CFs增殖率显著增高,ColⅠ和ColⅢ的含量显著升高(P<0.01),自噬体及自噬溶酶体数量均明显减少;LC3-Ⅱ、Beclin1蛋白和mRNA表达降低(P<0.05),而PI3K、Akt、mTOR蛋白和mRNA表达升高(P<0.05)。与模型组相比,益母草碱组和雷帕霉素组CFs增殖率显著降低,ColⅠ、ColⅢ含量降低(P<0.05),细胞自噬水平提高;LC3-Ⅱ、Beclin1蛋白和mRNA表达升高(P<0.05),PI3K、Akt、mTOR蛋白和mRNA表达降低(P<0.05)。结论益母草碱可抑制AngⅡ诱导的CFs增殖,降低ColⅠ和ColⅢ的表达水平,促进CFs自噬,其机制可能与调节PI3K/Akt/mTOR信号通路有关。 展开更多
关键词 益母草碱 心肌纤维化 自噬 磷酸肌醇3-激酶类
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Amelioration of mitochondrial dysfunction in heart failure through S-sulfhydration of Ca2Vcalmodulin-dependent protein kinase II
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作者 Dan WU Qing-xun HU +1 位作者 De-qiu zhu yi-zhun zhu 《中国药理学与毒理学杂志》 CSCD 北大核心 2017年第10期1025-1026,共2页
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Cardiac protection of new compounds from scientific Chinese medicine (SCM)
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作者 zhu yi-zhun(Department of Pharmacology,School of Pharmacy,Fudan University,Shanghai 200032,China) 《沈阳药科大学学报》 CAS CSCD 北大核心 2008年第S1期9-9,共1页
Objective Purification and Standardization of Chinese herbal extracts became a hot topic since last decade.Though traditional Chinese medicine(TCM)has been used as a mixture from several herbs for centuries,it has bee... Objective Purification and Standardization of Chinese herbal extracts became a hot topic since last decade.Though traditional Chinese medicine(TCM)has been used as a mixture from several herbs for centuries,it has been drawn much attention for studying the standardized Chinese herbs using modern technology.Methods Recently,we compared purified Salvia miltiorrhiza extract(PSME)with angiotensin-converting enzyme inhibitor,Ramipril,in in vitro experiments and also in vivo using animal model of myocardial infarction.Results PSME was found to have a significantly higher trolox equivalent antioxidant capacity which indicated a great capacity for scavenging free radicals.PSME could also prevent pyrogallo red bleaching and DNA damage.After 2 weeks treatment with PSME or Ramipril,survival rates of rats with experimental myocardial infarction were marginally increased(68.2% and 71.4%)compared with saline(61.5%).In another recent study,we evaluated the cardioprotective effects of PSME on myocardial ischemia/reperfusion injury in isolated rat hearts and in hypoxic vascular smooth muscle cells.We found that PSME treated hearts showed significant postischemic contractile function recovery(develop pressure recovered to 44.2±4.9% versus 17.1±5.7%,P<0.05;maximum contraction recovered to 57.2±5.9% versus 15.1±6.3%,P<0.001;maximum relaxation restored to 69.3±7.3% versus 15.4±6.3%,P<0.001 in PSME and control group respectively).Conclusions Significant elevated in end-diastolic pressure,which indicated LV stiffening in PSME hearts might be resulted by exceed dose of PSME used.Purified and standardized Chinese herb could provide an alternative regimen for the prevention of ischemic heart disease. 展开更多
关键词 traditional Chinese medicine purified SALVIA miltiorrhiza extract MYOCARDIAL INFARCTION RAMIPRIL
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Amelioration of mitochondrial dysfunction in heart failure through S-sulfhydration of Ca^2+/calmodulin-dependent protein kinase Ⅱ
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作者 Dan WU Qing-xun HU +1 位作者 De-qiu zhu yi-zhun zhu 《中国药理学与毒理学杂志》 CSCD 北大核心 2017年第10期976-976,共1页
OBJECTIVE To determine the functional role of hydrogen sulfide(H_2S) in protecting against mitochondrial dysfunction in heart failure through the inhibition of Ca^(2+)/calmodulin-dependent protein kinaseⅡ(Ca MKⅡ) us... OBJECTIVE To determine the functional role of hydrogen sulfide(H_2S) in protecting against mitochondrial dysfunction in heart failure through the inhibition of Ca^(2+)/calmodulin-dependent protein kinaseⅡ(Ca MKⅡ) using wild type and CSE knockout mouse models.METHODS Continuous subcutaneous injection isoprenaline(7.5 mg·kg^(-1) per day),once a day for 4 weeks to induce heart failure in male C57BL/6(6-8 weeks old) mice and CSE-/-mice.150 μmol·L^(-1) H_2O_2 was used to induce oxidative stress in H9c2 cells.Echocardiograph was used to detect cardiac parameters.H&E stain and Masson stain was to observation histopathological changes.Western blot was used to detect protein expression and activity.The si RNA was used to silence protein expression.HPLC was used to detect H_2S level.Biotin assay was used to detect the level of S-sulfhydration protein.RESULTS Treatment with S-propyl-L-cysteine(SPRC) or sodium hydrosulfide(Na HS),modulators of blood H_2S levels,attenuated the development of heart failure in animals,reduced lipid peroxidation,and preserved mitochondrial function.The inhibition Ca MKⅡ phosphorylation by SPRC and Na HS as demonstrated using both in vivo and in vitro models corresponded with the cardioprotective effects of these compounds.Interestingly,Ca MKⅡ activity was found to be elevated in CSE-/-mice as compared to wild type animals and the phosphorylation status of Ca MK Ⅱ appeared to relate to the severity of heart failure.Importantly,in wild type mice SPRC was found to promote S-sulfhydration of Ca MKⅡ leading to reduced activity of this protein however,in CSE-/-mice S-sulfhydration was abolished following SPRC treatment.CONCLUSION A novel mechanism depicting a role of S-sulfhydration in the regulation of Ca MKⅡ is presented.SPRC mediated S-sulfhydration of Ca MKⅡ was found to inhibit Ca MKⅡ activity and to preserve cardiovascular homeostasis. 展开更多
关键词 hydrogen sulfide MITOCHONDRIA heart failure Ca2+/calmodulin-dependent protein kinase S sulfhydration
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