OBJECTIVE The plant of Anchusa italicahas been traditionally used in Uighur medicine for the treatment of cardiovascular and cerebrovascular diseases in China.Our previous study showed that total flavonoids from Anchu...OBJECTIVE The plant of Anchusa italicahas been traditionally used in Uighur medicine for the treatment of cardiovascular and cerebrovascular diseases in China.Our previous study showed that total flavonoids from Anchusa italica(TFAI)exhibited potent cardioprotection on acute ischemia/reperfusion injured rats.This study was undertaken to investigate the effects of TFAI on chronic myocardial infarction in mice and the underlying mechanism.METHODS Total flavonoids were extracted from the whole herb of Anchusa italica and were characterized using HPLC-MS analysis.The left anterior descending branch of coronary artery was ligated to induce myocardial infarction in mice.After surgery,the mice were orally fed with TFAI at the doses of 10,30 and 50 mg·kg-1 body mass per day for a total of four weeks.Cardiac function and infarct size were measured,and the levels of inflammatory mediators were detected.Hematoxylin and eosin(HE)stain and Masson Trichrome stain were performed.The apoptotic factors such as Bax,Bcl-2 and cleaved caspase 3 as well as the key proteins in the PI3K/Akt/mTOR signaling pathway were examined by Western blotting.RESULTS The content of total flavonoids in TFAI was 56.2%.Four weeks following the MI surgery,TFAI enhanced the survival rate in post-MI mice.TFAI administration at the doses of 30 and 50 mg·kg-1 significantly reduced the infarct size and improved cardiac function indicated by elevated EF and FS.Assay of inflammation factors showed that the sera levels of TNF-α,IL-1β and IL-6 were significantly decreased by TFAI treatment as compared to the MI group.HE stain and Masson Trichrome stain demonstrated that TFAI suppressed myocyte hypertrophy and cardiac fibrosis indicated by decreased cross-section area and collagen volume.Western blot analysis showed that cleaved caspase 3 and Bax/Bcl-2 were signifi⁃cantly downregulated following TFAI treatment.Additionally,TFAI treatment significantly suppressed the activation of the PI3K/Akt/mTOR signaling pathway.CONCLUSION TFAI exerts a protective effect against chronic myocardial infarction and its beneficial effects on cardiac function and cardiac remodeling might be at least attributable to anti-inflammation and suppression of the PI3K/Akt/mTOR signaling pathway.展开更多
目的从炎症小体活化和活性氧/硫氧还蛋白互作蛋白/NOD样受体蛋白3(ROS/TXNIP/NLRP3)通路考察牛舌草总黄酮(total flavonoids of Anchusa italica Retz.,TF)抗心肌缺血再灌注损伤的作用机制。方法小鼠采用冠状动脉左前降支结扎模型模拟...目的从炎症小体活化和活性氧/硫氧还蛋白互作蛋白/NOD样受体蛋白3(ROS/TXNIP/NLRP3)通路考察牛舌草总黄酮(total flavonoids of Anchusa italica Retz.,TF)抗心肌缺血再灌注损伤的作用机制。方法小鼠采用冠状动脉左前降支结扎模型模拟心肌缺血再灌注(ischemia/reperfusion,I/R)损伤。将模型制备成功的30只小鼠随机分为模型组(I/R)、TF 30 mg·kg^(-1)处理组(I/R+TF30)和100 mg·kg^(-1)处理组(I/R+TF100),再灌同时给予生理盐水、TF。于再灌注24 h时,检测小鼠心功能,测定心肌梗死范围和血清心肌酶谱,心肌冰冻切片染色观察活性氧(ROS)水平,Western blotting分析NLRP3炎症小体活化以及TXNIP与NLRP3相互作用的变化。结果TF在剂量为30和100 mg·kg^(-1)时均可改善心功能,减少心肌梗死范围,降低血清心肌酶水平。另外,TF处理减少心肌炎症因子白细胞介素(IL)-1β、IL-6、肿瘤坏死因子(TNF)α含量,降低心肌ROS水平。TF在30和100 mg·kg^(-1)均显著降低TXNIP、NLRP3、cleaved caspase-1和cleaved IL-1β,并抑制TXNIP/NLRP3相互作用。结论牛舌草总黄酮通过抑制ROS/TXNIP/NLRP3通路,从而减轻NLRP3炎症小体活化,发挥抗心肌缺血再灌注损伤作用。展开更多
基金CAMS Innovation Fund for Medical Sciences(CIFMS)318(2016-I2M-3-007)National Natural Science Foundation of China(81673422and 81202538)
文摘OBJECTIVE The plant of Anchusa italicahas been traditionally used in Uighur medicine for the treatment of cardiovascular and cerebrovascular diseases in China.Our previous study showed that total flavonoids from Anchusa italica(TFAI)exhibited potent cardioprotection on acute ischemia/reperfusion injured rats.This study was undertaken to investigate the effects of TFAI on chronic myocardial infarction in mice and the underlying mechanism.METHODS Total flavonoids were extracted from the whole herb of Anchusa italica and were characterized using HPLC-MS analysis.The left anterior descending branch of coronary artery was ligated to induce myocardial infarction in mice.After surgery,the mice were orally fed with TFAI at the doses of 10,30 and 50 mg·kg-1 body mass per day for a total of four weeks.Cardiac function and infarct size were measured,and the levels of inflammatory mediators were detected.Hematoxylin and eosin(HE)stain and Masson Trichrome stain were performed.The apoptotic factors such as Bax,Bcl-2 and cleaved caspase 3 as well as the key proteins in the PI3K/Akt/mTOR signaling pathway were examined by Western blotting.RESULTS The content of total flavonoids in TFAI was 56.2%.Four weeks following the MI surgery,TFAI enhanced the survival rate in post-MI mice.TFAI administration at the doses of 30 and 50 mg·kg-1 significantly reduced the infarct size and improved cardiac function indicated by elevated EF and FS.Assay of inflammation factors showed that the sera levels of TNF-α,IL-1β and IL-6 were significantly decreased by TFAI treatment as compared to the MI group.HE stain and Masson Trichrome stain demonstrated that TFAI suppressed myocyte hypertrophy and cardiac fibrosis indicated by decreased cross-section area and collagen volume.Western blot analysis showed that cleaved caspase 3 and Bax/Bcl-2 were signifi⁃cantly downregulated following TFAI treatment.Additionally,TFAI treatment significantly suppressed the activation of the PI3K/Akt/mTOR signaling pathway.CONCLUSION TFAI exerts a protective effect against chronic myocardial infarction and its beneficial effects on cardiac function and cardiac remodeling might be at least attributable to anti-inflammation and suppression of the PI3K/Akt/mTOR signaling pathway.
