The protective and therapeutic effects of total flavonoids of Astragalus against bleomycin-induced pulmonary fibrosis are through the enhancement of autophagy  

作　　者：Changjun Xu Pengfei Wang Chang Lin Zhu Luo Yawei Huang Zongjiang Zhao Changfu Yang 

机构地区：[1]School of Traditional Chinese Medicine,Beijing University of Chinese Medicine,Beijing 100029,China [2]Guiyang University of Chinese Medicine,Guizhou 550025,China

出　　处：《Journal of Traditional Chinese Medical Sciences》2018年第4期380-389,共10页中医科学杂志（英文）

基　　金：the National Natural Science Foundation of China(81760817 and 81260587);the Science and Technology Foundation of Guizhou Province(Qian Science LH[2016]7119).

摘　　要：Background:Previously,we showed that total flavonoids from astragalus(TFA)had beneficial effects against transforming growth factor(TGF)-β1-mediated fibrosis,but whether these effects involved autophagy is not known.We attempt to explore the effects of TFA on autophagy in an animal model of idiopathic pulmonary fibrosis(IPF)induced by bleomycin,and to look for TFA components that may have an effect on autophagy.Methods:C57BL/6 mice were randomized to the sham group(SG),model group,low-dose TFA group(LDTG),and high-dose of TFA group(HDTG).The A549 cell line was treated with the TFA components including formononetin,calycosin,isorhamnetin,kaempferol,and quercetin.Lung tissues and cells were examined by histology,immunohistochemistry(anti-TGF-β1,α-smooth muscle actin(SMA),and cadherin),immunofluorescence(microtubule-associated protein light chain 3(LC3)),hydroxyproline content,and immunoblotting(smad3,smad7,phosphoinositide 3-kinase(PI3K),α-SMA,E-cadherin,beclin-1,and LC3-Ⅱ).Results:In vivo,TFA inhibited TGF-β1 expression and decreased collagen content in lung tissues induced by bleomycin.TFA increased autophagy following suppression of the smad pathway.In vitro,quercetin inhibited the epithelial-mesenchymal transition(EMT)of A549 cells induced by TGF-β1 through suppression of the smad pathway.Autophagy was also increased by quercetin through inhibition of the AKT/mTOR pathway,but without change in PI3K expression.Formononetin,calycosin,isorhamnetin,and kaempferol had no such effects.Conclusion:TFA can alleviate bleomycin-induced PF in C57BL/6 mice via enhanced autophagy.The smad and AKT/mTOR pathways are possibly involved in these effects.Quercetin was the main active compound in TFA.

关 键 词：Pulmonary FIBROSIS Total FLAVONOIDS of ASTRAGALUS QUERCETIN AUTOPHAGY 

分 类 号：R73[医药卫生—肿瘤]