title: Protective effects of astragaloside IV against ovalbumin-induced lung inflammation are regulated/mediated by T-bet/GATA-3.
abstract: Bronchial asthma is characterized by chronic lung inflammation, airway hyperresponsiveness, and airway remodelling. Astragaloside IV (3-O-β-D-xylopyranosyl-6-O-β-D-glucopyranosyl-cycloastragenol, AST), the primary pure saponin isolated from the root of Astragalus membranaceus, is an effective compound with distinct pharmacological effects including anti-inflammation, immunoregulation, and antifibrosis. However, the effect of AST on asthma remains unclear. In the present study, in the murine model of asthma, the airway hyperresponsiveness was relieved after treatment with AST, accompanied by a reduction of inflammatory cells. In addition, the levels of IL-4 and IL-5 decreased, while the IFN-γ level increased, in bronchoalveolar lavage fluid. The compound also significantly inhibited the synthesis of GATA-3-encoding mRNA and protein in addition to increasing the synthesis of T-bet-encoding mRNA and protein in both lung tissues and CD4+ T cells. Our findings indicate that AST treatment inhibits ovalbumin-induced airway inflammation by modulating the key master switches GATA-3 and T-bet, which results in committing T helper cells to a Th1 phenotype.
authors.affiliation: Department of Respiratory Medicine, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing, China.
authors.forename: Yu-Ying
authors.initials: YY
authors.lastname: Qiu
authors.forename: Jin-Xiao
authors.initials: JX
authors.lastname: Zhu
authors.forename: Tao
authors.initials: T
authors.lastname: Bian
authors.forename: Fei
authors.initials: F
authors.lastname: Gao
authors.forename: Xiu-Feng
authors.initials: XF
authors.lastname: Qian
authors.forename: Qiang
authors.initials: Q
authors.lastname: Du
authors.forename: Min-Yu
authors.initials: MY
authors.lastname: Yuan
authors.forename: Hua
authors.initials: H
authors.lastname: Sun
authors.forename: Ling-Zhi
authors.initials: LZ
authors.lastname: Shi
authors.forename: Ming-Hong
authors.initials: MH
authors.lastname: Yu
mesh_terms: D000818:Animals; D001249:Asthma / Q000276:immunology / Q000503:physiopathology / Q000517:prevention & control*; D027885:Astragalus propinquus / Q000737:chemistry*; D016535:Bronchial Hyperreactivity / Q000276:immunology / Q000517:prevention & control*; D001992:Bronchoalveolar Lavage Fluid; D004195:Disease Models, Animal; D005260:Female; D050990:GATA3 Transcription Factor / Q000235:genetics; D007371:Interferon-gamma / Q000276:immunology; D015847:Interleukin-4 / Q000276:immunology; D015848:Interleukin-5 / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000276:immunology; D011014:Pneumonia / Q000276:immunology / Q000517:prevention & control; D012333:RNA, Messenger / Q000378:metabolism; D012503:Saponins / Q000302:isolation & purification / Q000494:pharmacology*; D014315:Triterpenes / Q000302:isolation & purification / Q000494:pharmacology*
chemical_list: D050990:GATA3 Transcription Factor; D015848:Interleukin-5; D012333:RNA, Messenger; D012503:Saponins; D014315:Triterpenes; D015847:Interleukin-4; C052064:astragaloside A; D007371:Interferon-gamma; D010047:Ovalbumin