title: Astragaloside IV ameliorates allergic inflammation by inhibiting key initiating factors in the initial stage of sensitization.
abstract: To illuminate the anti-allergy mechanism of astragaloside IV (AS-IV), we assessed its effects in a murine model of allergic contact dermatitis (ACD). AS-IV administered in the sensitization phase, rather than in the elicitation phase, dramatically alleviated the symptoms of allergic inflammation. We hypothesized that AS-IV exerts its anti-allergy effects by regulating the production of key pro-allergic cytokines based on the fact that interleukin (IL)-33 and thymic stromal lymphopoietin (TSLP) levels increase significantly in the initial stage of the sensitization phase. AS-IV administered in the initial stage of ACD inhibited TSLP and IL-33 expression and reduced the proportion of type-2 innate lymphoid cells (ILC2s). An in vitro study showed that the production of pro-allergic cytokines was significantly inhibited in AS-IV presenting HaCaT cells. We also verified that AS-IV administered only in the initial stage markedly alleviated inflammation, including ear swelling, Th2 cytokine expression, and histological changes. Taken together, these results suggest that AS-IV effectively ameliorates the progression of allergic inflammation by inhibiting key initiating factors, including TSLP and IL-33, and can be used to prevent and/or treat patients with ACD. Our data also suggest that these key pro-allergic cytokines are potential therapeutic targets for allergic diseases.
authors.affiliation: Jiangsu Key Laboratory of Pediatric Respiratory Disease, Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing, 210046, China.
authors.forename: Kai-Fan
authors.initials: KF
authors.lastname: Bao
authors.affiliation: Jiangsu Key Laboratory of Pediatric Respiratory Disease, Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing, 210046, China.
authors.forename: Xi
authors.initials: X
authors.lastname: Yu
authors.affiliation: Jiangsu Key Laboratory of Pediatric Respiratory Disease, Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing, 210046, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Wei
authors.affiliation: Jiangsu Key Laboratory of Pediatric Respiratory Disease, Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing, 210046, China.
authors.forename: Li-Li
authors.initials: LL
authors.lastname: Gui
authors.affiliation: Jiangsu Key Laboratory of Pediatric Respiratory Disease, Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing, 210046, China.
authors.forename: Hai-Liang
authors.initials: HL
authors.lastname: Liu
authors.affiliation: Jiangsu Key Laboratory of Pediatric Respiratory Disease, Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing, 210046, China.
authors.forename: Xiao-Yu
authors.initials: XY
authors.lastname: Wang
authors.affiliation: Suzhou Hospital of Traditional Chinese Medicine, Suzhou, 215009, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Tao
authors.affiliation: Suzhou Hospital of Traditional Chinese Medicine, Suzhou, 215009, China.
authors.forename: Guo-Rong
authors.initials: GR
authors.lastname: Jiang
authors.affiliation: Jiangsu Key Laboratory of Pediatric Respiratory Disease, Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing, 210046, China.
authors.forename: Min
authors.initials: M
authors.lastname: Hong
mesh_terms: D000818:Animals; D016207:Cytokines / Q000276:immunology*; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D007249:Inflammation / Q000276:immunology / Q000473:pathology / Q000517:prevention & control; D000067596:Interleukin-33 / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D012503:Saponins / Q000494:pharmacology*; D018418:Th2 Cells / Q000276:immunology* / Q000473:pathology; D014315:Triterpenes / Q000494:pharmacology*; D000094632:Thymic Stromal Lymphopoietin
chemical_list: D016207:Cytokines; C506535:Il33 protein, mouse; D000067596:Interleukin-33; D012503:Saponins; D014315:Triterpenes; C052064:astragaloside A; D000094632:Thymic Stromal Lymphopoietin