title: Extract of Polygala tenuifolia Alleviates Stress-Exacerbated Atopy-Like Skin Dermatitis through the Modulation of Protein Kinase A and p38 Mitogen-Activated Protein Kinase Signaling Pathway.
abstract: Atopic dermatitis (AD) and stress create a vicious cycle: stress exacerbates atopic symptoms, and atopic disease elicits stress and anxiety. Targeting multiple pathways including stress and allergic inflammation is, therefore, important for treating AD. In this study, we investigated the remedial value ofPolygala tenuifoliaWilld. (PTW) for treating immobilization (IMO) stress-exacerbated atopy-like skin dermatitis and its underlying mechanism. Trimellitic anhydride (TMA) was applied to dorsal skin for sensitization and subsequently both ears for eliciting T-cell-dependent contact hypersensitivity in mice, which underwent 2 h-IMO stress and PTW administration for the latter 6 and 9 days in the ear exposure period of TMA, respectively. To elicit in vitro degranulation of human mast cell line-1 (HMC-1), 10 µM substance P (SP) and 200 nM corticotrophin-releasing factor (CRF) were sequentially added with 48 h-interval. PTW extract (500 µg/mL) was added 30 min before CRF treatment. IMO stress exacerbated TMA-induced scratching behavior by 252%, and increased their blood corticosterone levels by two-fold. Treatment with 250 mg/kg PTW significantly restored IMO stress-exacerbated scratching behavior and other indicators such as skin inflammation and water content, lymph node weights, and serum histamine and immunoglobulin E (lgE) levels. Furthermore, it also reversed TMA-stimulated expression of tumor necrosis factor (TNF)-α and interleukin (IL)-4 mRNAs in ear tissues. PTW significantly inhibited SP/CRF-stimulated degranulation of HMC-1 cells, subsequent tryptase secretion, and protein kinase A (PKA) activity. PTW also selectively inhibited p38 mitogen-activated protein kinase (MAPK) phosphorylation in SP/CRF-treated HMC-1 cells. PTW significantly inhibited HMC-1 cell degranulation and alleviated IMO stress-exacerbated atopic dermatitis symptoms by modulating the PKA/p38 MAPK signaling pathway.
authors.affiliation: Acupuncture and Meridian Science Research Center, College of Korean Medicine, Kyung Hee University, Seoul 02447, Korea. surzeus@naver.com.
authors.forename: Bongjun
authors.initials: B
authors.lastname: Sur
authors.affiliation: Acupuncture and Meridian Science Research Center, College of Korean Medicine, Kyung Hee University, Seoul 02447, Korea. bombi@khu.ac.kr.
authors.forename: Bombi
authors.initials: B
authors.lastname: Lee
authors.affiliation: Department of Life and Nanopharmaceutical Sciences, College of Pharmacy, Kyung Hee University, Seoul 02447, Korea. psycheb@naver.com.
authors.forename: Ye Seul
authors.initials: YS
authors.lastname: Yoon
authors.affiliation: Acupuncture and Meridian Science Research Center, College of Korean Medicine, Kyung Hee University, Seoul 02447, Korea. lpr911001@naver.com.|Department of Science in Korean Medicine, Graduate School, Kyung Hee University, Seoul 02447, Korea. lpr911001@naver.com.
authors.forename: Pooreum
authors.initials: P
authors.lastname: Lim
authors.affiliation: Acupuncture and Meridian Science Research Center, College of Korean Medicine, Kyung Hee University, Seoul 02447, Korea. smsmjhjh@naver.com.|Department of Science in Korean Medicine, Graduate School, Kyung Hee University, Seoul 02447, Korea. smsmjhjh@naver.com.
authors.forename: Riwon
authors.initials: R
authors.lastname: Hong
authors.affiliation: Acupuncture and Meridian Science Research Center, College of Korean Medicine, Kyung Hee University, Seoul 02447, Korea. myeom@khu.ac.kr.
authors.forename: Mijung
authors.initials: M
authors.lastname: Yeom
authors.affiliation: Acupuncture and Meridian Science Research Center, College of Korean Medicine, Kyung Hee University, Seoul 02447, Korea. erc633@khu.ac.kr.|Department of Science in Korean Medicine, Graduate School, Kyung Hee University, Seoul 02447, Korea. erc633@khu.ac.kr.
authors.forename: Hyang Sook
authors.initials: HS
authors.lastname: Lee
authors.affiliation: Acupuncture and Meridian Science Research Center, College of Korean Medicine, Kyung Hee University, Seoul 02447, Korea. acufind@khu.ac.kr.|Department of Science in Korean Medicine, Graduate School, Kyung Hee University, Seoul 02447, Korea. acufind@khu.ac.kr.
authors.forename: Hijoon
authors.initials: H
authors.lastname: Park
authors.affiliation: Acupuncture and Meridian Science Research Center, College of Korean Medicine, Kyung Hee University, Seoul 02447, Korea. ishim@khu.ac.kr.|Department of Science in Korean Medicine, Graduate School, Kyung Hee University, Seoul 02447, Korea. ishim@khu.ac.kr.
authors.forename: Insop
authors.initials: I
authors.lastname: Shim
authors.affiliation: Acupuncture and Meridian Science Research Center, College of Korean Medicine, Kyung Hee University, Seoul 02447, Korea. hjlee@khu.ac.kr.|Department of Science in Korean Medicine, Graduate School, Kyung Hee University, Seoul 02447, Korea. hjlee@khu.ac.kr.
authors.forename: Hyejung
authors.initials: H
authors.lastname: Lee
authors.affiliation: Department of Life and Nanopharmaceutical Sciences, College of Pharmacy, Kyung Hee University, Seoul 02447, Korea. ypjang@khu.ac.kr.
authors.forename: Young Pyo
authors.initials: YP
authors.lastname: Jang
authors.affiliation: Acupuncture and Meridian Science Research Center, College of Korean Medicine, Kyung Hee University, Seoul 02447, Korea. dhhahm@khu.ac.kr.|Department of Science in Korean Medicine, Graduate School, Kyung Hee University, Seoul 02447, Korea. dhhahm@khu.ac.kr.
authors.forename: Dae-Hyun
authors.initials: DH
authors.lastname: Hahm
mesh_terms: D000818:Animals; D001522:Behavior, Animal; D002460:Cell Line; D002851:Chromatography, High Pressure Liquid; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D003876:Dermatitis, Atopic / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D004423:Ear / Q000473:pathology; D006801:Humans; D007103:Immobilization; D007073:Immunoglobulin E / Q000097:blood; D015847:Interleukin-4 / Q000235:genetics / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008297:Male; D008407:Mast Cells / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D064209:Phytochemicals / Q000032:analysis; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use*; D031801:Polygala / Q000737:chemistry*; D011493:Protein Kinase C / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012867:Skin / Q000473:pathology; D021241:Spectrometry, Mass, Electrospray Ionization; D013315:Stress, Psychological / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D014867:Water; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D064209:Phytochemicals; D010936:Plant Extracts; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D014867:Water; D015847:Interleukin-4; D007073:Immunoglobulin E; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; D048051:p38 Mitogen-Activated Protein Kinases
keywords: Polygala tenuifolia Willd.; atopic dermatitis; corticotrophin-releasing factor; immobilization stress; trimellitic anhydride