PMID- 33388430 OWN - NLM STAT- MEDLINE DCOM- 20210803 LR - 20240226 IS - 1872-7573 (Electronic) IS - 0378-8741 (Linking) VI - 270 DP - 2021 Apr 24 TI - Qingxue jiedu formulation ameliorated DNFB-induced atopic dermatitis by inhibiting STAT3/MAPK/NF-kappaB signaling pathways. PG - 113773 LID - S0378-8741(20)33661-8 [pii] LID - 10.1016/j.jep.2020.113773 [doi] AB - ETHNOPHARMACOLOGICAL RELEVANCE: Qingxue jiedu Formulation (QF) is composed of two classic prescriptions which have been clinically used for more than 5 centuries and appropriately modified through basic theory of traditional Chinese medicine for treating various skin inflammation such as atopic dermatitis (AD), acute dermatitis and rash. Although QF possesses a prominent clinical therapeutic effect, seldom pharmacological studies on its anti-AD activity are conducted. AIM OF THE STUDY: We used AD mice model to investigate the anti-AD activities of QF, as well as its underlying molecular mechanisms which involved signal transducer and activator of transcription 3 (STAT3), nuclear factor-kappa B (NF-kappaB) and mitogen-activated protein kinase (MAPK) signaling pathways. MATERIALS AND METHODS: 2,4-dinitrofluorobenzene (DNFB)-induced AD mice were used to collect serum and skin tissues for consequential determination. The levels of various inflammatory factors [interleukin (IL)-12, Interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha, IL-4, IL-6 and immunoglobulin E (IgE)] were determined by enzyme-linked immunosorbent assay (ELISA). Real-time polymerase chain reaction (RT-PCR) was contributed to detect the effects of relevant inflammatory factors on mRNA. The roles of STAT3, NF-kappaB and MAPK signaling pathways in AD response were analyzed by Western blotting (WB), and the thickening of mice dorsal skin and inflammatory cell infiltration were observed by hematoxylin and eosin (H&E) staining. RESULTS: QF significantly reduced the skin thickening, inflammatory cell infiltration and other symptoms in AD mice. The levels of IL-12, TNF-alpha, IL-4, IL-6 and IgE were decreased, while IFN-gamma was increased by QF in the ELISA analysis. QF lessened the levels of lL-6 and elevated IFN-gamma on the mRNA level. In addition, WB analysis showed QF thoroughly inhibited the activation of NF-kappaB, STAT3 and phosphorylation of JAK1, JAK2, JAK3, while partially suppressed MAPK signaling pathways. CONCLUSIONS: QF inhibited the activations of STAT3, MAPK and NF-kappaB signaling pathways and possessed a significant therapeutic effect on AD. Therefore, QF deserves our continuous attention and research as a prominent medicine for AD. CI - Copyright (c) 2020 Elsevier B.V. All rights reserved. FAU - Xiong, Xin AU - Xiong X AD - Department of Pharmacy, Wuhan No.1 Hospital, Wuhan Hospital of Traditional and Western Medicine, Wuhan, China. Electronic address: pandaxin2020@126.com. FAU - Huang, Chuanqi AU - Huang C AD - Department of Pharmacy, Wuhan No.1 Hospital, Wuhan Hospital of Traditional and Western Medicine, Wuhan, China. Electronic address: chuanqi_huang@yahoo.com. FAU - Wang, Fuqian AU - Wang F AD - Department of Pharmacy, Wuhan No.1 Hospital, Wuhan Hospital of Traditional and Western Medicine, Wuhan, China. Electronic address: wangfuqian.c@163.com. FAU - Dong, Junli AU - Dong J AD - Department of Pharmacy, Wuhan No.1 Hospital, Wuhan Hospital of Traditional and Western Medicine, Wuhan, China. Electronic address: dongjunli0118@163.com. FAU - Zhang, Dan AU - Zhang D AD - Department of Pharmacy, Wuhan No.1 Hospital, Wuhan Hospital of Traditional and Western Medicine, Wuhan, China. Electronic address: 494990590@qq.com. FAU - Jiang, Jie AU - Jiang J AD - Department of Pharmacy, Wuhan No.1 Hospital, Wuhan Hospital of Traditional and Western Medicine, Wuhan, China. Electronic address: 18827613967@163.com. FAU - Feng, Yan AU - Feng Y AD - Department of Pathology, Wuhan No.1 Hospital, Wuhan Hospital of Traditional and Western Medicine, Wuhan, China. Electronic address: feng_yan027@163.com. FAU - Wu, Bin AU - Wu B AD - Department of Transfusion Medicine, Wuhan No.1 Hospital, Wuhan Hospital of Traditional and Western Medicine, Wuhan, China. Electronic address: drwubin_mdphd@outlook.com. FAU - Xie, Tingting AU - Xie T AD - School of Foreign Languages, Hubei University of Chinese Medicine, Wuhan, China. Electronic address: maylotus@126.com. FAU - Cheng, Lu AU - Cheng L AD - Department of Pharmacy, Wuhan No.1 Hospital, Wuhan Hospital of Traditional and Western Medicine, Wuhan, China. Electronic address: chenglu19810620@163.com. LA - eng PT - Journal Article DEP - 20201231 PL - Ireland TA - J Ethnopharmacol JT - Journal of ethnopharmacology JID - 7903310 RN - 0 (Cytokines) RN - 0 (Drugs, Chinese Herbal) RN - 0 (NF-kappa B) RN - 0 (STAT3 Transcription Factor) RN - 0 (Stat3 protein, mouse) RN - 37341-29-0 (Immunoglobulin E) RN - D241E059U6 (Dinitrofluorobenzene) RN - EC 2.7.11.24 (Mitogen-Activated Protein Kinases) SB - IM MH - Animals MH - Cytokines/blood/genetics MH - Dermatitis, Atopic/blood/chemically induced/*drug therapy/pathology MH - Dinitrofluorobenzene/toxicity MH - Disease Models, Animal MH - Drugs, Chinese Herbal/chemistry/*pharmacology/*therapeutic use MH - Immunoglobulin E/blood MH - MAP Kinase Signaling System/*drug effects MH - Male MH - Mice, Inbred C57BL MH - Mitogen-Activated Protein Kinases/*antagonists & inhibitors/metabolism MH - NF-kappa B/*antagonists & inhibitors/metabolism MH - STAT3 Transcription Factor/*antagonists & inhibitors/metabolism MH - Mice OTO - NOTNLM OT - Atopic dermatitis OT - Baicalin (PubChem CID: 64982) OT - Caffeic acid (PubChem CID: 689043) OT - Catechin (PubChem CID: 9064) OT - Gallic acid (PubChem CID: 370) OT - IgE OT - Inflammation OT - Liquiritin (PubChem CID: 503737) OT - Paeoniflorin (PubChem CID: 442534) OT - Protocatechuic aldehyde (PubChem CID: 8768) OT - Qingxue jiedu formulation OT - Traditional Chinese medicine EDAT- 2021/01/04 06:00 MHDA- 2021/08/04 06:00 CRDT- 2021/01/03 20:27 PHST- 2020/10/12 00:00 [received] PHST- 2020/12/17 00:00 [revised] PHST- 2020/12/24 00:00 [accepted] PHST- 2021/01/04 06:00 [pubmed] PHST- 2021/08/04 06:00 [medline] PHST- 2021/01/03 20:27 [entrez] AID - S0378-8741(20)33661-8 [pii] AID - 10.1016/j.jep.2020.113773 [doi] PST - ppublish SO - J Ethnopharmacol. 2021 Apr 24;270:113773. doi: 10.1016/j.jep.2020.113773. Epub 2020 Dec 31.