PMID- 35689898 OWN - NLM STAT- MEDLINE DCOM- 20220623 LR - 20220630 IS - 1618-095X (Electronic) IS - 0944-7113 (Linking) VI - 103 DP - 2022 Aug TI - Viola yedoensis Makino formula alleviates DNCB-induced atopic dermatitis by activating JAK2/STAT3 signaling pathway and promoting M2 macrophages polarization. PG - 154228 LID - S0944-7113(22)00307-5 [pii] LID - 10.1016/j.phymed.2022.154228 [doi] AB - BACKGROUND: Atopic dermatitis (AD), a common inflammatory skin disorder, severely affects the life quality of patients and renders heavy financial burden on patient's family. The Chinese medicine Viola yedoensis Makino formula (VYAC) has been widely used for treating various skin disorders. Previous studies have reported that VYAC is effective in relieving DNCB-induced AD and inflammation. However, the anti-inflammatory mechanism of VYAC is still ill-defined and poorly understood. This study aims to investigate the therapeutic effects of VYAC on DNCB-induced AD and to elucidate the underlying anti-inflammatory mechanisms. METHODOLOGY: VYAC were extracted with 70% ethanol and lyophilized for use. AD mice were established by DNCB. The therapeutic effects of VYAC were evaluated by oral administration VYAC (150, 300 and 600 mg/kg) daily in vivo. The histopathological and immunohistochemistry were used to analyze skin lesion and macrophages infiltration, RT-qPCR and Elisa were used to analyze the inflammatory factors in skin tissues and serum. To explore the underlying mechanism of VYAC against AD in vitro. RAW264.7 cells and bone-marrow-derived macrophages (BMDMs) were employed for macrophage polarization analysis. Flow cytometer, immunofluorescence and western blot were used to analyze M2 macrophages markers. STAT3 siRNA were transfected into both cells to validate the effects of VYAC-induced macrophages M2 polarization via JAK2/STAT3 signaling pathway. RESULTS: VYAC ameliorated skin lesion of DNCB-induced AD mice by decreased clinical scores and epidermal thickness, decreased the level of pro-inflammatory factors (IL-1beta, TNF-alpha and IL-18) and enhanced IL-10 anti-inflammatory factor level, inhibited macrophages infiltration and promoted M2 macrophages polarization in vivo. VYAC significantly promoted M2 macrophages polarization in vitro. It is observed that VYAC not only inhibited the phosphorylation of JAK2 and STAT3 in RAW264.7 cells and BMDMs, but also accelerated the translocation to the nucleus. What's more, VYAC reduced the polarization of M2 macrophage by activating JAK2/STAT3 signaling pathway was observed in both cells. CONCLUSIONS: Our findings demonstrate that VYAC significantly ameliorates skin lesion of DNCB-induced AD mice and reduces the levels of inflammatory factors by activating JAK2/STAT3 signaling pathway and promoting M2 macrophages polarization. CI - Copyright (c) 2022 Elsevier GmbH. All rights reserved. FAU - Zeng, Hairong AU - Zeng H AD - Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200062, China; Shanghai Frontiers Science Center of TCM Chemical Biology, Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China. FAU - Zhao, Bei AU - Zhao B AD - Shanghai Frontiers Science Center of TCM Chemical Biology, Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China. FAU - Zhang, Die AU - Zhang D AD - Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200062, China. FAU - Rui, Xin AU - Rui X AD - Baoshan Branch, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China. FAU - Hou, Xudong AU - Hou X AD - Shanghai Frontiers Science Center of TCM Chemical Biology, Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China. FAU - Chen, Xingxing AU - Chen X AD - Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200062, China. FAU - Zhang, Benrui AU - Zhang B AD - Shanghai University of Traditional Chinese Medicine, Shanghai 200062, China. FAU - Yuan, Yi AU - Yuan Y AD - Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200062, China. Electronic address: yuanyi0625@163.com. FAU - Deng, Hongping AU - Deng H AD - Shanghai Frontiers Science Center of TCM Chemical Biology, Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China. Electronic address: hpdeng@shutcm.edu.cn. FAU - Ge, Guangbo AU - Ge G AD - Shanghai Frontiers Science Center of TCM Chemical Biology, Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China. Electronic address: geguangbo@shutcm.edu.cn. LA - eng PT - Journal Article DEP - 20220602 PL - Germany TA - Phytomedicine JT - Phytomedicine : international journal of phytotherapy and phytopharmacology JID - 9438794 RN - 0 (Anti-Inflammatory Agents) RN - 0 (Cytokines) RN - 0 (Dinitrochlorobenzene) RN - 0 (Drugs, Chinese Herbal) RN - 0 (Plant Extracts) RN - 0 (STAT3 Transcription Factor) RN - 0 (Stat3 protein, mouse) RN - EC 2.7.10.2 (Jak2 protein, mouse) RN - EC 2.7.10.2 (Janus Kinase 2) SB - IM MH - Animals MH - Anti-Inflammatory Agents/therapeutic use MH - Cell Polarity MH - Cytokines/metabolism MH - *Dermatitis, Atopic/chemically induced/drug therapy/metabolism MH - Dinitrochlorobenzene MH - *Drugs, Chinese Herbal/pharmacology MH - *Janus Kinase 2/metabolism MH - *Macrophages/drug effects MH - Mice MH - Mice, Inbred BALB C MH - Plant Extracts/pharmacology MH - *STAT3 Transcription Factor/metabolism MH - Signal Transduction MH - *Viola/chemistry OTO - NOTNLM OT - Anti-inflammatory OT - Atopic dermatitis OT - JAK2/STAT3 signaling pathway OT - Macrophages polarization OT - Traditional Chinese medicine OT - Viola yedoensis Makino (VYAC) EDAT- 2022/06/12 06:00 MHDA- 2022/06/24 06:00 CRDT- 2022/06/11 18:18 PHST- 2022/02/18 00:00 [received] PHST- 2022/05/20 00:00 [revised] PHST- 2022/05/31 00:00 [accepted] PHST- 2022/06/12 06:00 [pubmed] PHST- 2022/06/24 06:00 [medline] PHST- 2022/06/11 18:18 [entrez] AID - S0944-7113(22)00307-5 [pii] AID - 10.1016/j.phymed.2022.154228 [doi] PST - ppublish SO - Phytomedicine. 2022 Aug;103:154228. doi: 10.1016/j.phymed.2022.154228. Epub 2022 Jun 2.