PMID- 33716079 OWN - NLM STAT- MEDLINE DCOM- 20211005 LR - 20221207 IS - 1872-7573 (Electronic) IS - 0378-8741 (Linking) VI - 274 DP - 2021 Jun 28 TI - Efficacy and action mechanisms of a Chinese herbal formula on experimental models of atopic dermatitis. PG - 114021 LID - S0378-8741(21)00248-8 [pii] LID - 10.1016/j.jep.2021.114021 [doi] AB - ETHNOPHARMACOLOGICAL RELEVANCE: Atopic dermatitis (AD) is a skin inflammatory disease characterized by erythema, eruption, lichenification and pruritus. Shi Zhen Formula (SZF), an empirical Chinese herbal preparation, has clinical efficacy in relieving the symptoms of AD patients. However, the underlying molecular mechanisms of SZF remained unclear. AIM OF THE STUDY: We aimed to investigate the anti-AD effects of SZF and elucidate its underlying molecular mechanisms using in vitro and in vivo models of AD. MATERIALS AND METHODS: High-performance liquid chromatography analysis was performed for quality control of SZF extract. The anti-inflammatory effect of SZF was investigated through evaluating the levels of nitric oxide (NO), chemokines and pro-inflammatory cytokines in the lipopolysaccharide (LPS) stimulated RAW264.7 cells. AD-like skin lesions in female BALB/c mice were induced by 2,4-dinitrochlorobenzene (DNCB). SZF (3.15, 6.30 and 9.45 g/kg) and dexamethasone (5 mg/kg) were administered by gavage daily for 15 consecutive days. The body weight, skin thickness, skin dermatitis severity and scratching behaviors were recorded throughout the study. Histological analysis, reverse transcription-quantitative polymerase chain reaction (RT-PCR), western blot (WB) and ELISA analysis were used to illuminate the molecular targets associated with the anti-AD effects of SZF. RESULTS: SZF markedly decreased the epidermal thickening and infiltration of mast cells in the ears and dorsal skin of the 2,4-dinitrochlorobenzene (DNCB)-treated mice. SZF not only suppressed the levels of immunoglobulin E (IgE), histamine, thymic stromal lymphopoietin (TSLP) and IL-4 in the serum but also suppressed the over-production of IL-4 and IL-6 and gene expressions of IL-4, IL-13, IL-31 and TSLP in the dorsal skin. Moreover, SZF improved epidermal barrier by increasing the protein expressions of filaggrin, involucrin and loricrin and inhibited the activation of NF-kappaB p65 pathway in the dorsal skin of the DNCB-treated mice. CONCLUSION: SZF alleviates DNCB induced AD-like skin lesions in mice through regulating Th1/Th2 balance, improving epidermal barrier and inhibiting skin inflammation. Our research findings provide scientific footing on the use of this Chinese herbal formula for the treatment of AD. CI - Copyright (c) 2021 Elsevier B.V. All rights reserved. FAU - Wang, Lan AU - Wang L AD - School of Chinese Medicine, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, NT, Hong Kong SAR, China. Electronic address: lanawang@cuhk.edu.hk. FAU - Xian, Yan-Fang AU - Xian YF AD - School of Chinese Medicine, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, NT, Hong Kong SAR, China. Electronic address: lisaxian@cuhk.edu.hk. FAU - Hu, Zhen AU - Hu Z AD - School of Chinese Medicine, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, NT, Hong Kong SAR, China. Electronic address: zhenhu@cuhk.edu.hk. FAU - Loo, Steven King Fan AU - Loo SKF AD - School of Chinese Medicine, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, NT, Hong Kong SAR, China. Electronic address: stevenderm@gmail.com. FAU - Ip, Siu Po AU - Ip SP AD - School of Chinese Medicine, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, NT, Hong Kong SAR, China. Electronic address: paulip@cuhk.edu.hk. FAU - Chan, Wood Yee AU - Chan WY AD - School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, NT, Hong Kong SAR, China. Electronic address: chan@cuhk.edu.hk. FAU - Lin, Zhi-Xiu AU - Lin ZX AD - School of Chinese Medicine, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, NT, Hong Kong SAR, China; Hong Kong Institute of Integrative Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China. Electronic address: linzx@cuhk.edu.hk. FAU - Wu, Justin Che Yuen AU - Wu JCY AD - Hong Kong Institute of Integrative Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China; Department of Medicine & Therapeutics, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, NT, Hong Kong SAR, China. Electronic address: justinwu@cuhk.edu.hk. LA - eng PT - Journal Article DEP - 20210311 PL - Ireland TA - J Ethnopharmacol JT - Journal of ethnopharmacology JID - 7903310 RN - 0 (Anti-Inflammatory Agents) RN - 0 (Cytokines) RN - 0 (Dinitrochlorobenzene) RN - 0 (Drugs, Chinese Herbal) RN - 0 (Il4 protein, mouse) RN - 0 (Lipopolysaccharides) RN - 0 (NF-kappa B) RN - 207137-56-2 (Interleukin-4) RN - 37341-29-0 (Immunoglobulin E) RN - 820484N8I3 (Histamine) RN - GT0IL38SP4 (Thymic Stromal Lymphopoietin) RN - 0 (TSLP protein, mouse) SB - IM MH - Animals MH - Anti-Inflammatory Agents/chemistry/*pharmacology/*therapeutic use MH - Cell Survival/drug effects MH - Cytokines/blood/metabolism MH - Dermatitis, Atopic/chemically induced/*drug therapy/metabolism/pathology MH - Dinitrochlorobenzene/toxicity MH - Drugs, Chinese Herbal/chemistry/*pharmacology/*therapeutic use MH - Female MH - Histamine/blood MH - Immunoglobulin E/blood MH - Interleukin-4/blood MH - Lipopolysaccharides/toxicity MH - Mast Cells/drug effects MH - Mice MH - Mice, Inbred BALB C MH - Models, Theoretical MH - NF-kappa B/metabolism MH - RAW 264.7 Cells MH - Skin/drug effects/pathology MH - Th1 Cells/metabolism MH - Th2 Cells/metabolism MH - Thymic Stromal Lymphopoietin OTO - NOTNLM OT - Atopic dermatitis OT - Chinese herbal formula OT - Epidermal barrier OT - NF-kappaB pathway OT - Skin inflammation OT - Th1/Th2 balance EDAT- 2021/03/16 06:00 MHDA- 2021/10/06 06:00 CRDT- 2021/03/15 06:08 PHST- 2020/07/19 00:00 [received] PHST- 2021/01/20 00:00 [revised] PHST- 2021/03/08 00:00 [accepted] PHST- 2021/03/16 06:00 [pubmed] PHST- 2021/10/06 06:00 [medline] PHST- 2021/03/15 06:08 [entrez] AID - S0378-8741(21)00248-8 [pii] AID - 10.1016/j.jep.2021.114021 [doi] PST - ppublish SO - J Ethnopharmacol. 2021 Jun 28;274:114021. doi: 10.1016/j.jep.2021.114021. Epub 2021 Mar 11.