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茶树提取物的抗炎和抗氧化特性:通过抑制NF-κB通路作为特应性皮炎的潜在治疗方法

Anti-inflammatory and antioxidant properties of Camellia sinensis L. extract as a potential therapeutic for atopic dermatitis through NF-κB pathway inhibition.

作者信息

Kim Min Jung, Yang Ye Jin, Min Ga-Yul, Heo Ji Woong, Son Jae Dong, You Young Zoo, Kim Hun Hwan, Kim Gon Sup, Lee Hu-Jang, Yang Ju-Hye, Park Kwang Il

机构信息

Department of Veterinary Physiology, College of Veterinary Medicine, Gyeongsang National University, Gazwa, Jinju, 52828, Republic of Korea.

Korean Medicine (KM) Application Center, Korea Institute of Oriental Medicine, 70 Cheomdan-ro, Dong-gu, Daegu, 41062, Republic of Korea.

出版信息

Sci Rep. 2025 Jan 18;15(1):2371. doi: 10.1038/s41598-025-86678-5.

DOI:10.1038/s41598-025-86678-5
PMID:39827243
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11742993/
Abstract

Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by immune dysregulation and excessive cytokine production. This study aimed to explore the potential of Camellia sinensis L. water extract (CSE) as a treatment for AD by the impact of CSE on inflammatory responses in keratinocytes, particularly concerning the production of inflammatory cytokines and the modulation of signaling pathways relevant to AD pathogenesis. CSE was obtained via hot water extraction from Camellia sinensis L. Ultra-high-performance liquid chromatography (UPLC) analyzed catechin and caffeine content. Cell viability was assessed with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), polyphenol and flavonoid content were determined. 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay measured antioxidant activity. Enzyme-Linked Immunosorbent Assay (ELISA), western blotting, and Immunofluorescence (IF) assays examined cytokines, pathways, and protein localization, respectively. Molecular docking assessed compound binding with inflammation-related proteins. UPLC identified six CSE components including epigallocatechin (EGC) epicatechin (EC), caffeine (CF), catechin (C), epigallocatechin gallate (EGCG), and epicatechin gallate (ECG). CSE demonstrated a significant reduction in the production of inflammatory cytokines interleukin (IL)-2 and IL-6 in TNF-α/IFN-γ activated keratinocytes. Treatment with CSE inhibited the mitogen-activated protein kinase (MAPK) pathway, which resulted in decreased phosphorylation of p38, Jun N-terminal kinase (JNK), and extracellular signal-regulated kinase (ERK). Exposure of TNF-α/IFN-γ- stimulated human keratinocytes (HaCaT) cells to CSE resulted in a 200 µg/mL dependent inhibition of p65 and signal transducer and activator of transcription 1 (STAT-1) translocation from the cytosol to the nucleus, as confirmed through immunofluorescence (IF) staining. Molecular docking simulations provided insights into the underlying mechanisms of CSE action, which supported its potential as a therapeutic agent for AD. CSE might be a potential candidate for its therapeutic efficacy for inflammatory skin conditions like AD. Thus, based on this evidence, the authors suggest that CSE should be studied further for its anti-inflammatory activities and topical application in the treatment of AD.

摘要

特应性皮炎(AD)是一种慢性炎症性皮肤病,其特征为免疫失调和细胞因子过度产生。本研究旨在通过观察茶树(Camellia sinensis L.)水提取物(CSE)对角质形成细胞炎症反应的影响,特别是对炎症细胞因子产生以及与AD发病机制相关信号通路的调节作用,来探索CSE作为AD治疗方法的潜力。CSE通过对茶树进行热水提取获得。采用超高效液相色谱(UPLC)分析儿茶素和咖啡因含量。用3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐(MTT)评估细胞活力,测定多酚和黄酮含量。用2,2-二苯基-1-苦基肼(DPPH)法测定抗氧化活性。分别用酶联免疫吸附测定(ELISA)、蛋白质免疫印迹法和免疫荧光(IF)测定法检测细胞因子、信号通路和蛋白质定位。分子对接评估化合物与炎症相关蛋白的结合情况。UPLC鉴定出CSE的六种成分,包括表没食子儿茶素(EGC)、表儿茶素(EC)、咖啡因(CF)、儿茶素(C)、表没食子儿茶素没食子酸酯(EGCG)和表儿茶素没食子酸酯(ECG)。CSE在肿瘤坏死因子-α/干扰素-γ激活的角质形成细胞中,显著降低了炎症细胞因子白细胞介素(IL)-2和IL-6的产生。CSE处理可抑制丝裂原活化蛋白激酶(MAPK)信号通路,导致p38、c-Jun氨基末端激酶(JNK)和细胞外信号调节激酶(ERK)的磷酸化水平降低。免疫荧光(IF)染色证实,将肿瘤坏死因子-α/干扰素-γ刺激的人角质形成细胞(HaCaT)细胞暴露于CSE中,可导致p65和信号转导及转录激活因子1(STAT-1)从细胞质向细胞核的转位受到200 μg/mL浓度依赖性抑制。分子对接模拟为CSE作用的潜在机制提供了见解,支持其作为AD治疗药物的潜力。CSE可能是治疗AD等炎症性皮肤病的潜在候选药物。因此,基于这些证据,作者建议应进一步研究CSE的抗炎活性及其在AD治疗中的局部应用。

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