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黄芫花95%乙醇提取物对二硝基氯苯诱导的小鼠特应性皮炎模型的改善作用。

Ameliorative effects of Wikstroemia trichotoma 95% EtOH extract on a mouse model of DNCB-induced atopic dermatitis.

作者信息

Keem Min-Ji, Jo Beom-Geun, Lee Sang Heon, Kim Tae-Young, Jung Young Suk, Jeong Eun-Ju, Kim Ki Hyun, Kim Su-Nam, Yang Min Hye

机构信息

Department of Pharmacy, College of Pharmacy and Research Institute for Drug Development, Pusan National University, Busan, 46241, Republic of Korea.

Natural Products Research Institute, Korea Institute of Science and Technology, Gangneung, 25451, Republic of Korea.

出版信息

J Ethnopharmacol. 2024 Oct 28;333:118398. doi: 10.1016/j.jep.2024.118398. Epub 2024 May 31.

Abstract

ETHNOPHARMACOLOGICAL RELEVANCE

The genus Wikstroemia has been extensively utilized in traditional Chinese medicine (TCM) for the management of conditions such as coughs, edema, arthritis, and bronchitis. Studies have indicated that the crude extracts of Wikstroemia exhibit anti-inflammatory, anti-allergy, anti-aging, skin psoriasis, anti-cancer, and antiviral properties. In addition, these extracts are known to contain bioactive substances, including flavonoids, coumarins, and lignans. However, few studies have investigated the anti-inflammatory or anti-allergic activities of Wikstroemia trichotoma (Thunb.) Makino against atopic dermatitis (AD).

AIM OF THE STUDY

The study aimed to explore the potential of a 95% ethanol extract of W. trichotoma (WTE) on the dysfunction of skin barrier and immune system, which are primary symptoms of AD, in 2,4-dinitrochlorobenzene (DNCB)-induced SKH-1 hairless mice and phorbol 12-myristate 13-acetate (PMA)/ionomycin or immunoglobulin E (IgE) + 2,4-dinitrophenylated bovine serum albumin (DNP-BSA) stimulated rat basophilic leukemia cell line (RBL-2H3). Furthermore, we sought to identify the chemical contents of WTE using high-performance liquid chromatography equipped with a photodiode array detector (HPLC-PDA).

MATERIALS AND METHODS

An in vitro study was conducted using RBL-2H3 cells stimulated with PMA/ionomycin or IgE + DNP-BSA to assess the inhibitory effects of WTE on mast cell degranulation and interleukin-4 (IL-4) mRNA expression levels. For the in vivo study, AD was induced in SKH-1 hairless mice by applying 1% DNCB to the dorsal skin daily for 7 days. Subsequently, 0.1% DNCB solution was applied on alternate days, and mice were orally administered WTE (at 30 or 100 mg/kg/day) dissolved in 0.5% carboxymethyl cellulose (CMC) daily for 2 weeks. Transepidermal water loss (TEWL), skin hydration, skin pH, and total serum IgE levels were measured.

RESULTS

In DNCB-stimulated SKH-1 hairless mice, WTE administration significantly improved AD symptoms and ameliorated dorsal skin inflammation. Oral administration of WTE led to a significant decrease in skin thickness, infiltration of mast cells, and level of total serum IgE, thus restoring skin barrier function in the DNCB-induced skin lesions. In addition, WTE inhibited β-hexosaminidase release and reduced IL-4 mRNA levels in RBL-2H3 cells. Chemical profile analysis of WTE confirmed the presence of three phenolic compounds, viz. chlorogenic acid, miconioside B, and matteucinol-7-O-β-apiofuranosyl (1 → 6)-β-glucopyranoside.

CONCLUSIONS

WTE ameliorates AD symptoms by modulating in the skin barrier and immune system dysfunction. This suggests that W. trichotoma extract may offer therapeutic benefits for managing AD.

摘要

民族药理学相关性

狼毒属植物在中国传统医学中已被广泛用于治疗咳嗽、水肿、关节炎和支气管炎等病症。研究表明,狼毒属植物的粗提取物具有抗炎、抗过敏、抗衰老、治疗皮肤银屑病、抗癌和抗病毒特性。此外,已知这些提取物含有生物活性物质,包括黄酮类化合物、香豆素和木脂素。然而,很少有研究调查了狼毒(Wikstroemia trichotoma (Thunb.) Makino)对特应性皮炎(AD)的抗炎或抗过敏活性。

研究目的

本研究旨在探讨狼毒95%乙醇提取物(WTE)对2,4-二硝基氯苯(DNCB)诱导的SKH-1无毛小鼠以及佛波酯12-肉豆蔻酸酯13-乙酸酯(PMA)/离子霉素或免疫球蛋白E(IgE)+2,4-二硝基苯基化牛血清白蛋白(DNP-BSA)刺激的大鼠嗜碱性白血病细胞系(RBL-2H3)中皮肤屏障和免疫系统功能障碍(AD的主要症状)的作用。此外,我们试图使用配备光电二极管阵列检测器的高效液相色谱法(HPLC-PDA)鉴定WTE的化学成分。

材料与方法

使用PMA/离子霉素或IgE + DNP-BSA刺激的RBL-2H3细胞进行体外研究,以评估WTE对肥大细胞脱颗粒和白细胞介素-4(IL-4)mRNA表达水平的抑制作用。对于体内研究,通过每天在SKH-1无毛小鼠背部皮肤涂抹1% DNCB,持续7天来诱导AD。随后,隔天涂抹0.1% DNCB溶液,并每天给小鼠口服溶解于0.5%羧甲基纤维素(CMC)中的WTE(30或100 mg/kg/天),持续2周。测量经表皮水分流失(TEWL)、皮肤水合作用、皮肤pH值和血清总IgE水平。

结果

在DNCB刺激的SKH-1无毛小鼠中,给予WTE可显著改善AD症状并减轻背部皮肤炎症。口服WTE导致皮肤厚度、肥大细胞浸润和血清总IgE水平显著降低,从而恢复了DNCB诱导的皮肤损伤中的皮肤屏障功能。此外,WTE抑制RBL-2H3细胞中β-己糖胺酶的释放并降低IL-4 mRNA水平。WTE的化学图谱分析证实存在三种酚类化合物,即绿原酸、米团花苷B和异瑞香素-7-O-β-芹菜糖基(1→6)-β-葡萄糖苷。

结论

WTE通过调节皮肤屏障和免疫系统功能障碍来改善AD症状。这表明狼毒提取物可能对治疗AD具有治疗益处。

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