关键词: 2,4-dinitrochlorobenzene Anti-inflammation Atopic dermatitis Rat basophilic leukemia cell line Skin barrier function Wikstroemia trichotoma

Mesh : Animals Dermatitis, Atopic / drug therapy chemically induced Dinitrochlorobenzene Wikstroemia / chemistry Plant Extracts / pharmacology chemistry Mice Ethanol / chemistry Immunoglobulin E / blood Disease Models, Animal Mice, Hairless Anti-Inflammatory Agents / pharmacology Mast Cells / drug effects metabolism Female Anti-Allergic Agents / pharmacology Cell Line, Tumor Skin / drug effects pathology metabolism Male Interleukin-4 / metabolism

来  源:   DOI:10.1016/j.jep.2024.118398

Abstract:
BACKGROUND: 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).
OBJECTIVE: 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).
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:
背景:Wikstroemia属已在中医(TCM)中广泛用于治疗咳嗽等疾病,水肿,关节炎,还有支气管炎.研究表明,Wikstromia的粗提物具有抗炎作用,抗过敏,抗衰老,皮肤牛皮癣,抗癌,和抗病毒特性。此外,这些提取物已知含有生物活性物质,包括类黄酮,香豆素,和木脂素。然而,很少有研究调查了Wikstroemia滴瘤的抗炎或抗过敏活性(Thunb。)牧野抗特应性皮炎(AD)。
目的:本研究旨在探讨滴眼虫(WTE)的95%乙醇提取物对皮肤屏障和免疫系统功能障碍的影响。这是AD的主要症状,在2,4-二硝基氯苯(DNCB)诱导的SKH-1无毛小鼠和佛波醇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)。此外,我们试图使用配备有光电二极管阵列检测器(HPLC-PDA)的高效液相色谱法鉴定WTE的化学成分.
方法:使用PMA/离子霉素或IgEDNP-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,在SKH-1无毛小鼠中通过每天向背部皮肤施用1%DNCB诱导AD,持续7天。随后,隔天施用0.1%DNCB溶液,每天口服给予小鼠溶于0.5%羧甲基纤维素(CMC)的WTE(30或100mg/kg/天),持续2周。经皮水分流失(TEWL),皮肤水合作用,皮肤pH值,测定血清总IgE水平。
结果:在DNCB刺激的SKH-1无毛小鼠中,WTE给药显著改善AD症状并改善背侧皮肤炎症。口服WTE导致皮肤厚度显着降低,肥大细胞浸润,血清总IgE水平,从而恢复DNCB诱导的皮肤损伤中的皮肤屏障功能。此外,WTE抑制β-己糖胺酶释放并降低RBL-2H3细胞中IL-4mRNA水平。WTE的化学剖面分析证实了三种酚类化合物的存在,viz.绿原酸,蜜糖苷B,和matteucinol-7-O-β-吡呋喃基(1→6)-β-吡喃葡萄糖苷。
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。这表明滴眼瘤提取物可能为管理AD提供治疗益处。
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