Zhang Huiyuan, Li Quanbin, Li Yaxing, Guan Jianhua, Li Kaidi, Chen Yunlong
School of Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, Tianjin, China.
Hubei College of Chinese Medicine, Jing Zhou, Hubei Province, China.
Front Pharmacol. 2024 Nov 20;15:1487402. doi: 10.3389/fphar.2024.1487402. eCollection 2024.
Atopic dermatitis (AD) is among the most frequently encountered skin diseases, bothering a considerable number of patients. Today, corticosteroids and antihistamines are among the numerous drugs applied for the therapy of AD. However, lengthy use of them contributes to side effects, such as physiological changes in skin. As an alternative and supplementary therapy, traditional Chinese medicine has become a trend for AD treatment. Huang-Lian-Jie-Du decoction (HLJDD), a renowned herbal formula has been employed to treat inflammatory diseases such as AD. However, its role in regulating immunity in AD remains unclear. The object of this study was to elucidate the efficacy of HLJDD and reveal the implicit mechanism from an immunological perspective in AD-like mice. In brief, 1-chloro-2,4-dinitrobenzene (DNCB) for the sensitization phase (1% DNCB) and stimulation phase (1.5% DNCB) were applied for BALB/c mice. HLJDD and dexamethasone (DXMS) were administered orally to the mice. Mice skin and spleens were collected to evaluate the efficacy of HLJDD. 16S rRNA sequencing was applied to evaluate the commensal microbiota changes in skin and fecal. , spleen CD4 T cells and bone marrow-derived mast cells (BMMCs) were co-cultured to explore the modulation of HLJDD in T helper (Th) cells phenotyping. HLJDD showcased a substantial amelioration in skin through the upregulation of FLG, LOR, AQP3, and reducing scratching behaviors in AD-like mice, Also, the quantity of infiltrated mast cells (MCs), pruritus-related mRNA were decreased. In addition, the expression of OX40/OX40L was decreased by HLJDD, which was critical in Th-cell phenotyping. With the treatment of HLJDD, Th1/Th2 and Th17/Treg ratios in AD-like mice became balanced. The structure of commensal microbiota in AD-like mice was affected by HLJDD. HLJDD could also improve the imbalance of Th17/Treg . HLJDD could improve the symptoms of AD-like mice by alleviating the scratching behaviors via decreased Th2 and pruritus-related mRNA expression. HLJDD also enhanced the relative diversity of skin microbiota and changed the structure of intestinal microbiota. An in-depth study found that HLJDD could balance the ratio of Th1/Th2, Th17/Treg in AD-like mice, and Th17/Treg by regulating the OX40/OX40L signaling pathway.
特应性皮炎（AD）是最常见的皮肤病之一，困扰着相当多的患者。如今，皮质类固醇和抗组胺药是众多用于治疗AD的药物。然而，长期使用这些药物会产生副作用，如皮肤的生理变化。作为一种替代和补充疗法，中药已成为治疗AD的一种趋势。黄连解毒汤（HLJDD），一种著名的中药配方，已被用于治疗如AD等炎症性疾病。然而，其在AD中调节免疫的作用仍不清楚。本研究的目的是阐明HLJDD的疗效，并从免疫学角度揭示AD样小鼠中的潜在机制。简而言之，将1-氯-2,4-二硝基苯（DNCB）用于致敏阶段（1% DNCB）和刺激阶段（1.5% DNCB），应用于BALB/c小鼠。将HLJDD和地塞米松（DXMS）口服给予小鼠。收集小鼠皮肤和脾脏以评估HLJDD的疗效。应用16S rRNA测序评估皮肤和粪便中共生微生物群的变化。将脾脏CD4 T细胞和骨髓来源的肥大细胞（BMMCs）共培养，以探索HLJDD对辅助性T（Th）细胞表型的调节作用。HLJDD通过上调FLG、LOR、AQP3改善了AD样小鼠的皮肤状况，并减少了抓挠行为。此外，浸润肥大细胞（MCs）的数量、瘙痒相关mRNA均减少。此外，HLJDD降低了OX40/OX40L的表达，这在Th细胞表型中起关键作用。通过HLJDD治疗，AD样小鼠中的Th1/Th2和Th17/Treg比例变得平衡。HLJDD影响了AD样小鼠中共生微生物群的结构。HLJDD还可以改善Th17/Treg的失衡。HLJDD可以通过降低Th2和瘙痒相关mRNA表达来减轻抓挠行为，从而改善AD样小鼠的症状。HLJDD还增强了皮肤微生物群的相对多样性，并改变了肠道微生物群的结构。深入研究发现，HLJDD可以通过调节OX40/OX40L信号通路来平衡AD样小鼠中Th1/Th2、Th17/Treg的比例以及Th17/Treg 。
