School of Chinese Medicine, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, NT, Hong Kong SAR, China.
School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, NT, Hong Kong SAR, China.
J Ethnopharmacol. 2021 Jun 28;274:114021. doi: 10.1016/j.jep.2021.114021. Epub 2021 Mar 11.
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.
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.
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.
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-κB p65 pathway in the dorsal skin of the DNCB-treated mice.
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.
特应性皮炎(AD)是一种以红斑、疹、苔藓化和瘙痒为特征的皮肤炎症性疾病。湿毒清方(SZF)是一种经验性的中药制剂,在缓解 AD 患者的症状方面具有临床疗效。然而,SZF 的潜在分子机制尚不清楚。
我们旨在通过 AD 的体外和体内模型研究 SZF 的抗 AD 作用,并阐明其潜在的分子机制。
采用高效液相色谱法对 SZF 提取物进行质量控制。通过评估脂多糖(LPS)刺激的 RAW264.7 细胞中一氧化氮(NO)、趋化因子和促炎细胞因子的水平来研究 SZF 的抗炎作用。用 2,4-二硝基氯苯(DNCB)诱导雌性 BALB/c 小鼠产生类似 AD 的皮肤损伤。SZF(3.15、6.30 和 9.45 g/kg)和地塞米松(5 mg/kg)灌胃给药,连续 15 天。在整个研究过程中记录体重、皮肤厚度、皮肤炎症严重程度和搔抓行为。进行组织学分析、逆转录定量聚合酶链反应(RT-PCR)、Western blot(WB)和 ELISA 分析,以阐明与 SZF 抗 AD 作用相关的分子靶点。
SZF 显著降低了 2,4-二硝基氯苯(DNCB)处理小鼠耳部和背部皮肤的表皮增厚和肥大细胞浸润。SZF 不仅抑制了血清中免疫球蛋白 E(IgE)、组胺、胸腺基质淋巴生成素(TSLP)和白细胞介素 4(IL-4)的水平,还抑制了白细胞介素 4 和白细胞介素 6 的过度产生以及白细胞介素 4、白细胞介素 13、白细胞介素 31 和 TSLP 在背部皮肤中的基因表达。此外,SZF 通过增加丝聚蛋白、兜甲蛋白和板层素的蛋白表达,改善了表皮屏障,并抑制了 DNCB 处理小鼠背部皮肤中 NF-κB p65 途径的激活。
SZF 通过调节 Th1/Th2 平衡、改善表皮屏障和抑制皮肤炎症,减轻 DNCB 诱导的小鼠类似 AD 的皮肤损伤。我们的研究结果为该中药配方治疗 AD 提供了科学依据。