Nie Wenkai, Zhao Xuan, Zhang Yan, Zeng Cheng, Yang Huiwen, Liu Bing
School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou, 510006, China.
Center for Drug Research and Development, Guangdong Pharmaceutical University, Guangzhou, 510006, China.
Eur J Pharmacol. 2025 Jul 5;998:177534. doi: 10.1016/j.ejphar.2025.177534. Epub 2025 Mar 19.
Atopic dermatitis (AD) is a prevalent chronic inflammatory skin disease that significantly impacts patients' quality of life. Chlorogenic acid (CGA), a polyphenol present in various dietary sources and plants, has been shown to reduce skin inflammation. However, its efficacy and mechanisms of action in AD have not been thoroughly investigated. This study aimed to evaluate the therapeutic effect of CGA on AD in mice and explored its mechanism.
To establish a BALB/c mouse model of AD induced by 2,4-dinitrochlorobenzene (DNCB) to evaluate the therapeutic potential of CGA. The anti-inflammatory effects of CGA were assessed by measuring IL-1β and IL-6 levels in TNF-α-stimulated HaCaT cells. The phosphorylation levels of PI3K, Akt, Akt1, NF-κB, and IκB-α were analyzed using Western blotting. Molecular docking was conducted to evaluate the binding affinity of CGA to Akt1.
Topical application of CGA significantly reduced dermatitis scores, spleen index, epidermal thickness, mast cell infiltration, and skin fibrosis. CGA reversed DNCB-induced increases in IgE, histamine, TNF-α, IL-1β, IL-6, and IL-8 levels. Western blot analysis showed that CGA inhibited the PI3K/Akt and NF-κB signaling pathways. In vitro, CGA exerts its anti-inflammatory effects by inhibiting the Akt1/NF-κB pathway, and the Akt activator (SC79) can counteract this effect. Molecular docking and dynamics simulations suggest that CGA may inhibit Akt1 activity by interacting with specific residues (ALA-50, GLY-37, TYR-326, ASP-323).
CGA improves AD by inhibiting the Akt1/NF-κB pathway, suggesting its potential as a natural treatment for AD.
特应性皮炎（AD）是一种常见的慢性炎症性皮肤病，严重影响患者的生活质量。绿原酸（CGA）是一种存在于多种饮食来源和植物中的多酚，已被证明可减轻皮肤炎症。然而，其在AD中的疗效和作用机制尚未得到充分研究。本研究旨在评估CGA对小鼠AD的治疗效果并探讨其机制。
通过2,4-二硝基氯苯（DNCB）诱导建立BALB/c小鼠AD模型，以评估CGA的治疗潜力。通过测量TNF-α刺激的HaCaT细胞中IL-1β和IL-6水平来评估CGA的抗炎作用。使用蛋白质印迹法分析PI3K、Akt、Akt1、NF-κB和IκB-α的磷酸化水平。进行分子对接以评估CGA与Akt1的结合亲和力。
局部应用CGA可显著降低皮炎评分、脾脏指数、表皮厚度、肥大细胞浸润和皮肤纤维化。CGA逆转了DNCB诱导的IgE、组胺、TNF-α、IL-1β、IL-6和IL-8水平升高。蛋白质印迹分析表明，CGA抑制PI3K/Akt和NF-κB信号通路。在体外，CGA通过抑制Akt1/NF-κB途径发挥其抗炎作用，Akt激活剂（SC79）可抵消这种作用。分子对接和动力学模拟表明，CGA可能通过与特定残基（ALA-50、GLY-37、TYR-326、ASP-323）相互作用来抑制Akt1活性。
CGA通过抑制Akt1/NF-κB途径改善AD，表明其作为AD天然治疗方法的潜力。
