Chlorogenic acid alleviates DNCB-induced atopic dermatitis by inhibiting the Akt1/NF-κB signaling pathway

  • Eur J Pharmacol. 2025 Mar 19:998:177534. doi: 10.1016/j.ejphar.2025.177534.
Wenkai Nie  1 ,  Xuan Zhao  1 ,  Yan Zhang  1 ,  Cheng Zeng  2 ,  Huiwen Yang  1 ,  Bing Liu  3
Affiliations
  • 1. School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou, 510006, China.
  • 2. Center for Drug Research and Development, Guangdong Pharmaceutical University, Guangzhou, 510006, China.
  • 3. School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou, 510006, China; Key Specialty of Clinical Pharmacy, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, 510699, China. Electronic address: [email protected].
PMID: 40118327 DOI: 10.1016/j.ejphar.2025.177534
Abstract

Objective: 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.

Methods: 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.

Results: 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).

Conclusions: CGA improves AD by inhibiting the Akt1/NF-κB pathway, suggesting its potential as a natural treatment for AD.

Keywords
Akt1; Anti-inflammatory; Atopic dermatitis; Chlorogenic acid; Molecular docking.
Products