2. Academic Validation
  3. Apigenin suppresses keratinocyte hyperproliferation and inflammation in psoriasis by inhibiting CDK2/E2F2 pathway

Apigenin suppresses keratinocyte hyperproliferation and inflammation in psoriasis by inhibiting CDK2/E2F2 pathway

  • Phytomedicine. 2025 Aug:144:156486. doi: 10.1016/j.phymed.2025.156486.
Abudureyimu Alimujiang 1,  Yutong Kang 2,  Wenjing Wei 3,  Zehua Zhang 4,  Yipeng Bai 4,  Yong Zhu 4,  Shixia Huo 5,  Dengqiu Xu 6,  Zhijian Li 7
Affiliations

Affiliations

  • 1 Uygur Medical Hospital of Xinjiang Uygur Autonomous Region, Urumqi Xinjiang Uygur Autonomous Region 830049, PR China; Key Laboratory of Evidence-Based and Translation, Xinjiang Hospital preparation of Traditional Chinese Medicine, Urumqi Xinjiang Uygur Autonomous Region 830049, PR China; Department of Pharmacology, School of Pharmacy, Xinjiang Medical University, Urumqi 830011, PR China.
  • 2 Uygur Medical Hospital of Xinjiang Uygur Autonomous Region, Urumqi Xinjiang Uygur Autonomous Region 830049, PR China; Key Laboratory of Evidence-Based and Translation, Xinjiang Hospital preparation of Traditional Chinese Medicine, Urumqi Xinjiang Uygur Autonomous Region 830049, PR China.
  • 3 Uygur Medical Hospital of Xinjiang Uygur Autonomous Region, Urumqi Xinjiang Uygur Autonomous Region 830049, PR China.
  • 4 Innovative Institute of Tumor Immunity and Medicine (ITIM), Hefei, Anhui, China, Anhui province key laboratory of tumor immune microenvironment and immunotherapy, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, PR China.
  • 5 Uygur Medical Hospital of Xinjiang Uygur Autonomous Region, Urumqi Xinjiang Uygur Autonomous Region 830049, PR China; Key Laboratory of Evidence-Based and Translation, Xinjiang Hospital preparation of Traditional Chinese Medicine, Urumqi Xinjiang Uygur Autonomous Region 830049, PR China. Electronic address: [email protected].
  • 6 Innovative Institute of Tumor Immunity and Medicine (ITIM), Hefei, Anhui, China, Anhui province key laboratory of tumor immune microenvironment and immunotherapy, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, PR China. Electronic address: [email protected].
  • 7 Uygur Medical Hospital of Xinjiang Uygur Autonomous Region, Urumqi Xinjiang Uygur Autonomous Region 830049, PR China; Key Laboratory of Evidence-Based and Translation, Xinjiang Hospital preparation of Traditional Chinese Medicine, Urumqi Xinjiang Uygur Autonomous Region 830049, PR China; Department of Pharmacology, School of Pharmacy, Xinjiang Medical University, Urumqi 830011, PR China. Electronic address: [email protected].
PMID: 40516287 DOI: 10.1016/j.phymed.2025.156486
Abstract

Background: Psoriasis is a long-lasting inflammatory skin condition marked by unusual growth of keratinocytes and infiltration of immune cells in the dermis and epidermis. Dijincao (DJC), a key component of Qing Xue Wan (QXW), is traditionally used to treat psoriasis. Although its clinical efficacy is well-recognized, the absence of pharmacological and mechanistic studies limits the validation of DJC as an effective and scientifically substantiated treatment for psoriasis.

Purpose: This study aimed to investigate the anti-psoriasis activity of QXW and DJC, identify their most effective constituents, and elucidate the underlying mechanisms of action.

Methods: Mice with imiquimod (IMQ)-induced psoriasis were treated with QXW or DJC, and the therapeutic effects were evaluated using the Psoriasis Area and Severity Index (PASI), histological analysis, immunohistochemistry, immunofluorescence, RT-PCR, and ELISA. Additionally, UPLC-QTOF/MS technology and lipopolysaccharide (LPS)-induced human keratinocytes (HaCaT) cells were employed to identify the main active components of DJC. Mechanistic insights were gained through RNA Sequencing, Western blotting, cell cycle analysis, and luciferase assays.

Results: Treatment with QXW and DJC resulted in a significant reduction of the PASI score, skin thickness, spleen index, and inflammatory cell infiltration. Moreover, both QXW and DJC reduced serum levels of pro-inflammatory cytokines. DJC alleviated psoriasis by inhibiting keratinocyte hyperproliferation and the inflammatory response. UPLC-QTOF/MS analysis and LPS-induced HaCaT cell studies identified Apigenin as the principal active compound of DJC. Transcriptomic analysis, along with WB, cell cycle, and luciferase assays, revealed that Apigenin mitigates keratinocyte hyperproliferation and the inflammatory response by modulating the CDK2/E2F2-mediated cell cycle and IL-17 signaling pathway.

Conclusion: This study represents the first comprehensive comparison of the anti-psoriatic effects of QXW, DJC, and Apigenin. The findings suggest that the therapeutic effects of QXW and DJC are primarily attributed to Apigenin, which exerts anti-proliferative properties by inhibiting the CDK2/E2F2 signaling pathway.

Keywords

Apigenin; Hyperproliferation; Inflammation; Keratinocyte; Psoriasis.

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