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

Area of Science:

• Dermatology and Pharmacology
• Traditional Chinese Medicine
• Immunology

Background:

• Psoriasis is a chronic inflammatory skin disease characterized by keratinocyte hyperproliferation and immune cell infiltration.
• Dijincao (DJC), a component of Qing Xue Wan (QXW), is traditionally used for psoriasis, but lacks scientific validation.
• Understanding DJC's pharmacological mechanisms is crucial for its therapeutic application.

Purpose of the Study:

• To evaluate the anti-psoriatic efficacy of QXW and DJC.
• To identify the primary active constituents responsible for the therapeutic effects.
• To elucidate the molecular mechanisms underlying their anti-psoriatic actions.

Main Methods:

• Imiquimod (IMQ)-induced psoriasis mouse model and lipopolysaccharide (LPS)-induced HaCaT cells were utilized.
• Therapeutic effects were assessed via PASI scoring, histology, immunohistochemistry, and cytokine analysis (ELISA, RT-PCR).
• Active components were identified using UPLC-QTOF/MS; mechanisms were explored through RNA sequencing, Western blotting, cell cycle, and luciferase assays.

Main Results:

• QXW and DJC significantly reduced PASI scores, skin thickness, and inflammatory markers in mice.
• Apigenin was identified as the principal active compound in DJC.
• Apigenin demonstrated anti-proliferative and anti-inflammatory effects by modulating the CDK2/E2F2 cell cycle and IL-17 signaling.

Conclusions:

• This study provides the first comprehensive comparison of QXW, DJC, and Apigenin for psoriasis treatment.
• Apigenin is identified as the key mediator of the anti-psoriatic effects of QXW and DJC.
• Apigenin's anti-proliferative action via the CDK2/E2F2 pathway offers a scientific basis for its use in psoriasis therapy.