Tanshinone IIA, a component of the self‐made Xiao‐Yin decoction, ameliorates psoriasis by inhibiting IL‐17/IL‐23 and PTGS2/NF‐κB/AP‐1 pathways

Abstract

AbstractBackgroundPsoriasis is a persistent inflammatory dermatological disorder. Tanshinone IIA (tan‐IIA) is a biologically active compound in the self‐made Xiao‐Yin decoction (SMXYD) and exhibits diverse biological properties, such as anti‐proliferative and anti‐inflammatory effects. The objective of this investigation was to assess the potential of tan‐IIA as a therapeutic agent against psoriasis.MethodsNetwork pharmacology was employed to ascertain the active constituents and potential pathways associated with SMXYD and psoriasis. We conducted CCK‐8, qRT‐PCR, and western blotting to assess the proliferation of HaCaT keratinocytes and the expression of IL‐17/IL‐23 and PTGS2/NF‐κB/AP‐1 pathways. Additionally, we used H&E staining, western blotting, and ELISA to evaluate the therapeutic effects and signaling pathways of tan‐IIA in psoriasis‐like mice induced by imiquimod (IMQ).ResultsNetwork pharmacology analysis identified eight hub compounds. The Th17/IL‐17 signaling was found to be a potential therapeutic pathway of SMXYD against psoriasis, with JUN (AP‐1) as the core molecule. Next, PTGS2 was selected as the target of tan‐IIA against psoriasis using network pharmacology analysis. Molecular docking showed a high affinity between PTGS2 and tan‐IIA. Tan‐IIA treatment attenuated M‐5‐induced hyperproliferation and inflammation in HaCaT keratinocytes. Additionally, Tan‐IIA downregulated the PTGS2/NF‐κB/AP‐1 pathway in HaCaT keratinocytes. In the IMQ‐induced psoriasis‐like mouse, tan‐IIA significantly reduced the severity of skin lesions and downregulated the PTGS2/NF‐κB/AP‐1 pathway. Moreover, the combination of methotrexate (MTX) and tan‐IIA further inhibited the IL‐17/IL‐23 and PTGS2/NF‐κB/AP‐1 pathways.ConclusionThe administration of tan‐IIA has shown a positive effect on psoriasis by inhibiting the IL‐17/IL‐23 and PTGS2/NF‐κB/AP‐1 pathways. The findings suggest that it has promising qualities that make it a potential candidate for the development of future anti‐psoriatic agents.