Ethanol extract of Herpetospermum caudigerum Wall ameliorates psoriasis-like skin inflammation and promotes degradation of keratinocyte-derived ICAM-1 and CXCL9

Objective:To explore whether the ethanol extract of Herpetospermum caudigerum Wall(EHC),a Xizang medicinal plant traditionally used for treating liver diseases,can improve imiquimod-induced psoriasis-like skin inflammation.Methods:Immunohistochemistry and immunofluorescence staining were used to determine the effects of topical EHC use in vivo on the skin pathology of imiquimod-induced psoriasis in mice.The protein levels of interferon-γ(IFN-γ),tumor necrosis factor-a(TNF-a),and interleukin-17A(IL-17A)in mouse skin samples were examined using immunohistochemical staining.In vitro,IFN-γ-induced HaCaT cells with or without EHC treatment were used to evaluate the expression of keratinocyte-derived intercellular cell adhesion molecule-1(ICAM-1)and chemokine CXC ligand 9(CXCL9)using Western blotting and reverse transcription-quantitative polymerase chain reaction.The protein synthesis inhibitor cycloheximide and proteasome inhibitor MG132 were utilized to validate the EHC-mediated mechanism underlying degradation of ICAM-1 and CXCL9.Results:EHC improved inflammation in the imiquimod-induced psoriasis mouse model and reduced the levels of IFN-γ,TNF-a,and IL-17A in psoriatic lesions.Treatment with EHC also suppressed ICAM-1 and CXCL9 in epidermal keratinocytes.Further mechanistic studies revealed that EHC suppressed keratinocyte-derived ICAM-1 and CXCL9 by promoting ubiquitin–proteasome-mediated protein degradation rather than transcriptional repression.Seven primary compounds including ehletianol C,dehydrodiconiferyl alcohol,herpetrione,herpetin,herpetotriol,herpetetrone and herpetetrol were identified from the EHC using ultra-performance liquid chromatography-quadrupole-time of flight-mass spectrometry.Conclusion:Topical application of EHC ameliorates psoriasis-like skin symptoms and improves the inflammation at the lesion sites.