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Journal of Integrative Medicine ›› 2023, Vol. 21 ›› Issue (6): 584-592.doi: 10.1016/j.joim.2023.11.004

• Original Experimental Research • Previous Articles     Next Articles

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

Ya Zhong a b c, Bo-wen Zhang a b c, Jin-tao Li a b d, Xin Zeng a b d, Jun-xia Pei a b c, Ya-mei Zhang e, Yi-xi Yang a b c, Fu-lun Li f, Yu Deng a b g, Qi Zhao a b c   

  1. a. Engineering Research Center of Sichuan-Xizang Traditional Medicinal Plant, Chengdu University, Chengdu 610106, Sichuan Province, China
    b. Institute of Cancer Biology and Drug Discovery, Chengdu University, Chengdu 610106, Sichuan Province, China
    c. School of Food and Biological Engineering, Chengdu University, Chengdu 610106, Sichuan Province, China
    d. School of Pharmacy, Chengdu University, Chengdu 610106, Sichuan Province, China
    e. Key Laboratory of Clinical Genetics, Affiliated Hospital of Chengdu University, Chengdu 610106, Sichuan Province, China
    f. Department of Dermatology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200437, China
    g. School of Basic Medical Sciences, Chengdu University, Chengdu 610106, Sichuan Province, China
  • Received:2023-06-04 Accepted:2023-10-25 Online:2023-12-08 Published:2023-12-12
  • Contact: Yu Deng; Qi Zhao;

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.

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-α (TNF-α), 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.

EHC improved inflammation in the imiquimod-induced psoriasis mouse model and reduced the levels of IFN-γ, TNF-α, 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.

Topical application of EHC ameliorates psoriasis-like skin symptoms and improves the inflammation at the lesion sites.

Key words: Psoriasis, Herpetospermum caudigerum , wall, Cytokines, Degradation

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