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

Ya Zhong; Bo-Wen Zhang; Jin-Tao Li; Xin Zeng; Jun-Xia Pei; Ya-Mei Zhang; Yi-Xi Yang; Fu-Lun Li; Yu Deng; Qi Zhao

doi:10.1016/j.joim.2023.11.004

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

J Integr Med. 2023 Nov;21(6):584-592. doi: 10.1016/j.joim.2023.11.004. Epub 2023 Nov 11.

Authors

Ya Zhong¹, Bo-Wen Zhang¹, Jin-Tao Li², Xin Zeng², Jun-Xia Pei¹, Ya-Mei Zhang³, Yi-Xi Yang¹, Fu-Lun Li⁴, Yu Deng⁵, Qi Zhao⁶

Affiliations

¹ Engineering Research Center of Sichuan-Xizang Traditional Medicinal Plant, Chengdu University, Chengdu 610106, Sichuan Province, China; Institute of Cancer Biology and Drug Discovery, Chengdu University, Chengdu 610106, Sichuan Province, China; School of Food and Biological Engineering, Chengdu University, Chengdu 610106, Sichuan Province, China.
² Engineering Research Center of Sichuan-Xizang Traditional Medicinal Plant, Chengdu University, Chengdu 610106, Sichuan Province, China; Institute of Cancer Biology and Drug Discovery, Chengdu University, Chengdu 610106, Sichuan Province, China; School of Pharmacy, Chengdu University, Chengdu 610106, Sichuan Province, China.
³ Key Laboratory of Clinical Genetics, Affiliated Hospital of Chengdu University, Chengdu 610106, Sichuan Province, China.
⁴ Department of Dermatology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200437, China.
⁵ Engineering Research Center of Sichuan-Xizang Traditional Medicinal Plant, Chengdu University, Chengdu 610106, Sichuan Province, China; Institute of Cancer Biology and Drug Discovery, Chengdu University, Chengdu 610106, Sichuan Province, China; School of Basic Medical Sciences, Chengdu University, Chengdu 610106, Sichuan Province, China. Electronic address: dengyu@cdu.edu.cn.
⁶ Engineering Research Center of Sichuan-Xizang Traditional Medicinal Plant, Chengdu University, Chengdu 610106, Sichuan Province, China; Institute of Cancer Biology and Drug Discovery, Chengdu University, Chengdu 610106, Sichuan Province, China; School of Food and Biological Engineering, Chengdu University, Chengdu 610106, Sichuan Province, China. Electronic address: Zhaoqi@cdu.edu.cn.

PMID: 37989697
DOI: 10.1016/j.joim.2023.11.004

Abstract

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-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.

Results: 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.

Conclusion: Topical application of EHC ameliorates psoriasis-like skin symptoms and improves the inflammation at the lesion sites. Please cite this article as: Zhong Y, Zhang BW, Li JT, Zeng X, Pei JX, Zhang YM, Yang YX, Li FL, Deng Y, Zhao Q. Ethanol extract of Herpetospermum caudigerum Wall ameliorates psoriasis-like skin inflammation and promotes degradation of keratinocyte-derived ICAM-1 and CXCL9. J Integr Med. 2023; 21(6): 584-592.

Keywords: Cytokines; Degradation; Herpetospermum caudigerum wall; Psoriasis.

MeSH terms

Animals
Chemokines / adverse effects
Chemokines / metabolism
Disease Models, Animal
Imiquimod / adverse effects
Inflammation / drug therapy
Intercellular Adhesion Molecule-1
Interferon-gamma / metabolism
Interleukin-17* / adverse effects
Interleukin-17* / metabolism
Keratinocytes
Ligands
Mice
Mice, Inbred BALB C
Psoriasis* / chemically induced
Psoriasis* / drug therapy
Tumor Necrosis Factor-alpha / metabolism

Substances

Interleukin-17
Intercellular Adhesion Molecule-1
Imiquimod
Tumor Necrosis Factor-alpha
Ligands
Chemokines
Interferon-gamma