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

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机构： [1]Engineering Research Center of Sichuan-Xizang Traditional Medicinal Plant, Chengdu University, Chengdu 610106, Sichuan Province, China [2]Institute of Cancer Biology and Drug Discovery, Chengdu University, Chengdu 610106, Sichuan Province, China [3]School of Food and Biological Engineering, Chengdu University, Chengdu 610106, Sichuan Province, China [4]School of Pharmacy, Chengdu University, Chengdu 610106, Sichuan Province, China [5]Key Laboratory of Clinical Genetics, Affiliated Hospital of Chengdu University, Chengdu 610106, Sichuan Province, China [6]Department of Dermatology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200437, China [7]School of Basic Medical Sciences, Chengdu University, Chengdu 610106, Sichuan Province, China

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关键词： Psoriasis Herpetospermum caudigerum wall Cytokines Degradation

摘要：

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. 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; Epub ahead of print.Copyright © 2023 Shanghai Changhai Hospital. Published by Elsevier B.V. All rights reserved.

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出版当年[2023]版：

大类 | 2 区医学

小类 | 3 区全科医学与补充医学

最新[2023]版：

大类 | 2 区医学

小类 | 3 区全科医学与补充医学

第一作者：

第一作者机构： [1]Engineering Research Center of Sichuan-Xizang Traditional Medicinal Plant, Chengdu University, Chengdu 610106, Sichuan Province, China [2]Institute of Cancer Biology and Drug Discovery, Chengdu University, Chengdu 610106, Sichuan Province, China [3]School of Food and Biological Engineering, Chengdu University, Chengdu 610106, Sichuan Province, China

通讯作者：

通讯机构： [1]Engineering Research Center of Sichuan-Xizang Traditional Medicinal Plant, Chengdu University, Chengdu 610106, Sichuan Province, China [2]Institute of Cancer Biology and Drug Discovery, Chengdu University, Chengdu 610106, Sichuan Province, China [3]School of Food and Biological Engineering, Chengdu University, Chengdu 610106, Sichuan Province, China [7]School of Basic Medical Sciences, Chengdu University, Chengdu 610106, Sichuan Province, China

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

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