Tanshinone I Ameliorates Psoriasis-Like Dermatitis by Suppressing Inflammation and Regulating Keratinocyte Differentiation
Qiao Wang,1,* Xin Luo,1,* Yuwen Su,1 Yi Jin,1 Qiqi Kuang,1 Siying Li,1 Weiyun Shen,2 Yanshan Zhu1 1Department of Dermatology, Second Xiangya Hospital, Hunan Key Laboratory of Medical Epigenomics, Clinical Medical Research Center of Major Skin Diseases and Skin Health of Hunan Provinc...
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Dove Medical Press
2025-01-01
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| author | Wang Q Luo X Su Y Jin Y Kuang Q Li S Shen W Zhu Y |
| author_facet | Wang Q Luo X Su Y Jin Y Kuang Q Li S Shen W Zhu Y |
| author_sort | Wang Q |
| collection | DOAJ |
| description | Qiao Wang,1,* Xin Luo,1,* Yuwen Su,1 Yi Jin,1 Qiqi Kuang,1 Siying Li,1 Weiyun Shen,2 Yanshan Zhu1 1Department of Dermatology, Second Xiangya Hospital, Hunan Key Laboratory of Medical Epigenomics, Clinical Medical Research Center of Major Skin Diseases and Skin Health of Hunan Province, Central South University, Changsha, Hunan, People’s Republic of China; 2Department of Anesthesiology, Second Xiangya Hospital, Anesthesiology Research Institute of Central South University, Changsha, Hunan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xin Luo; Yanshan Zhu, Department of Dermatology, Second Xiangya Hospital, Hunan Key Laboratory of Medical Epigenomics, Clinical Medical Research Center of Major Skin Diseases and Skin Health of Hunan Province, Central South University, 139 Renmin Middle Road, Changsha, Hunan, People’s Republic of China, Email 248201037@csu.edu.cn; 218202091@csu.edu.cnBackground: Psoriasis is an immune-related inflammatory systemic condition characterized by dysregulated keratinocyte proliferation and chronic inflammation. Tanshinone I (Tan-I) has recently been discovered to have immunomodulatory properties, but its role and mechanisms in treating psoriasis remain unclear.Objective: To evaluate the efficacy of Tan-I in the treatment of psoriasis and to determine the mechanisms involved.Methods: An imiquimod (IMQ)-induced psoriasis-like mouse model was treated topically with Tan-I (7.5 mg/kg/d) or a vehicle. Disease severity was evaluated using the Psoriasis Area and Severity Index (PASI), and histological changes were assessed via H&E staining and Ki67 immunofluorescence. TNF-α-stimulated HaCaT keratinocytes were used for in vitro analyses, including apoptosis, cell cycle progression, and inflammatory gene expression via RT-qPCR. RNA sequencing (RNA-seq) was performed to investigate Tan-I’s mechanisms in vivo and in vitro, while keratin expression was analyzed by immunofluorescence and Western blot.Results: Tan-I treatment significantly alleviated psoriasis-like lesions in the IMQ mouse model, improving skin pathology and reducing Ki67-positive cells. RNA-seq revealed that Tan-I modulated immune pathways, keratinocyte differentiation, and barrier function. In TNF-α-stimulated HaCaT cells, Tan-I induced G1-phase cell cycle arrest, reduced apoptosis, and suppressed inflammatory gene expression. RNA-seq further showed that Tan-I normalized cell cycle signaling and apoptosis pathways disrupted by TNF-α. Additionally, Tan-I restored keratin expression patterns, increasing K1 and decreasing K6 and K17 levels in both mouse skin and HaCaT cells.Conclusion: Tan-I is a promising therapeutic candidate for psoriasis, effectively mitigating inflammation, normalizing keratinocyte differentiation, and inhibiting abnormal keratinocyte apoptosis.Keywords: psoriasis, tanshinone I, immune modulation, keratinocyte, apoptosis |
| format | Article |
| id | doaj-art-ed392a0fa2cb486f8885670cbcadf9aa |
| institution | Kabale University |
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| language | English |
| publishDate | 2025-01-01 |
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| spelling | doaj-art-ed392a0fa2cb486f8885670cbcadf9aa2025-01-27T18:05:33ZengDove Medical PressDrug Design, Development and Therapy1177-88812025-01-01Volume 1953955299571Tanshinone I Ameliorates Psoriasis-Like Dermatitis by Suppressing Inflammation and Regulating Keratinocyte DifferentiationWang QLuo XSu YJin YKuang QLi SShen WZhu YQiao Wang,1,* Xin Luo,1,* Yuwen Su,1 Yi Jin,1 Qiqi Kuang,1 Siying Li,1 Weiyun Shen,2 Yanshan Zhu1 1Department of Dermatology, Second Xiangya Hospital, Hunan Key Laboratory of Medical Epigenomics, Clinical Medical Research Center of Major Skin Diseases and Skin Health of Hunan Province, Central South University, Changsha, Hunan, People’s Republic of China; 2Department of Anesthesiology, Second Xiangya Hospital, Anesthesiology Research Institute of Central South University, Changsha, Hunan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xin Luo; Yanshan Zhu, Department of Dermatology, Second Xiangya Hospital, Hunan Key Laboratory of Medical Epigenomics, Clinical Medical Research Center of Major Skin Diseases and Skin Health of Hunan Province, Central South University, 139 Renmin Middle Road, Changsha, Hunan, People’s Republic of China, Email 248201037@csu.edu.cn; 218202091@csu.edu.cnBackground: Psoriasis is an immune-related inflammatory systemic condition characterized by dysregulated keratinocyte proliferation and chronic inflammation. Tanshinone I (Tan-I) has recently been discovered to have immunomodulatory properties, but its role and mechanisms in treating psoriasis remain unclear.Objective: To evaluate the efficacy of Tan-I in the treatment of psoriasis and to determine the mechanisms involved.Methods: An imiquimod (IMQ)-induced psoriasis-like mouse model was treated topically with Tan-I (7.5 mg/kg/d) or a vehicle. Disease severity was evaluated using the Psoriasis Area and Severity Index (PASI), and histological changes were assessed via H&E staining and Ki67 immunofluorescence. TNF-α-stimulated HaCaT keratinocytes were used for in vitro analyses, including apoptosis, cell cycle progression, and inflammatory gene expression via RT-qPCR. RNA sequencing (RNA-seq) was performed to investigate Tan-I’s mechanisms in vivo and in vitro, while keratin expression was analyzed by immunofluorescence and Western blot.Results: Tan-I treatment significantly alleviated psoriasis-like lesions in the IMQ mouse model, improving skin pathology and reducing Ki67-positive cells. RNA-seq revealed that Tan-I modulated immune pathways, keratinocyte differentiation, and barrier function. In TNF-α-stimulated HaCaT cells, Tan-I induced G1-phase cell cycle arrest, reduced apoptosis, and suppressed inflammatory gene expression. RNA-seq further showed that Tan-I normalized cell cycle signaling and apoptosis pathways disrupted by TNF-α. Additionally, Tan-I restored keratin expression patterns, increasing K1 and decreasing K6 and K17 levels in both mouse skin and HaCaT cells.Conclusion: Tan-I is a promising therapeutic candidate for psoriasis, effectively mitigating inflammation, normalizing keratinocyte differentiation, and inhibiting abnormal keratinocyte apoptosis.Keywords: psoriasis, tanshinone I, immune modulation, keratinocyte, apoptosishttps://www.dovepress.com/tanshinone-i-ameliorates-psoriasis-like-dermatitis-by-suppressing-infl-peer-reviewed-fulltext-article-DDDTpsoriasistanshinone iimmune modulationkeratinocyteapoptosis. |
| spellingShingle | Wang Q Luo X Su Y Jin Y Kuang Q Li S Shen W Zhu Y Tanshinone I Ameliorates Psoriasis-Like Dermatitis by Suppressing Inflammation and Regulating Keratinocyte Differentiation Drug Design, Development and Therapy psoriasis tanshinone i immune modulation keratinocyte apoptosis. |
| title | Tanshinone I Ameliorates Psoriasis-Like Dermatitis by Suppressing Inflammation and Regulating Keratinocyte Differentiation |
| title_full | Tanshinone I Ameliorates Psoriasis-Like Dermatitis by Suppressing Inflammation and Regulating Keratinocyte Differentiation |
| title_fullStr | Tanshinone I Ameliorates Psoriasis-Like Dermatitis by Suppressing Inflammation and Regulating Keratinocyte Differentiation |
| title_full_unstemmed | Tanshinone I Ameliorates Psoriasis-Like Dermatitis by Suppressing Inflammation and Regulating Keratinocyte Differentiation |
| title_short | Tanshinone I Ameliorates Psoriasis-Like Dermatitis by Suppressing Inflammation and Regulating Keratinocyte Differentiation |
| title_sort | tanshinone i ameliorates psoriasis like dermatitis by suppressing inflammation and regulating keratinocyte differentiation |
| topic | psoriasis tanshinone i immune modulation keratinocyte apoptosis. |
| url | https://www.dovepress.com/tanshinone-i-ameliorates-psoriasis-like-dermatitis-by-suppressing-infl-peer-reviewed-fulltext-article-DDDT |
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