Wang Qiao, Luo Xin, Su Yuwen, Jin Yi, Kuang Qiqi, Li Siying, Shen Weiyun, Zhu Yanshan
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, Changsha, Hunan, People's Republic of China.
Department of Anesthesiology, Second Xiangya Hospital, Anesthesiology Research Institute of Central South University, Changsha, Hunan, People's Republic of China.
Drug Des Devel Ther. 2025 Jan 24;19:539-552. doi: 10.2147/DDDT.S504485. eCollection 2025.
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.
To evaluate the efficacy of Tan-I in the treatment of psoriasis and to determine the mechanisms involved.
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.
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.
Tan-I is a promising therapeutic candidate for psoriasis, effectively mitigating inflammation, normalizing keratinocyte differentiation, and inhibiting abnormal keratinocyte apoptosis.
银屑病是一种与免疫相关的炎症性全身性疾病，其特征为角质形成细胞增殖失调和慢性炎症。丹参酮 I（Tan-I）最近被发现具有免疫调节特性，但其在治疗银屑病中的作用和机制仍不清楚。
评估 Tan-I 治疗银屑病的疗效并确定其涉及的机制。
用咪喹莫特（IMQ）诱导建立银屑病样小鼠模型，局部给予 Tan-I（7.5 毫克/千克/天）或赋形剂。使用银屑病面积和严重程度指数（PASI）评估疾病严重程度，通过苏木精-伊红（H&E）染色和 Ki67 免疫荧光评估组织学变化。使用肿瘤坏死因子-α（TNF-α）刺激的 HaCaT 角质形成细胞进行体外分析，包括通过逆转录定量聚合酶链反应（RT-qPCR）检测细胞凋亡、细胞周期进程和炎症基因表达。进行 RNA 测序（RNA-seq）以研究 Tan-I 在体内和体外的作用机制，同时通过免疫荧光和蛋白质免疫印迹分析角蛋白表达。
Tan-I 治疗显著减轻了 IMQ 小鼠模型中的银屑病样病变，改善了皮肤病理学并减少了 Ki67 阳性细胞。RNA-seq 显示 Tan-I 调节免疫途径、角质形成细胞分化和屏障功能。在 TNF-α 刺激的 HaCaT 细胞中，Tan-I 诱导 G1 期细胞周期停滞，减少细胞凋亡，并抑制炎症基因表达。RNA-seq 进一步表明 Tan-I 使被 TNF-α 破坏的细胞周期信号和凋亡途径恢复正常。此外，Tan-I 恢复了角蛋白表达模式，增加了小鼠皮肤和 HaCaT 细胞中 K1 的水平，并降低了 K6 和 K17 的水平。
Tan-I 是一种有前途的银屑病治疗候选药物，可有效减轻炎症，使角质形成细胞分化正常化，并抑制角质形成细胞异常凋亡。
