Ai Xinyi, Guo Teng, Yang Jiayi, Zhang Chenming, Zhang Yangyang, Zhao Weimin, Zhu Shiguo, Feng Nianping
School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai 201203 China.
Natural Product Research Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203 China; University of Chinese Academy of Sciences, No. 19A Yuquan Road, Beijing 100049 China.
Int J Pharm. 2025 Feb 10;670:125180. doi: 10.1016/j.ijpharm.2025.125180. Epub 2025 Jan 4.
Psoriasis seriously affects the physical and mental health of patients. Rocaglamide (RocA), derived from Aglaia odorata, exhibits potent pharmacological activities. Although its efficacy in psoriasis is unclear, RocA could be a promising therapeutic drug. In this work, RocA showed a good therapeutic effect in psoriasis mice induced by imiquimod, and subsequent TMT-based proteomics analysis verified that the effect of RocA was related to IL-1 family cytokines. Furthermore, a RocA-loaded liposome (RocA@Lipo) was developed and encapsulated in the tip-layer of microneedles (MNs) to construct a MN-based nano drug delivery system (RocA@Lipo-MNs). In vitro HaCaT cell assays demonstrated that RocA@Lipo enhanced the cytotoxicity and cell uptake of RocA. In vivo, RocA@Lipo-MNs outperformed other RocA formulations in inhibiting psoriasis epidermal thickening and spleen enlargement. Immunohistochemical, ELISA, western blot, and PCR experiments further proved that RocA@Lipo-MNs could inhibit neutrophil infiltration in the skin, revealing that the anti-psoriasis mechanism of RocA was deemed to inhibit the binding of IL-1α and IL-1R1 to regulate the activation of MAPK and NF-κB pathways. Thus, the production of inflammatory factors and neutrophil chemokines was reduced, which was associated with apoptosis inhibition. Importantly, RocA@Lipo-MNs significantly improved the transdermal properties of RocA and exhibited good skin and blood safety. This work provides new ideas for the clinical application of RocA and the treatment options for psoriasis.
银屑病严重影响患者的身心健康。从米仔兰中提取的萝卡酰胺（RocA）具有强大的药理活性。尽管其对银屑病的疗效尚不清楚，但RocA可能是一种有前景的治疗药物。在这项研究中，RocA对咪喹莫特诱导的银屑病小鼠显示出良好的治疗效果，随后基于TMT的蛋白质组学分析证实RocA的作用与白细胞介素-1家族细胞因子有关。此外，还制备了负载RocA的脂质体（RocA@Lipo）并将其包裹在微针（MNs）的尖端层，构建了基于微针的纳米药物递送系统（RocA@Lipo-MNs）。体外HaCaT细胞实验表明，RocA@Lipo增强了RocA的细胞毒性和细胞摄取。在体内，RocA@Lipo-MNs在抑制银屑病表皮增厚和脾脏肿大方面优于其他RocA制剂。免疫组织化学、酶联免疫吸附测定、蛋白质印迹和聚合酶链反应实验进一步证明，RocA@Lipo-MNs可以抑制皮肤中的中性粒细胞浸润，表明RocA的抗银屑病机制被认为是抑制白细胞介素-1α和白细胞介素-1受体1的结合，从而调节丝裂原活化蛋白激酶和核因子κB信号通路的激活。因此，炎症因子和中性粒细胞趋化因子的产生减少，这与细胞凋亡抑制有关。重要的是，RocA@Lipo-MNs显著改善了RocA的透皮性能，并表现出良好的皮肤和血液安全性。这项工作为RocA的临床应用和银屑病的治疗方案提供了新思路。
