Luo Xin, Yang Suhan, Zhong Lian, Zhang Peng
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, China.
Department of Blood Transfusion, Pingxiang People's Hospital, Gannan Medical University, Pingxiang, China.
Front Pharmacol. 2025 May 22;16:1586829. doi: 10.3389/fphar.2025.1586829. eCollection 2025.
Rosacea is a common chronic inflammatory skin disorder and dysregulation of neuroimmune functions and neurovascular loops play critical roles in the development of rosacea. Huperzine A (Hup A) has several bioactive properties, including anti-inflammatory, antioxidant, and neuroprotective effects. However, the potential roles of Hup A in treating rosacea is unknown.
Network pharmacology, molecular docking, and molecular dynamics simulation techniques has been used to investigate the anti-rosacea mechanisms of Hup A in rosacea.
Our results predicted 21 potential anti-rosacea targets of Hup A through public databases. KEGG pathway enrichment analysis revealed that these key targets participated in the regulation of MAPK signaling, NF-kappa B signaling, and PI3KAKT signaling pathways. Further machine learning analysis identified six core targets (BCL2, RXRA, PKN2, XDH, PRKCA, and FAP). Analysis of the GSE65914 dataset showed that XDH was upregulated in rosacea lesions, while BCL2 and RXRA were downregulated, with no significant expression changes of the other genes. Molecular docking results indicated that Hup A could bind to key targets (XDH, BCL2, and RXRA), which were further confirmed by molecular dynamics simulations.
This study systematically elucidates the potential mechanisms of Hup A in the treatment of rosacea and provides a theoretical basis for its application in rosacea therapy.
酒渣鼻是一种常见的慢性炎症性皮肤病，神经免疫功能失调和神经血管环在酒渣鼻的发展中起关键作用。石杉碱甲（Hup A）具有多种生物活性，包括抗炎、抗氧化和神经保护作用。然而，Hup A在治疗酒渣鼻方面的潜在作用尚不清楚。
采用网络药理学、分子对接和分子动力学模拟技术研究Hup A治疗酒渣鼻的机制。
我们的研究结果通过公共数据库预测了Hup A的21个潜在抗酒渣鼻靶点。KEGG通路富集分析表明，这些关键靶点参与了丝裂原活化蛋白激酶（MAPK）信号通路、核因子κB（NF-κB）信号通路和磷脂酰肌醇3激酶-蛋白激酶B（PI3K-AKT）信号通路的调控。进一步的机器学习分析确定了六个核心靶点（BCL2、视黄酸受体α（RXRA）、蛋白激酶N2（PKN2）、黄嘌呤脱氢酶（XDH）、蛋白激酶Cα（PRKCA）和成纤维细胞激活蛋白（FAP））。对GSE65914数据集的分析表明，XDH在酒渣鼻皮损中上调，而BCL2和RXRA下调，其他基因无明显表达变化。分子对接结果表明，Hup A可与关键靶点（XDH、BCL2和RXRA）结合，分子动力学模拟进一步证实了这一点。
本研究系统阐明了Hup A治疗酒渣鼻的潜在机制，为其在酒渣鼻治疗中的应用提供了理论依据。
