Table1_EGCG identified as an autophagy inducer for rosacea therapy.DOCX

Background: Rosacea is a common facial skin inflammatory disease featured by hyperactivation of mTORC1 signaling in the epidermis. Due to unclear pathogenesis, the effective treatment options for rosacea remain limited.
Methods: Weighted gene co-expression network analysis (WGCNA) analyzed the relationship between epidermis autophagy and mTOR pathways in rosacea, and further demonstrated it through immunofluorescence and qPCR analysis. A potential therapeutic agent for rosacea was predicted based on the key genes of the WGCNA module. In vivo and in vitro experiments were conducted to verify its therapeutic role. Drug–target prediction (TargetNet, Swiss, and Tcmsp) and molecular docking offered potential pharmacological targets.
Results: WGCNA showed that epidermis autophagy was related to the activation of mTOR pathways in rosacea. Next, autophagy was downregulated in the epidermis of rosacea, which was regulated by mTOR. In addition, the in vivo experiment demonstrated that autophagy induction could be an effective treatment strategy for rosacea. Subsequently, based on the key genes of the WGCNA module, epigallocatechin-3-gallate (EGCG) was predicted as a potential therapeutic agent for rosacea. Furthermore, the therapeutic role of EGCG on rosacea was confirmed in vivo and in vitro. Finally, drug–target prediction and molecular docking revealed that AKT1/MAPK1/MMP9 could be the pharmacological targets of EGCG in rosacea.
Conclusion: Collectively, our findings revealed the vital role of autophagy in rosacea and identified that EGCG, as a therapeutic agent for rosacea, attenuated rosacea-like inflammation via inducing autophagy in keratinocytes.

Background: 玫瑰痤疮（rosacea）是一种常见的面部皮肤炎性疾病，以表皮中mTORC1信号通路过度激活为特征。由于其发病机制尚未明确，目前针对玫瑰痤疮的有效治疗手段仍较为有限。
Methods: 本研究采用加权基因共表达网络分析（Weighted gene co-expression network analysis, WGCNA）分析了玫瑰痤疮表皮自噬与mTOR通路的关联，并通过免疫荧光实验与qPCR分析进一步验证了该关联。基于WGCNA模块的关键基因，本研究预测了一种潜在的玫瑰痤疮治疗剂。通过体内与体外实验验证了其治疗作用。借助药物靶点预测工具（TargetNet、Swiss及Tcmsp）与分子对接技术，筛选出了潜在的药理学靶点。
Results: WGCNA分析显示，玫瑰痤疮患者表皮自噬与mTOR通路的激活密切相关。后续实验发现，玫瑰痤疮患者表皮中的自噬水平被下调，且该过程受mTOR通路调控。此外，体内实验证实，诱导自噬可作为一种有效的玫瑰痤疮治疗策略。随后，基于WGCNA模块的关键基因，本研究预测表没食子儿茶素没食子酸酯（epigallocatechin-3-gallate, EGCG）为潜在的玫瑰痤疮治疗剂。进一步的体内外实验验证了EGCG对玫瑰痤疮的治疗作用。最后，药物靶点预测与分子对接结果显示，AKT1、MAPK1及MMP9可能是EGCG治疗玫瑰痤疮的药理学靶点。
Conclusion: 综上，本研究揭示了自噬在玫瑰痤疮发病过程中的关键作用，并证实EGCG可通过诱导角质形成细胞中的自噬，减轻玫瑰痤疮样炎症，从而作为玫瑰痤疮的治疗剂。