目的 基于网络药理学及分子对接技术，研究藏医药经典名方五味甘露药浴组方治疗银屑病的关键靶点 及作用通路，并通过细胞实验验证有关结果。方法 运用超临界 CO2萃取藏药五味甘露药浴组方药材细叶亚 菊 、 烈 香杜鹃、刺柏、水柏枝、麻黄的精油，用气相色谱-质谱联用法（GC-MS）进行成分鉴别；利用 SwissTargetPrediction 等数据库筛选出关键成分及其靶点，从人类在线孟德尔遗传蛋白-蛋白相互作用（OMIM） 等数据库获取银屑病相关靶点，取交集后进行蛋白-蛋白相互作用（PPI）网络构建及基因本体（GO）分析和基因 组百科全书（KEGG）信号通路富集分析；采用 Autodock 等软件对核心成分和关键靶点进行分子对接验证。最 后，通过体外细胞实验对预测结果进行验证，以脂多糖（LPS）诱导人永生化角质形成细胞（HaCaT）构建银屑病 炎症模型，细胞计数试剂盒 8（CCK-8）法确定安全给药浓度，酶联免疫吸附测定（ELISA）法检测桃柁酚、反式- 橙花叔醇、醋酸桔梗、柳杉二醇对炎症因子白细胞介素 17（IL-17）、白细胞介素 23（IL-23）、白细胞介素 6（IL-6）、 干扰素 γ（IFN-γ）的调控作用。结果 GC-MS 鉴定的 174 个化合物经皮肤渗透系数（log Kp ）≥-6 cm·s-1筛选获得 42 个关键成分；获得 109 个药物-疾病交集靶点。PPI 网络和药物-成分-疾病-靶点网络筛选出信号转导和转 录激活因子 3（STAT3）、Janus 激酶 2（JAK2）、Janus 激酶 1（JAK1）、B 细胞淋巴瘤 2（BCL2）、表皮生长因子受 体（EGFR）等 7 个核心靶点，与桃柁酚、反式-橙花叔醇、醋酸桔梗、柳杉二醇、乙酸-（4-苯基）-2-丁酯等核 心成分相互作用，主要涉及细胞增殖凋亡、免疫调节及炎症反应通路。分子对接表明桃柁酚与 EGFR 和 JAK1、 BCL2 具有强结合能力。细胞实验验证发现，各成分在 20 µg·mL-1 浓度下均无细胞毒性，能明显抑制 IL-17、 IL-23 和 IFN-γ 的分泌（P＜0.01）；在 IL-6 抑制方面，醋酸桔梗及柳杉二醇作用明显（P＜0.01），桃柁酚效果 显著（P＜0.05），证实这些成分可通过多靶点抑制银屑病相关炎症因子表达。结论 藏药五味甘露药浴组方 因疗效良好成为藏医临床常见治疗银屑病的外治方法。通过“成分-靶点-通路”多维分析及实验验证发现， 其核心活性成分通过靶向 STAT3、JAK1 等关键靶点，主要经 JAK-STAT 信号通路，抑制 IL-17、IL-23、IFN-γ 等特征性炎症因子的表达，从而发挥抗炎与免疫调节作用。这从现代药理学角度阐明了其通过“黄水-皮肤- 银屑”路径发挥治疗作用的具体分子机制，为揭示五味甘露药浴组方治疗皮肤病的科学内涵提供了依据。

Objective To investigate the key targets and pathways of the classic Tibetan medicine formula Wuwei Ganlu Medicated Bath in the treatment of psoriasis using network pharmacology and molecular docking techniques， and to validate the relevant findings through cellular experiments. Methods Essential oils from the constituent herbs of the Wuwei Ganlu Medicated Bath formula—Vkhan Pa，Mtshe Ldum，Shug Pa，Da Lis，and Vom Bu—were extracted using supercritical CO2 extraction and identified by gas chromatography-mass spectrometry （GC-MS）. Key components and their targets were screened using databases such as SwissTargetPrediction. Psoriasis-related targets were obtained from databases including the Online Mendelian Inheritance in Man （OMIM）. After identifying intersecting targets，a protein-protein interaction （PPI） network was constructed，followed by Gene Ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analyses. Molecular docking validation between core components and key targets was performed using software such as Autodock. Finally，in vitro cellular experiments were conducted to validate the predictions. A psoriasis inflammation model was established using lipopolysaccharide （LPS）-induced human adult low calcium high temperature （HaCaT） keratinocytes. Safe administration concentrations were determined using the Cell Counting Kit-8（CCK-8） assay. The regulatory effects of totarol，trans-nerolidol，lobetyolin acetate， and cryptomeridiol on the inflammatory factors interleukin-17（IL-17），interleukin-23（IL-23），interleukin-6（IL-6）， and interferon- γ （IFN- γ） were detected by enzyme-linked immunosorbent assay （ELISA）. Results From the 174 compounds identified by GC-MS， 42 key components were selected based on a skin permeability coefficient （log Kp ）≥ -6 cm·s-1 . A total of 109 intersecting drug-disease targets were obtained. PPI network and drug-componentdisease-target network analyses identified 7 core targets， including signal transducer and activator of transcription 3（STAT3），Janus kinase 2（JAK2），Janus kinase 1（JAK1），B-cell lymphoma 2（BCL2），and epidermal growth factor receptor （EGFR）. These interacted with core components such as totarol，trans-nerolidol，lobetyolin acetate， cryptomeridiol，and （4-phenyl）but-2-yl acetate，primarily involving pathways related to cell proliferation，apoptosis， immune regulation， and inflammation. Molecular docking indicated strong binding affinity of totarol with EGFR， JAK1， and BCL2. Cellular experiments confirmed that all components were non-cytotoxic at 20 µg·mL-1 and significantly inhibited the secretion of IL-17，IL-23，and IFN-γ（P＜0.01）. Regarding IL-6 inhibition，lobetyolin acetate and cryptomeridiol showed significant effects （P＜0.01），and totarol also exhibited a notable effect （P＜0.05）， confirming that these components can inhibit the expression of psoriasis-related inflammatory factors through multiple targets. Conclusion The Tibetan medicine Wuwei Ganlu Medicated Bath formula is a clinically common external treatment for psoriasis in Tibetan medicine due to its favorable efficacy. Through multi-dimensional “component-targetpathway” analysis and experimental validation，this study found that its core active components exert anti-inflammatory and immunomodulatory effects by targeting key targets such as STAT3 and JAK1， primarily via the JAK-STAT signaling pathway， inhibiting the expression of characteristic inflammatory factors including IL-17， IL-23， and IFN- γ. This elucidates the specific molecular mechanism underlying its therapeutic effect via the “Yellow Water （a pathological body fluid in Tibetan medicine）-skin-psoriasis” pathway from a modern pharmacological perspective， providing a basis for revealing the scientific connotation of the Wuwei Ganlu Medicated Bath formula in treating skin diseases.

R285.5

国家自然科学基金项目（82460845）；青海省科技计划项目（2022-ZJ-958Q）；国家中医药管理局-全国名老中医药专家杨本扎西传承工 作室项目。