To screen Chinese herbal medicines for optimal inhibitory activity against Malassezia furfur (M. furfur), isolate and identify the most potent antimicrobial fraction, and investigate its underlying mechanism of action. The Chinese herbal extract and its polar fractions exhibiting the strongest inhibitory effect against M. furfur were initially screened from 20 Chinese herbal medicines using the Oxford cup method and broth microdilution assay. A highly active subfraction was subsequently obtained through silica gel column chromatography. The effects of this active subfraction on the growth and cell structural integrity of M. furfur were evaluated by turbidimetry, exogenous sorbitol hypertonic protection assay, extracellular alkaline phosphatase activity assay, propidium iodide fluorescence staining, and crystal violet staining. M. furfur-induced inflammatory models in HaCaT keratinocytes and SZ95 sebocytes were employed. The safety of the active subfraction was assessed by MTT assay for cell viability. Nitric oxide release was measured by Griess test, and the levels of IL-6 and tumor necrosis factorinduced inflammatory models in HaCaT keratinocytes and SZ95 sebocytes were employed. The safety of the active subfraction was assessed by MTT assay for cell viability. Nitric oxide release was measured by Griess test, and the levels of IL (TNF)-α in cell supernatants were determined by ELISA. Lipid synthesis in SZ95 cells was evaluated by Nile red staining. The chemical constituents of the highly active fraction obtained by silica gel column chromatography were analyzed and identified by ultra performance liquid chromatography-mass spectrometry (UPLC-MS). Potential anti-seborrheic dermatitis targets and pathways were predicted through construction of a protein-protein interaction network, Gene Ontology (GO) functional annotation, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Among the extracts of 20 Chinese herbal medicines, the extract of Rosa chinensis Jacq. demonstrated superior inhibitory activity against M. furfur. Its ethyl acetate fraction exhibited the most potent antimicrobial effect, from which subfraction Fr.2 was isolated as the most active component, with an inhibition zone diameter of (25.30±0.49) mm and a minimum inhibitory concentration of 1 mg/mL. Fr.2 effectively inhibited the growth of M. furfur (P<0.05) and disrupted cellular structures, including the cell wall, cell membrane, and biofilm. Within a safe concentration range (25-100 μg/mL), Fr.2 showed no cytotoxicity toward HaCaT and SZ95 cells and dose-dependently reduced the release of inflammatory factors and lipid synthesis in SZ95 cells. A total of 27 constituents were identified from Fr.2 by UPLC-MS, including organic acids, flavonoids (such as myricetin, quercetin, and kaempferol), and alkaloids. The anti-seborrheic dermatitis effect of Fr.2 was associated with the regulation of core targets including TNF, chemokine C-X-C motif ligand 8, prostaglandin G/H synthase 2, signal transducer and activator of transcription 3, and epidermal growth factor receptor. GO analysis indicated that common targets of the drug and disease were primarily involved in neural signal regulation, inflammatory modulation, and membrane structure localization; at the molecular function level, these targets were predominantly associated with protein binding. KEGG pathway analysis further revealed that Fr.2 may exert its therapeutic effect on seborrheic dermatitis by modulating immune-inflammatory pathways, lipid metabolism and vascular function-related pathways, and neural signaling pathways. Rosa chinensis Jacq. exerts its antimicrobial effect against M. furfur by disrupting cell wall, cell membrane, and biofilm structures, and also demonstrates anti-seborrheic dermatitis activity, which may be attributed to the inhibition of inflammatory signaling pathways and the reduction of lipid synthesis. 目的: 筛选对糠秕马拉色菌具有最优抑制活性的中草药，分离鉴定其最佳抗菌活性部位，并探究其作用机制。方法: 通过牛津杯法和微量液基稀释法，从20种中草药中初筛对糠秕马拉色菌抑制作用最佳的提取物及其极性部位，进一步通过硅胶柱层析分离获得高活性馏分。通过比浊法、外源山梨糖醇高渗保护实验、细胞外碱性磷酸酶活性检测实验、碘化丙啶荧光染色法和结晶紫染色法评价高活性馏分对糠秕马拉色菌生长、细胞结构完整性的影响。利用糠秕马拉色菌诱导HaCaT角质形成细胞炎症模型和SZ95皮脂腺细胞模型，采用MTT法检测细胞存活率评估高活性馏分的安全性，格里斯试验测定一氧化氮释放量，酶联免疫吸附试验检测细胞上清液中IL-6、肿瘤坏死因子（TNF）-α含量，并通过尼罗红染色法检测SZ95细胞脂质合成率。采用超高效液相色谱-质谱法（UPLC-MS）分析和鉴定硅胶柱层析分离获得高活性馏分的化学成分，并通过构建蛋白质-蛋白质相互作用网络、进行基因本体功能注释及京都基因与基因组百科全书通路富集分析，预测其抗脂溢性皮炎的靶点及通路。结果: 20种中草药提取物中，月季提取物对糠秕马拉色菌的抑制作用较好，其乙酸乙酯萃取部位对糠秕马拉色菌的抑制效果最佳，分离所得乙酸乙酯部位柱层析馏分2（Fr.2）活性最优，抑菌圈为（25.30±0.49）mm，最低抑菌浓度为1 mg/mL。Fr.2能有效抑制糠秕马拉色菌生长，破坏细胞壁、细胞膜及生物膜等细胞结构。在安全浓度范围（25~100 μg/mL）内，Fr.2对HaCaT细胞和SZ95细胞无毒性，并剂量依赖性地降低炎症因子释放和SZ95细胞的脂质合成。采用UPLC-MS从Fr.2中鉴定出27种成分，包括有机酸类、黄酮类（如杨梅素、槲皮素、山柰酚）、生物碱类等，其抗脂溢性皮炎作用与调节TNF、趋化因子CXC配体8、前列腺素G/H合酶2、信号转导及转录激活蛋白3、表皮生长因子受体等核心靶点相关。基因本体分析表明，药物与疾病共同靶点主要参与神经信号调节、炎症调控以及对膜结构的定位;在分子功能上，这些靶点多与蛋白质结合相关。京都基因与基因组百科全书分析进一步揭示，Fr.2可能通过调控免疫炎症通路、脂代谢与血管相关通路以及神经信号通路来发挥治疗脂溢性皮炎的作用。结论: 月季可破坏马拉色菌细胞壁、细胞膜和生物膜等结构发挥抑菌作用，且具有一定的抗脂溢性皮炎作用，这种作用可能与其抑制炎症信号通路和减少脂质合成有关。.
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