目的 基于多维数据分析方法探讨含白及Bletillae Rhizoma组方的用药规律及其潜在分子机制。方法 收集《中医方剂大辞典》中含白及的方剂，对其朝代、剂型、用法、制法、主治病症、药物使用频次及剂量、功效类别、性味归经等进行统计，通过关联规则、聚类分析探讨配伍规律。通过数据库获取白及-白蔹药对的活性成分及其作用靶点，筛选“痈疽、疮疡”疾病靶点，进一步进行拓扑分析，揭示白及-白蔹治疗“痈疽、疮疡”的潜在靶点，并对潜在靶点进行基因本体（gene ontology，GO）和京都基因与基因组百科全书（Kyoto encyclopedia of genes and genomes，KEGG）富集分析。根据网络药理学结果，对核心成分与靶点蛋白进行分子对接验证和分子动力学模拟。结果 获得含白及有效方剂531首，涉及中药579味，性味以寒、温、平，苦、辛、甘为主，主要归于肝经、肺经、胃经、脾经，剂型以膏剂或散剂为主，主要用油或水制得，多外敷用药。531首方剂共计主治病症179种，按《中医方剂大辞典》第十一册病证索引页分为29大类，其中频次较高的依次为“痈疽、疮疡”类、“皮肤科病证”类、“伤科病证”类、“气血津液病证”类。剂量分析发现白及常用剂量为3.73 g，与其他药物多以1∶1的比例配伍。网络药理学分析结果显示，白及-白蔹药对治疗“痈疽、疮疡”的核心活性成分有二氢菲并吡喃酚、没食子儿茶素、1-(2,7-dihydroxy-4-methoxy-1-phenanthryl)-4-methoxyphenanthrene-2,7-diol、菠甾醇、豆甾醇、谷甾醇、1-(4-hydroxybenzyl)-4-methoxy-9,10-dihydrophenanthrene-2,7-diol，主要是甾醇类和芳烃类成分。核心靶点有蛋白激酶B1（protein kinase B1，AKT1）、半胱天冬氨酸蛋白酶3（cysteinasparate protease 3，CASP3）、肿瘤坏死因子（tumor necrosis factor，TNF）、信号转导-转录活化因子3（signal transducers and activators of transcription 3，STAT3）、表皮生长因子受体（epidermal growth factor receptor，EGFR）、B淋巴细胞瘤-2（B-cell lymphoma-2，BCL2）、JUN原癌基因（JUN proto-oncogene，JUN），生物学通路主要作用于癌症、磷脂酰肌醇-3-羟激酶（phosphatidylinositol-3-hydroxykinase，PI3K）-Akt、丝裂原活化蛋白激酶等信号通路，其功能主要为抑制癌症转录因子、调节酶活性和炎症相关基因表达等。分子对接及分子动力学模拟结果显示白及-白蔹药对中的核心成分与靶点蛋白均具有较好的结合活性。其中二氢菲并吡喃酚可能通过调节PI3K-Akt通路影响STAT3表达，从抗炎及组织修复等方面有效治疗“痈疽、疮疡”。结论 白及可与多种药物配伍治疗不同疾病，与白蔹配伍通过多途径、多靶点、多通路治疗“痈疽、疮疡”。

Objective To explore the medication rules and potential molecular mechanisms of prescriptions containing Baiji (Bletillae Rhizoma) based on multi-dimensional data analysis methods. Method The prescriptions containing Bletillae Rhizoma in the Dictionary of Traditional Chinese Medicine Prescriptions were collected and organized. Statistical analyses were conducted on parameters including historical dynasties, dosage forms, administration routes, preparation methods, therapeutic indications, frequency of use and dosage, efficacy categories, and properties (nature, flavor, and meridian tropism). Association rule mining and cluster analysis were employed to explore the compatibility patterns. The active components and their potential targets of the Bletillae Rhizoma-Bailian (Ampelopsis Radix) herb pair were obtained from public databases, and the disease-related targets associated with “carbuncles and abscesses” were identified through database screening. Topological network analysis was performed to identify the potential targets of the herb pair in treating “carbuncles and abscesses”. Gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) enrichment analyses were subsequently conducted. Molecular docking validation was performed using AutoDock software based on the results of network pharmacology. The optimal binding energy complexes from molecular docking were subjected to 100 ns molecular dynamics simulation. Results A total of 531 effective prescriptions containing Bletillae Rhizoma were collected, involving 579 types of Chinese herbs. The herbs were mainly characterized by cold, warm, or neutral properties, and by bitter, pungent, or sweet flavors, predominantly entering the liver, lung, stomach, and spleen meridians. Most prescriptions were prepared as ointments or powders, typically processed with oil or water, and primarily administered externally. The 531 prescriptions were used to treat 179 symptoms, which were classified into 29 major categories according to the symptom index in Volume 11 of the Dictionary of Traditional Chinese Medicine Prescriptions. The categories with the highest frequency were “carbuncles and abscesses”, “dermatological diseases and syndromes”, “traumatological diseases and syndromes”, and “diseases and syndromes of qi, blood, essence, and body fluids.” Dosage analysis revealed that the common dosage of Bletillae Rhizoma was 3.73 g, usually combined with other Chinese herbs at an approximately 1∶1 ratio. Network pharmacology analysis showed that the core active components of Bletillae Rhizoma-Ampelopsis Radix herb pair for treating “carbuncles and abscesses” were bletlol A, (−)-catechin gallate, 1-(2,7-dihydroxy-4-methoxy-1-phenanthryl)-4-methoxyphenanthrene-2,7-diol, spinasterol, stigmasterol, sitosterol, and 1-(4-hydroxybenzyl)-4-methoxy-9,10-dihydrophenanthrene-2,7-diol, mainly belonging to sterols and aromatic hydrocarbon classes. The key targets included AKT1, TNF, BCL2, EGFR, JUN, CASP3, STAT3, and the biological pathways mainly involved cancer (pathways in cancer), phosphatidylinositol-3-hydroxykinase (PI3K)-protein kinase B (Akt), mitogen-activated protein kinase, etc. with functions mainly inhibiting cancer transcription factors, regulating enzyme activity, and regulating the expression of inflammation-related genes. Molecular docking and molecular dynamics simulation results showed that the core components of Bletillae Rhizoma-Ampelopsis Radix herb pair had good binding activity with the target proteins. Among them, bletlol A can regulate the PI3K-Akt pathway to affect STAT3 expression, effectively treating “carbuncles and abscesses” through anti-inflammatory and tissue repair effects. Conclusion Bletillae Rhizoma can be combined with various herbs to treat multiple diseases, mainly exerting the effects of reducing swelling, promoting tissue regeneration, and relieving pain and bleeding. Its combination with Ampelopsis Radix exerts therapeutic effects on “carbuncles and abscesses” through multi-component, multi-target, and multi-pathway mechanisms.

R285

四川省科技计划项目资助（2021ZHFP0137）