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通过发现关键药物靶点探索痹祺胶囊治疗痛风的潜在疗效

Exploring Therapeutic Potential of Bi-Qi Capsules in Treatment of Gout by Discovering Crucial Drug Targets.

作者信息

Xie Jing, Zhang Yu, Ren Rong, Bu Ruizhen, Chen Liying, Hou Juezhuo, Shang Dandan, Liu Yadong, Wang Dan, Wang Tao, Zhou Hong

机构信息

State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.

Tianjin Pharmaceutical Da Ren Tang Group Co., Ltd., 17 Baidi Road, Nankai District, Tianjin 300193, China.

出版信息

Pharmaceuticals (Basel). 2025 Apr 24;18(5):618. doi: 10.3390/ph18050618.

Abstract

: This research aims to explore the therapeutic potential of Bi-Qi capsules in the treatment of gout by identifying crucial drug targets through a multidimensional data analysis strategy. : Bi-Qi capsule drug targets and differentially expressed genes (DEGs) of gout were derived from public databases, such as Swiss Target Prediction, STITCH, and the GEO database. Subsequently, the overlapped targets were analyzed to elucidate the potential therapeutic mechanism and to identify candidate targets of Bi-Qi capsules against gout. Next, Mendelian randomization (MR) analysis was employed to screen and explore the causal relationship between candidate targets and gout. Finally, single-cell RNA sequencing (scRNA-seq), gene set enrichment analysis (GSEA), transcription factor and ceRNA regulatory networks, and molecular docking were performed to validate the role of the crucial targets of Bi-Qi capsules in the treatment of gout. : A total of 46 candidate targets were identified, in which KCNA5, PTGS2, and TNF exhibited significant causal relationships with gout ( < 0.05) and were regarded as the crucial targets. Through scRNA-seq and gene labeling, crucial targets were found to be expressed in eighteen cell clusters and eight cell types, which are closely associated with carbohydrate metabolism, nerve conduction, and the innate immunity process. Bi-Qi capsule active compounds such as tanshinone IIA, strychnine, tanshinaldehyde, cryptotanshinone, tumulosic acid, and glycyrrhetic acid exhibit a better binding ability to crucial targets. : The results not only elucidate the anti-gout mechanism of Bi-Qi capsules but also provide an insight into multi-target natural medication for metabolic disease treatment, which contributes to guiding the clinical application of Bi-Qi capsules in the future.

摘要

本研究旨在通过多维数据分析策略确定关键药物靶点,探索痹祺胶囊治疗痛风的潜在疗效。痹祺胶囊的药物靶点和痛风的差异表达基因(DEGs)来源于公共数据库,如瑞士靶点预测数据库、STITCH数据库和基因表达综合数据库(GEO数据库)。随后,对重叠靶点进行分析,以阐明潜在的治疗机制,并确定痹祺胶囊治疗痛风的候选靶点。接下来,采用孟德尔随机化(MR)分析筛选和探索候选靶点与痛风之间的因果关系。最后,进行单细胞RNA测序(scRNA-seq)、基因集富集分析(GSEA)、转录因子和ceRNA调控网络以及分子对接,以验证痹祺胶囊关键靶点在治疗痛风中的作用。共鉴定出46个候选靶点,其中钾电压门控通道亚家族A成员5(KCNA5)、前列腺素内过氧化物合酶2(PTGS2)和肿瘤坏死因子(TNF)与痛风表现出显著的因果关系(<0.05),被视为关键靶点。通过scRNA-seq和基因标记发现,关键靶点在18个细胞簇和8种细胞类型中表达,这些细胞簇和细胞类型与碳水化合物代谢、神经传导和先天免疫过程密切相关。痹祺胶囊的活性化合物如丹参酮IIA、士的宁、丹参醛、隐丹参酮、土贝母苷甲和甘草次酸对关键靶点具有较好的结合能力。研究结果不仅阐明了痹祺胶囊的抗痛风机制,还为代谢性疾病的多靶点天然药物治疗提供了思路,有助于指导痹祺胶囊未来的临床应用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7ec7/12114690/8d291a7e9a9c/pharmaceuticals-18-00618-g001.jpg

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