Gene set enrichment analysis and ingenuity pathway analysis to identify biomarkers in Sheng-ji Hua-yu formula treated diabetic ulcers

• Published in: Journal of ethnopharmacology 2022-03, Vol.285, p.114845-114845, Article 114845
• Main Authors: Ru, Yi, Zhang, Ying, Xiang, Yan-wei, Luo, Ying, Luo, Yue, Jiang, Jing-si, Song, Jian-kun, Fei, Xiao-ya, Yang, Dan, Zhang, Zhan, Zhang, Hui-ping, Liu, Tai-yi, Yin, Shuang-yi, Li, Bin, Kuai, Le
• Format: Article
• Language: English
• Subjects: Animals; Chinese herbs; Diabetes Complications; Diabetes Mellitus, Experimental; Diabetic ulcers; Drugs, Chinese Herbal - therapeutic use; Gene set enrichment analysis; Humans; Ingenuity pathway analysis; Mice; RNA, Messenger - genetics; RNA, Messenger - metabolism; Sheng-ji Hua-yu; Skin Ulcer - drug therapy; Skin Ulcer - etiology; Wound Healing - drug effects
• ISSN: 0378-8741; 1872-7573
• DOI: 10.1016/j.jep.2021.114845

Sheng-ji Hua-yu (SJHY) formula is a Chinese herbal prescription for diabetic ulcers (DUs) treatment, which can accelerate wound reconstruction and shorten the healing time. However, its mechanism role maintains unclear. To elucidate the molecular mechanisms of SJHY application on DUs. To begin with, transcriptome sequencing was adopted to identified differentially expression mRNAs among normal ulcers, DUs, and DUs + SJHY treatment in vivo. Liquid chromatography-tandem mass spectrometry was applied for the quality control of SJHY formula. GO and KEGG enrichment analysis were used to identify the mechanisms underlying the therapeutic effect of SJHY formula, and then gene set enrichment analysis and ingenuity pathway analysis were conducted for functional analysis. Further, qPCR detection was performed in vivo for validation. SJHY administration could regulate the glucose metabolic process, AMPK and HIF-1 pathway to accelerate healing processes of DUs. Besides, CRHR1, SHH, and GAL were identified as the critical targets, and SLC6A3, GRP, FGF23, and CYP27B1 were considered as the upstream genes of SJHY treatment. Combined with animal experiments, the prediction results were validated in DUs mice model. This study used modular pharmacology analysis to identify the biomarkers of SJHY formula and provide the potential therapeutic targets for DUs treatment as well. [Display omitted]