Yuting Lu , Yan Duan , Yuping Dai , Xiaoting Ni , Juan Li , Xinliang Zeng , Pei Cai , Shunxiang Li
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引用次数: 0
Abstract
Ethnopharmacological relevance
Fufang Tongye Shaoshang You (TYY) is an ethnomedicine derived from the traditional folk formula of the Tujia people in Hunan Province, which consists of Paulownia leaf and sesame oil, has shown promising potential in promoting diabetic ulcer (DU) healing. However, its pharmacological substance and mechanism of action require further elucidation.
Aims of the study
This study was designed to assess the healing effect of TYY on DU wounds in mice, and to explore systematically its potential mechanisms and pharmacodynamic material basis.
Methods
The combination of high-fat, high-sugar diet and streptozotocin injection was used to induce C57BL/6 J mouse diabetic model, and the ulcer was surgically introduced. After TYY treatment, the skin lesions of diabetic mice were observed by H&E, Masson staining and transmission electron microscopy over a period of time. The wound tissues were collected. Transcriptomics were used to predict the potential mechanism of TYY, and then immunohistochemistry, immunofluorescence, ELISA, Western blotting, and qRT-PCR were used to detect the expression levels of key proteins and mRNA in related signaling pathways. The effect of TYY on tight junction proteins was evaluated by Western blotting. The chemical components of 10 batches of TYY were analyzed by multivariate analysis, and the iconic components of TYY were screened by molecular docking and dynamics simulation. HMEC-1 cells were induced by lipopolysaccharide and high glucose concentrations to simulate a DU microenvironment and construct an endothelial cell injury model. Scratch test and RT-qPCR were used to evaluate the effects of TYY active ingredients on the endothelial cell injury model, finally determining the pharmacodynamic material basis of TYY.
Results
The study has demonstrated that TYY can not only effectively repair the skin barrier, but also regulate the IL-17-mediated NF-κB/AP-1 signaling pathway, inhibit the exacerbation of inflammation, and accelerate wound healing in DU mice. In addition, we further discovered the key active ingredients of TYY: maslinic acid, corosolic acid, oleanolic acid, ursolic acid and sesamin.
Conclusion
This study provides scientific evidence for TYY as a potential drug to repair DU, and also provides a theoretical basis for its further clinical application and drug development.
期刊介绍:
The Journal of Ethnopharmacology is dedicated to the exchange of information and understandings about people''s use of plants, fungi, animals, microorganisms and minerals and their biological and pharmacological effects based on the principles established through international conventions. Early people confronted with illness and disease, discovered a wealth of useful therapeutic agents in the plant and animal kingdoms. The empirical knowledge of these medicinal substances and their toxic potential was passed on by oral tradition and sometimes recorded in herbals and other texts on materia medica. Many valuable drugs of today (e.g., atropine, ephedrine, tubocurarine, digoxin, reserpine) came into use through the study of indigenous remedies. Chemists continue to use plant-derived drugs (e.g., morphine, taxol, physostigmine, quinidine, emetine) as prototypes in their attempts to develop more effective and less toxic medicinals.