Abstract
Objective To investigate the potential mechanism of action of Yi-Qi-Huo-Xue-Tong-Luo formula (YQHXTLF) in the treatment of diabetic peripheral neuropathy (DPN). Methods Network pharmacology and molecular docking techniques were used in this study. Firstly, the active ingredients and the corresponding targets of YQHXTLF were retrieved using the Traditional Chinese Medicine Systems Pharmacology (TCMSP) platform; subsequently, the targets related to DPN were retrieved using GeneCards, Online Mendelian Inheritance in Man (OMIM), Pharmgkb, Therapeutic Target Database (TTD) and Drugbank databases; the common targets of YQHXTLF and DPN were obtained by Venn diagram; afterwards, the “YQHXTLF Pharmacodynamic Component-DPN Target” regulatory network was visualized using Cytoscape 3.6.1 software, and Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed on the potential targets using R 3.6.3 software. Finally, molecular docking of the main chemical components in the PPI network with the core targets was verified by Autodock Vina software. Results A total of 86 active ingredients and 229 targets in YQHXTLF were screened, and 81 active ingredients and 110 targets were identified to be closely related to diabetic peripheral neuropathy disease. PPI network mapping identified TP53, MAPK1, JUN, and STAT3 as possible core targets. KEGG pathway analysis showed that these targets are mostly involved in AGE-RAGE signaling pathway in diabetic complications, TNF signaling pathway, and MAPK signaling pathway. The molecular docking results showed that the main chemical components of YQHXTLF have a stable binding activity to the core pivotal targets. Conclusion YQHXTLF may act on TP53, MAPK1, JUN, and STAT3 to regulate inflammatory response, apoptosis, or proliferation as a molecular mechanism for the treatment of diabetic peripheral neuropathy, reflecting its multitarget and multipathway action, and providing new ideas to further uncover its pharmacological basis and mechanism of action.
Highlights
Diabetic peripheral neuropathy (DPN) is one of the most common and serious microvascular complications of diabetes which is characterized by pain, sensory abnormalities, and loss of sensation [1, 2]
The active ingredients were screened by searching the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database with a threshold value of Oral bioavailability (OB) ≥ 30% and Drug-like properties (DL) ≥ 0 : 18
The results showed that TP53, MAPK1, JUN, and STAT3 were the key targets under different algorithms
Summary
Diabetic peripheral neuropathy (DPN) is one of the most common and serious microvascular complications of diabetes which is characterized by pain, sensory abnormalities, and loss of sensation [1, 2]. There is no specific treatment for DPN in modern medicine, which consists mainly of improving metabolic disorders and pain management [5, 6]. In TCM, DPN is often classified as “paralysis,” “impotence,” and “blood paralysis” [9]. It is often caused by prolonged thirst, depletion of Qi and blood, deficiency of both yin and yang, and loss of nourishment for the tendons and veins, resulting in coldness, numbness, and muscle atrophy [10, 11]. A large number of studies have shown that Chinese medicine is effective in treating DPN, significantly improving the clinical symptoms of patients and delaying the development of the disease, with few toxic side effects [13].
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