Understanding the Signaling Pathways Related to the Mechanism and Treatment of Diabetic Peripheral Neuropathy

Tang, He-Yong; Jiang, Ai-Juan; Ma, Jie; Wang, Fanjing; Shen, Guo-Ming

doi:10.1210/en.2019-00311

Cited by 34 publications

(24 citation statements)

References 96 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The exact etiology of DPN is still unclear, and its pathogenesis may be related to mitochondrial dysfunction and oxidative stress, polyol pathway activation, advanced glycosylation end products, and endoplasmic reticulum stress due to prolonged and severe hyperglycaemia [ 46 , 47 ]. In addition, metabolic inflammation, neurotrophic vasculopathy, insulin resistance, and neurotrophic factors are all involved, creating a complex and interrelated pathogenesis [ 48 ].…”

Section: Discussionmentioning

confidence: 99%

Network Pharmacology and Molecular Docking Study on the Potential Mechanism of Yi-Qi-Huo-Xue-Tong-Luo Formula in Treating Diabetic Peripheral Neuropathy

Lin

Shen

Wang

et al. 2021

Journal of Diabetes Research

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionmentioning

confidence: 99%

Network Pharmacology and Molecular Docking Study on the Potential Mechanism of Yi-Qi-Huo-Xue-Tong-Luo Formula in Treating Diabetic Peripheral Neuropathy

Lin

Shen

Wang

et al. 2021

Journal of Diabetes Research

View full text Add to dashboard Cite

show abstract

“…Neuropathic pain affects approximately one-third of patients with diabetes, 25 , 26 and DPN is a key factor in the development of diabetic foot ulcers, the most common cause of amputation. 14 With the discovery of risk factors for DPN and a deepening understanding of the pathogenesis, 27 many researchers have developed effective treatments for DPN. Clinical trials have focused on various treatment strategies for specific pathogeneses of DPN.…”

Section: Discussionmentioning

confidence: 99%

Interventional Clinical Trials on Diabetic Peripheral Neuropathy: A Retrospective Analysis

Wang¹,

Zhang

et al. 2021

JPR

View full text Add to dashboard Cite

Aims/Introduction Diabetic peripheral neuropathy (DPN) is the most common complication of diabetes. At present, there is no comprehensive summary of the clinical trials related to DPN. In this article, we summarized the basic characteristics of the interventional clinical trials pertaining to DPN to determine the current status of research in this field and the existing issues. Materials and Methods We searched the World Health Organization International Clinical Trial Registration Platform (ICTRP), PubMed and Web of Science for clinical trials from 2005 to April 2021 and extracted 149 registered and 459 published clinical trials on DPN. We summarized the characteristics of the clinical trials, including the source registration, recruitment status, stage, age group, allocation method, intervention, end point classification, funding source, and treatment. Results After excluding noninterventional and nontreatment trials, 149 registered clinical trials out of 292 records from 12 registration centers and 459 published articles were included in this study. Among the registered trials, 43% had been completed, and 34.4% had been published in peer-reviewed journals. Among these trials, more than half used random allocation and blinded placebo-controlled methodologies. A total of 40.3% of the trials were multicenter studies, 63.8% of the treatments were drug therapies, and the endpoint classifications of 49% were efficacy and safety. Of the 459 published interventional clinical trials on DPN, 69.7% of the trials used drug treatments; more than half were randomized, double-blind, placebo-controlled clinical trials; 94.1% had positive outcomes; 46.4% had a target size of 50; and 22.9% were multicenter. Conclusion This paper systematically summarizes the current status of interventional trials on DPN registered in the ICTRP and published clinical trials and provides a reference for the development of high-quality intervention strategies for DPN in the future.

show abstract

“…Indeed, the simultaneous production of superoxide and nitric oxide contributes to the production of peroxynitrite, which can rapidly cause the nitrification or nitrite of proteins for various cell types, lipid peroxidation, DNA damage, and cell apoptosis, and produce direct toxic effects on nerve tissues leading to neuropathy ( Tang et al., 2019 ; Zhou and Zhang, 2019 ). In addition, apoptosis induced by caspase-3 activation due to oxidative stress plays an important role in the progression of diabetic neuropathy ( Kamboj et al., 2010 ).…”

Section: Discussionmentioning

confidence: 99%

The Protective Effect and Mechanism of Dexmedetomidine on Diabetic Peripheral Neuropathy in Rats

et al. 2020

View full text Add to dashboard Cite

Objective: To investigate the role of dexmedetomidine (DEX) in the inhibition of diabetic peripheral neuropathy (DPN) and the protection in the nerve damage. Methods: Eighty male Sprague-Dawley (SD) rats were randomly allocated to four groups: the control group (C group), DPN model group (DPN group), DEX-treated group (DEX group), and the yohimbine treated group (YOH group). DPN was induced by intraperitoneal administration of streptozocin (STZ) (35 mg/kg). The body weights, blood glucose level, mechanical withdrawal threshold (MWT), thermal withdrawal latency (TWL), the motor, and sensory nerve conduction velocities (MNCV and SNCV) of sciatic nerve were measured. Then the sciatic nerve was isolated for H&E staining and immunohistochemical staining. The oxidative stress makers such as malondialdehyde (MDA), superoxide-dismutase (SOD), and glutathione peroxidase (GSH-Px) and apoptosis related cytokines such as Bax, Bcl-2, and caspase-3 were estimated. Results: There was no significant difference of the blood glucose and body weight among the DPN group, DEX group, and YOH group. H&E staining showed that DEX treatment can ameliorate the damage of sciatic nerve cells. In the DPN group, MWT, TWL, MNCV, and SNCV were significantly reduced compared with the C group (P < 0.05). In DEX group rats, MWT, TWL, MNCV, and SNCV were increased significantly (P < 0.05) compared with the DPN group and YOH group rats. Lower SOD and GSH-Px, and higher MDA were found in the DPN group compared with the C group (P < 0.01), and DEX treatment restored SOD, GSH-px, and MDA activity significantly (P < 0.01). The expression levels of Bax and caspase-3 were increased, while that of Bcl-2 was decreased significantly in the DPN group compared with the C group (P < 0.05). In the DEX group, the expression levels of Bax and caspase-3 were decreased significantly (P < 0.05), while that of Bcl-2 was increased significantly (P < 0.05) compared with the DPN group and the YOH group. Conclusion: The results of this study demonstrated that DEX has the inhibitory and protective effects on DPN of rats. This may be associated with its antioxidative and antiapoptosis responses.

show abstract

Understanding the Signaling Pathways Related to the Mechanism and Treatment of Diabetic Peripheral Neuropathy

Cited by 34 publications

References 96 publications

Network Pharmacology and Molecular Docking Study on the Potential Mechanism of Yi-Qi-Huo-Xue-Tong-Luo Formula in Treating Diabetic Peripheral Neuropathy

Network Pharmacology and Molecular Docking Study on the Potential Mechanism of Yi-Qi-Huo-Xue-Tong-Luo Formula in Treating Diabetic Peripheral Neuropathy

Interventional Clinical Trials on Diabetic Peripheral Neuropathy: A Retrospective Analysis

The Protective Effect and Mechanism of Dexmedetomidine on Diabetic Peripheral Neuropathy in Rats

Contact Info

Product

Resources

About