Systematic Elucidation of the Mechanism of in the Treatment of Diabetic Peripheral Neuropathy Based on Network Pharmacology

Overview

Journal Evid Based Complement Alternat Med

Specialty Rehabilitation Medicine

Date 2021 Jul 26

PMID 34306139

Citations 4

Authors

Xiaomin Kang

De Jin

Yuqing Zhang

Rongrong Zhou

YueHong Zhang

Fengmei Lian

Affiliations

Soon will be listed here.

Abstract

Background: Diabetic peripheral neuropathy (DPN) is one of the most common chronic complications of diabetes, which seriously affects the physical and mental health of patients. (SL) is effective in treating DPN. Previous reports have shown that SL has a clear hypoglycemic and anti-inflammatory effect. However, the study of SL in the treatment of DPN is still limited and rare.

Objective: To investigate the mechanism of SL in the treatment of DPN based on network pharmacology.

Methods: The active ingredients of SL were screened by related databases. The compound targets were collected by the target prediction platforms. The DPN-related targets were gathered through disease databases. The intersection targets were obtained by uploading the compound targets and disease targets to Venny 2.1.0, and a compound-target network was constructed by Cytoscape3.7.2. The protein-protein interaction (PPI) relationships were obtained by the STRING11.0 database. Genome Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed using the DAVID6.8 database. Molecular docking of key compounds and core targets was performed by DockThor.

Results: A total of 29 compounds and 51 intersection targets with potential therapeutic effects on DPN were obtained. The compound-target network construction resulted in four key compounds: protostemonine, 3-deoxysappanchalcone, 7,3',4'-trihydroxy-3-benzyl-2H-chromene, and o-12'-methylergocornine. PPI network analysis yielded 10 core targets: AKT1, MAPK3, CXCL8, TNF, OPRM1, MTOR, STAT3, MAPK8, SIRT1, and HSP90AA1. KEGG analysis resulted in 82 signaling pathways ( < 0.05), including insulin resistance, HIF-1 signaling pathway, and type II diabetes. The docking results indicated that the main active compounds could stably bind to core targets.

Conclusion: SL had the mechanism of multiple ingredients, multiple targets, and multiple pathways in the treatment of DPN. This study provided a scientific basis for further research on the treatment of DPN with SL and its extracts.

Citing Articles

The Multi-Target Action Mechanism for the Anti-Periodontitis Effect of Based on Bioinformatics Analysis and In Vitro Verification.

Li N, Wang B, Yang M, Feng M, Xu X, Xian C Nutrients. 2025; 17(4).

PMID: 40004956 PMC: 11858088. DOI: 10.3390/nu17040627.

Exploring the potential pharmacological mechanism of aripiprazole against hyperprolactinemia based on network pharmacology and molecular docking.

Yang L, Zhang Q, Li C, Tian H, Zhuo C Schizophrenia (Heidelb). 2024; 10(1):105.

PMID: 39511179 PMC: 11544107. DOI: 10.1038/s41537-024-00523-8.

Mechanisms of action of for prostate cancer treatment: network pharmacology, molecular docking and experimental validation.

Li W, Jiang H, Zhang W, Sun Q, Zhang Q, Xu J Front Pharmacol. 2024; 15:1407525.

PMID: 39318781 PMC: 11420528. DOI: 10.3389/fphar.2024.1407525.

Exploring the mechanism of active components from ginseng to manage diabetes mellitus based on network pharmacology and molecular docking.

Li M, Jin M, Hu R, Tang S, Li K, Gong X Sci Rep. 2023; 13(1):793.

PMID: 36646777 PMC: 9842641. DOI: 10.1038/s41598-023-27540-4.

Anti-Inflammatory Activities of the Ethanol Extract of , an Edible Freshwater Green Algae, and Its Various Solvent Fractions in LPS-Induced Macrophages and Carrageenan-Induced Paw Edema via the AP-1 Pathway.

Rahmawati L, Park S, Kim D, Lee H, Aziz N, Lee C Molecules. 2022; 27(1).

PMID: 35011425 PMC: 8746635. DOI: 10.3390/molecules27010194.

References

Wu Y, He H, Nie Y, Ding Y, Sun L, Qian F . Protostemonine effectively attenuates lipopolysaccharide-induced acute lung injury in mice. Acta Pharmacol Sin. 2017; 39(1):85-96. PMC: 5758663. DOI: 10.1038/aps.2017.131. View

Lin-Holderer J, Li L, Gruneberg D, Marti H, Kunze R . Fumaric acid esters promote neuronal survival upon ischemic stress through activation of the Nrf2 but not HIF-1 signaling pathway. Neuropharmacology. 2016; 105:228-240. DOI: 10.1016/j.neuropharm.2016.01.023. View

Wu L, Li M, Qu M, Li X, Pi L, Chen Z . High glucose up-regulates Semaphorin 3A expression via the mTOR signaling pathway in keratinocytes: A potential mechanism and therapeutic target for diabetic small fiber neuropathy. Mol Cell Endocrinol. 2017; 472:107-116. DOI: 10.1016/j.mce.2017.11.025. View

Daina A, Michielin O, Zoete V . SwissTargetPrediction: updated data and new features for efficient prediction of protein targets of small molecules. Nucleic Acids Res. 2019; 47(W1):W357-W364. PMC: 6602486. DOI: 10.1093/nar/gkz382. View

Kim J, Choo Y, Tae N, Min B, Lee J . The anti-inflammatory effect of 3-deoxysappanchalcone is mediated by inducing heme oxygenase-1 via activating the AKT/mTOR pathway in murine macrophages. Int Immunopharmacol. 2014; 22(2):420-6. DOI: 10.1016/j.intimp.2014.07.025. View

Nakahara H, Song J, Sugimoto M, Hagihara K, Kishimoto T, Yoshizaki K . Anti-interleukin-6 receptor antibody therapy reduces vascular endothelial growth factor production in rheumatoid arthritis. Arthritis Rheum. 2003; 48(6):1521-9. DOI: 10.1002/art.11143. View

Yang F, Zhou W, Liu A, Qin H, Lee S, Wang Y . The protective effect of 3-deoxysappanchalcone on in vitro influenza virus-induced apoptosis and inflammation. Planta Med. 2012; 78(10):968-73. DOI: 10.1055/s-0031-1298620. View

Xu L, Brink M . mTOR, cardiomyocytes and inflammation in cardiac hypertrophy. Biochim Biophys Acta. 2016; 1863(7 Pt B):1894-903. DOI: 10.1016/j.bbamcr.2016.01.003. View

Brunet A, Sweeney L, Sturgill J, Chua K, Greer P, Lin Y . Stress-dependent regulation of FOXO transcription factors by the SIRT1 deacetylase. Science. 2004; 303(5666):2011-5. DOI: 10.1126/science.1094637. View

10.

Keiser M, Roth B, Armbruster B, Ernsberger P, Irwin J, Shoichet B . Relating protein pharmacology by ligand chemistry. Nat Biotechnol. 2007; 25(2):197-206. DOI: 10.1038/nbt1284. View

11.

Milburn C, Deak M, Kelly S, Price N, Alessi D, van Aalten D . Binding of phosphatidylinositol 3,4,5-trisphosphate to the pleckstrin homology domain of protein kinase B induces a conformational change. Biochem J. 2003; 375(Pt 3):531-8. PMC: 1223737. DOI: 10.1042/BJ20031229. View

12.

Switon K, Kotulska K, Janusz-Kaminska A, Zmorzynska J, Jaworski J . Molecular neurobiology of mTOR. Neuroscience. 2016; 341:112-153. DOI: 10.1016/j.neuroscience.2016.11.017. View

13.

Niu J, Sun Y, Chen B, Zheng B, Jarugumilli G, Walker S . Fatty acids and cancer-amplified ZDHHC19 promote STAT3 activation through S-palmitoylation. Nature. 2019; 573(7772):139-143. PMC: 6728214. DOI: 10.1038/s41586-019-1511-x. View

14.

Santos K, Guedes I, Karl A, Dardenne L . Highly Flexible Ligand Docking: Benchmarking of the DockThor Program on the LEADS-PEP Protein-Peptide Data Set. J Chem Inf Model. 2020; 60(2):667-683. DOI: 10.1021/acs.jcim.9b00905. View

15.

Hopkins A . Network pharmacology: the next paradigm in drug discovery. Nat Chem Biol. 2008; 4(11):682-90. DOI: 10.1038/nchembio.118. View

16.

Triantafilou K, Triantafilou M, Dedrick R . A CD14-independent LPS receptor cluster. Nat Immunol. 2001; 2(4):338-45. DOI: 10.1038/86342. View

17.

Jing W, Zhang X, Zhou H, Wang Y, Yang M, Long L . Naturally occurring cassane diterpenoids (CAs) of Caesalpinia: A systematic review of its biosynthesis, chemistry and pharmacology. Fitoterapia. 2019; 134:226-249. DOI: 10.1016/j.fitote.2019.02.023. View

18.

Daina A, Michielin O, Zoete V . SwissADME: a free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules. Sci Rep. 2017; 7:42717. PMC: 5335600. DOI: 10.1038/srep42717. View

19.

Chen H, Bai J, Ye J, Liu Z, Chen R, Mao W . JWA as a functional molecule to regulate cancer cells migration via MAPK cascades and F-actin cytoskeleton. Cell Signal. 2007; 19(6):1315-27. DOI: 10.1016/j.cellsig.2007.01.007. View

20.

Noshita T, Fujita K, Koga T, Ouchi H, Tai A . Synthesis and biological activity of (±)-7,3',4'-trihydroxyhomoisoflavan and its analogs. Bioorg Med Chem Lett. 2020; 31:127674. DOI: 10.1016/j.bmcl.2020.127674. View