Potential Mechanism of the Shunaoxin Pill for Preventing Cognitive Impairment in Type 2 Diabetes Mellitus

Overview

Journal Front Neurol

Specialty Neurology

Date 2022 Nov 7

PMID 36341127

Authors

Yuejie Guo

Ning Luo

Xueran Kang

Affiliations

Soon will be listed here.

Abstract

Objective: This study aims to analyze the efficacy and mechanism of action of the Shunaoxin pill in preventing cognitive impairment in diabetic patients using network pharmacology.

Methods: The main active compounds of the Shunaoxin pills and their action targets were identified the TCMSP and Batman-TCM databases. The GEO database was used to identify the genes in type 2 diabetic individuals associated with cognitive impairment. Subsequently, a common target protein-protein interaction (PPI) network was constructed using the STRING database, and targets associated with diabetes and cognitive impairment were screened by performing a topological analysis of the PPI network. The AutoDock Vina software was used for molecular docking to evaluate the reliability of the bioinformatic analysis predictions and validate the interactions between the active ingredients of the Shunaoxin pill and proteins associated with diabetes and cognitive impairment.

Results: Based on the TCMSP and Batman-Tcm platform, 48 active ingredients of the Shunaoxin pill were identified, corresponding to 222 potential action targets. Further analysis revealed that 18 active components of the Shunaoxin pill might contribute to cognitive impairment in type 2 diabetic patients. Molecular docking simulations demonstrated that the active ingredients of the Shunaoxin pill (hexadecanoic acid, stigmasterol, beta-sitosterol, and angelicin) targeted four core proteins: OPRK1, GABRA5, GABRP, and SCN3B.

Conclusion: Active ingredients of the Shunaoxin pill may alleviate cognitive impairment in diabetic patients by targeting the proteins OPRK1, GABRA5, GABRP, and SCN3B.

Citing Articles

A novel colchicine-myricetin heterozygous molecule: design, synthesis, and effective evaluations on the pathological models of acute lung injury and .

Li Z, Yan X, Wei J, Pu L, Zhu G, Cao Y Front Pharmacol. 2023; 14:1224906.

PMID: 37456754 PMC: 10340118. DOI: 10.3389/fphar.2023.1224906.

References

You Y, Liu Z, Chen Y, Xu Y, Qin J, Guo S . The prevalence of mild cognitive impairment in type 2 diabetes mellitus patients: a systematic review and meta-analysis. Acta Diabetol. 2021; 58(6):671-685. DOI: 10.1007/s00592-020-01648-9. View

Cheong J, De Pablo-Fernandez E, Foltynie T, Noyce A . The Association Between Type 2 Diabetes Mellitus and Parkinson's Disease. J Parkinsons Dis. 2020; 10(3):775-789. PMC: 7458510. DOI: 10.3233/JPD-191900. View

Liu G, Ji H, Liu J, Xu C, Chang L, Cui W . Association of OPRK1 and OPRM1 methylation with mild cognitive impairment in Xinjiang Han and Uygur populations. Neurosci Lett. 2016; 636:170-176. DOI: 10.1016/j.neulet.2016.11.018. View

Dong Y, Chen Y, Yao B, Song P, Xu R, Li R . Neuropathologic damage induced by radiofrequency ablation at different temperatures. Clinics (Sao Paulo). 2022; 77:100033. PMC: 9035646. DOI: 10.1016/j.clinsp.2022.100033. View

Bonds J, Shetti A, Stephen T, Bonini M, Minshall R, Lazarov O . Deficits in hippocampal neurogenesis in obesity-dependent and -independent type-2 diabetes mellitus mouse models. Sci Rep. 2020; 10(1):16368. PMC: 7530538. DOI: 10.1038/s41598-020-73401-9. View

Ferreira S, Raimundo A, Menezes R, Martins I . Islet amyloid polypeptide & amyloid beta peptide roles in Alzheimer's disease: two triggers, one disease. Neural Regen Res. 2020; 16(6):1127-1130. PMC: 8224102. DOI: 10.4103/1673-5374.300323. View

Xu X, Pan X, Li S . Prospective analysis of the efficacy of beraprost sodium combined with alprostadil on diabetic nephropathy and influence on rennin-angiotensin system and TNF-α. Exp Ther Med. 2019; 19(1):639-645. PMC: 6913236. DOI: 10.3892/etm.2019.8265. View

Kim S, Chen J, Cheng T, Gindulyte A, He J, He S . PubChem in 2021: new data content and improved web interfaces. Nucleic Acids Res. 2020; 49(D1):D1388-D1395. PMC: 7778930. DOI: 10.1093/nar/gkaa971. View

Chin C, Chen S, Wu H, Ho C, Ko M, Lin C . cytoHubba: identifying hub objects and sub-networks from complex interactome. BMC Syst Biol. 2014; 8 Suppl 4:S11. PMC: 4290687. DOI: 10.1186/1752-0509-8-S4-S11. View

10.

Guariguata L, Whiting D, Hambleton I, Beagley J, Linnenkamp U, Shaw J . Global estimates of diabetes prevalence for 2013 and projections for 2035. Diabetes Res Clin Pract. 2014; 103(2):137-49. DOI: 10.1016/j.diabres.2013.11.002. View

11.

Zhang Q, Yang J, Yang C, Yang X, Chen Y . - L. Drug Pair Regulates Ferroptosis by Mediating the Neurovascular-Related Ligand-Receptor Interaction Pathway- A Potential Drug Pair for Treatment Hypertension and Prevention Ischemic Stroke. Front Neurol. 2022; 13:833922. PMC: 8957098. DOI: 10.3389/fneur.2022.833922. View

12.

Chen Y, Luo Z, Lin J, Qi B, Sun Y, Li F . Exploring the Potential Mechanisms of (L.) Pall. in Chronic Muscle Repair Patterns Using Single Cell Receptor-Ligand Marker Analysis and Molecular Dynamics Simulations. Dis Markers. 2022; 2022:9082576. PMC: 9177293. DOI: 10.1155/2022/9082576. View

13.

Zhou Q, Ge Q, Ding Y, Qu H, Wei H, Wu R . Relationship between serum adipsin and the first phase of glucose-stimulated insulin secretion in individuals with different glucose tolerance. J Diabetes Investig. 2018; 9(5):1128-1134. PMC: 6123022. DOI: 10.1111/jdi.12819. View

14.

Daumas S, Betourne A, Halley H, Wolfer D, Lipp H, Lassalle J . Transient activation of the CA3 Kappa opioid system in the dorsal hippocampus modulates complex memory processing in mice. Neurobiol Learn Mem. 2007; 88(1):94-103. DOI: 10.1016/j.nlm.2007.02.001. View

15.

Veber D, Johnson S, Cheng H, Smith B, Ward K, Kopple K . Molecular properties that influence the oral bioavailability of drug candidates. J Med Chem. 2002; 45(12):2615-23. DOI: 10.1021/jm020017n. View

16.

Zhu L, Li C, Du G, Pan M, Liu G, Pan W . High glucose upregulates myosin light chain kinase to induce microfilament cytoskeleton rearrangement in hippocampal neurons. Mol Med Rep. 2018; 18(1):216-222. PMC: 6059672. DOI: 10.3892/mmr.2018.8960. View

17.

Mao X, Cao D, Li X, Yin J, Wang Z, Zhang Y . Huperzine A ameliorates cognitive deficits in streptozotocin-induced diabetic rats. Int J Mol Sci. 2014; 15(5):7667-83. PMC: 4057698. DOI: 10.3390/ijms15057667. View

18.

Haberman R, Quigley C, Gallagher M . Characterization of CpG island DNA methylation of impairment-related genes in a rat model of cognitive aging. Epigenetics. 2012; 7(9):1008-19. PMC: 3515010. DOI: 10.4161/epi.21291. View

19.

Suviranta T, Timonen J, Martikainen J, Aarnio E . The effects of reimbursement reform of antidiabetic medicines from the patients' perspective - a survey among patients with type 2 diabetes in Finland. BMC Health Serv Res. 2019; 19(1):769. PMC: 6819478. DOI: 10.1186/s12913-019-4633-9. View

20.

Shi J, Li R, Yang S, Phang Y, Zheng C, Zhang H . The Protective Effects and Potential Mechanisms of : Focus on Anti-Inflammatory, Antioxidant, and Antiapoptotic Activities. Evid Based Complement Alternat Med. 2020; 2020:8205983. PMC: 7591981. DOI: 10.1155/2020/8205983. View