Abstract:Objective To study the combined action mechanism of tanshinone ⅡA in the treatment of diabetic neuropathy from the molecular level. Methods The structure, target, main biological functions and pathways of tanshinone ⅡA were collected through PubChem database, PharmMapper database and CTD database. Visualized by Pymol software. Results Seventeen target genes of tanshinone ⅡA in the treatment of diabetic neuropathy were obtained, the docking score showed that the compounds and targets were well docked. Gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis showed that tanshinone ⅡA in the treatment of diabetic neuropathy mainly involved 25 biological functions, including peptide serine phosphorylation, lipopolysaccharide mediated signaling pathway, negative regulation of apoptosis process, and so on. It mainly involved 19 pathways, such as TNF signaling pathway, FoxO signaling pathway, VEGF signaling pathway, PI3K-Akt signaling pathway, and so on. Among them, PI3K-Akt signaling pathway, MAPK signaling pathway, TNF signaling pathway and FoxO signaling pathway were the most enriched targets. Conclusion The reliability of tanshinone ⅡA binding to 17 targets has verified from the perspective of molecular docking. It is revealed that the role of tanshinone ⅡA in the treatment of diabetic neuropathy may be closely related to PI3K-Akt signaling pathway, MAPK signaling pathway, TNF signaling pathway, and FoxO signaling pathway.
李浩月 钟达源 邓奕辉. 基于分子对接技术探讨丹参酮ⅡA治疗糖尿病神经病变的结合作用机制[J]. 中国医药导报, 2021, 18(24): 107-110.
LI Haoyue ZHONG Dayuan DENG Yihui. Discussion on combined action mechanism of tanshinone ⅡA in the treatment of diabetic neuropathy based on molecular docking technology. 中国医药导报, 2021, 18(24): 107-110.
[1] van Dieren S,Beulens JW,van der Schouw YT,et al. The global burden of diabetes and its complications:an emerging pandemic [J]. Eur J Cardiovasc Prev Rehabil,2010, 17(suppl 1):S3-S8.
[2] Chahbi Z,Lahmar B,Hadri SE,et al. The prevalence of painful diabetic neuropathy in 300 Moroccan diabetics [J]. Pan Afr Med J,2018,31:158.
[3] Alsaloum M,Estacion M,Almomani R,et al. A gain-of-function sodium channel β2-subunit mutation in painful diabetic neuropathy [J]. Mol Pain,2019,15:1744806919 849802.
[4] Gao Z,Li Q,Wu X,et al. New insights into the mechanisms of Chinese herbal products on diabetes:a focus on the “bacteria-mucosal immunity-inflammation-diabetes” axis [J]. J Immunol Res,2017,2017:1813086.
[5] 段力,武凤震,梁庆顺,等.基于文献2型糖尿病周围神经病变中医证型规律及用药特点探讨[J].中医药导报,2018,24(10):31-35.
[6] 刘勇,霍金莲,龙永春,等.胰岛素与丹参酮ⅡA对大鼠糖尿病周围神经病变的保护作用[J].西北药学杂志,2015, 30(6):716-720.
[7] Mao S,Wang L,Chen P,et al. Nanoparticle-mediated delivery of Tanshinone ⅡA reduces adverse cardiac remodeling following myocardial infarctions in a mice model:role of NF-κB pathway [J]. Artif Cells Nanomed Biotechnol,2018,46(sup3):S707-S716.
[8] Kim S,Chen J,Cheng T,et al. PubChem 2019 update:improved access to chemical data [J]. Nucleic Acids Res,2019,47(D1):D1102-D1109.
[9] Wang X,Shen Y,Wang S,et al. PharmMapper 2017 update:a web server for potential drug target identification with a comprehensive target pharmacophore database [J]. Nucleic Acids Res,2017,45(W1):W356-W360.
[10] Davis AP,Grondin CJ,Johnson RJ,et al. The comparative toxicogenomics database:update 2019 [J]. Nucleic Acids Res,2019,47(D1):D948-D954.
[11] Huang da W,Sherman BT,Lempicki RA. Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources [J]. Nat Protoc,2009,4(1):44-57.
[12] Szklarczyk D,Gable AL,Lyon D,et al. STRING v11:protein-protein association networks with increased coverage,supporting functional discovery in genome-wide experimental datasets [J]. Nucleic Acids Res,2019,47(D1):D607-D613.
[13] Burley SK,Bhikadiya C,Bi C,et al. RCSB protein data bank:powerful new tools for exploring 3D structures of biological macromolecules for basic and applied research and education in fundamental biology,biomedicine,biotechnology,bioengineering and energy sciences [J]. Nucleic Acids Res,2021,49(D1):D437-D451.
[14] Wang L,Gao P,Zhang M,et al. Prevalence and ethnic pattern of diabetes and prediabetes in China in 2013 [J]. JAMA,2017,317(24):2515-2523.
[15] Hou QT,Li Y,Li SP,et al. The global burden of diabetes of mellitus [J]. Chin J Diabetes,2016,24(1):92-96.
[16] Feldman EL,Callaghan BC,Pop-Busui R,et al. Diabetic neuropathy [J]. Nat Rev Dis Primers,2019,5(1):42.
[17] 饶潇潇,姚广涛,文小平.中药干预糖尿病周围神经病变作用机制研究进展[J].中国中医药信息杂志,2017, 24(4):130.
[18] Chen J,Bi Y,Chen L,et al. Tanshinone ⅡA exerts neuroprotective effects on hippocampus-dependent cognitive impairments in diabetic rats by attenuating ER stress-induced apoptosis [J]. Biomed Pharmacother,2018,104:530-536.
[19] Zhang B,Yu Y,Aori G,et al. Tanshinone ⅡA attenuates diabetic peripheral neuropathic pain in experimental rats via inhibiting inflammation [J]. Evid Based Complement Alternat Med,2018,2018:2789847.
[20] Ri-Ge-le A,Guo ZL,Wang Q,et al. Tanshinone ⅡA improves painful diabetic neuropathy by suppressing the expression and activity of voltage-gated sodium channel in rat dorsal root ganglia [J]. Exp Clin Endocrinol Diabetes,2018,126(10):632-639.
[21] Feng F,Qiu H. Neuroprotective effect of tanshinone ⅡA against neuropathic pain in diabetic rats through the Nrf2/ARE and NF-κB signaling pathways [J]. Kaohsiung J Med Sci,2018,34(8):428-437.
[22] Xie W,Ji L,Zhao T,et al. Identification of transcriptional factors and key genes in primary osteoporosis by DNA microarray [J]. Med Sci Monit,2015,21:1333-1344.
[23] Liu AL,Du GH. Network pharmacology:new guidelines for drug discovery [J]. Acta Pharmaceutica Sinica,2010, 45(12):1472-1477.
[24] Chaudhuri J,Bose N,Gong J,et al. A caenorhabditis elegans model elucidates a conserved role for TRPA1-Nrf signaling in reactive α-dicarbonyl detoxification [J]. Curr Biol,2016,26(22):3014-3025.
[25] Mu ZP,Wang YG,Li CQ,et al. Association between tumor necrosis factor-α and diabetic peripheral neuropathy in patients with type 2 diabetes:a meta-analysis [J]. Mol Neurobiol,2017,54(2):983-996.
[26] Guo K,Elzinga S,Eid S,et al. Genome-wide DNA methylation profiling of human diabetic peripheral neuropathy in subjects with type 2 diabetes mellitus [J]. Epigenetics,2019,14(8):766-779.
[27] Atef MM,El-Sayed NM,Ahmed AAM,et al. Donepezil improves neuropathy through activation of AMPK signalling pathway in streptozotocin-induced diabetic mice [J]. Biochem Pharmacol,2019,159:1-10.
[28] Yang CT,Chen L,Chen WL,et al. Hydrogen sulfide primes diabetic wound to close through inhibition of NETosis [J]. Mol Cell Endocrinol,2019,480:74-82.