Login Register Cart 0
Generic placeholder image

Combinatorial Chemistry & High Throughput Screening

Editor-in-Chief

ISSN (Print): 1386-2073
ISSN (Online): 1875-5402

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

Research on the Material Basis and Mechanism of Kudzu Root in Preventing and Treating Cerebral Ischemia based on Network Pharmacology

Author(s): Wei Yao, Xiaopeng Qiu, Bingtao Li, Feixia Yan, Song Wang, Xudong Zhu, Longhui Lu, Jingjing Wang, Na Zhu, Shuaikang Wang, Yongyan Xie, Ziwei Xu, Weifeng Zhu, Ronghua Liu* and Liping Huang*

Volume 26, Issue 11, 2023

Published on: 27 December, 2022

Page: [2013 - 2029] Pages: 17

DOI: 10.2174/1386207326666221103120322

Price: $65

Abstract

Background: It has been shown that Kudzu root has significant pharmacological effects such as improving microcirculation, dilating coronary arteries, and increasing cerebral and coronary blood flow, but its material basis and mechanism of action are not clear.

Objective: The aim of this study was to investigate the mechanism of action of Kudzu root in the prevention and treatment of cerebral ischemia (CI) through network pharmacology combined with animal experiments.

Methods: The components of kudzu root were screened by using the Chemistry Database, Chinese Academy of Science. Linpinski's five rules were used to perform pharmacophore-like analysis to obtain the active ingredients of Kudzu root. The Swiss Target Prediction Service database was used to predict the potential protein targets of kudzu root components associated with CI. An active ingredient-target network was constructed by using Cytoscape 3.6.0. A rat model of middle cerebral artery occlusion (MCAO) was established, then the main targets and signaling pathways predicted were verified by observing the area of cerebral infarction and Western blot experiments.

Results: In total, 84 major active compounds and 34 targets included gerberoside, belonging to the isoflavone class, gallic acid, amino acid class, 4-Methylphenol, phenolic class, and quercetin, and flavonoid class (Flavonoids). The targets covered were proteins related to excitatory amino acids and calcium overload, including Excitatory amino acid transporter 2 (SLC1A2), Glutamate receptor ionotropic, kainate 1 (GRIK1), Glutamate receptor ionotropic, NMDA 1 (GRIN1), Glutamate receptor 2(GRIA2), Calcium/calmodulin-dependent protein kinase II (CaMKII), Neuronal nitric oxide synthase(nNOS). Glutamatergic energy is prominent, and calcium transport across the membrane is central to the network and occupies an important position.

Conclusion: Kudzu root can significantly reduce neurological damage in rats with CI, and also significantly reduce the rate of cerebral infarction. It is worth noting that Kudzu root can prevent and treat CI by reducing excitatory amino acid toxicity and improving calcium overload.

Keywords: Network pharmacology, Kudzu root, cerebral ischemia, glutamatergic synapses, dilating coronary arteries, glutamatergic energy.

« Previous Next »
Graphical Abstract

[1]
Silva, A.F.; de Arimatéia, R.D.R.J.; Da Costa, M.L. Piper nigrum Spectroscopic methods and in silico analyses using density functional theory to characterize and identify piperine alkaloid crystals isolated from pepper (L.). J. Biomol. Struct. Dyn., 2020, 38, 2792-2799.
[http://dx.doi.org/10.1080/07391102.2019.1639547] [PMID: 31282297]
[2]
Deng, G.; Wu, C.; Lin, J.; Chao, C.; Wang, S. molecular docking technology to virtually predict the material basis of ginseng in the treatment of ischemic stroke. Chin. Herb. Med., 2016, 39, 1377-1383.
[3]
Zhang, H.; Hui, Y. Progress of research on the protective effect of natural drugs against cerebral ischemia-reperfusion injury. J. Nephropharmacol., 2020, 10(4), 14-20.
[4]
Feng, W.; Ao, H.; Yue, S.; Peng, C. Systems pharmacology reveals the unique mechanism features of Shenzhu capsule for treatment of ulcerative colitis in comparison with synthetic drugs. Sci. Rep., 2018, 8(1), 16160.
[http://dx.doi.org/10.1038/s41598-018-34509-1] [PMID: 30385774]
[5]
Gfeller, D.; Grosdidier, A.; Wirth, M.; Daina, A.; Michielin, O.; Zoete, V. SwissTargetPrediction: a web server for target prediction of bioactive small molecules. Nucleic Acids Res., 2014, 42(W1), W32-W38.
[http://dx.doi.org/10.1093/nar/gku293] [PMID: 24792161]
[6]
Guo, W.; Fu, C.; Ge, D. Analysis on the origin and application of Gegen decoction. Clin. Med. Res., 2021, 34, 4-8.
[7]
He, L.; Wen, A.; Yan, Z.; Hu, J.; Xu, W.; Tan, H.; Key, K. Effects of Naoluo Xintong Recipe on 5-HT, DA, NE and 5-HIAA in the striatum of rats after cerebral ischemia. J. Beijing Univ. Trad. Chin. Med., 2015, 38, 740-744.
[8]
Huang, Y.; Wang, J.; Du, L.; Zhang, W.; Mei, Z. Puerarin regulates AMPK-mTOR signaling pathway and inhibits autophagy to improve cerebral ischemia-reperfusion injury in rats. Chin. Herb. Med., 2019, 50, 3127-3133.
[9]
Kang, X.; Su, S.; Hong, W.; Geng, W.; Tang, H. Research progress on the ability of astragaloside IV to protect the brain against ischemia-reperfusion injury. Front. Neurosci., 2021, 15, 755902.
[http://dx.doi.org/10.3389/fnins.2021.755902] [PMID: 34867166]
[10]
da Silva Júnior, O.S.; Franco, C.J.P.; de Moraes, A.A.B.; Cruz, J.N.; da Costa, K.S.; do Nascimento, L.D.; Andrade, E.H.A. In silico analyses of toxicity of the major constituents of essential oils from two Ipomoea L. species. Toxicon, 2021, 195, 111-118.
[http://dx.doi.org/10.1016/j.toxicon.2021.02.015] [PMID: 33667485]
[11]
Neto, R.A.M.; Santos, C.B.R.; Henriques, S.V.C.; Machado, L.O.; Cruz, J.N.; da Silva, C.H.T.P.; Federico, L.B.; Oliveira, E.H.C.; de Souza, M.P.C.; da Silva, P.N.B.; Taft, C.A.; Ferreira, I.M.; Gomes, M.R.F. Novel chalcones derivatives with potential antineoplastic activity investigated by docking and molecular dynamics simulations. J. Biomol. Struct. Dyn., 2022, 40(5), 2204-2216.
[http://dx.doi.org/10.1080/07391102.2020.1839562] [PMID: 33146078]
[12]
Costa, E.B.; Silva, R.C.; Espejo-Román, J.M.; Neto, M.F.A.; Cruz, J.N.; Leite, F.H.A.; Silva, C.H.T.P.; Pinheiro, J.C.; Macêdo, W.J.C.; Santos, C.B.R. Chemometric methods in antimalarial drug design from 1,2,4,5-tetraoxanes analogues. SAR QSAR Environ. Res., 2020, 31(9), 677-695.
[http://dx.doi.org/10.1080/1062936X.2020.1803961] [PMID: 32854545]
[13]
Kimura, I. Medical benefits of using natural compounds and their derivatives having multiple pharmacological actions. Yakugaku Zasshi, 2006, 126(3), 133-143.
[http://dx.doi.org/10.1248/yakushi.126.133] [PMID: 16508237]
[14]
Li, N.; Guo, X.; Li, R.; Zhou, J.; Yu, F.; Yan, X. p-Coumaric acid regulates macrophage polarization inmyocardial ischemia/reperfusion by promotingthe expression of indoleamine 2, 3-dioxygenase. Bioengineered, 2021, 12(2), 10971-10981.
[15]
Lipinski, C.A. Lead- and drug-like compounds: the rule-of-five revolution. Drug Discov. Today. Technol., 2004, 1(4), 337-341.
[http://dx.doi.org/10.1016/j.ddtec.2004.11.007] [PMID: 24981612]
[16]
Song, M.K.; Roufogalis, B.D.; Huang, T.H. Reversal of the caspase-dependent apoptotic cytotoxicity pathway by Taurine from Lycium barbarum (Goji Berry) in human retinal pigment epithelial cells: Potential benefit in DR. Evid. Based Complement. Alternat. Med., 2012, 2012, 323784.
[17]
Ma, F. Yijia; Wan, H.; Pan, Lujia; Zheng, Yanqiu; Yu, He Study on the mechanism of anti-cerebral ischemia of Astragalus-Safflower based on network pharmacology. Proprietary Chin. Med., 2020, 42, 222-226.
[18]
Zhang, R. Network pharmacology databases for traditional Chinese medicine: review and assessment. Front. Pharmacol., 2019, 10, 123.
[19]
Hopkins, A.L. Network pharmacology: the next paradigm in drug discovery. Nat. Chem. Biol., 2008, 4(11), 682-690.
[http://dx.doi.org/10.1038/nchembio.118] [PMID: 18936753]
[20]
Liu, B. Puerarin exerts a protective effect on cardiac hypertrophy by regulating autophagy through AMPK/mTOR signaling pathway; Southern Medical University, 2016.
[21]
Liu, J.; Kong, X. The relationship between serum calmodulin level and the degree of neurological deficit in acute ischemic stroke. J. Microcir., 2014, 24, 32-34.
[22]
Liu, S.; Yang, L.; Ma, C.; Li, S.; Li, C.; Meng, X. Chinese medicine on neurovascular unit after cerebral ischemia-reperfusion injury. Chin. J. Exper. Formulas, 2018, 24, 225-234.
[23]
Luli, Q.G.; Tian, Y.; Lin, J.; Liang, S.; Wang, S. Simulation and prediction of the material basis of rhubarb for ischemic stroke based on molecular docking technology. Chin. Herb. Med., 2015, 38, 781-785.
[24]
Pajarillo, E.; Rizor, A.; Lee, J.; Aschner, M.; Lee, E. The role of astrocytic glutamate transporters GLT-1 and GLAST in neurological disorders: Potential targets for neurotherapeutics. Neuropharmacology, 2019, 161, 107559.
[http://dx.doi.org/10.1016/j.neuropharm.2019.03.002] [PMID: 30851309]
[25]
Pang, D.; Hu, C.; Ze, Y. China’s population aging trend and countermeasures. Clin. Geriatr. Med., 2021, 19, 3-5.
[26]
Piñero, J.; Bravo, À.; Queralt-Rosinach, N.; Gutiérrez-Sacristán, A.; Deu-Pons, J.; Centeno, E.; García-García, J.; Sanz, F.; Furlong, L.I. DisGeNET: a comprehensive platform integrating information on human disease-associated genes and variants. Nucleic Acids Res., 2017, 45(D1), D833-D839.
[http://dx.doi.org/10.1093/nar/gkw943] [PMID: 27924018]
[27]
Qiang, X.; Chen, H.; Zhou, J.; Jiang, H.; Zheng, X.; Yang, Y.; Deng, Q.; Xu, X. Protective effect of puerarin on microvascular endothelial cells in the penumbra of rats with focal cerebral ischemia and its mechanism. Zhongguo Xin Yao Zazhi, 2019, 28, 151-158.
[28]
Sun, Y.; Liu, M.; Wang, J.; Chen, L. Josie; Chen, L.; Han, Z. Medicine Sun Mastery Tianjin University of Traditional Chinese. Effects of formononetin on blood-brain barrier integrity after cerebral ischemia-reperfusion. Tianjin Pharm., 2021, 33, 1-3.
[29]
Rego, C.M.A.; Francisco, A.F.; Boeno, C.N.; Paloschi, M.V.; Lopes, J.A.; Silva, M.D.S.; Santana, H.M.; Serrath, S.N.; Rodrigues, J.E.; Lemos, C.T.L.; Dutra, R.S.S.; da Cruz, J.N.; Dos Santos, C.B.R. da S Setúbal, S.; Fontes, M.R.M.; Soares, A.M.; Pires, W.L.; Zuliani, J.P. Inflammasome NLRP3 activation induced by Convulxin, a C-type lectin-like isolated from Crotalus durissus terrificus snake venom. Sci. Rep., 2022, 12(1), 4706.
[http://dx.doi.org/10.1038/s41598-022-08735-7] [PMID: 35304541]
[30]
Tang, K.; Zhu, Y. Research progress of PI3K/Akt-eNOS-NO signaling pathway and postconditioning after cerebral ischemia. Inter. J. Neurol. Neurosurg., 2013, 40, 67-70.
[31]
Thant, U.; Gao, Y.; Xiang, H.; Xing, J.; Han, Y.; Qin, X. Study on the antidepressant mechanism of Bupleurum chinensis based on network pharmacology. J. Pharm. (Cairo), 2018, 53, 210-219.
[32]
Kerkhof, D.L.; Nagy, M.; Wichapong, K.; Brouns, S.L.N.; Heemskerk, J.W.M.; Hackeng, T.M.; Dijkgraaf, I. Inhibition of platelet adhesion, thrombus formation, and fibrin formation by a potent αIIbβ3 integrin inhibitor from ticks. Res. Pract. Thromb. Haemost., 2021, 5(1), 231-242.
[http://dx.doi.org/10.1002/rth2.12466] [PMID: 33537548]
[33]
Weng, H.; Liu, Y. Chin. J. Clin. Pharmacol., 2012, 21, 265-270.
[34]
Wu, J.; Liu, R.; Danny, X.; Li, Y. full is always, Jiaxue Hao, Pu Jia, Sha Liao, and Zheng Xiaohui. ‘Based on GC-MS technology and network pharmacology to explore the mechanism of Xingnaojing injection’s brain-injecting components against cerebral ischemia injury’. Chin. Herb. Med., 2021, 52, 808-820.
[35]
Wudan, H.Y.; Zhu, D. The role of calcium ion/calmodulin-dependent protein kinase II in cardiovascular diseases. Zhongnan Pharm., 2020, 18, 1021-1026.
[36]
Yang, K.; Liu, H.; Wu, H.; Zhu, X.; Jiang, Z. Protective effect of curcumin preconditioning on cerebral ischemia/reperfusion injury in rats. Zhongguo Yaolixue Tongbao, 2013, 29, 1432-1436.
[37]
Yao, D.; Chen, X.; Yun, L. Effects of stroke Xingnao liquid on early neurological recovery of ischemic stroke. Chin. J. Experi. Formulas, 2020, 26, 104-109.
[38]
Yu, H.; Meng, X.; Li, J.; Hui, O.; Yin, Q.; Lin, L.; Zhu, W.; Liu, R. Comparative study on serum medicinal chemistry of Pueraria lobata and Pueraria lobata rats based on UPLC-Q-TOF-MS. Chin. J. Trad. Chin. Med., 2021, 47, 528-536.
[39]
Zhang, P.; Zhang, B.; Sulika, H.L.; Zhang, X. Effects of tetrandrine on calcium ions and oxygen free radicals in brain tissue after cerebral ischemia-reperfusion in rats. Chin. J. Modern Med., 2009, 19, 2098-2101.
[40]
Zhao, L.; Wu, Y.; Gao, Y.; Xiang, H.; Qin, X.; Tian, J. Study on the mechanism of Baihe Dihuang Decoction’s intervention on mental sub-health based on network pharmacology. J. Pharm. (Cairo), 2017, 52, 99-105.
[41]
Pinto, Vinícius de S.; Araújo Janay, S.C.; Silva Rai, C. In silico study to identify new antituberculosis molecules from natural sources by hierarchical virtual screening and molecular dynamics simulations. Pharmaceuticals (Basel), 2019, 12(1), 36.

Rights & Permissions Print Cite
Article Metrics
44
3
Wayfinder Image
© 2024 Bentham Science Publishers | Privacy Policy