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Therapeutic Targets and Molecular Mechanisms of Resveratrol in Amyotrophic Lateral Sclerosis: A Systematic Study of Network Pharmacology Incorporating Molecular Docking

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DOI: 10.23977/medsc.2023.040713 | Downloads: 6 | Views: 182

Author(s)

Xu Zhang 1, Bingcang Yan 2, Chengbao Fu 2, Lan Li 1, Ruoxue Bai 1, Nan Cheng 1, Jun Chen 3

Affiliation(s)

1 Shaanxi University of Chinese Medicine, Xianyang, Shaanxi, 712046, China
2 Xi'an TCM Hospital of Encephalopathy, Xi'an, Shaanxi, 710032, China
3 Shaanxi Provincial Hospital of Chinese Medicine, Xi'an, Shaanxi, 710003, China

Corresponding Author

Jun Chen

ABSTRACT

In order to explore the therapeutic targets and molecular mechanisms of resveratrol in amyotrophic lateral sclerosis based on network pharmacology and molecular docking techniques. In this study, we obtained the active compounds of resveratrol from TCMSP Chinese Medicine System Pharmacology database and used the Swiss Target Prediction platform to predict the potential targets of the active compounds. The effective targets of amyotrophic lateral sclerosis were obtained from GeneCards database, and the intersection was taken with the potential targets of resveratrol. Protein interaction networks were performed using the STRING database, and further network topology analysis was performed using Cytoscape 3.9.1 software. Meanwhile, gene ontology (GO) functional analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed on the intersecting targets by Metascape database; finally, molecular docking validation was carried out by Pubchem and PDB databases as well as by Pymol and Autodocktools software. Resultly, forty-nine potential targets of resveratrol and 1599 potential targets of amyotrophic lateral sclerosis were obtained. The enrichment analysis showed that resveratrol could have therapeutic effects on amyotrophic lateral sclerosis through multi-targets and multi-pathways. The molecular docking results showed that the core components could bind to the core targets better. Resveratrol mainly acts on Pathways in cancer pathway, Proteoglycans in cancer proteoglycans, Relaxin signaling pathway, Lipid and atherosclerosis lipids and atherosclerosis pathway through the core targets such as EGFR, PTGS2, SRC, MMP9, IGF1R and so on. In conclusion, this study obtained the potential targets and molecular mechanisms of resveratrol for the treatment of amyotrophic lateral sclerosis, which provides a theoretical basis for promoting the development and clinical application of targeted drugs.

KEYWORDS

Resveratrol; Amyotrophic lateral sclerosis (ALS); Network Pharmacology; Molecular docking; Mechanisms of action

CITE THIS PAPER

Xu Zhang, Bingcang Yan, Chengbao Fu, Lan Li, Ruoxue Bai, Nan Cheng,  Jun Chen, Therapeutic Targets and Molecular Mechanisms of Resveratrol in Amyotrophic Lateral Sclerosis: A Systematic Study of Network Pharmacology Incorporating Molecular Docking. MEDS Clinical Medicine (2023) Vol. 4: 71-80. DOI: http://dx.doi.org/10.23977/medsc.2023.040713.

REFERENCES

[1] Cleveland D W, Rothstein J D. From Charcot to Lou Gehrig: deciphering selective motor neuron death in ALS [J]. Nature reviews. Neuroscience, 2001, 2(11):806-819.
[2] Brown RH, Al-Chalabi A. Amyotrophic Lateral Sclerosis [J]. N Engl J Med, 2017, 377(2):162-172.
[3] Feldman EL, Goutman SA, Petri S, et al. Amyotrophic lateral sclerosis [J]. Lancet, 2022, 400(10360):1363-1380.
[4] Pasinelli Piera, Brown Robert H. Molecular biology of amyotrophic lateral sclerosis: insights from genetics [J]. Nature reviews. Neuroscience, 2006, 7(9):710-723.
[5] Séverine Boillée, Christine Vande Velde, Don W. Cleveland, et al. ALS: A Disease of Motor Neurons and Their Nonneuronal Neighbors [J]. Neuron, 2006, 52(1):39-59.
[6] Karch Celeste M, Prudencio Mercedes, Winkler Duane D, et al. Role of mutant SOD1 disulfide oxidation and aggregation in the pathogenesis of familial ALS [J]. Proceedings of the National Academy of Sciences of the United States of America, 2009, 106(19):7774-7779.
[7] Blokhuis Anna M, Groen Ewout J N, Koppers Max, et al. Protein aggregation in amyotrophic lateral sclerosis [J]. Acta neuropathologica, 2013, 125(6):777-794.  
[8] Gao Fenbiao, Almeida Sandra, Lopez-Gonzalez Rodrigo, et al. Dysregulated molecular pathways in amyotrophic lateral sclerosis-frontotemporal dementia spectrum disorder [J]. The EMBO journal, 2017, 36(20):2931-2950. 
[9] Miller R G, Mitchell J D, Lyon M, et al. Riluzole for amyotrophic lateral sclerosis (ALS)/motor neuron disease (MND) [J]. Cochrane database of systematic reviews (Online), 2002, 3(1):CD001447.
[10] Rothstein Jeffrey D. Edaravone: A new drug approved for ALS [J]. Cell, 2017, 171(4):725. 
[11] Shrikanta Akshatha, Kumar Anbarasu, Govindaswamy Vijayalakshmi, et al. Resveratrol content and antioxidant properties of underutilized fruits [J]. Journal of food science and technology, 2015, 52(1):383-390. 
[12] Marco Fiore, et al. Antioxidant properties of plant polyphenols in the counteraction of alcohol-abuse induced damage: Impact on the Mediterranean diet [J]. Journal of Functional Foods, 2020, 71:104012. 
[13] Ebru Öztürk, Ayşe Kübra Karaboğa Arslan, Mükerrem Betül Yerer, et al. Resveratrol and diabetes: A critical review of clinical studies [J]. Biomedicine & Pharmacotherapy, 2017, 95:230-234. 
[14] Rauf Abdur, Imran Muhammad, Suleria Hafiz Ansar Rasul, et al. A comprehensive review of the health perspectives of resveratrol [J]. Food & function, 2017, 8(12):4284-4305. 
[15] Jardim Fernanda Rafaela, de Rossi Fernando Tonon, Nascimento Marielle Xavier, et al. Resveratrol and Brain Mitochondria: a Review [J]. Molecular neurobiology, 2018, 55(3):2085-2101.
[16] Li Yirong, et al. Effect of Resveratrol and Pterostilbene on Aging and Longevity [J]. Biofactors, 2018, 44(1): 69-82. 
[17] Bahare Salehi, et al. Resveratrol: A Double-Edged Sword in Health Benefits [J]. Biomedicines, 2018, 6(3):91. 
[18] Mancuso Renzo, et al. Resveratrol improves motoneuron function and extends survival in SOD1 (G93A) ALS mice [J]. Neurotherapeutics: the journal of the American Society for Experimental NeuroTherapeutics, 2014, 11(2):419-432. 
[19] Mancuso Renzo, Del Valle Jaume, Morell Marta, et al. Lack of synergistic effect of resveratrol and sigma-1 receptor agonist (PRE-084) in SOD1G⁹³A ALS mice: overlapping effects or limited therapeutic opportunity? [J]. Orphanet journal of rare diseases, 2014, 9(1):78. 
[20] Dong Yankai, et al. Molecular mechanism of Epicedium treatment for depression based on network pharmacology and molecular docking technology [J]. BMC Complementary Medicine and Therapies, 2021, 21(1):222-222. 
[21] Zhang Jing, et al. Multi-target mechanism of Tripteryguim wilfordii Hook for treatment of ankylosing spondylitis based on network pharmacology and molecular docking [J]. Annals of medicine, 2021, 53(1):1090-1098. 
[22] Luca Pinzi, Giulio Rastelli. Molecular Docking: Shifting Paradigms in Drug Discovery [J]. International Journal of Molecular Sciences, 2019, 20(18):4331. 
[23] Zhang Dongdong, Wang Zhaoye, Li Jin, et al. Exploring the possible molecular targeting mechanism of Saussurea involucrata in the treatment of COVID-19 based on bioinformatics and network pharmacology [J]. Computers in Biology and Medicine, 2022, 146:105549-105549.
[24] Yu Tang, Min Li, Jianxin Wang, et al. CytoNCA: A cytoscape plugin for centrality analysis and evaluation of protein interaction networks [J]. BioSystems, 2015, 127:67-72. 
[25] Shi Longyan, et al. Inflammation-related pathways involved in damaged articular cartilage of rats exposed to T-2 toxin based on RNA-sequencing analysis [J]. Frontiers in Genetics, 2022, 13:1079739-1079739. 
[26] Cao Ying, et al. Network Pharmacology and Experimental Validation to Explore the Molecular Mechanisms of Bushen Huoxue for the Treatment of Premature Ovarian Insufficiency [J]. Bioengineered, 2021, 12(2):10345-10362. 
[27] Brown CA, Lally C, Kupelian V, Flanders WD. Estimated Prevalence and Incidence of Amyotrophic Lateral Sclerosis and SOD1 and C9orf72 Genetic Variants [J]. Neuroepidemiology, 2021, 55(5):342-353. 
[28] Longinetti Elisa, Fang Fang, Epidemiology of amyotrophic lateral sclerosis: an update of recent literature [J]. Current opinion in neurology, 2019, 32(5):771-776. 
[29] Marie Ryan, Mark Heverin, Russell L. McLaughlin, et al. Lifetime Risk and Heritability of Amyotrophic Lateral Sclerosis [J]. JAMA Neurology, 2019, 76(11):1367. 
[30] Wang Jing, Zhang Yun, Tang Lu, et al. Protective effects of resveratrol through the up-regulation of SIRT1 expression in the mutant hSOD1-G93A-bearing motor neuron-like cell culture model of amyotrophic lateral sclerosis [J]. Neuroscience Letters, 2011, 503(3):250-255. 
[31] Matilde Yáñez, Lucía Galán, Jorge Matías-Guiu, et al. CSF from amyotrophic lateral sclerosis patients produces glutamate independent death of rat motor brain cortical neurons: Protection by resveratrol but not riluzole [J]. Brain Research, 2011, 1423:77-86. 
[32] Srinivasan E, Rajasekaran R. Quantum chemical and molecular mechanics studies on the assessment of interactions between resveratrol and mutant SOD1 (G93A) protein [J]. Journal of computer-aided molecular design, 2018, 32(12):1347-1361. 
[33] Giusy Laudati, Luigi Mascolo, Natascia Guida, et al. Resveratrol treatment reduces the vulnerability of SH-SY5Y cells and cortical neurons overexpressing SOD1-G93A to Thimerosal toxicity through SIRT1/DREAM/PDYN pathway [J]. Neurotoxicology, 2019, 71:6-15. 
[34] Soyoung Han, Jong-Ryoul Choi, Ki Soon Shin, et al. Resveratrol upregulated heat shock proteins and extended the survival of G93A-SOD1 mice [J]. Brain Research, 2012, 1483:112-117.
[35] de Almeida Lúcia Maria Vieira, Piñeiro Cristopher Celintano, Leite Marina Concli, et al. Resveratrol increases glutamate uptake, glutathione content, and S100B secretion in cortical astrocyte cultures [J]. Cellular and molecular neurobiology, 2007, 27(5):661-668. 
[36] Smith Joshua A, Das Arabinda, Butler Jonathan T, et al. Estrogen or estrogen receptor agonist inhibits lipopolysaccharide induced microglial activation and death [J]. Neurochemical research, 2011, 36(9):1587-1593. 
[37] Xia Q, Hu Q, Wang H, et al. Induction of COX-2-PGE2 synthesis by activation of the MAPK/ERK pathway contributes to neuronal death triggered by TDP-43-depleted microglia [J]. Cell death & disease, 2015, 6(6):e1702.  
[38] Keiko Imamura, Yuishin Izumi, Akira Watanabe, et al. The Src/c-Abl pathway is a potential therapeutic target in amyotrophic lateral sclerosis [J]. Science Translational Medicine, 2017, 9(391):3962. 
[39] Imamura Keiko, Izumi Yuishin, Banno Haruhiko, et al. Induced pluripotent stem cell-based Drug Repurposing for Amyotrophic lateral sclerosis Medicine (iDReAM) study: protocol for a phase I dose escalation study of bosutinib for amyotrophic lateral sclerosis patients [J]. BMJ open, 2019, 9(12):e033131. 
[40] Kaur Avileen, Sharma Saurabh. Mammalian target of rapamycin (mTOR) as a potential therapeutic target in various diseases [J]. Inflammopharmacology, 2017, 25(3):293-312. 
[41] Robert A. Saxton, David M. Sabatini. mTOR Signaling in Growth, Metabolism, and Disease [J]. Cell, 2017, 168(6):960-976. 
[42] Liu Zhongyuan, Yao Xinqiang, Jiang Wangsheng, et al. Advanced oxidation protein products induce microglia-mediated neuroinflammation via MAPKs-NF-κB signaling pathway and pyroptosis after secondary spinal cord injury [J]. Journal of neuroinflammation, 2020, 17(1):90. 
[43] Wang Jianglin, et al. Oleanolic acid inhibits mouse spinal cord injury through suppressing inflammation and apoptosis via the blockage of p38 and JNK MAPKs [J]. Biomedicine & Pharmacotherapy, 2020, 123:109752. 
[44] Sahana TG, Zhang Ke. Mitogen-Activated Protein Kinase Pathway in Amyotrophic Lateral Sclerosis [J]. Biomedicines, 2021, 9(8):969-969.

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