Abstract
Alzheimer's disease is the most common neurodegenerative disease. Acanthopanax senticosus, also known as Ciwujia or Siberian ginseng in Chinese, has a wide range of antioxidant and anti-inflammatory activities. The study aims to explore the action mechanism of A. senticosus against Alzheimer's disease using network pharmacology and molecular docking. The active ingredients and targets of A. senticosus were searched through the ETCM database, and Alzheimer's disease-related targets were obtained through the OMIM and GeneCards databases. The Cytoscape 3.7.2 software was used to construct a “drug-component-target” relationship network, and the target genes of A. senticosus against Alzheimer's disease were imported into the String database to establish a protein interaction (PPI) network. The Gene Ontology and Kyoto Encyclopedia of Genes and Genomes gene enrichment analyses were performed through the Metascape database to obtain potential pathways of action of A. senticosus for the treatment of Alzheimer's disease, and the ability of these active ingredients to bind to core targets was then verified by molecular docking. 51 active ingredients were screened from A. senticosus, and 88 effective targets for Alzheimer's disease were screened. Topological and pathway-enrichment analyses revealed that A. senticosus could play a beneficial role in the treatment of Alzheimer's disease by regulating apoptosis and inflammation. Molecular docking results showed that Ciwujianoside B, Chiisanoside, and Ciwujianoside D1 had strong binding abilities to key target proteins (TNFα, IL1β, and CASP3). Collectively, A. senticosus is feasible in the treatment of Alzheimer's disease.
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Sonkusare SK, Kaul CL, Ramarao P (2005) Dementia of Alzheimer’s disease and other neurodegenerative disorders—memantine, a new hope. Pharmacol Res 51:1–17. https://doi.org/10.1016/j.phrs.2004.05.005
Association A (2016) 2016 Alzheimer’s disease facts and figures. Alzheimers Dement 12:459–509. https://doi.org/10.1016/j.jalz.2016.03.001
Hodson R (2018) Alzheimer’s disease. Nature 559:S1. https://doi.org/10.1038/d41586-018-05717-6
Tiwari S, Atluri V, Kaushik A, Yndart A, Nair M (2019) Alzheimer’s disease: pathogenesis, diagnostics, and therapeutics. Int J Nanomed 14:5541–5554. https://doi.org/10.2147/ijn.S200490
Joe E, Ringman JM (2019) Cognitive symptoms of Alzheimer’s disease: clinical management and prevention. BMJ 367:l6217. https://doi.org/10.1136/bmj.l6217
Li S, Wu Z, Le W (2021) Traditional Chinese medicine for dementia. Alzheimers Dement 17:1066–1071. https://doi.org/10.1002/alz.12258
Pei H, Ma L, Cao Y, Wang F, Li Z, Liu N, Liu M, Wei Y, Li H (2020) Traditional Chinese medicine for Alzheimer’s disease and other cognitive impairment: a review. Am J Chin Med 48:487–511. https://doi.org/10.1142/s0192415x20500251
Wang ZY, Liu J, Zhu Z, Su CF, Sreenivasmurthy SG, Iyaswamy A, Lu JH, Chen G, Song JX, Li M (2021) Traditional Chinese medicine compounds regulate autophagy for treating neurodegenerative disease: a mechanism review. Biomed Pharmacother 133:110968. https://doi.org/10.1016/j.biopha.2020.110968
Jia A, Zhang Y, Gao H, Zhang Z, Zhang Y, Wang Z, Zhang J, Deng B, Qiu Z, Fu C (2021) A review of Acanthopanax senticosus (Rupr and Maxim.) harms: from ethnopharmacological use to modern application. J Ethnopharmacol 268:113586. https://doi.org/10.1016/j.jep.2020.113586
Li T, Ferns K, Yan ZQ, Yin SY, Kou JJ, Li D, Zeng Z, Yin L, Wang X, Bao HX, Zhou YJ, Li QH, Zhao ZY, Liu H, Liu SL (2016) Acanthopanax senticosus: photochemistry and anticancer potential. Am J Chin Med 44:1543–1558. https://doi.org/10.1142/s0192415x16500865
Wang YH, Meng Y, Zhai C, Wang M, Avula B, Yuk J, Smith KM, Isaac G, Khan IA (2019) The chemical characterization of Eleutherococcus senticosus and Ci-wu-jia tea using UHPLC-UV-QTOF/MS. Int J Mol Sci. https://doi.org/10.3390/ijms20030475
Li XJ, Tang SQ, Huang H, Luo J, Zhang XD, Yook CS, Whang WK, Kim YC, Liu XQ (2021) Acanthopanax henryi: review of botany, phytochemistry and pharmacology. Molecules. https://doi.org/10.3390/molecules26082215
Huang L, Zhao H, Huang B, Zheng C, Peng W, Qin L (2011) Acanthopanax senticosus: review of botany, chemistry and pharmacology. Pharmazie 66:83–97
Zhang H, Wang S, Jin LH (2020) Acanthopanax senticosus polysaccharide regulates the intestinal homeostasis disruption induced by toxic chemicals in Drosophila. Phytother Res 34:193–200. https://doi.org/10.1002/ptr.6522
Chen RH, Du WD, Wang Q, Li ZF, Wang DX, Yang SL, Feng YL (2021) Effects of Acanthopanax senticosus (Rupr. & Maxim) Harms on cerebral ischemia-reperfusion injury revealed by metabolomics and transcriptomics. J Ethnopharmacol 264:113212. https://doi.org/10.1016/j.jep.2020.113212
Li XT, Zhou JC, Zhou Y, Ren YS, Huang YH, Wang SM, Tan L, Yang ZY, Ge YW (2022) Pharmacological effects of Eleutherococcus senticosus on the neurological disorders. Phytother Res. https://doi.org/10.1002/ptr.7555
Li W, Liu M, Feng S, Wu B, Zhang S, Yang W, Liu GJ (2009) Acanthopanax for acute ischaemic stroke. Cochrane Database Syst Rev. https://doi.org/10.1002/14651858.CD007032.pub2
Song C, Li S, Duan F, Liu M, Shan S, Ju T, Zhang Y, Lu W (2022) The therapeutic effect of Acanthopanax senticosus components on radiation-induced brain injury based on the pharmacokinetics and neurotransmitters. Molecules. https://doi.org/10.3390/molecules27031106
Hadni H, Elhallaoui M (2020) 3D-QSAR, docking and ADMET properties of aurone analogues as antimalarial agents. Heliyon 6:e03580. https://doi.org/10.1016/j.heliyon.2020.e03580
Onodera K, Satou K, Hirota H (2007) Evaluations of molecular docking programs for virtual screening. J Chem Inf Model 47:1609–1618. https://doi.org/10.1021/ci7000378
Kroemer RT, Vulpetti A, McDonald JJ, Rohrer DC, Trosset JY, Giordanetto F, Cotesta S, McMartin C, Kihlén M, Stouten PF (2004) Assessment of docking poses: interactions-based accuracy classification (IBAC) versus crystal structure deviations. J Chem Inf Comput Sci 44:871–881. https://doi.org/10.1021/ci049970m
Kirchmair J, Markt P, Distinto S, Wolber G, Langer T (2008) Evaluation of the performance of 3D virtual screening protocols: RMSD comparisons, enrichment assessments, and decoy selection—what can we learn from earlier mistakes? J Comput Aided Mol Des 22:213–228. https://doi.org/10.1007/s10822-007-9163-6
Gao YD, Hu Y, Crespo A, Wang D, Armacost KA, Fells JI, Fradera X, Wang H, Wang H, Sherborne B, Verras A, Peng Z (2018) Workflows and performances in the ranking prediction of 2016 D3R Grand Challenge 2: lessons learned from a collaborative effort. J Comput Aided Mol Des 32:129–142. https://doi.org/10.1007/s10822-017-0072-z
Fischer A, Smieško M, Sellner M, Lill MA (2021) Decision making in structure-based drug discovery: visual inspection of docking results. J Med Chem 64:2489–2500. https://doi.org/10.1021/acs.jmedchem.0c02227
Li S, Zhang B (2013) Traditional Chinese medicine network pharmacology: theory, methodology and application. Chin J Nat Med 11:110–120. https://doi.org/10.1016/s1875-5364(13)60037-0
Huang K, Zhang P, Zhang Z, Youn JY, Wang C, Zhang H, Cai H (2021) Traditional Chinese Medicine (TCM) in the treatment of COVID-19 and other viral infections: efficacies and mechanisms. Pharmacol Ther 225:107843. https://doi.org/10.1016/j.pharmthera.2021.107843
Chen Y, Dong J, Yang D, Qian Q, Wang P, Yang X, Li W, Li G, Shen X, Wang F (2021) Synergistic network pharmacology for traditional Chinese medicine Liangxue Tongyu formula in acute intracerebral hemorrhagic stroke. Neural Plast 2021:8874296. https://doi.org/10.1155/2021/8874296
Lane CA, Hardy J, Schott JM (2018) Alzheimer’s disease. Eur J Neurol 25:59–70. https://doi.org/10.1111/ene.13439
Zhang XD, Liu XQ, Kim YH, Whang WK (2014) Chemical constituents and their acetyl cholinesterase inhibitory and antioxidant activities from leaves of Acanthopanax henryi: potential complementary source against Alzheimer’s disease. Arch Pharm Res 37:606–616. https://doi.org/10.1007/s12272-013-0252-x
Holmes C (2013) Review: systemic inflammation and Alzheimer’s disease. Neuropathol Appl Neurobiol 39:51–68. https://doi.org/10.1111/j.1365-2990.2012.01307.x
Karlawish J, Jack CR Jr, Rocca WA, Snyder HM, Carrillo MC (2017) Alzheimer’s disease: the next frontier-special report 2017. Alzheimers Dement 13:374–380. https://doi.org/10.1016/j.jalz.2017.02.006
Vassar R (2007) Caspase-3 cleavage of GGA3 stabilizes BACE: implications for Alzheimer’s disease. Neuron 54:671–673. https://doi.org/10.1016/j.neuron.2007.05.018
D’Amelio M, Sheng M, Cecconi F (2012) Caspase-3 in the central nervous system: beyond apoptosis. Trends Neurosci 35:700–709. https://doi.org/10.1016/j.tins.2012.06.004
Obulesu M, Lakshmi MJ (2014) Apoptosis in Alzheimer’s disease: an understanding of the physiology, pathology and therapeutic avenues. Neurochem Res 39:2301–2312. https://doi.org/10.1007/s11064-014-1454-4
Clark I, Atwood C, Bowen R, Paz-Filho G, Vissel B (2012) Tumor necrosis factor-induced cerebral insulin resistance in Alzheimer’s disease links numerous treatment rationales. Pharmacol Rev 64:1004–1026. https://doi.org/10.1124/pr.112.005850
Baril AA, Beiser AS, Redline S, McGrath ER, Gottlieb DJ, Aparicio H, Seshadri S, Himali JJ, Pase MP (2021) Interleukin-6 interacts with sleep Apnea severity when predicting incident Alzheimer’s disease dementia. J Alzheimers Dis 79:1451–1457. https://doi.org/10.3233/jad-200545
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The authors gratefully acknowledge the financial support from the Project of Hunan Provincial Health Commission 2021 (No. 202110000052; to Feng Kuang).
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Kuang, F., Xiang, T. Molecular mechanism of Acanthopanax senticosus in the treatment of Alzheimer’s disease based on network pharmacology and molecular docking. Mol Divers 27, 2849–2865 (2023). https://doi.org/10.1007/s11030-022-10586-3
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DOI: https://doi.org/10.1007/s11030-022-10586-3