Generic placeholder image

Combinatorial Chemistry & High Throughput Screening

Editor-in-Chief

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

Research Article

High-throughput Sequencing and Bioinformatics Analysis Reveals the Neurogenesis Key Targets of Curcumin Action in Mouse Brain with MCAO

Author(s): Litao Li, Jinming Cheng, Yingxiao Ji, Jihong Liu, Rui Zhai and Hebo Wang*

Volume 26, Issue 6, 2023

Published on: 02 September, 2022

Page: [1233 - 1241] Pages: 9

DOI: 10.2174/1386207325666220803090112

Price: $65

Abstract

Background: Experimental studies have shown that curcumin exerts neuroprotective effects in animal models with middle cerebral artery occlusion (MCAO). However, the mechanisms of protective effects of curcumin in MCAO are not fully understood.

Objective: This study aims to investigate the key neurogenesis targets of curcumin action in mouse brain with MCAO.

Methods: The MCAO models were established in mice. High-throughput sequencing was used to identify differentially expressed mRNA, lncRNA, and circRNA. The reverse expressed mRNAs, lncRNA, and circRNA in sham vs. MCAO and MCAO vs. curcumin were identified. Biological functions were determined by gene ontology (GO) analyses. The protein-protein interaction (PPI) network of neurogenesis-related genes was constructed. Next, neurogenesis-related lncRNA/ circRNA-miRNA-mRNA ceRNA networks were constructed.

Results: The total of reverse expressed 1215 mRNAs, 32 lncRNAs, and 43 circRNAs were filtered based on the 2 series (sham vs. MCAO and MCAO vs. Curcumin). The functional enrichment analysis of 1215 reverse expressed mRNAs found that they were involved in neurogenesis, neuron generation, neurogenesis regulation, and others. The PPI network of neurogenesis-related genes consisted of 115 nodes, including 27 down-regulated genes and 36 up-regulated genes. Furthermore, the neurogenesis-related lncRNA/circRNA-miRNA-mRNA ceRNAs networks were constructed, and 5 lncRNA ceRNA networks and 3 circRNA ceRNA networks were explored.

Conclusion: Our study revealed that curcumin exerts neuroprotective effects by regulating neurogenesis. The neurogenesis-related lncRNA/circRNA-miRNA-mRNA ceRNA networks are potential therapeutic targets of curcumin in MCAO. This study provided a theoretical basis for curcumin exerting neuroprotective effects in MCAO.

Keywords: High-throughput sequencing, curcumin, MCAO, bioinformatics analysis, ceRNA, ischemic cerebrovascular diseases.

Graphical Abstract
[1]
Mehanna, R.; Jankovic, J. Movement disorders in cerebrovascular disease. Lancet Neurol., 2013, 12(6), 597-608.
[http://dx.doi.org/10.1016/S1474-4422(13)70057-7] [PMID: 23602779]
[2]
Johansen, M.C.; Gottesman, R.F. Cerebrovascular disease and cognitive outcome in patients with cardiac disease. Semin. Neurol., 2021, 41(4), 463-472.
[http://dx.doi.org/10.1055/s-0041-1726330] [PMID: 33851395]
[3]
Wang, Y.J.; Li, Z.X.; Gu, H.Q.; Zhai, Y.; Jiang, Y.; Zhao, X.Q.; Wang, Y.L.; Yang, X.; Wang, C.J.; Meng, X.; Li, H.; Liu, L.P.; Jing, J.; Wu, J.; Xu, A.D.; Dong, Q.; Wang, D.; Zhao, J.Z.; China Stroke Statistics Writing, C. China stroke statistics 2019: a report from the national center for healthcare quality management in neurological diseases, china national clinical research center for neurological diseases, the Chinese stroke association, national center for chronic and non-communicable disease control and prevention, Chinese center for disease control and prevention and institute for global neuroscience and stroke collaborations. Stroke Vasc. Neurol., 2020, 5(3), 211-239.
[http://dx.doi.org/10.1136/svn-2020-000457] [PMID: 32826385]
[4]
Liu, L.; Chen, W.; Zhou, H.; Duan, W.; Li, S.; Huo, X.; Xu, W.; Huang, L.; Zheng, H.; Liu, J.; Liu, H.; Wei, Y.; Xu, J.; Wang, Y. Chinese Stroke Association guidelines for clinical management of cerebrovascular disorders: Executive summary and 2019 update of clinical management of ischaemic cerebrovascular diseases. Stroke Vasc. Neurol., 2020, 5(2), 159-176.
[http://dx.doi.org/10.1136/svn-2020-000378] [PMID: 32561535]
[5]
Huang, L.; Li, X.; Liu, Y.; Liang, X.; Ye, H.; Yang, C.; Hua, L.; Zhang, X. Cur-cumin alleviates cerebral ischemia-reperfusion injury by inhibiting NLRP1-dependent neuronal pyroptosis. Curr. Neurovasc. Res., 2021, 18(2), 189-196.
[http://dx.doi.org/10.2174/1567202618666210607150140] [PMID: 34109908]
[6]
Xu, L.; Ding, L.; Su, Y.; Shao, R.; Liu, J.; Huang, Y. Neuroprotective effects of curcumin against rats with focal cerebral ischemia-reperfusion injury. Int. J. Mol. Med., 2019, 43(4), 1879-1887.
[http://dx.doi.org/10.3892/ijmm.2019.4094] [PMID: 30816425]
[7]
Kotha, R.R.; Luthria, D.L. Curcumin: Biological, pharmaceutical, nutraceutical, and analytical aspects. Molecules, 2019, 24(16), E2930.
[http://dx.doi.org/10.3390/molecules24162930] [PMID: 31412624]
[8]
Cui, X.; Lin, L.; Sun, X.; Wang, L.; Shen, R. Curcumin protects against renal ischemia/reperfusion injury by regulating oxidative stress and inflammatory response. Evid. Based Complement. Alternat. Med., 2021, 2021, 8490772.
[http://dx.doi.org/10.1155/2021/8490772] [PMID: 34812266]
[9]
Zia, A.; Farkhondeh, T.; Pourbagher-Shahri, A.M.; Samarghandian, S. The role of curcumin in aging and senescence: Molecular mechanisms. Biomed. Pharmacother., 2021, 134, 111119.
[http://dx.doi.org/10.1016/j.biopha.2020.111119] [PMID: 33360051]
[10]
Chainoglou, E.; Hadjipavlou-Litina, D. Curcumin in health and diseases: Alzheimer’s disease and curcumin analogues, derivatives, and hybrids. Int. J. Mol. Sci., 2020, 21(6), E1975.
[http://dx.doi.org/10.3390/ijms21061975] [PMID: 32183162]
[11]
Voulgaropoulou, S.D.; van Amelsvoort, T.A.M.J.; Prickaerts, J.; Vingerhoets, C. The effect of curcumin on cognition in Alzheimer’s disease and healthy aging: A systematic review of pre-clinical and clinical studies. Brain Res., 2019, 1725, 146476.
[http://dx.doi.org/10.1016/j.brainres.2019.146476] [PMID: 31560864]
[12]
Shabbir, U.; Rubab, M.; Tyagi, A.; Oh, D.H. Curcumin and its derivatives as theranostic agents in Alzheimer’s disease: The implication of nanotechnology. Int. J. Mol. Sci., 2020, 22(1), E196.
[http://dx.doi.org/10.3390/ijms22010196] [PMID: 33375513]
[13]
Algc, A.; Jnc, B.; Dfs, C.; Cb, A.; Ra, A.; Msdo, B.; Jedss, D.; Ncdrg, E.; Mdob, F.; Rmrbe, F. J. A. J. o. C. Evaluation of the genotoxicity and mutagenicity of isoeleutherin and eleutherin isolated from Eleutherine plicata herb. using bioassays and in silici approaches. 2021, 14(4), 103084.
[14]
Santana de Oliveira, M.; Pereira da Silva, V.M.; Cantão Freitas, L.; Gomes Silva, S.; Nevez Cruz, J.; de Aguiar Andrade, E.H. Extraction yield, chemical composition, preliminary toxicity of Bignonia nocturna (Bignoniaceae) essential oil and in silici evaluation of the interaction. Chem. Biodivers., 2021, 18(4), e2000982.
[http://dx.doi.org/10.1002/cbdv.202000982] [PMID: 33587821]
[15]
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]
[16]
Galucio, N.C.R.; Moysés, D.A.; Pina, J.R.S.; Marinho, P.S.B.; Gomes Júnior, P.C.; Cruz, J.N.; Vale, V.V.; Khayat, A.S.; Marinho, A.M.R. Antiproliferative, genotoxic activities and quantification of extracts and cucurbitacin B obtained from Luffa operculata (L.). Cogn. Arab. J. Chem., 2022, 15(2), 103589.
[http://dx.doi.org/10.1016/j.arabjc.2021.103589]
[17]
Duan, Y.; Wang, S.; Chen, Y.; Yang, R.; Li, H.; Zhu, H.; Tong, Y.; Wu, W.; Fu, Y.; Hu, S.; Wang, J.; Xin, Y.; Zhao, F.; Bao, Y.; Zhang, W.; Li, J.; Zeng, M.; Niu, H.; Zhou, X.; Li, Y.; Cui, S.; Yuan, J.; Li, J.; Wang, J.; Liu, D.; Ni, M.; Sun, Q.; Deng, Y.; Zhu, B. Expert consensus on microbiome sequencing and analysis. Chin. J. Biotechnol., 2020, 36(12), 2516-2524.
[PMID: 33398950]
[18]
Yang, F.; Chen, Y.; Xue, Z.; Lv, Y.; Shen, L.; Li, K.; Zheng, P.; Pan, P.; Feng, T.; Jin, L.; Yao, Y. High-throughput sequencing and exploration of the lncRNA-circRNA-miRNA-mRNA network in type 2 diabetes mellitus. BioMed Res. Int., 2020, 2020, 8162524.
[http://dx.doi.org/10.1155/2020/8162524] [PMID: 32596376]
[19]
Longa, E.Z.; Weinstein, P.R.; Carlson, S.; Cummins, R. Reversible middle cerebral artery occlusion without craniectomy in rats. Stroke, 1989, 20(1), 84-91.
[http://dx.doi.org/10.1161/01.STR.20.1.84] [PMID: 2643202]
[20]
Zhang, H.; Meltzer, P.; Davis, S. RCircos: An R package for Circos 2D track plots. BMC Bioinformatics, 2013, 14(1), 244.
[21]
Agarwal, V.; Bell, G.W.; Nam, J.W.; Bartel, D.P. Predicting effective microRNA target sites in mammalian mRNAs. eLife, 2015, 4, 4.
[http://dx.doi.org/10.7554/eLife.05005] [PMID: 26267216]
[22]
Chen, Y.; Wang, X. miRDB: An online database for prediction of functional microRNA targets. Nucleic Acids Res., 2020, 48(D1), D127-D131.
[http://dx.doi.org/10.1093/nar/gkz757] [PMID: 31504780]
[23]
Jeggari, A.; Marks, D.S.; Larsson, E. miRcode: A map of putative microRNA target sites in the long non-coding transcriptome. Bioinformatics, 2012, 28(15), 2062-2063.
[http://dx.doi.org/10.1093/bioinformatics/bts344] [PMID: 22718787]
[24]
Guo, P.; Jin, Z.; Wu, H.; Li, X.; Ke, J.; Zhang, Z.; Zhao, Q. Effects of irisin on the dysfunction of blood-brain barrier in rats after focal cerebral ischemia/reperfusion. Brain Behav., 2019, 9(10), e01425.
[http://dx.doi.org/10.1002/brb3.1425] [PMID: 31566928]
[25]
Qin, Y.; Zhang, Q.; Liu, Y. Analysis of knowledge bases and research focuses of cerebral ischemia-reperfusion from the perspective of mapping knowledge domain. Brain Res. Bull., 2020, 156, 15-24.
[http://dx.doi.org/10.1016/j.brainresbull.2019.12.004] [PMID: 31843561]
[26]
Wang, C.M.; Liu, H.F.; Zhang, M.; Shi, L.; Cui, M.; Wu, S.T.; Tian, J.R.; Zhang, Y.D. Effect of metformin combined with intermittent fasting on endoplasmic reticulum stress after cerebral ischemia-reperfusion in mice. Zhonghua Yi Xue Za Zhi, 2022, 102(5), 363-369.
[PMID: 35092978]
[27]
Ran, Y.; Su, W.; Gao, F.; Ding, Z.; Yang, S.; Ye, L.; Chen, X.; Tian, G.; Xi, J.; Liu, Z. Curcumin ameliorates white matter injury after ischemic stroke by inhibiting microglia/macrophage pyroptosis through NF-κB suppression and NLRP3 inflammasome inhibition. Oxid. Med. Cell. Longev., 2021, 2021, 1552127.
[http://dx.doi.org/10.1155/2021/1552127] [PMID: 34630845]
[28]
Liu, S.; Cao, Y.; Qu, M.; Zhang, Z.; Feng, L.; Ye, Z.; Xiao, M.; Hou, S.T.; Zheng, R.; Han, Z. Curcumin protects against stroke and increases levels of Notch intracellular domain. Neurol. Res., 2016, 38(6), 553-559.
[http://dx.doi.org/10.1080/01616412.2016.1187804] [PMID: 27320251]
[29]
Wang, Y.; Luo, J.; Li, S.Y. Nano-curcumin simultaneously protects the blood-brain barrier and reduces M1 microglial activation during cerebral ischemia-reperfusion injury. ACS Appl. Mater. Interfaces, 2019, 11(4), 3763-3770.
[http://dx.doi.org/10.1021/acsami.8b20594] [PMID: 30618231]
[30]
Zhu, T.; Wang, L.; Xie, W.; Meng, X.; Feng, Y.; Sun, G.; Sun, X. Notoginsenoside R1 improves cerebral ischemia/reperfusion injury by promoting neurogenesis via the BDNF/Akt/CREB pathway. Front. Pharmacol., 2021, 12, 615998.
[http://dx.doi.org/10.3389/fphar.2021.615998] [PMID: 34025400]
[31]
Belayev, L.; Hong, S.H.; Menghani, H.; Marcell, S.J.; Obenaus, A.; Freitas, R.S.; Khoutorova, L.; Balaszczuk, V.; Jun, B.; Oriá, R.B.; Bazan, N.G. Do-cosanoids promote neurogenesis and angiogenesis, blood-brain barrier integrity, penumbra protection, and neurobehavioral recovery after experimental ischemic stroke. Mol. Neurobiol., 2018, 55(8), 7090-7106.
[http://dx.doi.org/10.1007/s12035-018-1136-3] [PMID: 29858774]
[32]
Chen, J.; Wang, Z.; Zheng, Z.; Chen, Y.; Khor, S.; Shi, K.; He, Z.; Wang, Q.; Zhao, Y.; Zhang, H.; Li, X.; Li, J.; Yin, J.; Wang, X.; Xiao, J. Neuron and microglia/macrophage-derived FGF10 activate neuronal FGFR2/PI3K/Akt signaling and inhibit microglia/macrophages TLR4/NF-κB-dependent neuroinflammation to improve functional recovery after spinal cord injury. Cell Death Dis., 2017, 8(10), e3090.
[http://dx.doi.org/10.1038/cddis.2017.490] [PMID: 28981091]
[33]
Lu, Y.; Sareddy, G.R.; Wang, J.; Zhang, Q.; Tang, F.L.; Pratap, U.P.; Tekmal, R.R.; Vadlamudi, R.K.; Brann, D.W. Neuron-derived estrogen is critical for astrocyte activation and neuroprotection of the ischemic brain. J. Neurosci., 2020, 40(38), 7355-7374.
[http://dx.doi.org/10.1523/JNEUROSCI.0115-20.2020] [PMID: 32817249]
[34]
Griffin, J.H.; Fernández, J.A.; Lyden, P.D.; Zlokovic, B.V. Activated protein C promotes neuroprotection: Mechanisms and translation to the clinic. Thromb. Res., 2016, 141(Suppl. 2), S62-S64.
[http://dx.doi.org/10.1016/S0049-3848(16)30368-1] [PMID: 27207428]
[35]
Li, M.; Li, S.C.; Dou, B.K.; Zou, Y.X.; Han, H.Z.; Liu, D.X.; Ke, Z.J.; Wang, Z.F. Cycloastragenol upregulates SIRT1 expression, attenuates apoptosis and suppresses neuroinflammation after brain ischemia. Acta Pharmacol. Sin., 2020, 41(8), 1025-1032.
[http://dx.doi.org/10.1038/s41401-020-0386-6] [PMID: 32203080]
[36]
Lv, H.; Li, Y.; Cheng, Q.; Chen, J.; Chen, W. Neuroprotective effects against cerebral ischemic injury exerted by dexmedetomidine via the HDAC5/NPAS4/MDM2/PSD-95 Axis. Mol. Neurobiol., 2021, 58(5), 1990-2004.
[http://dx.doi.org/10.1007/s12035-020-02223-7] [PMID: 33411316]
[37]
Liu, J.; Zhang, K.S.; Hu, B.; Li, S.G.; Li, Q.; Luo, Y.P.; Wang, Y.; Deng, Z.F. Systematic analysis of RNA regulatory network in rat brain after ischemic stroke. BioMed Res. Int., 2018, 2018, 8354350.
[http://dx.doi.org/10.1155/2018/8354350] [PMID: 29516010]
[38]
Zhang, S.; Zhu, T.; Li, Q.; Sun, G.; Sun, X. Long non-coding RNA-mediated competing endogenous rna networks in ischemic stroke: Molecular mechanisms, therapeutic implications, and challenges. Front. Pharmacol., 2021, 12, 765075.
[http://dx.doi.org/10.3389/fphar.2021.765075] [PMID: 34867389]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy