Login Register Cart 0
Generic placeholder image

CNS & Neurological Disorders - Drug Targets

Editor-in-Chief

ISSN (Print): 1871-5273
ISSN (Online): 1996-3181

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

The Effects and Mechanism of Scutellaria baicalensis Georgi Stems and Leaves Flavonoids on Myelin Sheath Degeneration Induced by Composite Aβ in Rats

Author(s): Xu Congcong, Ye Yuanyuan, Li Caixia* and Shang Yazhen*

Volume 23, Issue 4, 2024

Published on: 19 June, 2023

Page: [504 - 511] Pages: 8

DOI: 10.2174/1871527322666230510103540

Price: $65

conference banner
Abstract

Background: Alzheimer's disease is a degenerative disease of the central nervous system, and its characteristic pathological changes are closely associated with Aβ deposition and neurofibrillary tangles. Many studies have found that malignant changes in the myelin sheath and oligodendrocyte (OL) are accompanied by the occurrence and development of AD. Therefore, any method that can resist myelin sheath and OL disorders may be a potential strategy for AD.

Objective: To investigate the effects and mechanism of Scutellaria baicalensis Georgi stem and leaf flavonoids (SSFs) on the myelin sheath degeneration induced by Aβ25-35 combined with AlC13 and RHTGF-β1 (composite Aβ) in rats.

Methods: A rat AD model was established by intracerebroventricular injection of composite Aβ. The Morris water maze was used to screen the memory impairment rat model. The successful model rats were divided into the model group and the 35, 70, and 140 mg/kg SSFS groups. The myelin sheath changes in the cerebral cortex were observed with an electron microscope. The expression of the oligodendrocyte- specific protein claudin 11 was detected with immunohistochemistry. The protein expression levels of myelin oligodendrocyte glycoprotein (MOG), myelin-associated glycoprotein (MAG) and myelin basic protein (MBP), sphingomyelin synthase-1 (SMS1), and sphingomyelinase-2 (SMPD2) were assayed by Western blotting.

Results: The intracerebroventricular injection of composite Aβ caused degeneration of the myelin sheath structure and was accompanied by the decreased claudin 11, MOG, MAG, MBP, and SMS1, and increased SMPD2 protein expression in the cerebral cortex. However, 35, 70, and 140 mg/kg SSFs can differentially ameliorate the above abnormal changes induced by composite Aβ.

Conclusion: SSFs can alleviate myelin sheath degeneration and increase the protein expression of claudin 11, MOG, MAG, and MBP, and the effective mechanism may be related to the positive regulation of SMS1 and SMPD2 activities.

« Previous Next »
Graphical Abstract

[1]
Zhang H, Zheng Y. β-amyloid hypothesis in Alzheimer’s disease: Pathogenesis, prevention, and mpanagement. Zhongguo Yi Xue Ke Xue Yuan Xue Bao 2019; 41(5): 702-8.
[http://dx.doi.org/10.3881/j.issn.1000-503X.10875] [PMID: 31699204]
[2]
Glasser MF, Goyal MS, Preuss TM, et al. Trends and properties of human cerebral cortex: Correlations with cortical myelin content. Neuroimage 2014; 93(Pt 2): 165-75.
[http://dx.doi.org/10.1016/j.neuroimage.2013.03.060] [PMID: 23567887]
[3]
Zheng M, Liu Z, Mana L, et al. Shenzhiling oral liquid protects the myelin sheath against Alzheimer’s disease through the PI3K/Akt-mTOR pathway. J Ethnopharmacol 2021; 278: 114264.
[http://dx.doi.org/10.1016/j.jep.2021.114264] [PMID: 34082015]
[4]
Jęśko H, Wencel PL, Wójtowicz S, et al. Fingolimod affects transcription of genes encoding enzymes of ceramide metabolism in animal model of Alzheimer’s disease. Mol Neurobiol 2020; 57(6): 2799-3811.
[http://dx.doi.org/10.1007/s12035-020-01908-3] [PMID: 32356173]
[5]
Butt AM, De La Rocha IC, Rivera A. Oligodendroglial cells in Alzheimer’s disease. Adv Exp Med Biol 2019; 1175: 325-33.
[http://dx.doi.org/10.1007/978-981-13-9913-8_12] [PMID: 31583593]
[6]
Liu YP, Cao KP, Miao H, et al. Flavonoids from the stems and leaves of Scutellaria baicalensis Georgi attenuate H2O2-induced oxidative damage to rat cortical neurons. Neural Regen Res 2011; 6(27): 2100-4.
[http://dx.doi.org/10.3969/J.ISSN.1673-5374.2011.27.003]
[7]
Jiang W. Research progress on pharmacological activities of scutellarin. Chinese Pharmacol Bull 2018; 34(12): 1634-7.
[http://dx.doi.org/10.3969/j.issn.1001-1978.2018.12.002]
[8]
Zhang SF, Dong YC, Zhang XF, et al. Flavonoids from Scutellaria attenuate okadaic acid-induced neuronal damage in rats. Brain Inj 2015; 29(11): 1376-82.
[http://dx.doi.org/10.3109/02699052.2015.1042053] [PMID: 26083050]
[9]
Shang YZ, Gong MY, Zhou XX, et al. Improving effects of SSF on memory deficits and pathological changes of neural and immunological systems in senescent mice. Acta Pharmacol Sin 2001; 22(12): 1078-83.
[PMID: 11749803]
[10]
Shang YZ, Miao H, Cheng JJ, et al. Effects of total flavonoids from stems and leaves of Scutellaria baicalensis on memory impairment in mice with aluminum poisoning. Chinese Pharmacol Bull 2005; 21(3): 361-5.
[http://dx.doi.org/10.3321/j.issn:1001-1978.2005.03.027]
[11]
Ding SK. liu QQ, Shang YZ. The effects and regulatory mechanism of flavonoids from stems and leaves of Scutellaria baicalensis Georgi in promoting neurogenesis and improving memory impairment mediated by the BDNF-ERK-CREB signaling pathway in rats. CNS Neurol Disord Drug Targets 2022; 21(4): 354-66.
[http://dx.doi.org/10.2174/1871527320666210827112048] [PMID: 34455975]
[12]
Wu XG, Cheng JJ, Cao QY, et al. Establishment of a valuable mimic of Alzheimer’s disease in rat animal model by intracerebroventricular injection of composited amyloid beta-protein. J Vis Exp 2018; (137): 56157.
[http://dx.doi.org/10.3791/56157]
[13]
Nasrabady SE, Rizvi B, Goldman JE, et al. White matter changes in Alzheimer's disease: A focus on myelin and oligodendrocytes. Acta Neuropathol Commun 2018; 6(1): 22.
[http://dx.doi.org/10.1186/s40478-018-0515-3]
[14]
DeFlitch L, Gonzalez-Fernandez E, Crawley I, et al. Age and Alzheimer’s disease-related oligodendrocyte changes in hippocampal subregions. Front Cell Neurosci 2022; 16: 847097.
[http://dx.doi.org/10.3389/fncel.2022.847097] [PMID: 35465615]
[15]
Han S, Gim Y, Jang EH, et al. Functions and dysfunctions of oligodendrocytes in neurodegenerative diseases. Front Cell Neurosci 2022; 16: 1083159.
[http://dx.doi.org/10.3389/fncel.2022.1083159] [PMID: 36605616]
[16]
Cheng JJ, Guo Q, Wu XG, et al. Scutellaria barbata favonoids improve the composited Aβ-induced abnormal changes in glial cells of the brains of rats. Comb Chem High Throughput Screen 2021; 25(1): 64-76.
[http://dx.doi.org/10.2174/1386207323666201209092358] [PMID: 33297910]
[17]
Mathews R, Ramya L. A comparative study for the intermediate states of myelin oligodendrocyte glycoprotein in the absence and presence of glycan-A computational approach. J Mol Graph Model 2020; 96: 107517.
[http://dx.doi.org/10.1016/j.jmgm.2019.107517]
[18]
Niu R, Chen H, Manthari RK. Effects of fluoride on synapse morphology and myelin damage in mouse hippocampus. Chemosphere 2018; 194: 628-33.
[19]
Li SR, Wang L, Liu R, et al. Changes in expression and significance of myelin-related proteins MBP and MAG in epilepsy rat hippocampal tissue. Shandong Yiyao 2018; 58(10): 29-32.
[http://dx.doi.org/10.3969/j.issn.1002-266X.2018.10.008]
[20]
Yi HA, Won KS, Chang HW, et al. Association between white matter lesions and cerebral Aβ burden. PLoS One 2018; 13(9): e0204313.
[http://dx.doi.org/10.1371/journal.pone.0204313] [PMID: 30248123]
[21]
Ferrer I, Andrés-Benito P. White matter alterations in Alzheimer’s disease without concomitant pathologies. Neuropathol Appl Neurobiol 2020; 46(7): 654-72.
[http://dx.doi.org/10.1111/nan.12618] [PMID: 32255227]
[22]
Yu H, Shi J, Lin Y, et al. Icariin ameliorates Alzheimer’s disease pathology by alleviating myelin injury in 3×Tg-AD mice. Neurochem Res 2022; 47(4): 1049-59.
[http://dx.doi.org/10.1007/s11064-021-03507-7] [PMID: 35037164]
[23]
Lu MH, Ji WL, Xu DE, et al. Inhibition of sphingomyelin synthase 1 ameliorates alzheimer-like pathology in APP/PS1 transgenic mice through promoting lysosomal degradation of BACE1. Exp Neurol 2019; 311: 67-79.
[http://dx.doi.org/10.1016/j.expneurol.2018.09.012] [PMID: 30243987]
[24]
Tu R, Yang W, Hu Z. Inhibition of sphingomyelin synthase 1 affects ceramide accumulation and hydrogen peroxide-induced apoptosis in Neuro-2a cells. Neuroreport 2016; 27(13): 967-73.
[http://dx.doi.org/10.1097/WNR.0000000000000639] [PMID: 27391427]
[25]
Liu QQ, Ding S,, Zhang H, et al. The molecular mechanism of Scutellaria baicalensis Georgi stems and leaves flavonoids in promoting neurogenesis and improving memory impairment by the PI3K-AKT-CREB signaling pathway in rats. Comb Chem High Throughput Screen 2022; 25(5): 919-33.
[http://dx.doi.org/10.2174/1386207324666210506152320] [PMID: 33966617]
[26]
Zhang H, Liu QQ, Ding SK, et al. Flavonoids from stems and leaves of Scutellaria baicalensis Georgi improve composited Aβ-induced Alzheimer’s disease model rats’ memory and neuroplasticity disorders. Comb Chem High Throughput Screen 2022; 26(8): 1519-32.
[http://dx.doi.org/10.2174/13862073-25666221003092627] [PMID: 36200197]
[27]
Guo X, Chen ZH, Wang HL, et al. WSKY, a traditional Chinese decoction, rescues cognitive impairment associated with NMDA receptor antagonism by enhancing BDNF/ERK/CREB signaling. Mol Med Rep 2015; 11(4): 2927-34.
[http://dx.doi.org/10.3892/mmr.2014.3086] [PMID: 25503442]
[28]
Yamashita H, Surapureddi S, Kovi RC, et al. Unique microRNA alterations in hepatocellular carcinomas arising either spontaneously or due to chronic exposure to Ginkgo biloba extract (GBE) in B6C3F1/N mice. Arch Toxicol 2020; 94(7): 2523-41.
[http://dx.doi.org/10.1007/s00204-020-02749-8] [PMID: 32306082]

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