Login Register Cart 0
Generic placeholder image

Current Pharmaceutical Design

Editor-in-Chief

ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

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

Neuro-protective Effect of Acetyl-11-keto-β-boswellic Acid in a Rat Model of Scopolamine-induced Cholinergic Dysfunction

Author(s): Amir Hossein Assaran, Mahmoud Hosseini, Matin Shirazinia, Mohammad Hosein Eshaghi Ghalibaf, Farimah Beheshti, Leila Mobasheri, Farshad Mirzavi and Arezoo Rajabian*

Volume 30, Issue 2, 2024

Published on: 16 January, 2024

Page: [140 - 150] Pages: 11

DOI: 10.2174/0113816128269289231226115446

Price: $65

conference banner
Abstract

Background: Acetyl-11-keto-β-boswellic acid (AKBA) is a major component of the oleo-gum resin of B. serrata with multiple pharmacological activities. The objective of this study was to explore the underlying mechanisms of neuroprotective potential of AKBA against scopolamine-mediated cholinergic dysfunction and memory deficits in rats.

Methods: The rats received AKBA (2.5, 5, and 10 mg/kg, oral) for 21 days. In the third week, scopolamine was administered 30 min before the Morris water maze and passive avoidance tests. In order to perform biochemical assessments, the hippocampus and prefrontal cortex were extracted from the rats euthanized under deep anesthesia.

Results: In the MWM test, treatment with AKBA (5 and 10 mg/kg) decreased the latency and distance to find the platform. Moreover, in the PA test, AKBA remarkably increased latency to darkness and stayed time in lightness while decreasing the frequency of entry and time in the darkness. According to the biochemical assessments, AKBA decreased acetylcholinesterase activity and malondialdehyde levels while increasing antioxidant enzymes and total thiol content. Furthermore, AKBA administration restored the hippocampal mRNA and protein levels of brain-derived neurotrophic factor (BDNF) and mRNA expression of B-cell lymphoma (Bcl)- 2 and Bcl-2- associated X genes in brain tissue of scopolamine-injured rats.

Conclusion: The results suggested the effectiveness of AKBA in preventing learning and memory dysfunction induced by scopolamine. Accordingly, these protective effects might be produced by modulating BDNF, cholinergic system function, oxidative stress, and apoptotic markers.

Keywords: Bcl-2, cholinergic function, oxidative stress, brain-derived neurotrophic factor, apoptosis, acetyl-11-keto-β-boswellic acid.

« Previous Next »
[1]
Nichols E, Szoeke CEI, Vollset SE, et al. Global, regional, and national burden of Alzheimer’s disease and other dementias, 1990–2016: A systematic analysis for the Global Burden of Disease Study 2016. Lancet Neurol 2019; 18(1): 88-106.
[http://dx.doi.org/10.1016/S1474-4422(18)30403-4] [PMID: 30497964]
[2]
Tiwari S, Atluri V, Kaushik A, Yndart A, Nair M. Alzheimer’s disease: Pathogenesis, diagnostics, and therapeutics. Int J Nanomed 2019; 14: 5541-54.
[http://dx.doi.org/10.2147/IJN.S200490] [PMID: 31410002]
[3]
Mecocci P, Boccardi V, Cecchetti R, et al. A long journey into aging, brain aging, and Alzheimer’s disease following the oxidative stress tracks. J Alzheimers Dis 2018; 62(3): 1319-35.
[http://dx.doi.org/10.3233/JAD-170732] [PMID: 29562533]
[4]
Hassan NA, Alshamari AK, Hassan AA, et al. Advances on therapeutic strategies for Alzheimer’s disease: From medicinal plant to nanotechnology. Molecules 2022; 27(15): 4839.
[http://dx.doi.org/10.3390/molecules27154839] [PMID: 35956796]
[5]
Muhammad T, Ali T, Ikram M, Khan A, Alam SI, Kim MO. Melatonin rescue oxidative stress-mediated neuroinflammation/neurodegeneration and memory impairment in scopolamine-induced amnesia mice model. J Neuroimmune Pharmacol 2019; 14(2): 278-94.
[http://dx.doi.org/10.1007/s11481-018-9824-3] [PMID: 30478761]
[6]
Rosa ÉVF, Da Silveira AR, Sari MHM, et al. Beta-caryophyllene mitigates the cognitive impairment caused by repeated exposure to aspartame in rats: Putative role of BDNF-TrKB signaling pathway and acetylcholinesterase activity. Behav Brain Res 2023; 453: 114615.
[http://dx.doi.org/10.1016/j.bbr.2023.114615] [PMID: 37558167]
[7]
Ng T, Ho C, Tam W, Kua E, Ho R. Decreased serum brain-derived neurotrophic factor (BDNF) levels in patients with Alzheimer’s disease (AD): A systematic review and meta-analysis. Int J Mol Sci 2019; 20(2): 257.
[http://dx.doi.org/10.3390/ijms20020257] [PMID: 30634650]
[8]
Caviedes A, Lafourcade C, Soto C, Wyneken U. BDNF/NF-κB signaling in the neurobiology of depression. Curr Pharm Des 2017; 23(21): 3154-63.
[PMID: 28078988]
[9]
Karami A, Eriksdotter M, Kadir A, Almkvist O, Nordberg A, Darreh-Shori T. CSF cholinergic index, a new biomeasure of treatment effect in patients with Alzheimer’s disease. Front Mol Neurosci 2019; 12(12): 239.
[http://dx.doi.org/10.3389/fnmol.2019.00239] [PMID: 31680850]
[10]
Rajabian A, Farzanehfar M, Hosseini H, Arab FL, Nikkhah A. Boswellic acids as promising agents for the management of brain diseases. Life Sci 2023; 312: 121196.
[http://dx.doi.org/10.1016/j.lfs.2022.121196] [PMID: 36400202]
[11]
Gomaa AA, Mohamed HS, Abd-ellatief RB, Gomaa MA, Hammam DS. Advancing combination treatment with glycyrrhizin and boswellic acids for hospitalized patients with moderate COVID-19 infection: a randomized clinical trial. Inflammopharmacology 2022; 30(2): 477-86.
[http://dx.doi.org/10.1007/s10787-022-00939-7] [PMID: 35233748]
[12]
Wei C, Fan J, Sun X, et al. Acetyl-11-keto-β-boswellic acid ameliorates cognitive deficits and reduces amyloid-β levels in APPswe/PS1dE9 mice through antioxidant and anti-inflammatory pathways. Free Radic Biol Med 2020; 150: 96-108.
[http://dx.doi.org/10.1016/j.freeradbiomed.2020.02.022] [PMID: 32109514]
[13]
Beheshti F, Akbari HR, Baghcheghi Y, Mansouritorghabeh F, Mortazavi Sani SS, Hosseini M. Beneficial effects of angiotensin converting enzyme inhibition on scopolamine-induced learning and memory impairment in rats, the roles of brain-derived neurotrophic factor, nitric oxide and neuroinflammation. Clin Exp Hypertens 2021; 43(6): 505-15.
[http://dx.doi.org/10.1080/10641963.2021.1901112] [PMID: 33724113]
[14]
Forero MG, Hernández NC, Morera CM, Aguilar LA, Aquino R, Baquedano LE. A new automatic method for tracking rats in the Morris water maze. Heliyon 2023; 9(7): e18367.
[http://dx.doi.org/10.1016/j.heliyon.2023.e18367] [PMID: 37519749]
[15]
Amirahmadi S, Farimani FD, Akbarian M, et al. Minocycline attenuates cholinergic dysfunction and neuro-inflammation-mediated cognitive impairment in scopolamine-induced Alzheimer’s rat model. Inflammopharmacology 2022; 30(6): 2385-97.
[http://dx.doi.org/10.1007/s10787-022-01071-2] [PMID: 36138304]
[16]
Hosseini Z, Mansouritorghabeh F, Kakhki FSH, et al. Effect of Sanguisorba minor on scopolamine-induced memory loss in rat: Involvement of oxidative stress and acetylcholinesterase. Metab Brain Dis 2022; 37(2): 473-88.
[http://dx.doi.org/10.1007/s11011-021-00898-y] [PMID: 34982352]
[17]
Tang KS. The cellular and molecular processes associated with scopolamine-induced memory deficit: A model of Alzheimer’s biomarkers. Life Sci 2019; 233: 116695.
[http://dx.doi.org/10.1016/j.lfs.2019.116695] [PMID: 31351082]
[18]
Marefati N, Beheshti F, Memarpour S, et al. The effects of acetyl-11-keto-β-boswellic acid on brain cytokines and memory impairment induced by lipopolysaccharide in rats. Cytokine 2020; 131: 155107.
[http://dx.doi.org/10.1016/j.cyto.2020.155107] [PMID: 32380425]
[19]
Minj E, Upadhayay S, Mehan S. Nrf2/HO-1 signaling activator acetyl-11-keto-beta Boswellic acid (AKBA)-mediated neuroprotection in methyl mercury-induced experimental model of ALS. Neurochem Res 2021; 46(11): 2867-84.
[http://dx.doi.org/10.1007/s11064-021-03366-2] [PMID: 34075522]
[20]
Slater C, Liu Y, Weiss E, Yu K, Wang Q. The neuromodulatory role of the noradrenergic and cholinergic systems and their interplay in cognitive functions: A focused review. Brain Sci 2022; 12(7): 890.
[http://dx.doi.org/10.3390/brainsci12070890] [PMID: 35884697]
[21]
Venkatesan K. Anti-amnesic and anti-cholinesterase activities of α-asarone against scopolamine-induced memory impairments in rats. Eur Rev Med Pharmacol Sci 2022; 26(17): 6344-50.
[PMID: 36111936]
[22]
Nandi A, Yan LJ, Jana CK, Das N. Role of catalase in oxidative stress-and age-associated degenerative diseases. Oxid Med Cell Longev 2019; 2019: 1-19.
[http://dx.doi.org/10.1155/2019/9613090] [PMID: 31827713]
[23]
Ozcankaya R, Delibas N. Malondialdehyde, superoxide dismutase, melatonin, iron, copper, and zinc blood concentrations in patients with Alzheimer disease: cross-sectional study. Croat Med J 2002; 43(1): 28-32.
[PMID: 11828555]
[24]
Zalewska A, Klimiuk A, Zięba S, et al. Salivary gland dysfunction and salivary redox imbalance in patients with Alzheimer’s disease. Sci Rep 2021; 11(1): 23904.
[http://dx.doi.org/10.1038/s41598-021-03456-9] [PMID: 34903846]
[25]
Rajabian A, Sadeghnia HR, Hosseini A, Mousavi SH, Boroushaki MT. 3-Acetyl-11-keto-β-boswellic acid attenuated oxidative glutamate toxicity in neuron-like cell lines by apoptosis inhibition. J Cell Biochem 2020; 121(2): 1778-89.
[http://dx.doi.org/10.1002/jcb.29413] [PMID: 31642100]
[26]
He R, Jiang Y, Shi Y, Liang J, Zhao L. Curcumin-laden exosomes target ischemic brain tissue and alleviate cerebral ischemia-reperfusion injury by inhibiting ROS-mediated mitochondrial apoptosis. Mater Sci Eng C 2020; 117: 111314.
[http://dx.doi.org/10.1016/j.msec.2020.111314] [PMID: 32919674]
[27]
Saeed MM, Fernández-Ochoa Á, Saber FR, et al. The potential neuroprotective effect of Cyperus esculentus L. extract in scopolamine-induced cognitive impairment in rats: Extensive biological and metabolomics approaches. Molecules 2022; 27(20): 7118.
[http://dx.doi.org/10.3390/molecules27207118] [PMID: 36296710]
[28]
Ravichandran V, Kim M, Han S, Cha Y. Stachys sieboldii extract supplementation attenuates memory deficits by modulating BDNF-CREB and its downstream molecules, in animal models of memory impairment. Nutrients 2018; 10(7): 917.
[http://dx.doi.org/10.3390/nu10070917] [PMID: 30018265]
[29]
Sharma VK, Singh TG, Singh S, Garg N, Dhiman S. Apoptotic pathways and Alzheimer’s disease: Probing therapeutic potential. Neurochem Res 2021; 46(12): 3103-22.
[http://dx.doi.org/10.1007/s11064-021-03418-7] [PMID: 34386919]
[30]
Li N, Liu G. The novel squamosamide derivative FLZ enhances BDNF/TrkB/CREB signaling and inhibits neuronal apoptosis in APP/PS1 mice. Acta Pharmacol Sin 2010; 31(3): 265-72.
[http://dx.doi.org/10.1038/aps.2010.3] [PMID: 20154710]
[31]
Al-Ayadhi LY. Relationship between Sonic hedgehog protein, brain-derived neurotrophic factor and oxidative stress in autism spectrum disorders. Neurochem Res 2012; 37(2): 394-400.
[http://dx.doi.org/10.1007/s11064-011-0624-x] [PMID: 21984201]
[32]
Qu Z, Zhang J, Yang H, et al. Prunella vulgaris, L. Prunella vulgaris L., an edible and medicinal plant, attenuates scopolamine-induced memory impairment in rats. J Agric Food Chem 2017; 65(2): 291-300.
[http://dx.doi.org/10.1021/acs.jafc.6b04597] [PMID: 28001065]
[33]
Ning F, Chen L, Chen L, et al. Combination of polygoni multiflori radix praeparata and acori tatarinowii rhizoma alleviates learning and memory impairment in scopolamine-treated mice by regulating synaptic-related proteins. Front Pharmacol 2021; 12: 679573.
[http://dx.doi.org/10.3389/fphar.2021.679573] [PMID: 34393775]
[34]
Jahan R, Yousaf M, Khan H, et al. Zinc ortho methyl carbonodithioate improved pre and post-synapse memory impairment via SIRT1/p-JNK pathway against scopolamine in adult mice. J Neuroimmune Pharmacol 2023; 18(1-2): 183-94.
[http://dx.doi.org/10.1007/s11481-023-10067-w] [PMID: 37261605]
[35]
Jebelli A, Khalaj-Kondori M, Bonyadi M, Hosseinpour Feizi MA, Rahmati-Yamchi M. Beta-boswellic acid and ethanolic extract of olibanum regulating the expression levels of CREB-1 and CREB-2 genes. Iran J Pharm Res 2019; 18(2): 877-86.
[http://dx.doi.org/10.22037/ijpr.2019.1100665] [PMID: 31531070]
[36]
Ahmad S, Khan A, Tabassum S, et al. Co-administration of saffron and chamomile give additive effects of antidiabetic and antioxidant activity with in vivo augmentation of brain BDNF, acetylcholine levels and cognitive functions in streptozotocininduced diabetic rats. Curr Psychopharmacol 2022; 11(1): 56-69.
[http://dx.doi.org/10.2174/2211556010666210906153253]
[37]
Tönnies E, Trushina E. Oxidative stress, synaptic dysfunction, and Alzheimer’s disease. J Alzheimers Dis 2017; 57(4): 1105-21.
[http://dx.doi.org/10.3233/JAD-161088] [PMID: 28059794]

Rights & Permissions Print Cite
Article Metrics
15
2
Wayfinder Image
World Suicide Prevention Day
© 2024 Bentham Science Publishers | Privacy Policy