Neuroprotective Effect of Boswellia serrata against 3-NP Induced Experimental Huntington’s Disease

Article ID: e180124225809 Pages: 14

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Abstract

Objectives: The study aimed to assess the neuroprotective effect of Boswellia serrata against 3-NP-induced experimental Huntington’s disease.

Background: Previous studies have shown Boswellia to have sedative, analgesic, and anti-tumour effects. Boswellia serrata yields four pentacyclic triterpene acids and boswellic acid, a bioactive substance that prevents leukotriene biogenesis.

Methods: The potential neuroprotective effect of Boswellia serrata against 3-nitro propionic acid (3-NP)-induced Huntington's disease (HD) was examined at oral doses of 45 mg/kg, 90 mg/kg, and 180 mg/kg. In this study, HD was induced by 3-NP at a dose of 10 mg/kg in Wistar rats. The study used 56 Wistar rats (8 per group) for biochemical (inflammatory markers, acetylcholinesterase activity) and behavioural (elevated plus maze, Y-maze, open-field, tail suspension tests, etc.) assessments. Additionally, a histological examination of the brain was carried out. In addition, the analysis of Boswellia serrata extract was performed by different analytical techniques, like UV spectrophotometer, FTIR, and HPLC methods.

Results: In the brain, succinate dehydrogenase is a mitochondrial enzyme irreversibly inhibited by 3-NP. Administration of 3-NP resulted in HD with altered behavioural and motor changes in rats. Treatment with Boswellia serrata resulted in remarkable protection of rats against 3-NP-induced behaviour and motor deficits in a dose-dependent manner. Moreover, in rats administered with 3-NP, Boswellia serrata improved memory performance and lowered levels of inflammatory biomarkers. These results have also been supported by histopathological analysis. Acetyl-11-keto-p-boswellic acid was found to be the main active component of Boswellia serrata extract.

Conclusion: Boswellia serrata at a dose of 180 mg/kg exhibited better protection compared to the other doses against HD induced by 3-NP. More detailed studies based on molecular targets are needed for the Boswellia serrata to transition from the bench to the bedside for use as an adjuvant in HD patients.

Graphical Abstract

[1]
Malik, J.; Choudhary, S.; Kumar, P. Plants and phytochemicals for Huntington's disease. Pharmacogn. Rev., 2013, 7(14), 81-91.
[http://dx.doi.org/10.4103/0973-7847.120505] [PMID: 24347915]
[2]
Roos, R.A.C. Huntington’s disease: A clinical review. Orphanet J. Rare Dis., 2010, 5(1), 40.
[http://dx.doi.org/10.1186/1750-1172-5-40] [PMID: 21171977]
[3]
Ajitkumar, A.; De Jesus, O. Huntington Disease. In: In: StatPearls; Stat Pearls Publishing: Treasure Island, 2022.
[4]
Mukherjee, A.; Hussain, Z.; Ganguly, G.; Joardar, A.; Roy, S.; Guin, D.; Sinharoy, U.; Biswas, A.; Das, S. Clinical profile of genetically proven huntington’s disease patients from Eastern India. Ann. Indian Acad. Neurol., 2020, 23(2), 195-200.
[http://dx.doi.org/10.4103/aian.AIAN_505_19] [PMID: 32189861]
[5]
Hong, J.C.; Liu, Y.; Liu, Y.; Zhao, L. High school students’ online learning ineffectiveness in experimental courses during the COVID-19 Pandemic. Front. Psychol., 2021, 12, 738695.
[http://dx.doi.org/10.3389/fpsyg.2021.738695]
[6]
Finkbeiner, S. Huntington’s Disease. Cold Spring Harb. Perspect. Biol., 2011, 3(6), a007476.
[http://dx.doi.org/10.1101/cshperspect.a007476] [PMID: 21441583]
[7]
Agrawal, M.; Biswas, A. Molecular diagnostics of neurodegenerative disorders. Front. Mol. Biosci., 2015, 54.
[http://dx.doi.org/10.3389/fmolb.2015.00054]
[8]
Shacham, T.; Sharma, N.; Lederkremer, G.Z. Protein Misfolding and ER Stress in Huntington’s Disease. Front. Mol. Biosci., 2019, 6, 20.
[http://dx.doi.org/10.3389/fmolb.2019.00020] [PMID: 31001537]
[9]
Guo, C.; Sun, L.; Chen, X.; Zhang, D. Oxidative stress, mitochondrial damage and neurodegenerative diseases. Neural Regen. Res., 2013, 8(21), 2003-2014.
[http://dx.doi.org/10.3969/j.issn.1673-5374.2013.21.009] [PMID: 25206509]
[10]
Brouillet, E.; Jenkins, B.G.; Hyman, B.T.; Ferrante, R.J.; Kowall, N.W.; Srivastava, R.; Roy, D.S.; Rosen, B.R.; Beal, M.F. Age-dependent vulnerability of the striatum to the mitochondrial toxin 3-nitropropionic acid. J. Neurochem., 1993, 60(1), 356-359.
[http://dx.doi.org/10.1111/j.1471-4159.1993.tb05859.x] [PMID: 8417157]
[11]
Kumar, P.; Kumar, A. Prolonged pretreatment with carvedilol prevents 3-nitropropionic acid-induced behavioral alterations and oxidative stress in rats. Pharmacol. Rep., 2008, 60(5), 706-715.
[PMID: 19066418]
[12]
Gupta, S.; Sharma, B. Protective effects of phosphodiesterase-1 (PDE1) and ATP sensitive potassium (KATP) channel modulators against 3-nitropropionic acid induced behavioral and biochemical toxicities in experimental Huntington's disease. Eur. J. Pharmacol., 2014, 732, 111-122.
[http://dx.doi.org/10.1016/j.ejphar.2014.03.032] [PMID: 24690258]
[13]
Jurcau, A.; Jurcau, M.C. Therapeutic strategies in huntington’s disease: From genetic defect to gene therapy. Biomedicines, 2022, 10(8), 1895.
[http://dx.doi.org/10.3390/biomedicines10081895] [PMID: 36009443]
[14]
Kenney, C.; Jankovic, J. Tetrabenazine in the treatment of hyperkinetic movement disorders. Expert Rev. Neurother., 2006, 6(1), 7-17.
[http://dx.doi.org/10.1586/14737175.6.1.7] [PMID: 16466307]
[15]
Yero, T.; Rey, J.A. Tetrabenazine (Xenazine), An FDA-approved treatment option for huntington’s disease-related chorea. P&T, 2008, 33(12), 690-694.
[PMID: 19750050]
[16]
Kumar, G.P.; Khanum, F. Neuroprotective potential of phytochemicals. Pharmacogn. Rev., 2012, 6(12), 81-90.
[http://dx.doi.org/10.4103/0973-7847.99898] [PMID: 23055633]
[17]
Hassan, S.S.U.; Samanta, S.; Dash, R.; Karpinski, T.M.; Habibi, E.; Sadiq, A.; Ahmadi, A.; Bunagu, S. The neuroprotective effects of fisetin, a natural flavonoid in neurodegenerative diseases: Focus on the role of oxidative stress. Front. Pharmacol., 2022, 13, 1015835.
[http://dx.doi.org/10.3389/fphar.2022.1015835]
[18]
Yu, G.; Xiang, W.; Zhang, T.; Zeng, L.; Yang, K.; Li, J. Effectiveness of Boswellia and Boswellia extract for osteoarthritis patients: A systematic review and meta-analysis. BMC Complement Med Ther, 2020, 20(1), 255.
[http://dx.doi.org/10.1186/s12906-020-02985-6]
[19]
Chacko, K.M.; Bhat, B.; Khandal, R.K.; Sultana, S.; Kuruvilla, B.T.; Singh, P.; Aggarwal, M.L. A-90 day gavage safety assessment of Boswellia serrata in rats. Toxicol. Int., 2012, 19(3), 273-278.
[http://dx.doi.org/10.4103/0971-6580.103668] [PMID: 23293466]
[20]
Xu, C.; Wang, B.; Pu, Y.; Tao, J.; Zhang, T. Techniques for the analysis of pentacyclic triterpenoids in medicinal plants. J. Sep. Sci., 2018, 41(1), 6-19.
[http://dx.doi.org/10.1002/jssc.201700201] [PMID: 28862795]
[21]
Mannino, G.; Occhipinti, A.; Maffei, M. Quantitative Determination of 3-O-Acetyl-11-Keto-βBoswellic Acid (AKBA) and other boswellic acids in Boswellia sacra flueck (syn. B. carteri Birdw) and boswellia serrata roxb. Molecules, 2016, 21(10), 1329.
[http://dx.doi.org/10.3390/molecules21101329] [PMID: 27782055]
[22]
Kumar, R.; Kumar, R.; Singh, S.; Saksena, A.K.; Pal, R.; Jaiswal, R. Effect of Boswellia serrata extract on acute inflammatory parameters and tumor necrosis factor-α in complete Freund’s adjuvant-induced animal model of rheumatoid arthritis. Int. J. Appl. Basic Med. Res., 2019, 9(2), 100-106.
[http://dx.doi.org/10.4103/ijabmr.IJABMR_248_18] [PMID: 31041173]
[23]
Roy, N.K.; Parama, D.; Banik, K.; Bordoloi, D.; Devi, A.K.; Thakur, K.K.; Padmavathi, G.; Shakibaei, M.; Fan, L.; Sethi, G.; Kunnumakkara, A.B. An update on pharmacological potential of boswellic acids against chronic diseases. Int. J. Mol. Sci., 2019, 20(17), 4101.
[http://dx.doi.org/10.3390/ijms20174101] [PMID: 31443458]
[24]
Catanzaro, D.; Rancan, S.; Orso, G.; Acqua, S.D.; Brun, P.; Giron, M.C.; Carrara, M.; Castagliuolo, L.; Ragazzi, E.; Caparrotta, L.; Montopoli, M. Boswellia serrata preserves intestinal epithelial barrier from oxidative and inflammatory damage. PLoS One, 2015, 10(5), e0125375.
[http://dx.doi.org/10.1371/journal.pone.0125375]
[25]
Iram, F.; Khan, S.A.; Husain, A. Phytochemistry and potential therapeutic actions of Boswellic acids: A mini-review. Asian Pac. J. Trop. Biomed., 2017, 7(6), 513-523.
[http://dx.doi.org/10.1016/j.apjtb.2017.05.001]
[26]
Gomaa, A.A.; Farghaly, H.A.; Abdel-Wadood, Y.A.; Gomaa, G.A. Potential therapeutic effects of boswellic acids/Boswellia serrata extract in the prevention and therapy of type 2 diabetes and Alzheimer’s disease. Naunyn Schmiedebergs Arch. Pharmacol., 2021, 394(11), 2167-2185.
[http://dx.doi.org/10.1007/s00210-021-02154-7] [PMID: 34542667]
[27]
Mabasa, X.E.; Mathomu, L.M.; Madala, N.E.; Musie, E.M. Sigidi, MT Molecular spectroscopic (FTIR and UV-Vis) and hyphenated chromatographic (UHPLC-qTOF-MS) analysis and in vitro bioactivities of the Momordica balsamina leaf extract. Biochem. Res. Int., 2021, 2854217.
[http://dx.doi.org/10.1155/2021/2854217]
[28]
Boulekbache-Makhlouf, L.; Meudec, E.; Mazauric, J.P.; Madani, K.; Cheynier, V. Qualitative and semi-quantitative analysis of phenolics in Eucalyptus globulus leaves by high-performance liquid chromatography coupled with diode array detection and electrospray ionisation mass spectrometry. Phytochem. Anal., 2013, 24(2), 162-170.
[http://dx.doi.org/10.1002/pca.2396] [PMID: 22930658]
[29]
Tariq, M.; Khan, H.A.; Elfaki, I.; Deeb, S.A.; Moutaery, K.A. Neuroprotective effect of nicotine against 3-nitropropionic acid (3-NP)-induced experimental Huntington’s disease in rats. Brain Res. Bull., 2005, 67(1-2), 161-168.
[http://dx.doi.org/10.1016/j.brainresbull.2005.06.024] [PMID: 16140176]
[30]
El-Sahar, A.E.; Rastanawi, A.A.; El-Yamany, M.F.; Saad, M.A. Dapagliflozin improves behavioral dysfunction of Huntington’s disease in rats via inhibiting apoptosis-related glycolysis. Life Sci., 2020, 257, 118076.
[http://dx.doi.org/10.1016/j.lfs.2020.118076] [PMID: 32659371]
[31]
Bortolatto, C.F.; Jesse, C.R.; Wilhelm, E.A.; Chagas, P.M.; Nogueira, C.W. Organoselenium bis selenide attenuates 3-nitropropionic acid-induced neurotoxicity in rats. Neurotox. Res., 2013, 23(3), 214-224.
[http://dx.doi.org/10.1007/s12640-012-9336-5] [PMID: 22739838]
[32]
Wexler, P.; Anderson, B.D.; Gad, S.C.; Hakkinen, P.B.; Kamrin, M. Encyclopedia of toxicology; Shugart, A., Ed.; Academic Press, 2005, p. 1.
[33]
Shadfar, S.; Khanal, S.; Bohara, G.; Kim, G.; Sadigh-Eteghad, S.; Ghavami, S.; Choi, H.; Choi, D.Y. Methanolic extract of boswellia serrata gum protects the nigral dopaminergic neurons from rotenone-induced neurotoxicity. Mol. Neurobiol., 2022, 59(9), 5874-5890.
[http://dx.doi.org/10.1007/s12035-022-02943-y] [PMID: 35804280]
[34]
Mason, L.H.; Harp, J.P.; Han, D.Y. Pb neurotoxicity: neuropsychological effects of lead toxicity. BioMed Res. Int., 2014, 2014, 1-8.
[http://dx.doi.org/10.1155/2014/840547] [PMID: 24516855]
[35]
Khafaga, A.F.; El-Kazaz, S.E.; Noreldin, A.E. Boswellia serrata suppress fipronil-induced neuronal necrosis and neurobehavioral alterations via promoted inhibition of oxidative/inflammatory/] apoptotic pathways. Sci. Total Environ., 2021, 785, 147384.
[http://dx.doi.org/10.1016/j.scitotenv.2021.147384] [PMID: 33933775]
[36]
Khalaj-Kondori, M.; Sadeghi, F. Published, 1578, 2016(Nov), 17.
[http://dx.doi.org/10.3906/sag-1503-43] [PMID: 27966331]
[37]
Frank-Cannon, T.C.; Alto, L.T.; McAlpine, F.E.; Tansey, M.G. Does neuroinflammation fan the flame in neurodegenerative diseases? Mol. Neurodegener., 2009, 47.
[http://dx.doi.org/10.1186/1750-1326-4-47]
[38]
Khan, A.; Jamwal, S.; Bijjem, K.R.V.; Prakash, A.; Kumar, P. Neuroprotective effect of hemeoxygenase-1/glycogen synthase kinase-3β modulators in 3-nitropropionic acid-induced neurotoxicity in rats. Neuroscience, 2015, 287, 66-77.
[http://dx.doi.org/10.1016/j.neuroscience.2014.12.018] [PMID: 25536048]
[39]
Wang, W.Y.; Tan, M.S.; Yu, J.T.; Tan, L. Role of pro-inflammatory cytokines released from microglia in Alzheimer’s disease. Ann. Transl. Med., 2015, 3(10), 136.
[http://dx.doi.org/10.3978/j.issn.2305-5839.2015.03.49] [PMID: 26207229]
[40]
Shawki, S.M.; Saad, M.A.; Rahmo, R.M.; Wadie, W.; El-Abhar, H.S. Liraglutide improves cognitive and neuronal function in 3-NP rat model of huntington’s disease. Front. Pharmacol., 2021, 12, 731483.
[http://dx.doi.org/10.3389/fphar.2021.731483] [PMID: 35002691]
[41]
Gomaa, A.A.; Farghaly, H.S.M.; El-Sers, D.A.; Farrag, M.M.; Al-Zokeim, N.I. Inhibition of adiposity and related metabolic disturbances by polyphenol-rich extract of Boswellia serrata gum through alteration of adipo/cytokine profiles. Inflammopharmacology, 2019, 27(3), 549-559.
[http://dx.doi.org/10.1007/s10787-018-0519-4] [PMID: 30069718]
[42]
Umar, S.; Umar, K.; Sarwar, A.H.M.G.; Khan, A.; Ahmad, N.; Ahmad, S.; Katiyar, C.K.; Husain, S.A.; Khan, H.A. Boswellia serrata extract attenuates inflammatory mediators and oxidative stress in collagen induced arthritis. Phytomedicine, 2014, 21(6), 847-856.
[http://dx.doi.org/10.1016/j.phymed.2014.02.001] [PMID: 24667331]
[43]
Túnez, I.; Tasset, I.; Pérez-De La Cruz, V.; Santamaría, A. 3-Nitropropionic acid as a tool to study the mechanisms involved in Huntington’s disease: past, present and future. Molecules, 2010, 15(2), 878-916.
[http://dx.doi.org/10.3390/molecules15020878] [PMID: 20335954]
[44]
Kumar, P.; Kalonia, H.; Kumar, A. Expression of Concern: Role of LOX/COX pathways in 3-nitropropionic acid-induced Huntington’s Disease-like symptoms in rats: protective effect of licofelone. Br. J. Pharmacol., 2011, 164(2b), 644-654.
[http://dx.doi.org/10.1111/j.1476-5381.2011.01418.x] [PMID: 21486276]
[45]
Solesio, M.E.; Saez-Atienzar, S.; Jordan, J.; Galindo, M.F. 3-Nitropropionic acid induces autophagy by forming mitochondrial permeability transition pores rather than activatiing the mitochondrial fission pathway. Br. J. Pharmacol., 2013, 168(1), 63-75.
[http://dx.doi.org/10.1111/j.1476-5381.2012.01994.x] [PMID: 22509855]
[46]
Assimopoulou, A.; Zlatanos, S.; Papageorgiou, V. Antioxidant activity of natural resins and bioactive triterpenes in oil substrates. Food Chem., 2005, 92(4), 721-727.
[http://dx.doi.org/10.1016/j.foodchem.2004.08.033]
[47]
Sadeghnia, H.R.; Arjmand, F.; Ghorbani, A. Neuroprotective effect of Boswellia serrata and its active constituent acetyl 11-keto-β-boswellic acid against oxygen-glucose-serum deprivation-induced cell injury. Acta Pol. Pharm., 2017, 74(3), 911-920.
[PMID: 29513961]