Effects of Boswellia serrata resin extract on motor dysfunction and brain oxidative stress in an experimental model of Parkinson’s disease

Document Type: Original Research Article

Authors

1 Department of Physiology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran.

2 Department of Physiology, School of Medicine, Shahed University of Medical Sciences, Tehran, Iran.

3 Department of Physiology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, I. R. Iran

4 Department of Pharmacognosy, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran

Abstract

Objective:Boswellia serrata oleo-gum resin (frankincense) exerted antioxidant and anti-inflammatory effects against several diseases, such as; asthma, rheumatoid arthritis and irritable bowel syndrome. In the current study, the influences of B. serrata resin extracton motor dysfunction and oxidative stress markers were investigated in the intrastriatal 6-hydroxydopamine (6-OHDA) model of Parkinson’s disease (PD).
Materials and Methods:The animals were randomly assigned to sham, lesion (6-OHDA), and three lesion groups treated with ethyl alcoholic extract of B. serrata at doses of 125, 250 and 500 mg/kg for 3 weeks. The neurotoxin 6-OHDA (12.5 µg) was microinjected into the left striatum to induce PD in male rats. Motor behavior was assessed by rotational and elevated narrow beam tests. Oxidative stress markers were measured in striatal and midbrain homogenates. 
Results: There was a significant increase in contralateral rotations in 6-OHDA group versus sham group (p<0.001), and treatment with B. serrata resin extract at doses of 125 and 250 mg/kg significantly decreased the rotations in comparison to 6-OHDA group (pB. serrata extract at doses of 125, 250 and 500 mg/kg caused a significant reduction in the latency and total time (p<0.001, p<0.001, and p<0.01, respectively). Biochemical analysis showed no significant difference in oxidative stress markers levels among the groups.
Conclusion: Our findings suggest that B. serrata resin extract acts as an anti-inflammatory and antioxidant agent that protects nigrostriatal dopaminergic neurons and improve motor impairments in PD.

Keywords

Main Subjects


Abdel-Tawab M, Werz O, Schubert-Zsilavecz M. 2011. Boswellia serrata: an overall assessment of in vitro, preclinical, pharmacokinetic and clinical data.Clin Pharmacokinet, 50: 349-369.

Ahmad M, Saleem S, Ahmad AS, Yousuf S, Ansari MA, Khan MB, Ishrat T, Chaturvedi RK, Agrawal AK, Islam F. 2005b. Ginkgo biloba affords dose-dependent protection against 6-hydroxydopamine-induced Parkinsonism in rats: neurobehavioural, neurochemical and immunohistochemical evidences. J Neurochem, 93: 94–104.

Allbutt HN, Henderson JM. 2007. Use of the narrow beam test in the rat, 6-hydroxydopamine model of Parkinson's disease. J Neurosci Methods, 159: 195-202.

Ammon H. 2010. Modulation of the immune system by Boswellia serrata extracts and boswellic acids. Phytomedicine, 17: 862-867.

Ammon HP. 2006. Boswellic acids in chronic inflammatory diseases. Planta Med, 72: 1100-1116.

Beghelli D, Isani G, Roncada P, Andreani G, Bistoni O, Bertocchi M, Lupidi G, Alunno A. 2017. Antioxidant and Ex vivo immune system regulatory properties of Boswellia serrata extracts. Oxid Med Cell Longev, 2017: 7468064.

Baluchnejadmojarad T, Roghani M, Nadoushan MRJ, Bagheri M. 2009. Neuroprotective effect of genistein in 6‐hydroxydopamine hemi‐parkinsonian rat model. Phytother Res, 23: 132-135.

Blesa J, Trigo-Damas I, Quiroga-Varela A, Jackson-Lewis VR. 2015. Oxidative stress and Parkinson’s disease. Front Neuroanat, 9: 91.

Brieger K, Schiavone S, Miller Jr FJ, Krause K-H. 2012. Reactive oxygen species: from health to disease. Swiss Med Wkly, 142: w13659.

Claiborne A. 1985. Catalase activity In: Greenwald RA (ed) Handbook of methods for oxygen free radical research. CRC Press, Boca Raton, FL. 283-284.

Dalla Libera D, Colombo B, Pavan G, Comi G. 2014. Complementary and alternative medicine (CAM) use in an Italian cohort of pediatric headache patients: the tip of the iceberg. Neurol Sci, 35: 145-148.

Darshan S, Doreswamy R. 2004. Patented antiinflammatory plant drug development from traditional medicine. Phytother Res, 18: 343–357.

Ding Y, Chen M, Wang M, Wang M, Zhang T, Park J, Park J, Zhu Y, Guo C, Jia Y, Li Y, Wen A. 2014. Neuroprotection by acetyl-11-keto-β-boswellic acid, in ischemic brain injury involves the Nrf2/HO-1 defense pathway. Sci Rep, 4: 7002.

Doorn KJ, Goudriaan A, Blits-Huizinga C, Bol JG, Rozemuller AJ, Hoogland PV, Lucassen PJ, Drukarch B, van de Berg WD, van Dam AM. 2014. Increased amoeboid microglial density in the olfactory bulb of Parkinson’s and Alzheimer’spatients. Brain Pathol, 24: 152–165.

Doorn KJ, Moors T, Drukarch B, van de Berg W, Lucassen PJ, van Dam AM. 2014b. Microglial phenotypes and toll-like receptor 2 in the substantia nigra and hippocampus of incidental Lewy body disease cases and Parkinson’s disease patients. Acta Neuropathol Commun, 2: 90.

Ferrari CC, Godoy MCP, Tarelli R, Chertoff M, Depino AM, Pitossi FJ. 2006. Progressive neurodegeneration and motor disabilities induced by chronic expression of IL-1β in the substantia nigra. Neurobio Dis, 24: 183-193.

Fujita M, Nishino H, Kumazaki M, Shimada S, Tohyama M, Nishimura T. 1996. Expression of dopamine transporter mRNA and its binding site in fetal nigral cells transplanted into the striatum of 6-OHDA lesioned rat. Mol Brain Res, 39: 127–136.

Gupta I, Parihar A, Malhotra P, Gupta S, Lüdtke R, Safayhi H, Ammon HP. 2001. Effects of gum resin of Boswellia serrata in patients withchronic colitis. Planta Medica, 67: 391-395.

Haddadi H, Rajaei Z, Alaei H, Shahidani S. 2018. Chronic treatment with carvacrol improves passive avoidance memory in a rat model of Parkinson's disease. Arq Neuropsiquiatr, 76: 71-77.

Henderson J, Watson S, Halliday G, Heinemann T, Gerlach M. 2003. Relationships between various behavioural abnormalities and nigrostriatal dopamine depletion in the unilateral 6-OHDA-lesioned rat. Behav Brain Res, 139: 105-113.

Hosseini H, Rajaei Z, Alaei H, Tajadini M. 2016. The effects of crocin on 6-OHDA-induced oxidative/nitrosative damage and motor behaviour in hemiparkinsonian rats. Malays J Med Sci, 23: 35–43.

Kazmi S, Kafami L, Ebrahimi A, Jameie B, Joghataiee MT. 2011. The effects of boswellia resin extract on dopaminergic cell line, SK-N-SH, against MPP+-induced neurotoxicity. Basic Clin Neurosci, 3: 16-21.

Khuwaja G, Khan MM, Ishrat T, Ahmad A, Raza SS, Ashafaq M, Javed H, Khan MB, Khan A, Vaibhav K, Safhi MM, Islam F.  2011. Neuroprotective effects of curcumin on 6-hydroxydopamine-induced Parkinsonism in rats: Behavioral, neurochemical and immunohistochemical studies. Brain Res, 1368: 254-263.

Kirik D, Rosenblad C, Bjorklund A. 1998. Characterization of behavioral and neurodegenerative changes following partial lesions of the nigrostriatal dopamine system induced by intrastriatal 6-hydroxydopamine in the rat. Exp Neurol, 152: 259–277.

Kokkiripati PK, Bhakshu LM, Marri S, Padmasree K, Row AT, Raghavendra AS, Tetali SD. 2011. Gum resin of Boswellia serrata inhibited human monocytic (THP-1) cell activation and platelet aggregation. J Ethnopharmacol, 137: 893-901.

McCoy MK, Martinez TN, Ruhn KA, Szymkowski DE, Smith CG, Botterman BR, Tansey KE, Tansey MG. 2006. Blocking soluble tumor necrosis factor signaling with dominant-negative tumor necrosis factor inhibitor attenuates loss of dopaminergic neurons in models of Parkinson's disease. J Neurosci, 26: 9365-9375.

Paxinos G, Watson C. 2005. The rat brain in stereotaxic coordinates: Elsevier Academic Press. San Diego, CA.

Phaniendra A, Jestadi DB, Periyasamy L. 2015. Free radicals: properties, sources, targets, and their implication in various diseases. Indian J Clin Biochem, 30: 11-26.

Pringsheim T, Jette N, Frolkis A, Steeves TD. 2014. The prevalence of Parkinson's disease: A systematic review and meta‐analysis. Mov Disord, 29: 1583-1590.

Pringsheim T, Fiest K, Jette N. 2014. The international incidence and prevalence of neurologic conditions How common are they? Neurology, 83: 1661-1664.

Rocha NP, de Miranda AS, Teixeira AL. 2015. Insights into neuroinflammation in Parkinson’s disease: from biomarkers to anti-inflammatory based therapies. Biomed Res Int, 2015:628192.

Roghani M, Niknam A, Jalali-Nadoushan M-R, Kiasalari Z, Khalili M, Baluchnejadmojarad T. 2010. Oral pelargonidin exerts dose-dependent neuroprotection in 6-hydroxydopamine rat model of hemi-parkinsonism. Brain Res Bulletin, 82: 279-283.

Ryan BJ, Hoek S, Fon EA, Wade-Martins R. 2015. Mitochondrial dysfunction and mitophagy in Parkinson’s: from familial to sporadic disease. Trends Biochem Sci, 40: 200–210.

Sander O, Herborn G, Rau R. 1998. Is H15 (resin extract of Boswellia serrata," incense") a useful supplement to established drug therapy of chronic polyarthritis? Results of a double-blind pilot study. Z Rheumatol, 57: 11-16.

Schwarting RK, Huston JP. 1997. Behavioral and neurochemical dynamics of neurotoxic mesostriatal dopamine lesions. Neurotoxicol, 18: 689–708.

Sedlak J, Linsay RH. 1968. Estimation of total protein bound and nonprotein bound sulphydryl group in tissue with Ellman’s reagents. Anal Biochem, 25: 192–205.

Sian‐Hülsmann J, Mandel S, Youdim MB, Riederer P. 2011. The relevance of iron in the pathogenesis of Parkinson’s disease. J Neurochem, 118: 939-957.

Siddiqui M. 2011. Boswellia serrata, a potential antiinflammatory agent: an overview. Indian J Pharm Sci, 73: 255.

Singh HP, Yadav IK, Chandra D, Jain DA. 2012. In vitro antioxidant and free radical scavenging activity of different extracts of Boerhavia diffusa and Boswellia serrata. Int J Pharma Sci Res, 3: 503–511.

Smith MP, Cass WA. 2007. Oxidative stress and dopamine depletion in an intrastriatal 6-hydroxydopamine model of Parkinson’s disease. Neurosci, 144: 1057-1066.

Tsang AH, Chung KK. 2009. Oxidative and nitrosative stress in Parkinson's disease. Biochim Biophys Acta, 1792: 643-650.

Umar S, Umar K, Sarwar AH, Khan A, Ahmad N, Ahmad S. 2014. Boswellia serrata extract attenuates inflammatory mediators and oxidative stress in collagen induced arthritis. Phytomedicine, 21: 847–856.

Wang Q, Liu Y, Zhou J. 2015. Neuroinflammation in Parkinson’s disease and its potential as therapeutic target. Transl Neurodegener, 4: 19.

Wang JY, Yang JY, Wang F, Fu SY, Hou Y, Jiang B, Ma J, Song C, Wu CF. 2013. Neuroprotective effect of pseudoginsenoside-f11 on a rat model of Parkinson's disease induced by 6-hydroxydopamine. Evid Based Complement Alternat Med, 2013: 152798.

Winking M, Sarikaya S, Rahmanian A, Jödicke A, Böker D-K. 2000. Boswellic acids inhibit glioma growth: a new treatment option? J Neurooncol, 46: 97–103.

Zafar KS, Siddiqui A, Sayeed I, Ahmad M, Saleem S, Islam F. 2003. Protective effect of adenosine in rat model of Parkinson's disease: neurobehavioral and neurochemical evidences. J Chem Neuroanat, 26: 143-151.

Ziv I, Melamed E, Nardi N. 1998. Role of apoptosis in the pathogenesis of Parkinson's disease: A novel therapeutic opportunity. Mov Disord, 13: 865–870.