• Hanaa H. Ahmed Hormones Department, National Research Centre, Cairo, Egypt
  • Ehab M. Mohamed Chemistry Department, Biochemistry Division, Faculty of Science, Tanta University, Tanta, Egypt
  • Samar M. El-dsoki Chemistry Department, Biochemistry Division, Faculty of Science, Tanta University, Tanta, Egypt


Nil, Boswellia serrata, Neuroinflammation, Apoptosis, Rat


Objective: The current study was planned to investigate the anti-inflammatory and antiapoptotic effects of Boswellia serrata methanolic extract against neurodegeneration characterizing Alzheimer's disease (AD) in rat model.

Methods: Adult male Wistar rats were classified into five groups. Group (1) control group; group (2) AD group which was administered orally with AlCl3 daily for one month; group (3) AD group which was treated orally with rivastigmine daily for three months; group (4) AD group which was treated orally with B. serrata (137.5 mg/kg b. wt) daily for three months and group (5) AD group which was treated orally with B. serrata (68.75 mg/kg b. wt) daily for three months. Brain acetylcholine (Ach), brain and serum acetylcholine (AchE) activity, C-reactive protein (CRP), nuclear factor kappa B (NF-KB), monocyte chemotactic protein-1 (MCP-1), leukotriene B4 (LTB4) and B-cell lymphoma 2 (Bcl-2) levels were detected. Brain histological investigation of all studied groups was carried out.

Results: The data of the current study showed that AlCl3 administration resulted in significant reduction in brain Ach and brain and serum Bcl-2 levels accompanied with significant elevation in brain and serum AchE, CRP, NF-KB, MCP-1 and LTB4 levels. Brain histological investigation of rats administered AlCl3 showed appearance of Aβ plaques characterizing AD. Treatment of rats with B. serrata methanolic extracts caused marked improvement in the measured biochemical parameters as well as in the histological feature of the brain.

Conclusion: B. serrata possesses anti-inflammatory and antiapoptotic effect against neuroinflammation characterizing AD.


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Nie K, Yu J, Fu Y, Cheng H, Chen F, Qu Y. Age-related decrease in constructive activation of Akt/PKB in SAMP10 hippocampus. Biochem Biophys Res Commun 2009;378:103-7.

Driscoll I, Resnick SM. Testosterone and cognition in normal aging and Alzheimer’s disease: an update. Curr Alzheimer Res 2007;4:33-45.

Wenk GL. Neuropathologic changes in Alzheimer's disease. J Clin Psychiatry 2007;9:7-10.

Tiraboschi P, Hansen LA, Thal LJ, Corey-Bloom J. The importance of neuritic plaques and tangles to the development and evolution of AD. Neurol 2004;62(11):1984–9.

Von Bernhardi R. Glial cell dysregulation: a new perspective on Alzheimers disease. Neurotox. Res 2007;12:215-32.

Navaratinam D, Priddle J, McDonald B, Esiri M, Robinson J, Smith A. Anomalous molecular form of acetylcholinesterase in cerebrospinal fluid in histologically diagnosed Alzheimer’s disease. Lancet 1991;337:447–9.

Massoulié J, Pezzementi L, Bon S, Krejci E, Vallette F. Molecular and cellular biology of cholinesterases. Prog Neurobiol 1991;41:31-91.

Kitazawa M, Yamasaki F, LaFerla FM. Microglia as a potential bridge between the amyloid beta-peptide and Tau. Ann NY Acad Sci 2004;1035:85-103.

Salem A, Sabry G, Hanaa H, Ahmed A, Soheir E. Amelioration of neuroinflmmation and apoptosis characterizing Alzheimer’s disease by natural products. Int J Pharm Pharm Sci 2013;5 Suppl 2:87-94.

Mattson MB, Magnus T. Aging and neuronal vulnerability. Nat Rev Neurosci 2006;7:278-94.

Banks W, Maness L, Banks M, Kastin A. Aluminum-sensitive degradation of amyloid beta-protein 1–40 by murine and human intracellular enzymes. Neurotoxicol Teratol 1996;18:671–7.

Simpson J, Yates C, Whyler D, Wilson H, Dewar A, Gordon A. Biochemical studies on rabbits with aluminium induced neurofilament accumulation. Neurochem Res 1985;10:229-38.

Campbell A, Kumar A, La Rosa FG, Prasad KN, Bondy SC. Aluminum increases levels of beta-amyloid and ubiquitin in neuroblastoma but not in glioma cells. Proc Soc Exp Biol Med 2000;223(4):397-402.

Madhuri S, Pandey G. Some anticancer medicinal plants of foreign origin. Curr Sci 2009;96:6-25.

Sharma A, Mann A, Gajbhiye V, Kharya M. Plant review, phytochemical profile of boswellia serrata. an overview. Pharm Rev 2007;1(1):137-42.

Cuaz-Pérolin C, Billiet L, Baugé E, Copin C, Scott-Algara D, Genze F, et al. Anti-inflammatory and antiatherogenic effects of the NF-kappaB inhibitor acetyl-11-keto-beta-boswellic acid in LPS-challenged ApoE-/-mice. Arterioscler Thromb Vasc Biol 2008;28(2):272-7.

Krasovskii GN, Vasukovich LY, Chariev OG. Experimental study of biological effects of leads and aluminum following oral administration. Environ Health Perspect 1979;30:47-51.

Carageorgious H, Sideris A, Messaril E. The effect of rivastigmine and selegilin on brain acetylcholinesterase, (Na+, K+), Mg2+, Atpase activities, antioxidant status and learning performance of aged rats. Neuropsychiatr Dis Treat 2008;4(4):687-99.

Van Herck H, Baumans V, Brandt C, Boere H, Hesp A, Van Lith H, et al. Blood sampling from the retro-orbital plexus, the saphenous vein and the tail vein in rats: comparative effects on selected behavioral and blood variables. Lab Anim 2001;35:131­9.

Tsakiris S, Schulpis K, Marinou K, Behrakis P. Protective effect of L-cysteine and glutathione on the modulated suckling rat brain Na+, K+-ATPase and Mg2+-ATPase activities induced by the in vitro galactosaemia. Pharmacol Res 2004;49:475-9.

Lowry O, Rosebrough N, Farr A, Randall R. Protein measurement with the folin phenol reagent. J Biol Chem 1951;193:265-75.

Oswald C, Smits S, Hoing M, Sohn-Bosser L, Dupont L, Le Rudulier D, et al. Crystal structures of choline/acetylcholine substrate-binding protein chox from sinorhizobium meliloti in the liganded and unligznded-closed states. J Biol Chem 2008;283:32848-59.

Den Blaauwen D, Poppe W, Tritschler W. Acetylcholinesterase with acetylthiocholine iodide as substrate. J Clin Chem Clin Biochem 1983;21:381-6.

Wilkins J. Quantitative determination of C-reactive protein by enzyme immunoassay in human serum. Clin Chem 1998;44:1358.

Ikawa T, Ikeda M, Yamaguchi A, Tsai WC, Tamura N, Seta N, et al. Expression of arthritis-causing HLAB27 on Hela cells promotes induction of c-fos in response to in vitro invasion by salmonella typhimurium. J Clin Invest 1998;101:263-72.

Chard T. An introduction to radioimmunoassay and related techniques 4th Ed. Amsterdam Elsevier; 1990.

Adams J. Proteasome inhibition in cancer development of PS-341. Semin Oncol 2001;28(6):613-9.

Barbareschi M, Caffo O, Veronese S, Leek R, Fina P, Fox S, et al. Bcl-2 and P53 expression in node negative breast carcinoma a study with long term follow up. Human Pathol 1996;27:1149-55.

Banchroft J, Stevens A, Turner D. Theory and practice of histological techniques. 4th Ed. Churchil Livingstone, New York; 1996.

Armitage P, Berry G. Comparison of several groups. In: statistical method in medical research 2th Ed. Blockwell Significant Publication, Oxford; 1987. p. 186-213.

Bielarczyk H, Tomaszewicz M, Szutowicz A. Effect of aluminum on acetyl-CoA and acetylcholine metabolism in nerve terminals. J Neurochem 1998;70:1175-81.

Ahmed H, Salem A, Gilane M, Ahmed A, Soheir E. Possible therapeutic uses of Salvia triloba and Piper nigrum in Alzheimer’s disease–induced rats. J Med Food 2013;16(5):437-46.

Szutowicz A. Aluminum, NO and nerve growth factor neurotoxicity in cholinergic neurons. J Neurosci Res 2001;66:1009-18.

Alleva K, Rankin J, Santucci D. Neurobehavioural alteration in rodents following developmental exposure to aluminum. Toxicol Ind Health 1998;14:209–21.

Kaizer R, Corrêa M, Spanevello R, Morsch V, Mazzanti C, Goncalves J, et al. Acetylcholinesterase activation and enhanced lipid peroxidation after long-term exposure to low levels of aluminum on different mouse brain regions. J Inorg Biochem 2005;99:1865-70.

Zhang J, Yang J, He B, Zhou Q, Yu H, Tang Y. Berberine and total base from rhizoma coptis chinensis attenuate brain injury in an aluminum-induced rat model of neurodegenerative disease. Saud Med J 2009;30:760-6.

Kaizer R, Correa M, Gris L, Da Rosa C, Bohrer D, Morsch V, et al. Effect of long term exposure to aluminum on the acetylcholinesterase activity in the central nervous system and erythrocytes. Neurochem Res 2008;33:2294-301.

Liang Y, Tang X. Comparative effects of huperzine A, donepezil and rivastigmine on cortical acetylcholine level and acetylcholinesterase activity in rats. Neurosci Lett 2004;361:56–9.

Foye W, Lemke T, Williams D. Principles of Medicinal Chemistry, 4th ed. Williams and Wilkins USA; 1995.

Howes M, Perry N, Houghton P. Plants with traditional uses and activities, relevant to the management of Alzheimer’s disease and other cognitive disorders. Phytother Res 2003;17:1–18.

Ota M, Houghton P. Boswellic acids with acetylcholinesterase inhibitory properties from frankincense. Nat Prod Commun 2008;3(1):21-6.

Ingkaninan K, Temkitthawon P, Chuenchom K, Yuyaem T, Thongnoi W. Screening for acetylcholinestrase inhibitory activity in plant sused in Thai traditional rejuvenating and neurotonic remedies. J Ethnopharmacol 2003;89:261-4.

Chattipakorn S, Pongpanparadorn A, Pratchayasakul W, Pongchaidacha A, Ingkaninan K, Chattipakorn N. Tabernaemontana divaricate extract inhibits neuronal acetylcholinestrase activity in rats. J Ethnopharmacol 2007;110:61-8.

Nakdook W, Onrawee K, Pornnarin T, Niwat T, Kornkanok I. The effects of Tabernaemontana divaricate root extract on amyloid β-peptide 25-35 peptides induced cognitive deficits in mice. J Ethnopharmacol 2010;130:122-6.

Engelhart MJ, Geerlings MI, Meijer J, Kiliaan A, Ruitenberg A, van Swieten JC, et al. Inflammatory proteins in plasma and the risk of dementia. The Rotterdam Study Arch Neurol 2004;61:668–72.

Yoshiyama Y, Arai K, Hattori T. Enhanced expression of I-kappaB with neurofibrillary pathology in Alzheimer’s disease. Neuro Report 2001;12:2641–5.

Grammas P, Ovase R. Inflammatory factors are elevated in brain microvessels in Alzheimer's disease. Neurobiol Aging 2001;22(6):837-42.

Paris D, Town T, Parker TA, Tan J, Humphrey J, Crawford F, et al. Inhibition of Alzheimer's beta-amyloid induced vasoactivity and proinflammatory response in microglia by a cGMP-dependent mechanism. Exp Neurol 1999;157(1):211-21.

McGeer PL, McGeer EG. Inflammation, autotoxicity and Alzheimer’s disease. Neurobiol Aging 2001;22:799–809.

Ravaglia G, Forti P, Maioli F, Chiappelli M, Montesi F, Tumini E, et al. Blood inflammatory markers and risk of dementia. The conselice study of brain aging. Neurobiol Aging 2007;28:1810–20.

Teunissen CE, van Boxtel MP, Bosma H. Inflammation markers in relation to cognition in a healthy aging population. J Neuroimmunol 2003;134:142–50.

Yasojima K, Schwab C, McGeer EG, McGeer PL. Human neurons generate C-reactive protein and amyloid P. Upregulation in Alzheimer’s disease. Brain Res 2000;887:80–9.

Nayak P. Aluminum impacts and disease. Environ Res 2002;89:111–5.

Campbell A, Becaria A, Sharman K, Bondy SC. Chronic exposure to aluminum in drinking water increases inflammatory parameters selectively in the brain. J Neurosci Res 2004;75:565-72.

Lukiw W, Percy M, Kruck T. Nanomolar aluminum induces pro-inflammatory and pro-apoptotic gene expression in human brain cells in primary culture. J Inorg Biochem 2005;99:1895–8.

Pizzi M, Spano P. Distinct roles of diverse nuclear factor-kappa B complexes in neuropathological mechanisms. Eur J Pharmacol 2006;545:22-8.

Huang Y, Liu F, Grundke-Iqbal I, Iqbal K, Gong CX. NF-κB precursor, p105, and NF-κB inhibitor, IκBγ, are both elevated in Alzheimer disease brain. Neurosci Lett 2005;373:115–8.

Reale M, Iarlori C, Feliciani C, Gambi D. Peripheral chemokine receptors, their ligands, cytokines and Alzheimer's disease. J Alzh Dis 2008;14(2):147-59.

El Khoury J, Toft M, Hickman S, Means T, Terada K, Geula C, et al. Ccr2 deficiency impairs microglial accumulation and accelerates progression of Alzheimer-like disease. Nat Med 2007;13:432–8.

Wang GJ, Chen YM, Wang TM, Lee CK, Chen KJ, Lee TH. Flavonoids with iNOS inhibitory activity from Pogonatherum crinitum. J Ethnopharmacol 2008;118(1):71–8.

Jiang J, Borisenko GG, Osipov A, Martin I, Chen R, Shvedova A, et al. Arachidonic acid-induced carbon-centered radicals and phospholipid peroxidation in cyclo-oxygenase-2-transfected PC12 cells. J Neurochem 2004;90:1036–49.

Nizri E, Irony-Tur-Sinai M, Lavon I, Meshulam H, Amitai G, Brenner T. IBU-octyl-cytisine, a novel bifunctional molecule eliciting anti-inflammatory and cholinergic activity ameliorate CNS inflammation by inhibition of T-cell activity. Int Immunopharmacol 2007;7:1129–39.

Nizri E, Irony-Tur-Sinai M, Faranesh N, Lavon I, Lavi E, Weinstock M, et al. Suppression of neuroinflammation and immunomodulation by the acetylcholinesterase inhibitor rivastigmine. J Neuroimmunol 2008;203:12–22.

Moshage HJ, Roelofs HM, Van Pelt JF, Hazenberg BP, van Leeuwen MA, Limburg PC, et al. The effect of interleukin-1, interleukin-6 and its interrelationship on the synthesis of serum amyloid A and C-reactive protein in primary cultures of adult human hepatocytes. Biochem Biophys Res Commun 1988;155:112–7.

Dantoine T, Auriacombe S, Sarazin M, Becker H, Pere J, Bourdeix I. Rivastigmine monotherapy and combination therapy with memantine in patients with moderately severe Alzheimer's disease who failed to benefit from previous cholinesterase inhibitor treatment. Int J Clin Pract 2006;60:110–8.

Cummings J. Alzheimer’s disease. New England J Med 2004;351(1):56-67.

Wang J, Slunt H, Gonzales V, Fromholt D, Coonfield M, Copeland NG, et al. Copper-binding-site-null SOD1 causes ALS in transgenic mice: aggregates of non-native SOD1 delineate a common feature. Hum Mol Genet 2003;12:2753–64.

Wang H, Liao H, Ochani M, Justiniani M, Lin X, Yang L, et al. Cholinergic agonists inhibit HMGB1 release and improve survival in experimental sepsis. Nat Med 2004;10:1216–21.

Tabet N. Acetylcholinesterase inhibitors for Alzheimer’s disease: anti-inflammatories in acetylcholine clothing. Age Ageing 2006;35:336–8.

Conductier G, Blondeau N, Guyon A, Nahon JL, Rovère C. The role of monocyte chemoattractant protein MCP1/CCL2 in neuroinflammatory diseases. J Neuroimmunol 2010;224:93–100.

Chakraborty A, Brantner A. Study of alkaloids Adhatoda vasica Nees ontheir anti-inflammatory activity. Phytother 2001;15:532-4.

Krüger P, Daneshfar R, Eckert G, Klein J, Volmer D, Bahr U, et al. Metabolism of boswellic acids in vitro and in vivo. Drug Metab Dispos 2008;36(6):1135-42.

Ammon H. Modulation of the immune system by Boswellia serrata extracts and boswellic acids. Int J Phytother Phytopharmacol 2010;17(11):862-7.

Syrovets T, Büchele B, Krauss C, Laumonnier Y, Simmet T. Acetyl-boswellic acids inhibit lipopolysaccharide-mediated TNF-α induction in monocytes by direct interaction with IκB kinases. J Immunol 2005;174:498–506.

Safayhi H, Mack T, Sabieraj J. Boswellic acids: novel, specific, nonredox inhibitors of 5-lipoxygenase. J Pharmacol Exp Ther 1992;261:1143-6.

Jin C, Liu Q, Wang J, Cai Y. Effect of aluminum on neural behavior and the expression of Bcl-2 and Fas in hippocampus of weaning rats. Wei Sheng Yan Jiu 2009; 38:1-3.

Savory J, Herman M, Ghribi O. Intracellular mechanisms underlying aluminum-induced apoptosis in rabbit brain. J Inorg Biochem 2003;97:151-4.

Takada-Takatori Y, Kume T, Sugimoto M, Katsuki H, Sugimoto H, Akaike A. Acetylcholinesterase inhibitors used in treatment of Alzheimer's disease prevent glutamate neurotoxicity via nicotinic acetylcholine receptors and phosphatidylinositol 3-kinase cascade. Neuropharmacol 2006;51(3):474-86.

Pan Y, Xu X, Wang X. Rivastigmine blocks voltage-activated K currents in dissociated rat hippocampal neurons. Br J Pharmacol 2003;140:907–12.

Badmaev V, Majeed M. Boswellia: NSAID alternative. Nutrition Industry Executive Magazine for dietary supplement industry manufacturers; 2004.

Mukherjee P, Rachita C, Aisen P, Pasinetti G. Non-steroidal anti-inflammatory drugs protect against chondrocyte apoptotic death. Clin Exp Rheumatol 2001;19:7-11.

Klatzo I, Wisniewski H, Streicher E. Experimental production of neurofibrillary degeneration I. Light microscopic observation. J Neuropathol Exp Neurol 1965;24:187–99.

Praticò D, Uryu K, Sung S, Tang S, Trojanowski JQ, Lee VM. Aluminum modulates brain amyloidosis through oxidative stress in APP transgenic mice. FASEB J 2002;16(9):1138–40.

Rodella LF, Ricci F, Borsani E. Aluminium exposure induces Alzheimer’s disease-like histopathological alterations in mouse brain. Histol Histopathol 2008;23(4-6):433–9.

Coleman P, Federoff H, Kurlan R. A focus on the synapse for neuroprotection in Alzheimer disease and other dementias. Neurol 2004;63:1155–62.

Bihaqi SW, Sharma M, Singh AP, Tiwari M. Neuroprotective role of Convolvulus pluricaulis on aluminium induced neurotoxicity in rat brain. J Ethnopharmacol 2009;124:409–15.

Karima O, Riazi G, Yousefi R, Movahedi AA. The enhancement effect of beta-boswellic acid on hippocampal neurites outgrowth and branching. Neurol Sci 2010;31:315-20.

Kirste S, Treier M, Sabine J, Gerhild B, Mona A, Kathleen G, et al. Boswellia serrata acts on cerebral edema in patients irradiated for brain tumors. 2011;117(16):3788–95.



How to Cite

Ahmed, H. H., E. M. Mohamed, and S. M. El-dsoki. “EVIDENCES FOR THE PROMISING THERAPEUTIC POTENTIAL OF BOSWELLIA SERRATA AGAINST ALZHEIMER’S DISEASE: PRE-CLINICAL STUDY”. International Journal of Pharmacy and Pharmaceutical Sciences, vol. 6, no. 11, Nov. 2014, pp. 384-92, https://journals.innovareacademics.in/index.php/ijpps/article/view/3401.



Original Article(s)