Beta Boswellic Acid Reduces Tau Phosphorylation Level and Enhances Reelin Expression in the brain
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Abstract
Objectives: Learning and memory retention are processes that involve a permanent change in the behavior based on environmental adaptation. Reelin protein participates in the learning and memory. It has not received much attention in the presence of herbal components. The present study focused on the effect of an optimum dose of Beta-Boswellic Acid (BBA) on the reduction of tau phosphorylation level and enhancement of Reelin expression on the hippocampus regions to improve cognitive behavioural therapy.
Methods: Spatial memory, learning, and locomotor activity were assessed. The histological analysis was performed. The Western blot analysis was employed.
Results: The results represented the significant effect of BBA (35 mg/kg of body weight) on the degree of memory consolidation in the probe trial of MWM test. The BBA treatment reduced dark neuron formation in the hippocampus. This component promoted the Reelin expression.
Conclusion: A certain dose of BBA improved memory consolidation in the adult rats, and Reelin protein was more expressed in the presence of BBA that it may be due to the anti-inflammatory property of BBA as one of the main factors involved in enhancing memory consolidation among rats.
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2. Jivad N, Rabiei Z. A review study on medicinal plants used in the treatment of learning and memory impairments. Asian Pac J Trop Biomed. 2014;4(10):780-9. https://doi.org/10.12980/apjtb.4.2014apjtb-2014-0412
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6. Siddhu NSS, Guru A, Satish Kumar RC, Almutairi BO, Almutairi MH, Juliet A, et al. Pro-inflammatory cytokine molecules from Boswellia serrate suppresses lipopolysaccharides induced inflammation demonstrated in an in-vivo zebrafish larval model. Mol Biol Rep. 2022;49(8):7425-35. https://doi.org/10.1007/s11033-022-07544-5
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8. Karima O, Riazi G, Yousefi R, Movahedi AA. The enhancement effect of beta-boswellic acid on hippocampal neurites outgrowth and branching (an in vitro study). Neurol Sci. 2010;31(3):315-20. https://doi.org/10.1007/s10072-010-0220-x
9. Bashar A, Kadhem W. Study of the effect of Boswellia serrata in reducing the effects associated with induced arthritis in male albino rats. Agric Biotechnol J. 2025;17(1):177-92.
10. Alahmari A, Al-Doaiss AA. Impact of Boswellia serrata Supplementation on Cytokines Profile, Antioxidant Status and NF-kB Expression in the Spleen and Thymus of Rats. Indian J Anim Res. 2025;59(2). https://doi.org/10.18805/ijar.bf-1888
11. Khalaj-Kondori M, Sadeghi F, Hosseinpourfeizi MA, Shaikhzadeh-Hesari F, Nakhlband A, Rahmati-Yamchi M. Boswellia serrata gum resin aqueous extract upregulatesBDNF but not CREB expression in adult male rat hippocampus. Turk J Med Sci. 2016;46(5):1573-8. https://doi.org/10.3906/sag-1503-43
12. Mahboubi M, Taghizadeh M, Talaei SA, Firozeh SMT, Rashidi AA, Tamtaji OR. Combined administration of Melissa officinalis and Boswellia serrata extracts in an animal model of memory. Iran J Psychiatry Behav Sci. 2016;10(3):e681-e7. https://doi.org/10.17795/ijpbs-681
13. Vinay P, Balamurugan K, Rajan KE. Reduced Reelin Expression Induces Memory Deficits through Dab-1/NMDAR Signaling Pathway: Cronobacter sakazakii Infection in a Rat Model of Experimental Meningitis. Dev Neurosci. 2023;44(6):547-56. https://doi.org/10.1159/000525821
14. Jossin Y. Reelin functions, mechanisms of action and signaling pathways during brain development and maturation. Biomolecules. 2020;10(6):964. https://doi.org/10.3390/biom10060964
15. Council NR. Guide for the care and use of laboratory animals: National Academies Press; 2010.
16. Paxinos G, Watson C, Carrive P, Kirkcaldie M, Ashwell K. Chemoarchitectonic atlas of the rat brain. 2009.
17. Zhou S, Yu G, Chi L, Zhu J, Zhang W, Zhang Y, et al. Neuroprotective effects of edaravone on cognitive deficit, oxidative stress and tau hyperphosphorylation induced by intracerebroventricular streptozotocin in rats. Neurotoxicology. 2013;38:136-45. https://doi.org/10.1016/j.neuro.2013.07.007
18. Ameen AM, Elkazaz AY, Mohammad HM, Barakat BM. Anti-inflammatory and neuroprotective activity of boswellic acids in rotenone parkinsonian rats. Can J Physiol Pharmacol. 2017;95(7):819-29. https://doi.org/10.1139/cjpp-2016-0158
19. Ebrahimpour S, Fazeli M, Mehri S, Taherianfard M, Hosseinzadeh H. Boswellic Acid Improves Cognitive Function in a Rat Model Through Its Antioxidant Activity:-Neuroprotective effect of Boswellic acid. J Pharmacopunct. 2017;20(1):10-7. https://doi.org/10.3831/kpi.2017.20.001
20. Gokaraju GR, Gokaraju RR, Gokaraju VKRR, Golakoti T, Bhupathiraju K, Alluri VKR. Boswellia oil, its fractions and compositions for enhancing brain function. Google Patents; 2014.
21. Altmann A, Fischer L, Schubert-Zsilavecz M, Steinhilber D, Werz O. Boswellic acids activate p42(MAPK) and p38 MAPK and stimulate Ca(2+) mobilization. Biochem Biophys Res Commun. 2002;290(1):185-90. https://doi.org/10.1006/bbrc.2001.6153
22. Gerbeth K, Husch J, Fricker G, Werz O, Schubert-Zsilavecz M, Abdel-Tawab M. In vitro metabolism, permeation, and brain availability of six major boswellic acids from Boswellia serrata gum resins. Fitoterapia. 2013;84:99-106. https://doi.org/10.1016/j.fitote.2012.10.009
23. Sailer ER, Subramanian LR, Rall B, Hoernlein RF, Ammon HP, Safayhi H. Acetyl-11-keto-beta-boswellic acid (AKBA): structure requirements for binding and 5-lipoxygenase inhibitory activity. Br J Pharmacol. 1996;117(4):615-8. https://doi.org/10.1111/j.1476-5381.1996.tb15235.x
24. Goel A, Ahmad FJ, Singh RM, Singh GN. 3-Acetyl-11-keto-beta-boswellic acid loaded-polymeric nanomicelles for topical anti-inflammatory and anti-arthritic activity. J Pharm Pharmacol. 2010;62(2):273-8. https://doi.org/10.1211/jpp.62.02.0016
25. Fathi E, Katouli FH, Riazi GH, Shasaltaneh MD, Parandavar E, Bayati S, et al. The Effects of Alpha Boswellic Acid on Reelin Expression and Tau Phosphorylation in Human Astrocytes. Neuromolecular Med. 2017;19(1):136-46. https://doi.org/10.1007/s12017-016-8437-3
26. Altmann A, Poeckel D, Fischer L, Schubert-Zsilavecz M, Steinhilber D, Werz O. Coupling of boswellic acid-induced Ca2+ mobilisation and MAPK activation to lipid metabolism and peroxide formation in human leucocytes. Br J Pharmacol. 2004;141(2):223-32. https://doi.org/10.1038/sj.bjp.0705604
27. Taghizadeh M, Maghaminejad F, Aghajani M, Rahmani M. The effect of tablet containing Boswellia serrata and Melisa officinalis extract on older adults' memory: A randomized controlled trial. Arch Gerontol Geriatr. 2018;75:146-50. https://doi.org/10.1016/j.archger.2017.12.008
28. Siddiqui M. Boswellia serrata, a potential antiinflammatory agent: an overview. Indian J Pharm Sci. 2011;73(3):255-354.
29. Hosseini-Sharifabad M, Kamali-Ardakani R, Hosseini-Sharifabad A. Beneficial effect of Boswellia serrata gum resin on spatial learning and the dendritic tree of dentate gyrus granule cells in aged rats. Avicenna J Phytomed. 2016;6(2):189-97.
30. Cuchillo-Ibanez I, Balmaceda V, Botella-Lopez A, Rabano A, Avila J, Saez-Valero J. Beta-amyloid impairs reelin signaling. PLoS One. 2013;8(8):e72297-e307. https://doi.org/10.1371/journal.pone.0072297
31. Minegishi T, Kastian RF, Inagaki N, editors. Mechanical regulation of synapse formation and plasticity. Semin Cell Dev Biol; 2023: Elsevier.
32. Tsuneura Y, Nakai T, Mizoguchi H, Yamada K. New strategies for the treatment of neuropsychiatric disorders based on reelin dysfunction. Int J Mol Sci. 2022;23(3):1829. https://doi.org/10.3390/ijms23031829
2. Jivad N, Rabiei Z. A review study on medicinal plants used in the treatment of learning and memory impairments. Asian Pac J Trop Biomed. 2014;4(10):780-9. https://doi.org/10.12980/apjtb.4.2014apjtb-2014-0412
3. Mahmoudi A, Hosseini-Sharifabad A, Monsef-Esfahani HR, Yazdinejad AR, Khanavi M, Roghani A, et al. Evaluation of systemic administration of Boswellia papyrifera extracts on spatial memory retention in male rats. J Nat Med. 2011;65(3-4):519-25. https://doi.org/10.1007/s11418-011-0533-y
4. Alam-Siddiqui F, Ghayur A, Ul-Haq Z, Ghayur MN. Herbal Medicine for the Mind: Traditionally Used Medicinal Plants for Memory Loss from the Indian Subcontinent. Fut Integr Med. 2025(000):0-. https://doi.org/10.14218/fim.2024.00050
5. Jalili C, Salahshoor MR, Pourmotabbed A, Moradi S, Roshankhah S, Darehdori AS, et al. The effects of aqueous extract of Boswellia Serrata on hippocampal region CA1 and learning deficit in kindled rats. Res Pharm Sci. 2014;9(5):351-8.
6. Siddhu NSS, Guru A, Satish Kumar RC, Almutairi BO, Almutairi MH, Juliet A, et al. Pro-inflammatory cytokine molecules from Boswellia serrate suppresses lipopolysaccharides induced inflammation demonstrated in an in-vivo zebrafish larval model. Mol Biol Rep. 2022;49(8):7425-35. https://doi.org/10.1007/s11033-022-07544-5
7. Forouzanfar F, Hosseinzadeh H, Ebrahimzadeh Bideskan A, Sadeghnia HR. Aqueous and ethanolic extracts of Boswellia serrata protect against focal cerebral ischemia and reperfusion injury in rats. Phytother Res. 2016;30(12):1954-67. https://doi.org/10.1002/ptr.5701
8. Karima O, Riazi G, Yousefi R, Movahedi AA. The enhancement effect of beta-boswellic acid on hippocampal neurites outgrowth and branching (an in vitro study). Neurol Sci. 2010;31(3):315-20. https://doi.org/10.1007/s10072-010-0220-x
9. Bashar A, Kadhem W. Study of the effect of Boswellia serrata in reducing the effects associated with induced arthritis in male albino rats. Agric Biotechnol J. 2025;17(1):177-92.
10. Alahmari A, Al-Doaiss AA. Impact of Boswellia serrata Supplementation on Cytokines Profile, Antioxidant Status and NF-kB Expression in the Spleen and Thymus of Rats. Indian J Anim Res. 2025;59(2). https://doi.org/10.18805/ijar.bf-1888
11. Khalaj-Kondori M, Sadeghi F, Hosseinpourfeizi MA, Shaikhzadeh-Hesari F, Nakhlband A, Rahmati-Yamchi M. Boswellia serrata gum resin aqueous extract upregulatesBDNF but not CREB expression in adult male rat hippocampus. Turk J Med Sci. 2016;46(5):1573-8. https://doi.org/10.3906/sag-1503-43
12. Mahboubi M, Taghizadeh M, Talaei SA, Firozeh SMT, Rashidi AA, Tamtaji OR. Combined administration of Melissa officinalis and Boswellia serrata extracts in an animal model of memory. Iran J Psychiatry Behav Sci. 2016;10(3):e681-e7. https://doi.org/10.17795/ijpbs-681
13. Vinay P, Balamurugan K, Rajan KE. Reduced Reelin Expression Induces Memory Deficits through Dab-1/NMDAR Signaling Pathway: Cronobacter sakazakii Infection in a Rat Model of Experimental Meningitis. Dev Neurosci. 2023;44(6):547-56. https://doi.org/10.1159/000525821
14. Jossin Y. Reelin functions, mechanisms of action and signaling pathways during brain development and maturation. Biomolecules. 2020;10(6):964. https://doi.org/10.3390/biom10060964
15. Council NR. Guide for the care and use of laboratory animals: National Academies Press; 2010.
16. Paxinos G, Watson C, Carrive P, Kirkcaldie M, Ashwell K. Chemoarchitectonic atlas of the rat brain. 2009.
17. Zhou S, Yu G, Chi L, Zhu J, Zhang W, Zhang Y, et al. Neuroprotective effects of edaravone on cognitive deficit, oxidative stress and tau hyperphosphorylation induced by intracerebroventricular streptozotocin in rats. Neurotoxicology. 2013;38:136-45. https://doi.org/10.1016/j.neuro.2013.07.007
18. Ameen AM, Elkazaz AY, Mohammad HM, Barakat BM. Anti-inflammatory and neuroprotective activity of boswellic acids in rotenone parkinsonian rats. Can J Physiol Pharmacol. 2017;95(7):819-29. https://doi.org/10.1139/cjpp-2016-0158
19. Ebrahimpour S, Fazeli M, Mehri S, Taherianfard M, Hosseinzadeh H. Boswellic Acid Improves Cognitive Function in a Rat Model Through Its Antioxidant Activity:-Neuroprotective effect of Boswellic acid. J Pharmacopunct. 2017;20(1):10-7. https://doi.org/10.3831/kpi.2017.20.001
20. Gokaraju GR, Gokaraju RR, Gokaraju VKRR, Golakoti T, Bhupathiraju K, Alluri VKR. Boswellia oil, its fractions and compositions for enhancing brain function. Google Patents; 2014.
21. Altmann A, Fischer L, Schubert-Zsilavecz M, Steinhilber D, Werz O. Boswellic acids activate p42(MAPK) and p38 MAPK and stimulate Ca(2+) mobilization. Biochem Biophys Res Commun. 2002;290(1):185-90. https://doi.org/10.1006/bbrc.2001.6153
22. Gerbeth K, Husch J, Fricker G, Werz O, Schubert-Zsilavecz M, Abdel-Tawab M. In vitro metabolism, permeation, and brain availability of six major boswellic acids from Boswellia serrata gum resins. Fitoterapia. 2013;84:99-106. https://doi.org/10.1016/j.fitote.2012.10.009
23. Sailer ER, Subramanian LR, Rall B, Hoernlein RF, Ammon HP, Safayhi H. Acetyl-11-keto-beta-boswellic acid (AKBA): structure requirements for binding and 5-lipoxygenase inhibitory activity. Br J Pharmacol. 1996;117(4):615-8. https://doi.org/10.1111/j.1476-5381.1996.tb15235.x
24. Goel A, Ahmad FJ, Singh RM, Singh GN. 3-Acetyl-11-keto-beta-boswellic acid loaded-polymeric nanomicelles for topical anti-inflammatory and anti-arthritic activity. J Pharm Pharmacol. 2010;62(2):273-8. https://doi.org/10.1211/jpp.62.02.0016
25. Fathi E, Katouli FH, Riazi GH, Shasaltaneh MD, Parandavar E, Bayati S, et al. The Effects of Alpha Boswellic Acid on Reelin Expression and Tau Phosphorylation in Human Astrocytes. Neuromolecular Med. 2017;19(1):136-46. https://doi.org/10.1007/s12017-016-8437-3
26. Altmann A, Poeckel D, Fischer L, Schubert-Zsilavecz M, Steinhilber D, Werz O. Coupling of boswellic acid-induced Ca2+ mobilisation and MAPK activation to lipid metabolism and peroxide formation in human leucocytes. Br J Pharmacol. 2004;141(2):223-32. https://doi.org/10.1038/sj.bjp.0705604
27. Taghizadeh M, Maghaminejad F, Aghajani M, Rahmani M. The effect of tablet containing Boswellia serrata and Melisa officinalis extract on older adults' memory: A randomized controlled trial. Arch Gerontol Geriatr. 2018;75:146-50. https://doi.org/10.1016/j.archger.2017.12.008
28. Siddiqui M. Boswellia serrata, a potential antiinflammatory agent: an overview. Indian J Pharm Sci. 2011;73(3):255-354.
29. Hosseini-Sharifabad M, Kamali-Ardakani R, Hosseini-Sharifabad A. Beneficial effect of Boswellia serrata gum resin on spatial learning and the dendritic tree of dentate gyrus granule cells in aged rats. Avicenna J Phytomed. 2016;6(2):189-97.
30. Cuchillo-Ibanez I, Balmaceda V, Botella-Lopez A, Rabano A, Avila J, Saez-Valero J. Beta-amyloid impairs reelin signaling. PLoS One. 2013;8(8):e72297-e307. https://doi.org/10.1371/journal.pone.0072297
31. Minegishi T, Kastian RF, Inagaki N, editors. Mechanical regulation of synapse formation and plasticity. Semin Cell Dev Biol; 2023: Elsevier.
32. Tsuneura Y, Nakai T, Mizoguchi H, Yamada K. New strategies for the treatment of neuropsychiatric disorders based on reelin dysfunction. Int J Mol Sci. 2022;23(3):1829. https://doi.org/10.3390/ijms23031829
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| Issue | Vol 3 No 1 (2025) | |
| Section | Original Articles | |
| Keywords | ||
| Boswellic acid Histological analysis Reellin Memory consolidation learning. | ||
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How to Cite
1.
Dehghan Shasaltaneh M, Ramezani S, Naghdi N, Riazi GH. Beta Boswellic Acid Reduces Tau Phosphorylation Level and Enhances Reelin Expression in the brain. ABI. 2025;3(1):46-54.
