Frankincense Upregulates the FMR1 Gene and Alleviates AlCl3-Induced Memory Impairment in Rats

Document Type : Research Article


Department of Animal Biology, Faculty of Natural Sciences, University of Tabriz, Tabriz, Iran


Alzheimer's disease (AD) is a multifactorial disorder that its progress and development are related to various genetic and environmental factors. The disease onset is affected by both genetic and environmental factors such as oxidative stress, inflammation, and mitochondrial dysfunction, and is remarkably related to age progress. Aluminum, a neurotoxic environmental factor, impairs memory performance and can cause neurodegenerative diseases such as AD. On the other hand, the regulatory RNA-binding product of Fragile X mental retardation (FMR1) gene exerts a translational inhibitory effect on the expression of amyloid precursor protein (APP), the main culprit in AD development. In the present study, we treated AlCl3-induced Alzheimer’s disease model rats with Frankincense and investigated its protective and therapeutic effects on the AlCl3-induced memory disturbance by behavioral and molecular assays. Also, Rivastigmine was used as a standard control. Morris Water Maze (MWM) was used to assay special memory working of the rats and quantitative real-time PCR (qRT-PCR) was applied to investigate the expression profile of the FMR1 gene in the hippocampus of the treated rats. MWM behavioral tests indicated that both Frankincense and Rivastigmine not only may prevent AlCl3-induced memory impairment but also may alleviate the memory declines induced by AlCl3 in the rats. Expression analysis showed significant upregulation of the FMR1 gene in response to both Frankincense and Rivastigmin treatments. Further, qRT-PCR results revealed that the AlCl3-induced downregulation of the FMR1 gene expression could significantly be reversed by both Frankincense and Rivastigmine, though Rivastigmine was more effective than Frankincense. In conclusion, our results highlighted that Frankincense might be effective both in the prevention and treatment of memory impairments, to some extent, by affecting the FMR1 gene expression.


Asadi E, Kaseb MR, Zeidabadi R, Hamedinia MR. 2019. Effect of 4 weeks of frankincense consumption on explicit motor memory and serum BDNF in elderly men. Turk J Med Sci 49:1033-1040.
Beheshti S, Aghaie R. 2016. Therapeutic effect of frankincense in a rat model of Alzheimer’s disease. AJP 6:468-475.
Beheshti S, Karimi B. 2016. Frankincense improves memory retrieval in rats treated with lipopolysaccharide. J HerbMed Pharmacol 5.
Bejar C, Wang RH, Weinstock M. 1999. Effect of rivastigmine on scopolamine-induced memory impairment in rats. Eur J Pharmacol 383:231-240.
Al-Amin M, Chowdury M, Amin I, Saifullah AR, Alam MN, Raish M. 2019. Levocarnitine improves AlCl3-induced spatial working memory impairment in Swiss albino mice. Front Neurosci 13:278.
Ebrahimpour S, Fazeli M, Mehri S, Taherianfard M, Hosseinzadeh H. 2017. Boswellic acid improves cognitive function in a rat model through its antioxidant activity-neuroprotective effect of boswellic acid. J Pharmacopunct 20:10-17.
El-Magd MA, Khalifa SF, Alzahrani FA, Badawy AA, El-Shetry ES, Marei HE. 2018. Incensole acetate prevents beta-amyloid-induced neurotoxicity in human olfactory bulb neural stem cells. Biomed Pharmacother 105:813-823.
Estelami N, Khalaj-Kondori M, Sheikhzadeh-Hesari F, Hosseinpour-Feizi MA. 2016. Aqueous extract of frankincense impedes aluminum chloride-induced memory impairment in adult male rats. J Physiol Pharmacol Adv 6:839-845.
Fathi E, Katouli FH, Riazi GH, Shasaltaneh MD, Parandavar E, Nazari R. 2017. The effects of alpha boswellic acid on reelin expression and tau phosphorylation in human astrocytes. Neuromolecular Med19:136-46.
Fotuhi SN, Khalaj-Kondori M, Feizi MA, Talebi M. 2019. Long non-coding RNA BACE1-AS may serve as an Alzheimer’s disease blood-based biomarker. J Mol Neurosci 69:351-359.
Fotuhi SN, Khalaj-Kondori M, Feizi MA, Talebi M. 2020. Memory-related process in physiological status and alzheimer’s disease. Mol Biol Rep 47:4651-4657.
Gomaa AA, Makboul RM, Al-Mokhtar MA, Nicola MA. 2019. Polyphenol-rich Boswellia serrata gum prevents cognitive impairment and insulin resistance of diabetic rats through inhibition of GSK3β activity, oxidative stress and pro-inflammatory cytokines. Biomed Pharmacother 109:281-292.
Hajipour S, Sarkaki A, Farbood Y, Eidi A, Mortazavi P, Valizadeh Z. 2016. Effect of gallic acid on dementia type of Alzheimer disease in rats: electrophysiological and histological studies. Basic Clin Neurosci 7:97-106.
Hosseini-Sharifabad M, Kamali-Ardakani R, Hosseini-Sharifabad A. 2016. 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 6:189-197.
Jebelli A, Khalaj-Kondori M, Bonyadi M, Feizi MA, Rahmati-Yamchi M. 2019. Beta-boswellic acid and ethanolic extract of olibanum regulating the expression levels of CREB-1 and CREB-2 genes. Iran J Pharm Res 18:877-886.
Khalaj KM, Amiri S, Hosseinpour FM, Shaikhzadeh HF. 2016. Comparing the effects of rivastigmin and aqueous extract of olibanum on gene expression of amyloid precursor protein in rats treated with aluminum chloride. J Police Med 4: 279-286.
Kraan CM, Hocking DR, Georgiou-Karistianis N, Metcalfe SA, Archibald AD, Cornish KM. 2014. Age and CGG-repeat length are associated with neuromotor impairments in at-risk females with the FMR1 premutation. Neurobiol Aging 35: e2177-e2179.
Kumar SP, Bairy KL, Nayak V, Reddy SK, Kiran A, Ballal A. 2019. Amelioration of Aluminium Chloride (AlCl3) Induced Neurotoxicity by Combination of Rivastigmine and Memantine with Artesunate in Albino Wistar Rats. Biomed Pharmacol J 12:703-711.
Lakshmi BV, Sudhakar M, Prakash KS. 2015. Protective effect of selenium against aluminum chloride-induced Alzheimer’s disease: behavioral and biochemical alterations in rats. Biol Trace Elem Res 165:67-74.
Lee EK, Kim HH, Kuwano Y, Abdelmohsen K, Srikantan S, Worley PF. 2010. hnRNP C promotes APP translation by competing with FMRP for APP mRNA recruitment to P bodies. Nat Struct Mol Biol 17:732-739.
Lee T, Lee H. 2020. Prediction of Alzheimer’s disease using blood gene expression data. Sci Rep 10:1-3.
Lin AL, Parikh I, Yanckello LM, White RS, Hartz AM, Ubele M. 2020. APOE genotype-dependent pharmacogenetic responses to rapamycin for preventing Alzheimer's disease. Neurobiol Dis 139:104834.
Mahboubi M, Taghizadeh M, Talaei SA, Firozeh SM, Rashidi AA, Tamtaji OR. 2016. Combined administration of Melissa officinalis and Boswellia serrata extracts in an animal model of memory. Iran J Psychiatry Behav Sci 10: e681.
Rashid MH, Zahid MF, Zain S, Kabir A, Hassan SU. 2020. The neuroprotective effects of exercise on cognitive decline: a preventive approach to Alzheimer disease. Cureus 12: e6958.
Real MA, Simón MP, Heredia R, de Diego Y, Guirado S. 2011. Phenotypic changes in calbindin D28K immunoreactivity in the hippocampus of Fmr1 knockout mice. J Comp Neurol 519:2622-2636.
Renoux AJ, Carducci NM, Ahmady AA, Todd PK. 2014. Fragile X mental retardation protein expression in Alzheimer’s disease. Front Genet 5:360.
Sedighi F, Khalaj-Kondori M, HosseinpourFeizi MA, ShaikhzadehHesari F. 2014. The effect of aqueous extract of Boswellia on spatial learning and memory in adult male rats. J Adv Med Biomed Res 22:122-131.
Sedighi B, Pardakhty A, Kamali H, Shafiee K, Hasani BN. 2014. Effect of Boswellia papyrifera on cognitive impairment in multiple sclerosis. Iran J Neurol 13:149-153.
Singh S, Singh R, Kushwah AS, Gupta G. 2014. Neuroprotective role of antioxidant and pyranocarboxylic acid derivative against AlCl3 induced Alzheimer’s disease in rats. J Coast Life Med 2:547-554.
Westmark CJ, Malter JS. 2007. FMRP mediates mGluR5-dependent translation of amyloid precursor protein. PLoS Biol 5: e52.
Wu Z, Du Y, Xue H, Wu Y, Zhou B. 2012. Aluminum induces neurodegeneration and its toxicity arises from increased iron accumulation and reactive oxygen species (ROS) production. Neurobiol Aging 33(1):199e1-12.