Cinnamon and cognitive function: a systematic review of preclinical and clinical studies

References

• Gruenwald J, Freder J, Armbruester N. Cinnamon and health. Crit Rev Food Sci Nutr. 2010;50:822–834.
   PubMed Web of Science ®Google Scholar
• Jayaprakasha GK, Rao LJM. Chemistry, biogenesis, and biological activities of Cinnamomum zeylanicum. Crit Rev Food Sci Nutr. 2011;51:547–562.
   PubMed Web of Science ®Google Scholar
• Frydman-Marom A, Levin A, Farfara D, Benromano T, Scherzer-Attali R, Peled S, et al. Orally administrated cinnamon extract reduces β-amyloid oligomerization and corrects cognitive impairment in Alzheimer’s disease animal models. PLoS One. 2011;6:e16564.
   PubMed Web of Science ®Google Scholar
• Busche MA, Hyman BT. Synergy between amyloid-β and tau in Alzheimer’s disease. Nat Neurosci. 2020;23:1183–1193.
   PubMed Web of Science ®Google Scholar
• Park J-H, Seo SW, Kim C, Kim SH, Kim GH, Kim ST, et al. Effects of cerebrovascular disease and amyloid beta burden on cognition in subjects with subcortical vascular cognitive impairment. Neurobiol Aging. 2014;35:254–260.
   PubMed Web of Science ®Google Scholar
• Morley JE, Farr SA. The role of amyloid-beta in the regulation of memory. Biochem Pharmacol. 2014;88:479–485.
   PubMed Web of Science ®Google Scholar
• Momtaz S, Hassani S, Khan F, Ziaee M, Abdollahi M. Cinnamon, a promising prospect towards Alzheimer’s disease. Pharmacol Res. 2018;130:241–258.
   PubMed Web of Science ®Google Scholar
• Barceloux DG. Medical toxicology of natural substances: foods, fungi, medicinal herbs, plants, and venomous animals. NJ: Hoboken: John Wiley & Sons; 2008.
   Google Scholar
• Ranasinghe P, Pigera S, Premakumara GAS, Galappaththy P, Constantine GR, Katulanda P. Medicinal properties of ‘true’ cinnamon (Cinnamomum zeylanicum): a systematic review. BMC Complement Altern Med. 2013;13:275.
   PubMed Web of Science ®Google Scholar
• Hajimonfarednejad M, Ostovar M, Raee MJ, Hashempur MH, Mayer JG, Heydari M. Cinnamon: a systematic review of adverse events. Clin Nutr. 2019;38:594–602.
   PubMed Web of Science ®Google Scholar
• Yeh H-F, Luo C-Y, Lin C-Y, Cheng S-S, Hsu Y-R, Chang S-T. Methods for thermal stability enhancement of leaf essential oils and their main constituents from indigenous cinnamon (Cinnamomum osmophloeum). J Agric Food Chem. 2013;61:6293–6298.
   PubMed Web of Science ®Google Scholar
• Hemmati AA, Alboghobeish S, Ahangarpour A. Effects of cinnamic acid on memory deficits and brain oxidative stress in Streptozotocin-induced diabetic mice. KJPP. 2018;22:257–267.
   Google Scholar
• Vo QV, Van Bay M, Nam PC, Quang DT, Flavel M, Hoa NT, et al. Theoretical and experimental studies of the antioxidant and antinitrosant activity of syringic acid. J Org Chem. 2020;85:15514–15520.
   PubMed Web of Science ®Google Scholar
• Zhao J, Zhang X, Dong L, Wen Y, Zheng X, Zhang C, et al. Cinnamaldehyde inhibits inflammation and brain damage in a mouse model of permanent cerebral ischaemia. Br J Pharmacol. 2015;172:5009–5023.
   PubMed Web of Science ®Google Scholar
• Taheri P, Yaghmaei P, Tehrani HS, Ebrahim-Habibi A. Effects of eugenol on Alzheimer’s disease-like manifestations in insulin- and Aβ-induced Rat models. Neurophysiology. 2019;51:114–119.
   Web of Science ®Google Scholar
• Seibel R, Schneider RH, Gottlieb MGV. Effects of spices (saffron, rosemary, cinnamon, turmeric and ginger) in Alzheimer’s disease. Curr Alzheimer Res. 2021;18:347–357.
   PubMed Web of Science ®Google Scholar
• Abou El-Ezz D, Maher A, Sallam N, El-Brairy A, Kenawy S. Trans-cinnamaldehyde modulates hippocampal Nrf2 factor and inhibits amyloid beta aggregation in LPS-induced neuroinflammation mouse model. Neurochem Res. 2018;43:2333–2342.
   PubMed Web of Science ®Google Scholar
• Ataie Z, Mehrani H, Ghasemi A, Farrokhfall K. Cinnamaldehyde has beneficial effects against oxidative stress and nitric oxide metabolites in the brain of aged rats fed with long-term, high-fat diet. J Funct Foods. 2019;52:545–551.
   Web of Science ®Google Scholar
• Dubey K, Anand BG, Shekhawat DS, Kar K. Ror2 signaling regulates Golgi structure and transport through IFT20 for tumor invasiveness. Sci Rep. 2017;7:1–11.
   PubMed Web of Science ®Google Scholar
• Chandra S, Roy A, Jana M, Pahan K. Cinnamic acid activates PPARα to stimulate lysosomal biogenesis and lower amyloid plaque pathology in an Alzheimer’s disease mouse model. Neurobiol Dis. 2019;124:379–395.
   PubMed Web of Science ®Google Scholar
• Zeisel SH, Caudill MA. Choline. Adv Nutr. 2010;1:46–48.
   PubMed Web of Science ®Google Scholar
• Gasparini L, Netzer WJ, Greengard P, Xu H. Does insulin dysfunction play a role in Alzheimer’s disease? Trends harmacol Sci. 2002;23:288–293.
   PubMed Web of Science ®Google Scholar
• Hunniford VT, Montroy J, Fergusson DA, Avey MT, Wever KE, McCann SK, et al. Epidemiology and reporting characteristics of preclinical systematic reviews. PLoS Biol. 2021;19:e3001177.
   PubMed Web of Science ®Google Scholar
• JBI’s critical appraisal tools available at: https://jbi.global/critical-appraisal-tools. Accessed: december 2021.
   Google Scholar
• Du Sert NP, Ahluwalia A, Alam S, Avey MT, Baker M, Browne WJ, et al. Reporting animal research: explanation and elaboration for the ARRIVE guidelines 2.0. PLoS Biol. 2020;18(7):e3000411.
   PubMed Web of Science ®Google Scholar
• Du Sert NP, Ahluwalia A, Alam S, Avey MT, Baker M, Browne WJ, et al. The ARRIVE guidelines 2.0, available at: https://arriveguidelines.org/arrive-guidelines, accessed: march 2022.
   Google Scholar
• George RC, Lew J, Graves DJ. Interaction of cinnamaldehyde and epicatechin with tau: implications of beneficial effects in modulating Alzheimer’s disease pathogenesis. J Alzheimer’s Dis. 2013;36:21–40.
   PubMed Web of Science ®Google Scholar
• Emamghoreishi M, Farrokhi MR, Amiri A, Keshavarz M. The neuroprotective mechanism of cinnamaldehyde against amyloid-β in neuronal SHSY5Y cell line: the role of N-methyl-D-aspartate, ryanodine, and adenosine receptors and glycogen synthase kinase-3β. Avicenna J Phytomedicine. 2019;9:271.
   PubMed Web of Science ®Google Scholar
• Bai L, Li X, Chang Q, Wu R, Zhang J, Yang X. Cinnamaldehyde promotes mitochondrial function and reduces Aβ toxicity in neural cells. J Chinese Pharm Sci. 2016;25:605.
   Google Scholar
• Kang YJ, Seo D-G, Park S-Y. Phenylpropanoids from cinnamon bark reduced β-amyloid production by the inhibition of β-secretase in Chinese hamster ovarian cells stably expressing amyloid precursor protein. Nutr Res. 2016;36:1277–1284.
   PubMed Web of Science ®Google Scholar
• Fu Y, Yang P, Zhao Y, Zhang L, Zhang Z, Dong X, et al., trans-cinnamaldehyde inhibits microglial activation and improves neuronal survival against neuroinflammation in BV2 microglial cells with lipopolysaccharide stimulation. Evidence-Based Complement Altern Med. 2017;2017:1–12.
   Web of Science ®Google Scholar
• Katherina Rajan U. Effectiveness of cinnamon chewing gum on memory and anxiety among adolescents at selected seventh day adventist high schools, Andhra Pradesh. Namakkal: Dhanvantri College of Nursing; 2012.
   Google Scholar
• Lee M-S, Wahlqvist ML, Chou Y-C, Fang W-H, Lee J-T, Kuan J-C, et al. Turmeric improves post-prandial working memory in pre-diabetes independent of insulin. Asia Pac J Clin Nutr. 2014;23:581–591.
   PubMed Web of Science ®Google Scholar
• YanXin Z, Dong W, Souravh B, HongXin W. Modulation of pro-inflammatory mediators by eugenol in AlCl3 induced dementia in rats. Int J Pharmacol. 2019;15:457–464.
   Google Scholar
• Anderson RA, Qin B, Canini F, Poulet L, Roussel AM. Cinnamon counteracts the negative effects of a high fat/high fructose diet on behavior, brain insulin signaling and Alzheimer-associated changes. PLoS One. 2013;8:e83243.
   PubMed Web of Science ®Google Scholar
• Malik J, Munjal K, Deshmukh R. Attenuating effect of standardized lyophilized Cinnamomum zeylanicum bark extract against Streptozotocin-induced experimental dementia of Alzheimer’s type. J Basic Clin Physiol Pharmacol. 2015;26:275–285.
   PubMedGoogle Scholar
• Madhavadas S, Subramanian S. Cognition enhancing effect of the aqueous extract of Cinnamomum zeylanicumon non-transgenic Alzheimer’s disease rat model: biochemical, histological, and behavioural studies. Nutr Neurosci. 2017;20:526–537.
   PubMed Web of Science ®Google Scholar
• Edalatmanesh MA, Khodabandeh H, Yazdani N, Rafiei S. Effect of Cinnamomum zeylanicum extract on memory and hippocampal cell density in animal model of diabetes. ARAK Med Univ J. 2018;21:56–66.
   Google Scholar
• Saeed M, Ghadiri A, Hadizadeh F, Attaranzadeh A, Alavi MS, Etemad L. Cinnamaldehyde improves methamphetamine-induced spatial learning and memory deficits and restores ERK signaling in the rat prefrontal cortex. Iran J Basic Med Sci. 2018;21:1316–1321.
   PubMedGoogle Scholar
• Pan Z, He X, Zhou X, Li X, Rong B, Wang F. Combination of Ellagic acid and trans-cinnamaldehyde alleviates aging-induced cognitive impairment via modulation of mitochondrial function and inflammatory and apoptotic mediators in the prefrontal cortex of aged rats. Chin J Physiol. 2020;63:218.
   PubMed Web of Science ®Google Scholar
• Pandit C, Sai Latha S, Usha Rani T, Anilakumar KR. Pepper and cinnamon improve cold induced cognitive impairment via increasing non-shivering thermogenesis; a study. Int J Hyperth Off J Eur Soc Hyperth Oncol North Am Hyperth Gr. 2018;35:518–527.
   PubMed Web of Science ®Google Scholar
• Ahmadi R, Toloeghamary M, Pishghadam S. Intraperitoneal injection of cinnamon extract (Cinnamomum zeylanicum) on passive avoidance learning in rats with Streptozotocin-induced Alzheimers disease. Ambient Sci. 2017;04.
   Google Scholar
• Salehi O, Sheikholeslami-Vatani D, Negarandeh Z, Yarahmadi J. The effect of swimming training at different temperatures with cinnamon consumption on avoidance memory. Spatial Memory and Aerobic Power in Streptozotocin- Induced Diabetic Rats. 2020;1:67–78.
   Google Scholar
• Vahidi A, Dashti MH, Mojdeh M, Soltani HR. Effects of cinnamon on learning and short memory in mice. Med Sci J Islam Azad Univesity-Tehran Med Branch. 2012;22:105–109.
   Google Scholar
• Liu Z, Niu W, Yang X, Wang Y. Effects of combined acupuncture and eugenol on learning-memory ability and antioxidation system of hippocampus in Alzheimer disease rats via olfactory system stimulation. J Tradit Chinese Med. 2013;33:399–402.
   PubMed Web of Science ®Google Scholar
• Mustafa HN. Neuro-amelioration of cinnamaldehyde in aluminum-induced Alzheimer’s disease rat model. J Histotechnol. 2020;43:11–20.
   PubMed Web of Science ®Google Scholar
• Sayad-Fathi S, Zaminy A, Babaei P, Yousefbeyk F, Azizi N, Nasiri E. The methanolic extract of Cinnamomum zeylanicum bark improves formaldehyde-induced neurotoxicity through reduction of phospho-tau (Thr231), inflammation, and apoptosis. EXCLI J. 2020;19:671–686.
   PubMed Web of Science ®Google Scholar
• Jawale A, Datusalia AK, Bishnoi M, Sharma SS. Reversal of diabetes-induced behavioral and neurochemical deficits by cinnamaldehyde. Phytomedicine. 2016;23:923–930.
   PubMed Web of Science ®Google Scholar
• Nikbin S, Derakhshideh A, Kanozi F, Hozouri Tarighe M, Niknia S, Khojasteh Z, et al. Combination effect of exercise training and eugenol supplementation on the hippocampus apoptosis induced by chlorpyrifos. Mol Biol Rep. 2020;47:5985–5996.
   PubMed Web of Science ®Google Scholar
• SoukhakLari R, Borhani-Haghighi A, Farsadrooh A, Moezi L, Pirsalami F, Kazerouni A, et al. The effect of cinnamaldehyde on passive avoidance memory and hippocampal Akt, ERK and GSK-3β in mice. Eur J Pharmacol. 2019;859:172530.
   PubMed Web of Science ®Google Scholar
• Qubty D, Rubovitch V, Benromano T, Ovadia M, Pick CG. Orally administered cinnamon extract attenuates cognitive and neuronal deficits following traumatic brain injury. J Mol Neurosci. 2021;71:178–186.
   PubMed Web of Science ®Google Scholar
• Kazerouni A, Nazeri M, Karimzadeh A, SoukhakLari R, Moezi L, Pirsalami F, et al. Sub-chronic oral cinnamaldehyde treatment prevents scopolamine-induced memory retrieval deficit and hippocampal Akt and MAPK dysregulation in male mice. Neurol Res. 2020;42:99–107.
   PubMed Web of Science ®Google Scholar
• Do J, Kim N, Jeon SH, Gee MS, Ju Y-J, Kim J-H, et al. Trans-cinnamaldehyde alleviates amyloid-beta pathogenesis via the SIRT1-PGC1α-PPARγ pathway in 5XFAD transgenic mice. Int J Mol Sci. 2020;21:4492.
   PubMed Web of Science ®Google Scholar
• Zhang L, Zhang Z, Fu Y, Yang P, Qin Z, Chen Y, et al. Trans-cinnamaldehyde improves memory impairment by blocking microglial activation through the destabilization of iNOS mRNA in mice challenged with lipopolysaccharide. Neuropharmacology. 2016;110:503–518.
   PubMed Web of Science ®Google Scholar
• Zhao Y, Deng H, Li K, Wang L, Wu Y, Dong X, et al. Trans-cinnamaldehyde improves neuroinflammation-mediated NMDA receptor dysfunction and memory deficits through blocking NF-κB pathway in presenilin1/2 conditional double knockout mice. Brain Behav Immun. 2019;82:45–62.
   PubMed Web of Science ®Google Scholar
• Akbar L, Juliandi B, Boediono A, Batubara I, Subangkit M. Effects of eugenol on memory performance, neurogenesis, and dendritic complexity of neurons in mice analyzed by behavioral tests and Golgi staining of brain tissue. J Stem Cells Regen Med. 2021;17:35.
   PubMed Web of Science ®Google Scholar
• Pham HM, Xu A, Schriner SE, Sevrioukov EA, Jafari M. Cinnamaldehyde improves lifespan and healthspan in drosophila melanogaster models for Alzheimer’s disease. Biomed Res Int. 2018;2018:3570830.
   PubMed Web of Science ®Google Scholar
• Teymuori M, Yegdaneh A, Rabbani M. Effects of piper nigrum fruit and cinnamum zeylanicum bark alcoholic extracts, alone and in combination, on scopolamine-induced memory impairment in mice. Res. Pharm. Sci. 2021;16:474.
   PubMed Web of Science ®Google Scholar
• Raha S, Dutta D, Roy A, Pahan K. Reduction of Lewy body pathology by oral cinnamon. J. Neuroimmune Pharmacol. 2021;16:592–608.
   PubMed Web of Science ®Google Scholar
• Modi KK, Roy A, Brahmachari S, Rangasamy SB, Pahan K. Cinnamon and Its metabolite sodium benzoate attenuate the activation of p21rac and protect memory and learning in an animal model of Alzheimer’s disease. PLoS One. 2015;10:e0130398–e0130398.
   PubMed Web of Science ®Google Scholar
• Ryu J-S, Kang H-Y, Lee JK. Effect of treadmill exercise and trans-cinnamaldehyde against d-galactose- and aluminum chloride-induced cognitive dysfunction in mice. Brain Sci. 2020;10:793.
   PubMed Web of Science ®Google Scholar
• Al Shoyaib A, Archie SR, Karamyan VT. Intraperitoneal route of drug administration: should it be used in experimental animal studies? Pharm Res. 2020;37:1–17.
   Web of Science ®Google Scholar
• Rao PV, Gan SH. Cinnamon: a multifaceted medicinal plant. Evidence-Based Complement Altern Med. 2014: 1-12, ID: 642942. https://doi.org/10.1155/2014/642942.
   Google Scholar
• Danik UNM, Martirosyan M. Functional Foods and Mental Health. PART 4.9: The Effects of Bioactive Compounds in Spices and Seeds on Alzheimer’s, Khadijeh Farrokhfall, Mohammad Dastjerdi, Zomorrod Ataie, and Fatemeh Nikoomanesh. food science publisher, volume 7, first edition, Dallas, TX, 2019, page 192–224.
   Google Scholar
• Kondo H, Sugiyama H, Katayama S, Nakamura S. Enhanced antiamyloidal activity of hydroxy cinnamic acids by enzymatic esterification with alkyl alcohols. Biotechnol Appl Biochem. 2014;61:401–407.
   PubMed Web of Science ®Google Scholar
• Shimmyo Y, Kihara T, Akaike A, Niidome T, Sugimoto H. Epigallocatechin-3-gallate and curcumin suppress amyloid beta-induced beta-site APP cleaving enzyme-1 upregulation. Neuroreport. 2008;19(13):1329–33.
   PubMed Web of Science ®Google Scholar
• Prifti E, Tsakiri EN, Vourkou E, Stamatakis G, Samiotaki M, Papanikolopoulou K. The two cysteines of tau protein are functionally distinct and contribute differentially to its pathogenicityin vivo. J Neurosci. 2021;41:797–810.
   PubMed Web of Science ®Google Scholar
• Wyss-Coray T. Inflammation in Alzheimer disease: driving force, bystander or beneficial response? Nat Med. 2006;12:1005–1015.
   PubMed Web of Science ®Google Scholar
• Gabbouj S, Ryhänen S, Marttinen M, Wittrahm R, Takalo M, Kemppainen S, et al. Altered insulin signaling in Alzheimer’s disease brain – special emphasis on PI3K-Akt pathway. Front Neurosci. 2019;13:629.
   PubMed Web of Science ®Google Scholar
• Iloun P, Abbasnejad Z, Janahmadi M, Ahmadiani A, Ghasemi R. Investigating the role of P38, JNK and ERK in LPS induced hippocampal insulin resistance and spatial memory impairment: effects of insulin treatment. EXCLI J. 2018;17:825.
   PubMed Web of Science ®Google Scholar
• Lee C-C, Huang C-C, Hsu K-S. Insulin promotes dendritic spine and synapse formation by the PI3K/Akt/mTOR and Rac1 signaling pathways. Neuropharmacology. 2011;61:867–879.
   PubMed Web of Science ®Google Scholar
• Cohen-Cory S, Kidane AH, Shirkey NJ, Marshak S. Brain-derived neurotrophic factor and the development of structural neuronal connectivity. Dev Neurobiol. 2010;70:271–288.
   PubMed Web of Science ®Google Scholar
• Irie Y, Itokazu N, Anjiki N, Ishige A, Watanabe K, Keung WM. Eugenol exhibits antidepressant-like activity in mice and induces expression of metallothionein-III in the hippocampus. Brain Res. 2004;1011:243–246.
   PubMed Web of Science ®Google Scholar
• Huang J, Lee Y, Chuang L, Guh J, Hwang J. Cinnamaldehyde and nitric oxide attenuate advanced glycation end products-induced the JAK/STAT signaling in human renal tubular cells. J Cell Biochem. 2015;116:1028–1038.
   PubMed Web of Science ®Google Scholar
• Jana A, Modi KK, Roy A, Anderson JA, van Breemen RB, Pahan K. Up-regulation of neurotrophic factors by cinnamon and its metabolite sodium benzoate: therapeutic implications for neurodegenerative disorders. J Neuroimmune Pharmacol. 2013;8:739–755.
   PubMed Web of Science ®Google Scholar
• Cole SL, Vassar R. The Alzheimer’s disease β-secretase enzyme, BACE1. Mol Neurodegener. 2007;2:1–25.
   PubMed Web of Science ®Google Scholar