Evaluation of spatial memory and anti-fatigue function of long-term supplementation of β-alanine and confirmation through cAMP-PKA and apoptosis pathways in mice
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Collaborative Innovation Center for Food Production and Safety, School of Biological Science and Engineering,, North Minzu University, China
School of Food and Biological Engineering, Hefei University of Technology, Hefei 230009, China
Department of Basic Sciences, Research Group in Chemistry and Biotechnology of Bioactive Natural Products, Faculty of Sciences, University of Bio-Bío, Andrés Bello Avenue, Chillan, Chile
Submission date: 2021-11-02
Final revision date: 2021-11-28
Acceptance date: 2021-12-01
Online publication date: 2021-12-15
Publication date: 2021-12-20
Corresponding author
Zhao-Jun Wei   

Collaborative Innovation Center for Food Production and Safety, School of Biological Science and Engineering,, North Minzu University, China
eFood 2021;2(4):185-192
With an aim to explore the effects of β-alanine (β-A) on spatial memory and fatigue resistance, Kunming mice were treated with different concentrations of β-A (418, 836, and 2090 mg·kg -1·day -1). After gavage feeding with β-A for 10 weeks, results of the maze and MWM tests showed that β-A can enhance spatial learning and memory in mice. After evaluating the fatigue resistance, biochemical parameters (LG, GG, BUN, SOD, and MDA) showed significant differences in the low concentration treatment group compared to control group. Our data demonstrated that the appropriate dose of β-A can alleviate the oxidative stress and muscle fatigue in mice. Subsequently, expression of mRNA of key genes involved in cAMP-PKA pathway (PDE4A, MAPK1, adcy1, cAMP and CREB) was up regulated. Also, expression levels of apoptotic pathway genes were significantly affected as confirmed by qPCR and Western blotting. Our results demonstrated that β-A can enhance spatial learning and memory in mice via regulation of cAMP-PKA and apoptotic pathway.
Dunnett M, Harris RC. Influence of oral beta-alanine and L-histidine supplementation on the carnosine content of the gluteus medius. Equine Veterinary Journal. 1999;31(s30):499– 504. doi:10.1111/j.2042-3306.1999.tb05273.x.
Harris RC, Tallon M, Dunnett M, Boobis L, Coakley J, Kim HJ, et al. The absorption of orally supplied beta-alanine and its effect on muscle carnosine synthesis in human vastus lateralis. Amino Acids. 2006;30(3):279–289. doi:10.1007/s00726-006-0299-9.
Hoffman JR, Stout JR, Harris RC, Moran DS. β-Alanine supplementation and military performance. Amino Acids. 2015;47(12):2463–2474. doi:10.1007/s00726-015-2051-9.
Hill CA, Harris RC, Kim HJ, Harris BD, Sale C, Boobis LH, et al. Influence of β-alanine supplementation on skeletal muscle carnosine concentrations and high intensity cycling capacity. Amino Acids. 2007;32(2):225–233. doi:10.1007/s00726-006- 0364-4.
Stout JR, Cramer JT, Zoeller RF, Torok D, Costa P, Hoffman JR, et al. Effects of beta-alanine supplementation on the onset of neuromuscular fatigue and ventilatory threshold in women. Amino Acids. 2007;32:381–386. doi:10.1007/s00726-006-0474-z.
Decombaz J, Beaumont M, Vuichoud J, Bouisset F, StellingwerffT. Effect of slow-release beta-alanine tablets on absorption kinetics and paresthesia. Amino Acids. 2012;43(1):67–76. doi:10.1007/s00726-011-1169-7.
Caldwell JA, Caldwell JL, Thompson LA, Lieberman HR. Fatigue and its management in the workplace. Neuroscience & Biobehavioral Reviews. 2019;96:272–289. doi:10.1016/j.neubiorev.2018.10.024.
Lee N, Lee SH, Yoo HR, Yoo HS. Anti-Fatigue Effects of Enzyme-Modified Ginseng Extract: A Randomized, Double-Blind, Placebo-Controlled Trial. The Journal of Alternative and Complementary Medicine. 2016;22(11):859–864. doi:10.1089/acm.2016.0057.
Teng YS, Wu D. Anti-Fatigue Effect of Green Tea Polyphenols (-)- Epigallocatechin-3-Gallate (EGCG). . Pharmacognosy Magazine. 2017;13:326–331. doi:10.4103/0973-1296.204546.
Finsterer J. Biomarkers of peripheral muscle fatigue during exercise. BMC Musculoskeletal Disorders. 2012;13:218–218. doi:10.1186/1471-2474-13-218.
Suzuki Y, Ito O, Mukai N, Takahashi H, Takamatsu K. High level of skeletal muscle carnosine contributes to the latter half of exercise performance during 30-s maximal cycle ergometer sprinting. The Japanese Journal of Physiology. 2002;52(2):199– 205. doi:10.2170/jjphysiol.52.199.
Chasovnikova LV, Formazyuk VE, Sergienko VI, Boldyrev AA, Severin SE. The antioxidative properties of carnosine and other drugs. Biochemistry international. 1990;20(6):1097–1103.
Dutka TL, Lamboley CR, Mckenna MJ, Murphy RM, Lamb GD. Effects of carnosine on contractile apparatus Ca2+ sensitivity and sarcoplasmic reticulum Ca2+ release in human skeletal muscle fibers. Journal of Applied Physiology. 2012;112(5):728–736. doi:10.1152/japplphysiol.01331.2011.
Hosseini M, Headari R, Oryan S, Hadjzadeh MA, Saffarzadeh F, Khazaei M. The effect of chronic administration of L-arginine on the learning and memory of estradiol-treated ovariectomized rats tested in the morris water maze. Clinics. 2010;65(8):803–807. doi:10.1590/s1807-59322020000800012.
Sase A, Dahanayaka S, Höger H, Wu G, Lubec G. Changes of hippocampal beta-alanine and citrulline levels are paralleling early and late phase of retrieval in the Morris Water Maze. Behavioural Brain Research. 2013;249:104–108. doi:10.1016/j.bbr.2013.04.033.
Pence BD, Bhattacharya TK, Park P, Rytych JL, Allen JM, Sun Y, et al. Long-term supplementation with EGCG and beta- alanine decreases mortality but does not affect cognitive or muscle function in aged mice. Experimental Gerontology. 2017;98:22–29. doi:10.1016/j.exger.2017.08.020.
Stout JR, Graves BS, Smith AE, Hartman MJ, Cramer JT, Beck TW, et al. The effect of beta-alanine supplementation on neuromuscular fatigue in elderly (55-92 Years): a double-blind randomized study. Journal of the International Society of Sports Nutrition. 2008;5:21–21. doi:10.1186/1550-2783-5-21.
Gde PC, Bortolotto JW, Blazina AR, Christoff RR, Lara DR, Vianna MR, et al. Y-Maze memory task in zebrafish (Danio rerio): The role of glutamatergic and cholinergic systems on the acquisition and consolidation periods. Neurobiology of Learning and Memory. 2012;98(4):321–328. doi:10.1016/j.nlm.2012.09.008.
Akwa Y, Ladurelle N, Covey DF, Baulieu EE. The synthetic enantiomer of pregnenolone sulfate is very active on memory in rats and mice, even more so than its physiological neurosteroid counterpart: distinct mechanisms? Proceedings of the National Academy of Sciences of the United States of America. 2001;98(24):14033–14037. doi:10.1073/pnas.241503698.
Péczely L, Ollmann T, László K, Kovács A, Gálosi R, Szabó A, et al. Effects of ventral pallidal D1 dopamine receptor activation on memory consolidation in morris water maze test. Behavioural Brain Research. 2014;274:211–218. doi:10.1016/j.bbr.2014.07.031.
Wang W, Liu L, Jiang P, Chen C, Zhang T. Levodopa improves learning and memory ability on global cerebral ischemia-reperfusion injured rats in the Morris water maze test. Neuroscience Letters. 2017;636:233–240. doi:10.1016/j.neulet.2016.11.026.
Duda W, Wesierska M, Ostaszewski P, Vales K, Nekovarova T, Stuchlik A. MK-801 and memantine act differently on short- term memory tested with different time-intervals in the Morris water maze test. Behavioural Brain Research. 2016;311:15–23. doi:10.1016/j.bbr.2016.05.024.
Taridi NM, Yahaya MF, Teoh SL, Latiff AA, Ngah WZ, Das S, et al. Tocotrienol rich fraction (TRF) supplementation protects against oxidative DNA damage and improves cognitive functions in Wistar rats. La Clinica terapeutica. 2011;162(2):93–98.
Li XL, Ma RH, Ni ZJ, Thakur K, Cespedes-Acuña CL, Wang S, et al. Dioscin inhibits human endometrial carcinoma proliferation via G0/G1 cell cycle arrest and mitochondrial-dependent signaling pathway. Food and Chemical Toxicology. 2021;148:111941– 111941. doi:10.1016/j.fct.2020.111941.
Zhang F, Ni ZJ, Ye L, Zhang YY, Thakur K, Cespedes- Acuña CL, et al. Asparanin A inhibits cell migration and invasion in human endometrial cancer via Ras/ERK/MAPK pathway. Food and Chemical Toxicology. 2021;150:112036– 112036. doi:10.1016/j.fct.2021.112036.
Zhang YY, Ni ZJ, Elam E, Zhang F, Thakur K, Wang S, et al. Juglone, a novel activator of ferroptosis, induces cell death in endometrial carcinoma Ishikawa cells. Food & Function. 2021;12(11):4947– 4959. doi:10.1039/d1fo00790d.
Yin Q, Chen H, Ma RH, Zhang YY, Liu MM, Thakur K, et al. Ginsenoside CK induces apoptosis of human cervical cancer HeLa cells by regulating autophagy and endoplasmic reticulum stress. Food & Function. 2021;12(12):5301–5316. doi:10.1039/d1fo00348h.
Gibbons TE, Pence BD, Petr G, Ossyra JM, Mach HC, Bhattacharya TK, et al. Voluntary wheel running, but not a diet containing ( )-epigallocatechin-3-gallate and β-alanine, improves learning, memory and hippocampal neurogenesis in aged mice. Behavioural Brain Research. 2014;272:131–140. doi:10.1016/j.bbr.2014.05.049.
Huang WC, Chiu WC, Chuang HL, Tang DW, Lee ZM, Wei L, et al. Effect of Curcumin Supplementation on Physiological Fatigue and Physical Performance in Mice. Nutrients. 2015;7(2):905–921. doi:10.3390/nu7020905.
Xi X, Guo S, Guo H, Cui X, Cao H, Xu F, et al. Anti- exercise-fatigue and promotion of sexual interest activity of total flavonoids from wasps drone-pupae in male mice. Biomedicine & Pharmacotherapy. 2018;107:254–261. doi:10.1016/j.biopha.2018.07.172.
Li Y, Xin Y, Xu F, Zheng M, Xi X, Cui X, et al. Maca polysaccharides: Extraction optimization, structural features and anti-fatigue activities. International Journal of Biological Macromolecules. 2018;115:618–624. doi:10.1016/j.ijbiomac.2018.04.063.
Qi B, Liu L, Zhang H, Zhou GX, Wang S, Duan XZ, et al. Anti-fatigue effects of proteins isolated from Panax quinquefolium. Journal of Ethnopharmacology. 2014;153(2):430–434. doi:10.1016/j.jep.2014.02.045.
Fukuda S, Nojima J, Motoki Y, Yamaguti K, Nakatomi Y, Okawa N, et al. A potential biomarker for fatigue: Oxidative stress and anti-oxidative activity. Biological Psychology. 2016;118:88–93. doi:10.1016/j.biopsycho.2016.05.005.
Coqueiro AY, Raizel R, Bonvini A, Rogero MM, Tirapegui J. Effects of glutamine and alanine supplementation on muscle fatigue parameters of rats submitted to resistance training. Nutrition. 2019;65:131–137. doi:10.1016/j.nut.2018.09.025.
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