Jobelyn^®, a Sorghum-Based Nutritional Supplement Attenuates Unpredictable Chronic Mild Stress-Induced Memory Deficits in Mice

Solomon Umukoro^1,2*, Osarume Omorogbe¹, Oritoke Modupe Aluko¹, Taghogho Anthony Eduviere³, Olatunde Owoeye⁴, Oluwafemi Gabriel Oluwole¹

¹Neuropharmacology Unit, Department of Pharmacology and Therapeutics, University of Ibadan, Ibadan, Nigeria.
²Department of Pharmacology and Therapeutics, College of Health Sciences, Osun State University, Osogbo, Nigeria.
³Department of Pharmacology and Therapeutics, College of Medicine and Health Sciences, Afe Babalola University, Ado-Ekiti, Nigeria.
⁴Department of Anatomy, Faculty of Basic Medical Sciences, University of Ibadan, Ibadan, Nigeria.

DOI: 10.4236/jbbs.2015.513056                

Abstract

The ability of an organism to adapt to aversive stressful situations or life challenging circumstances is very crucial to its state of health and survival. However, breakdown in adaptation due to persistent uncontrollable stress, leads to impairment of bodily functions and onset of a variety of pathological disorders especially memory decline. This study was designed to evaluate the effect of Jobelyn^® (JB), a potent antioxidant sorghum-based food supplement on unpredictable chronic mild stress (UCMS)-induced memory impairment in mice. Male Swiss mice were given JB (5 - 50 mg/kg, p.o) 30 min prior to exposure to UCMS for 14 consecutive days before testing for memory. Thereafter, the serum corticosterone level was estimated by using ELISA kits. The levels of malondialdehyde (MDA) and glutathione (GSH) as well as acetylcholinesterase activity were estimated in the brain homogenate using spectrophotometer. Histology of the brain tissues and estimation of the populations of viable neurons in the hippocampal region were done after staining with hematoxyline and eosin. Our results showed that JB reversed memory impairment and suppressed corticosterone concentrations induced by UCMS. Moreover, JB reduced oxidative stress in the brain of UCMS-mice as shown by decreased MDA levels and elevated GSH concentrations. It also decreased brain acetylcholinesterase activity when compared with chronic stress group (p < 0.05). Furthermore, JB (5 - 10 mg/kg, p.o) offered significant protection against UCMS-induced degeneration and death of neuronal cells of the cornu ammonis 3 (CA3) of the hippocampal region of the brain indicating neuroprotection. Taken together, these findings suggest that JB attenuates memory deficits induced by UCMS in mice and may be useful therapeutically for stress-related cognitive dysfunctions. The reduction in the levels of serum corticosterone, antioxidation, neuroprotection and inhibition of cholinesterase enzyme might be contributing significantly to the positive effect of JB on memory in mice exposed to unpredictable chronic mild stress.

Keywords

Jobelyn^®, Unpredictable Chronic Mild Stress, Memory Performance, Oxidative Stress, Neuroprotection

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1]	Oken, B.S., Chamine, I. and Wakeland, W. (2015) A Systems Approach to Stress, Stressors and Resilience in Humans. Behavioral Brain Research, 282, 144-154. www.ncbi.nlm.nih.gov/pubmed/25549855 http://dx.doi.org/10.1016/j.bbr.2014.12.047
[2]	de Kloet, E.R., Joels, M. and Holsboer, F. (2005) Stress and the Brain: From Adaptation to Disease. Nature Reviews Neuroscience, 6, 463-475. www.ncbi.nlm.nih.gov/pubmed/15891777 http://dx.doi.org/10.1038/nrn1683
[3]	Henckens, M.J.A.G., Hermans, E.J., Pu, Z., Joels, M. and Fernandez G. (2009) Stressed Memories: How Acute Stress Affects Memory Formation in Humans. Journal Neuroscience, 29, 10111-10119. www.jneurosci.org/content/29/32/10111 http://dx.doi.org/10.1523/jneurosci.1184-09.2009
[4]	McEwen, B.S., Gray, J.D. and Nasca, C. (2015) Recognizing Resilience: Learning from the Effects of Stress on the Brain. Neurobiology of Stress, 1, 1-11. http://www.ncbi.nlm.nih.gov/pubmed http://dx.doi.org/10.1016/j.ynstr.2014.09.001
[5]	Kuhlmann, S., Piel, M. and Wolf, O.T. (2005) Impaired Memory Retrieval after Psychological Stress in Healthy Young Men. Journal of Neuroscience, 25, 2977-2982. www.jneurosci.org/content/25/11/2977 http://dx.doi.org/10.1523/JNEUROSCI.5139-04.2005
[6]	Magarino, A.M. and McEwen, B.S. (1995) Stress-Induced Atrophy of Apical Dendrites of Hippocampal CA3c Neurons: Involvement of Glucocorticoid Secretion and Excitatory Amino Acid Receptors. Neuroscience, 69, 89-98. http://www.ncbi.nlm.nih.gov/pubmed/8637636 http://dx.doi.org/10.1016/0306-4522(95)00259-l
[7]	Sapolsky, R.M. (2000) Stress Hormones: Good and Bad. Neurobiology and Disease, 7, 540-542. www.ncbi.nlm.nih.gov/pubmed/11042072 http://dx.doi.org/10.1006/nbdi.2000.0350
[8]	Watanabe, Y., Gould, E. and McEwen, B.S. (1992) Stress Induces Atrophy of Apical Dendrites of Hippocampal CA3 Pyramidal Neurons. Brain Research, 588, 341-345. www.ncbi.nlm.nih.gov/pubmed/1393587 http://dx.doi.org/10.1016/0006-8993(92)91597-8
[9]	Starkman, M.N., Gebarski, S.S., Berent, S. and Schteingart, D.E. (1992). Hippocampal Formation Volume, Memory Dysfunction, and Cortisol Levels in Patients with Cushing’s Syndrome. Biological Psychiatry, 32, 756-765. www.ncbi.nlm.nih.gov/pubmed/1450290 http://dx.doi.org/10.1016/0006-3223(92)90079-F
[10]	Luine, V.M., Martinez, V.C. and McEwen, B.S. (1994) Repeated Stress Causes Reversible Impairments of Spatial Memory Performance. Brain Research, 639, 167-170. www.ncbi.nlm.nih.gov/pubmed/8180832 http://dx.doi.org/10.1016/0006-8993(94)91778-7
[11]	Rodriguez, E.L., Gonzalez, A.S., Cabrera, R. and Fracchia, L.N. (1988) A Further Analysis of Behavioral and Endocrine Effects of Unpredictable Chronic Stress. Physiology & Behaviour, 43, 789-795. www.ncbi.nlm.nih.gov/pubmed/3237793 http://dx.doi.org/10.1016/0031-9384(88)90378-2
[12]	Bodnoff, S.R., Humphreys, A.G., Lehman, J.C., Diamond, D.M., Rose, G.M. and Meaney, M.J. (1995) Enduring Effects of Chronic Corticosterone Treatment on Spatial Learning, Synaptic Plasticity, and Hippocampal Neuropathology in Young and Mid-Aged Rats. Journal of Neuroscience, 15, 61-69. www.ncbi.nlm.nih.gov/pubmed/7823152
[13]	Baker, K.B. and Kim, J.J. (2002) Effects of Stress and Hippocampal NMDA Receptor Antagonism on Recognition Memory in Rats. Learning and Memory, 9, 58-65. http://dx.doi.org/10.1101/lm.46102
[14]	Awika, J.M. and Rooney, L.W. (2004) Sorghum Phytochemicals and Their Potential Impact on Human Health. Phytochemistry, 65, 1199-1221. www.ncbi.nlm.nih.gov/pubmed/15184005 http://dx.doi.org/10.1016/j.phytochem.2004.04.001
[15]	Benson, K.F., Beaman, J.L., Ou, B., Okubena, A., Okubena, O. and Jensen, G.S. (2013) West African Sorghum Bicolor Leaf Sheaths Have Anti-Inflammatory and Immune-Modulating Properties in Vitro. Journal of Medicinal Food, 16, 230-238. www.ncbi.nlm.nih.gov/pubmed/23289787 http://dx.doi.org/10.1089/jmf.2012.0214
[16]	Erah, P.O., Asonye, C.C. and Okhamafe, A.O. (2003) Response of Trypanosoma brucei Brucei-Induced Anaemia to a Commercial Herbal Preparation. African Journal of Biotechnology, 2, 307-311. www.academicjournals.org/journal/AJB/article-stat/4E882F510159 http://dx.doi.org/10.5897/AJB2003.000-1063
[17]	Nabavi, S.F., Braidy, N., Gortzi, O., Sobarzo-Sanchez, E., Daglia, M., Skalicka-Wozniak, K. and Nabavi, S.M. (2015) Luteolin as an Anti-Inflammatory and Neuroprotective Agent: A Brief Review. Brain Research Bulletin, 119, 1-11. www.ncbi.nlm.nih.gov/pubmed/26361743 http://dx.doi.org/10.1016/j.brainresbull.2015.09.002
[18]	Umukoro, S., Eduviere, A.T., Aladeokin, A.C. and Olugbemide, A.S. (2014) Antidepressant-Like Property of Jobelyn®, an African Unique Herbal Formulation, in Mice. Drug Research, 64, 146-150. www.ncbi.nlm.nih.gov/pubmed/24002928
[19]	Umukoro, S., Ugbomah, A., Aderibigbe, A.O. and Omogbiya, A.I. (2013) Antioxidant Property of Jobelyn as the Possible Mechanism Underlying Its Anti-Amnesic Activity in Rodents. Basic and Clinical Neuroscience, 4, 42-49. www.ncbi.nlm.nih.gov/pubmed/25337327
[20]	Yalcin, I., Aksu, F. and Belzung, C. (2005) Effects of Desipramine and Tramadol in a Chronic Mild Stress Model in Mice Are Altered by Yohimbine but Not by Pindolol. European Journal of Pharmacology, 514, 165-174. www.ncbi.nlm.nih.gov/pubmed/15910803 http://dx.doi.org/10.1016/j.ejphar.2005.03.029
[21]	Casadesus, G., Webber, K.M., Atwood, C.S., Pappolla, M.A., Perry, G., Bowen, R.L. and Smith, M.A. (2006) Luteinizing Hormone Modulates Cognition and Amyloid-Beta Deposition in Alzheimer APP Transgenic Mice. Biochimica et Biophysica Acta, 1762, 447-452. www.ncbi.nlm.nih.gov/pubmed/16503402 http://dx.doi.org/10.1016/j.bbadis.2006.01.008
[22]	Moron, M.S., Depierre, J.W. and Mannervik, B. (1979) Levels of Glutathione, Glutathione Reductase and Glutathione S-Transferase Activities in Rat Lung and Liver. Biochimica et Biophysica Acta, 582, 67-78. www.ncbi.nlm.nih.gov/pubmed/760819 http://dx.doi.org/10.1016/0304-4165(79)90289-7
[23]	Okhawa, H., Ohishi, N. and Yagi, K. (1979) Assay for Lipid Peroxides in Animal Tissues by Thiobarbituric Acid Reaction. Analytical Biochemist, 95, 351-358.
[24]	Ellman, G.L., Courtney, K.D., Andre, J.V. and Featherstone, R.M. (1961) A New and Rapid Colorimetric Determination of Acetylcholinesterase Activity. Biochemical Pharmacology, 7, 88-95. www.ncbi.nlm.nih.gov/pubmed/13726518 http://dx.doi.org/10.1016/0006-2952(61)90145-9
[25]	Sugihara, I., Bailly, Y. and Mariani, J. (2000) Olivocerebellar Climbing Fibers in the Granuloprival Cerebellum: Morphological Study of Individual Axonal Projections in the X-Irradiated Rat. Journal of Neuroscience, 20, 3745-3760. www.ncbi.nlm.nih.gov/pubmed/10804216
[26]	Blokland, A. (2005) Scopolamine-Induced Deficits in Cognitive Performance: A Review of Animal Studies. Scopolamine Review, 1, 1-76.
[27]	Loizzo, M.R., Tundis, R. and Menichini, F. (2008) Natural Products and Their Derivatives as Cholinesterase Inhibitors in the Treatment of Neurodegenerative Disorders: An Update. Current Medicinal Chemistry, 15, 1209-1228. www.ncbi.nlm.nih.gov/pubmed/18473814 http://dx.doi.org/10.2174/092986708784310422
[28]	Sembulingam, K., Sembulingam, P. and Namasivayam, A. (2003) Effect of Acute Noise Stress on Acetylcholinesterase Activity in Discrete Areas of Rat Brain. Indian Journal of Medical Science, 57, 487-492. www.ncbi.nlm.nih.gov/pubmed/14646156
[29]	Fatranská, M., Kiss, A., Oprsalová, Z. and Kvetnansky, R. (1989) Acetylcholinesterase and Choline Acetyltransferase Activity in Some Hypothalamic Nuclei under Immobilization Stress in Rats. Endocrinologia Experimentalis, 23, 3-10. www.ncbi.nlm.nih.gov/pubmed/2714225
[30]	Fatranská, M., Budai, D., Oprsalová, Z. and Kvetnansky, R. (1987) Acetylcholine and Its Enzymes in Some Brain Areas of the Rat under Stress. Brain Research, 20, 109-114. www.ncbi.nlm.nih.gov/pubmed/3690292 http://dx.doi.org/10.1016/0006-8993(87)91198-x
[31]	Terry Jr, A.W. and Buccafusco, J.J. (2003) The Cholinergic Hypothesis of Age and Alzheimer’s Disease-Related Cognitive Deficits: Recent Challenges and Their Implications for Novel Drug Development. Journal of Pharmacology and Experimental Therapeutics, 306, 821-827. www.ncbi.nlm.nih.gov/pubmed/12805474 http://dx.doi.org/10.1124/jpet.102.041616
[32]	Conrad, C.D., Galea, L.A., Kuroda, Y. and McEwen, B.S. (1996) Chronic Stress Impairs Rat Spatial Memory on the Y Maze, and This Effect Is Blocked by Tianeptine Pretreatment. Behavioral Neuroscience, 110, 1321-1334. www.ncbi.nlm.nih.gov/pubmed/8986335 http://dx.doi.org/10.1037/0735-7044.110.6.1321
[33]	McEwen, B.S. (2008) Central Effects of Stress Hormones in Health and Disease: Understanding the Protective and Damaging Effects of Stress and Stress Mediators. European Journal of Pharmacology, 583, 174-185. www.ncbi.nlm.nih.gov/pubmed/18282566 http://dx.doi.org/10.1016/j.ejphar.2007.11.071
[34]	Rothman, S.M. and Mattson, P.M. (2010) Adverse Stress, Hippocampal Networks, and Alzheimer’s Disease. Neuromolecular Medicine, 12, 56-70. www.ncbi.nlm.nih.gov/pubmed/19943124 http://dx.doi.org/10.1007/s12017-009-8107-9
[35]	Natalie, A., Kelsey, I., Heather, M., Wilkins, I. and Linseman, D.A. (2010) Nutraceutical Antioxidants as Novel Neuroprotective Agents. Molecules, 15, 7792-7814. www.ncbi.nlm.nih.gov/pubmed/21060289 http://dx.doi.org/10.3390/molecules15117792
[36]	Ming, T.H., Wen, H.P., Chi, R.W., Kit, Y.N., Chuen, L.C. and Hong, X.X. (2010) Review on Experimental Research of Herbal Medicines with Anti-Amnesic Activity. Planta Medicine, 76, 203-217. www.ncbi.nlm.nih.gov/pubmed/20033863 http://dx.doi.org/10.1055/s-0029-1240707
[37]	Moreira, P.I., Santos, M.S., Oliveira, C.R., Shenk, J.C., Nunomura, A., Smith, M.A., Zhu, X. and Perry, G. (2008) Alzheimer Disease and the Role of Free Radicals in the Pathogenesis of the Disease. CNS Neurological Disorder and Drug Targets, 7, 3-10. www.ncbi.nlm.nih.gov/pubmed/18289026
[38]	Heo, H.J., Kim, M., Lee, J., Cho, S., Cho, H., Hong, B., Kim, H., Kim, E. and Shin, D. (2004) Naringenin from Citrus junos Has an Inhibitory Effect on Acetylcholinesterase and a Mitigating Effect on Amnesia. Dementia and Geratric Cognitive Disorders, 17, 151-157. www.ncbi.nlm.nih.gov/pubmed/14739537 http://dx.doi.org/10.1159/000076349
[39]	Kaulaskar, S., Bhutada, P., Rahigude, A., Jain, D. and Harle, U. (2012) Effects of Naringenin on Allodynia and Hyperalgesia in Rats with Chronic Constriction Injury-Induced Neuropathic Pain. Journal of Chinese Integrative Medicine, 10, 1482-1489. www.ncbi.nlm.nih.gov/pubmed/23257145 http://dx.doi.org/10.3736/jcim20121223
[40]	Pinheiro, M.M., Boylan, F. and Fernandes, P.D. (2012) Antinociceptive Effect of the Orbignya speciosa Mart. (Babassu) Leaves: Evidence for the Involvement of Apigenin. Life Science, 91, 293-300. www.sciencedirect.com/science/article/pii/S0024320512003219 http://dx.doi.org/10.1016/j.lfs.2012.06.013
[41]	Liu, R., Gao, M., Qiang, G.-F., Zhang, T.-T., Lan, X., Ying, J. and Du, G.-H. (2009) The Anti-Amnesic Effects of Luteolin against Amyloid β25-35 Peptide-Induced Toxicity in Mice Involve the Protection of Neurovascular Unit. Neuroscience, 162, 1232-1243. www.sciencedirect.com/science/article/pii/S0306452209007830 http://dx.doi.org/10.1016/j.neuroscience.2009.05.009
[42]	Kelly, G.S. (1999) Nutritional and Botanical Interventions to Assist with the Adaptation to Stress. Alternative Medicine Review, 4, 249-265. www.ncbi.nlm.nih.gov/pubmed/10468649
[43]	Zandi, P.P., Anthony, J.C., Khachaturian, A.S., Stone, S.V. and Gustafson, D. (2004) Reduced Risk of Alzheimer Disease in Users of Antioxidant Vitamin Supplements: The Cache County Study. Archives of Neurology, 61, 82-88. www.ncbi.nlm.nih.gov/pubmed/14732624 http://dx.doi.org/10.1001/archneur.61.1.82