Skip to content
Licensed Unlicensed Requires Authentication Published by De Gruyter July 20, 2019

Fenugreek seed extract ameliorates cognitive deficits in streptozotocin-induced diabetic rats

  • Praveen K. Kodumuri ORCID logo , Christofer Thomas , Raghu Jetti and Anil Kumar Pandey EMAIL logo

Abstract

Background

Natural medicinal plants have been the focus of current research for developing neuroprotective agents to be used in the diabetes-linked cognitive dysfunction. Trigonella foenum-graecum seeds (known as fenugreek, methi in Hindi), is a well-known traditional medicinal herb and possesses anti-diabetic, anti-oxidant, and anti-inflammatory properties.

Purpose

This study was undertaken to explore the ameliorative effects of T. foenum-graecum seed extract on diabetes-induced cognitive dysfunction.

Methods

Experimental diabetes was induced by administering a single dose of streptozotocin (60 mg/kg) through intraperitoneal dose. Cognitive function was assessed using a T-maze and the Morris water maze. Lipid peroxidation levels and oxidative stress in the hippocampus was measured. Quantification of hippocampal CA1 and CA3 regions was done using cresyl violet stain.

Results

Diabetic rats demonstrated learning and memory impairment, which was evident from poor performance in behavioral tasks, i.e. T-maze and Morris water maze tasks. Learning and memory impairment in diabetic animals is associated with increased blood glucose levels, increased oxidative stress in the hippocampus and decreased number of neurons in the CA1 and CA3 regions of the hippocampus. The diabetic rats administered with T. foenum-graecum showed improved performance in behavioral tasks, and these changes were associated with decreased blood glucose levels, decreased oxidative stress in the hippocampus, and decreased neuronal loss from the CA1 and CA3 regions of the hippocampus.

Conclusion

In conclusion, administration of T. foenum-graecum seed extract ameliorates diabetes-linked cognitive dysfunction in rats by decreasing blood glucose levels, reducing lipid peroxidation and oxidative stress in the hippocampus, and preventing neuronal loss from the hippocampus.

Acknowledgments

The authors are sincerely grateful to Mamata Educational Society, Khammam, for providing financial assistance to carry out this research project.

  1. Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

  2. Research funding: None declared.

  3. Employment or leadership: None declared.

  4. Honorarium: None declared.

  5. Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.

References

[1] Biessels GJ, Deary IJ, Ryan CM. Cognition and diabetes: a lifespan perspective. Lancet Neurol 2008;7:184–90.10.1016/S1474-4422(08)70021-8Search in Google Scholar

[2] Cukierman T, Gerstein HC, Williamson JD. Cognitive decline and dementia in diabetes – systematic overview of prospective observational studies. Diabetologia 2005;48:2460–9.10.1007/s00125-005-0023-4Search in Google Scholar

[3] Mijnhout GS, Scheltens P, Diamant M, Biessels GJ, Wessels AM, Simsek S, et al. Diabetic encephalopathy: a concept in need of a definition. Diabetologia 2006;49:1447–8.10.1007/s00125-006-0221-8Search in Google Scholar

[4] Morabito MV, Berman DE, Schneider RT, Zhang Y, Leibel RL, Small SA. Hyperleucinemia causes hippocampal retromer deficiency linking diabetes to Alzheimer’s disease. Neurobiol Dis 2014;65:188–92.10.1016/j.nbd.2013.12.017Search in Google Scholar

[5] Fukui K, Onodera K, Shinkai T, Suzuki S, Urano S. Impairment of learning and memory in rats caused by oxidative stress and aging, and changes in antioxidative defense systems. Ann N Y Acad Sci 2001;928:168–75.10.1111/j.1749-6632.2001.tb05646.xSearch in Google Scholar

[6] Mastrocola R, Restivo F, Vercellinatto I, Danni O, Brignardello E, Aragno M, et al. Oxidative and nitrosative stress in brain mitochondria of diabetic rats. J Endocrinol 2005;187:37–44.10.1677/joe.1.06269Search in Google Scholar

[7] Brown NJ. Cardiovascular effects of antidiabetic agents: focus on blood pressure effects of incretin-based therapies. J Am Soc Hypertens 2012;6:163–8.10.1016/j.jash.2012.02.003Search in Google Scholar

[8] Patil R, Patil R, Ahirwar B, Ahirwar D. Current status of Indian medicinal plants with antidiabetic potential: a review. Asian Pac J Trop Biomed 2011;1:S291–8.10.1016/S2221-1691(11)60175-5Search in Google Scholar

[9] Medagama AB, Bandara R. The use of complementary and alternative medicines (CAMs) in the treatment of diabetes mellitus: is continued use safe and effective? Nutr J 2014;13:102.10.1186/1475-2891-13-102Search in Google Scholar PubMed PubMed Central

[10] Goyal S, Gupta N, Chatterjee S. Investigating therapeutic potential of Trigonella foenum-graecum L. As our defense mechanism against several human diseases. J Toxicol 2016;2016:1–10.10.1155/2016/1250387Search in Google Scholar PubMed PubMed Central

[11] Baquer NZ, Kumar P, Taha A, Kale RK, Cowsik SM, McLean P. Metabolic and molecular action of Trigonella foenum-graecum (fenugreek) and trace metals in experimental diabetic tissues. J Biosci 2011;36:383–96.10.1007/s12038-011-9042-0Search in Google Scholar PubMed

[12] Kaviarasan S, Ramamurty N, Gunasekaran P, Varalakshmi E, Anuradha CV. Fenugreek (Trigonella foenum graecum) seed extract prevents ethanol-induced toxicity and apoptosis in chang liver cells. Alcohol Alcohol 2006;41:267–73.10.1093/alcalc/agl020Search in Google Scholar PubMed

[13] Sauvaire Y, Petit P, Broca C, Manteghetti M, Baissac Y, Fernandez-Alvarez J, et al. 4-Hydroxyisoleucine: a novel amino acid potentiator of insulin secretion. Diabetes 1998;47:206–10.10.2337/diab.47.2.206Search in Google Scholar PubMed

[14] Raghuram TC, Sharma RD, Sivakumar B, Sahay BK. Effect of fenugreek seeds on intravenous glucose disposition in non-insulin dependent diabetic patients. Phyther Res 1994;8:83–6.10.1002/ptr.2650080206Search in Google Scholar

[15] Ali L, Azad Khan AK, Hassan Z, Mosihuzzaman M, Nahar N, Nasreen T, et al. Characterization of the hypoglycemic effects of Trigonella foenum graecum seed. Planta Med 1995;61:358–60.10.1055/s-2006-958100Search in Google Scholar PubMed

[16] Bhutada P, Mundhada Y, Bansod K, Tawari S, Patil S, Dixit P, et al. Protection of cholinergic and antioxidant system contributes to the effect of berberine ameliorating memory dysfunction in rat model of streptozotocin-induced diabetes. Behav Brain Res 2011;220:30–41.10.1016/j.bbr.2011.01.022Search in Google Scholar PubMed

[17] Vijayakumar MV, Singh S, Chhipa RR, Bhat MK. The hypoglycaemic activity of fenugreek seed extract is mediated through the stimulation of an insulin signalling pathway. Br J Pharmacol 2005;146:41–8.10.1038/sj.bjp.0706312Search in Google Scholar PubMed PubMed Central

[18] Basch E, Ulbricht C, Kuo G, Szapary P, Smith M. Therapeutic applications of fenugreek. Altern Med Rev 2003;8:20–7.Search in Google Scholar

[19] Deacon RM, Rawlins JN. T-maze alternation in the rodent. Nat Protoc 2006;1:7–12.10.1038/nprot.2006.2Search in Google Scholar PubMed

[20] Bhutada P, Mundhada Y, Bansod K, Dixit P, Umathe S, Mundhada D. Anticonvulsant activity of berberine, an isoquinoline alkaloid in mice. Epilepsy Behav 2010;18:207–10.10.1016/j.yebeh.2010.03.007Search in Google Scholar PubMed

[21] Narayanan SN, Kumar RS, Karun KM, Nayak SB. Possible cause for altered spatial cognition of prepubescent rats exposed to chronic radiofrequency electromagnetic radiation. Metab Brain Dis 2015;30:1193–206.10.1007/s11011-015-9689-6Search in Google Scholar PubMed

[22] Glowinski J, Iversen LL. Regional studies of catecholamines in the rat brain. I. The disposition of [3H]norepinephrine, [3H]dopamine and [3H]dopa in various regions of the brain. J Neurochem 1966;13:655–69.10.1111/j.1471-4159.1966.tb09873.xSearch in Google Scholar

[23] Ohkawa H, Ohishi N, Yagi K. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem 1979;95:351–8.10.1016/0003-2697(79)90738-3Search in Google Scholar

[24] Akerboom TP, Sies H. Assay of glutathione, glutathione disulfide, and glutathione mixed disulfides in biological samples. Methods Enzymol 1981;77:373–82.10.1016/S0076-6879(81)77050-2Search in Google Scholar

[25] Flohé L, Günzler WA. Assays of glutathione peroxidase. Methods Enzymol 1984;105:114–21.10.1016/S0076-6879(84)05015-1Search in Google Scholar

[26] Misra HP, Fridovich I. The role of superoxide anion in the autoxidation of epinephrine and a simple assay for superoxide dismutase. J Biol Chem 1972;247:3170–5.10.1016/S0021-9258(19)45228-9Search in Google Scholar

[27] Aebi H. Catalase in vitro. Methods Enzymol 1984;105:121–6.10.1016/S0076-6879(84)05016-3Search in Google Scholar

[28] King AJ. The use of animal models in diabetes research. Br J Pharmacol 2012;166:877–94.10.1111/j.1476-5381.2012.01911.xSearch in Google Scholar PubMed PubMed Central

[29] Liu Z, Chen H, Wu P, Yao Q, Cheng H, Yu W, et al. Flos puerariae extract ameliorates cognitive impairment in streptozotocin-induced diabetic mice. Evid-Based Complement Alternat Med 2015;2015:1–7.10.1155/2015/873243Search in Google Scholar PubMed PubMed Central

[30] Zarros A, Liapi C, Galanopoulou P, Marinou K, Mellios Z, Skandali N, et al. Effects of adult-onset streptozotocin-induced diabetes on the rat brain antioxidant status and the activities of acetylcholinesterase, (Na +, K +) - and Mg2 + -ATPase: modulation by L-cysteine. Metab Brain Dis 2009;24:337–48.10.1007/s11011-009-9133-xSearch in Google Scholar PubMed

[31] Biessels GJ, Kerssen A, de Haan EH, Kappelle LJ. Cognitive dysfunction and diabetes: implications for primary care. Prim Care Diabetes 2007;1:187–93.10.1016/j.pcd.2007.10.002Search in Google Scholar PubMed

[32] Yin Q, Pei J, Xu S, Luo D, Dong S, Sun M, et al. Pioglitazone improves cognitive function via increasing insulin sensitivity and strengthening antioxidant defense system in fructose-drinking insulin resistance rats. PLoS One 2013;8:e59313.10.1371/journal.pone.0059313Search in Google Scholar

[33] Kodl CT, Seaquist ER. Cognitive dysfunction and diabetes mellitus. Endocr Rev 2008;29:494–511.10.1210/er.2007-0034Search in Google Scholar

[34] Vats V, Grover J, Rathi S. Evaluation of anti-hyperglycemic and hypoglycemic effect of Trigonella foenum-graecum Linn, Ocimum sanctum Linn and Pterocarpus marsupium Linn in normal and alloxanized diabetic rats. J Ethnopharmacol 2002;79:95–100.10.1016/S0378-8741(01)00374-9Search in Google Scholar

[35] Xue WL, Li XS, Zhang J, Liu YH, Wang ZL, Zhang RJ. Effect of Trigonella foenum-graecum (fenugreek) extract on blood glucose, blood lipid and hemorheological properties in streptozotocin-induced diabetic rats. Asia Pac J Clin Nutr 2007;16(Suppl 1):422–6.Search in Google Scholar

[36] Shu S-Y, Jiang G, Zeng Q-Y, Wang B, Li H, Ma L, et al. The marginal division of the striatum and hippocampus has different role and mechanism in learning and memory. Mol Neurobiol 2015;51:827–39.10.1007/s12035-014-8891-6Search in Google Scholar

[37] Pandey SP, Singh HK, Prasad S. Alterations in hippocampal oxidative stress, expression of AMPA receptor GluR2 subunit and associated spatial memory loss by Bacopa monnieri extract (CDRI-08) in streptozotocin-induced diabetes mellitus type 2 mice. PLoS One 2015;10:1–23.10.1371/journal.pone.0131862Search in Google Scholar

[38] Kamal A, Biessels GJ, Urban IJ, Gispen WH. Hippocampal synaptic plasticity in streptozotocin-diabetic rats: impairment of long-term potentiation and facilitation of long-term depression. Neuroscience 1999;90:737–45.10.1016/S0306-4522(98)00485-0Search in Google Scholar

[39] Nishikawa T, Edelstein D, Du XL, Yamagishi S, Matsumura T, Kaneda Y, et al. Normalizing mitochondrial superoxide production blocks three pathways of hyperglycaemic damage. Nature 2000;404:787–90.10.1038/35008121Search in Google Scholar

[40] Popoviç M, Biessels GJ, Isaacson RL, Gispen WH. Learning and memory in streptozotocin-induced diabetic rats in a novel spatial/object discrimination task. Behav Brain Res 2001;122:201–7.10.1016/S0166-4328(01)00186-3Search in Google Scholar

[41] Franco-robles E, Campos-cervantes A, Murillo-ortiz BO, Segovia J, López-briones S, Vergara P, et al. Effects of curcumin on brain-derived neurotrophic factor levels and oxidative damage in obesity and diabetes. Appl Physiol Nutr Metab 2014;218:211–8.10.1139/apnm-2013-0133Search in Google Scholar

[42] Watanabe Y, Gould E, McEwen BS. Stress induces atrophy of apical dendrites of hippocampal CA3 pyramidal neurons. Brain Res 1992;588:341–5.10.1016/0006-8993(92)91597-8Search in Google Scholar

[43] Sato N, Morishita R. Brain alterations and clinical symptoms of dementia in diabetes: AÎ2/tau-dependent and independent mechanisms. Front Endocrinol (Lausanne). 2014;5:1–8.10.3389/fendo.2014.00143Search in Google Scholar PubMed PubMed Central

[44] Hasanein P, Shahidi S. Effects of combined treatment with vitamins C and E on passive avoidance learning and memory in diabetic rats. Neurobiol Learn Mem 2010;93:472–8.10.1016/j.nlm.2010.01.004Search in Google Scholar PubMed

[45] Marzouk M, Solimana M, Omar TY. Hypoglycemic and antioxidative effects of fenugreek and termis seeds powder in streptozotocin-diabetic rats. Eur Rev Med Pharmacol Sci 2013;17:559–65.Search in Google Scholar

[46] Bhatnagar M, Shukla SD, Bhatnagar R. Experimental neurodegeneration in hippocampus and its phytoremidation. J Herb Pharmacother 2005;5:21–30.10.1080/J157v05n02_03Search in Google Scholar

[47] Piotrowski P, Gajkowska B, Olszewska H, Smiałek M. Electron microscopy studies on experimental diabetes and cerebral ischemia in the rat brain. Folia Neuropathol 1999;37:256–63.Search in Google Scholar

[48] Wang J, Zhang Y-W, Zhang J-Q, Liu C, Wei P, Zhang X, et al. Memory dysfunction in type 2 diabetes mellitus correlates with reduced hippocampal CA1 and subiculum volumes. Chin Med J (Engl) 2015;128:465–71.10.4103/0366-6999.151082Search in Google Scholar PubMed PubMed Central

[49] Pugazhenthi S, Nesterova A, Jambal P, Audesirk G, Kern M, Cabell L, et al. Oxidative stress-mediated down-regulation of bcl-2 promoter in hippocampal neurons. J Neurochem 2003;84:982–96.10.1046/j.1471-4159.2003.01606.xSearch in Google Scholar PubMed

[50] Piotrowski P, Wierzbicka K, Smialek M. Neuronal death in the rat hippocampus in experimental diabetes and cerebral ischaemia treated with antioxidants. Folia Neuropathol 2001;39:147–54.Search in Google Scholar

Received: 2018-11-15
Accepted: 2019-02-25
Published Online: 2019-07-20

© 2019 Walter de Gruyter GmbH, Berlin/Boston

Downloaded on 25.4.2024 from https://www.degruyter.com/document/doi/10.1515/jbcpp-2018-0140/html
Scroll to top button