Abstract
Carvacrol (CAR), a naturally occurring phenolic monoterpene, has been demonstrated to possess various biological actions. The present study was designed to investigate the neuroprotective effect of CAR on diabetes-associated cognitive deficit (DACD) in a rat model of diabetes and exploring its potential molecular mechanism. Diabetic rats were treated with CAR by the doses of 25, 50, and 100 mg/kg for 7 weeks. Morris water maze was used for behavioral evaluation of memory. Cytoplasmic and nuclear fractions of cerebral cortex and hippocampus were prepared for the quantification of oxidative stress (MDA, SOD, and GSH), NF-κB p65 unit, TNF-α, IL-1β, and caspase-3. After 7 weeks of streptozotocin injection, the rats produced remarkable increase in escape latency, coupled with increased oxidative stress (increased MDA level and decreased SOD as well as reduced GSH), NF-κB p65 unit, TNF-α, IL-1β, and caspase-3 in different regions of diabetic rat brain. Interestingly, coadministration of CAR significantly and dose-dependently prevented behavioral, biochemical, and molecular changes associated with diabetes. In summary, our findings provide the first evidence that CAR can remarkably attenuate DACD and suggest the involvement of oxidative stress, inflammation, and apoptotic cascades in the development of cognitive impairment caused by diabetes. The pharmacological effect of CAR suggests that it may be used as a promising agent for the treatment of conventional antihyperglycemic regiments as well as DACD.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Baser KH (2008) Biological and pharmacological activities of carvacrol and carvacrol bearing essential oils. Curr Pharm Des 14:3106–3119
Bayramoglu G, Senturk H, Bayramoglu A, et al. (2013) Cavcrol partially reverses symptoms of diabetes in STZ-induced diabetic rats. Cytotechnology. In press
Biessels GJ, Deary IJ, Ryan CM (2008) Cognition and diabetes: a lifespan perspective. Lancet Neurol 7:184–190
Bloomgarden ZT (2007) Diabetic neuropathy. Diabetes Care 30:1027–1032
Brown CM, Marthol H, Zikeli U et al (2008) A simple deep breathing test reveals altered cerebral autoregulation in type 2 diabetic patients. Diabetologia 51:756–761
Canbek M, Uyanoglu M, Bayramoglu G et al (2008) Effects of carvacrol on defects of ischemia-reperfusion in the rat liver. Phytomedicine 15:447–452
Cumiskey D, Butler MP, Moynagh PN et al (2007) Evidence for a role for the group I metabotropic glutamate receptor in the inhibitory effect of tumor necrosis factor-alpha on long-term potentiation. Brain Res 1136:13–19
Dobretsov M, Romanovsky D, Stimers JR (2007) Early diabetic neuropathy: triggers and mechanisms. World J Gastroenterol 13:175–191
Droge W (2002) Free radicals in the physiological control of cell function. Physiol Rev 82:47–95
Elias MF, Elias PK, Sullivan LM et al (2005) Obesity, diabetes, and cognitive deficit: The Framingham Heart Study. Neurobiol Aging 26(Suppl 1):11–16
Fukui K, Onodera K, Shinkai T et al (2001) Impairment of learning and memory in rats caused by oxidative stress and aging and changes in antioxidative defense systems. Ann N Y Acad Sci 928:168–175
Guimaraes AG, Oliveira GF, Melo MS et al (2010) Bioassay-guided evaluation of antioxidant and antinociceptive activities of carvacrol. Basic Clin Pharmacol Toxicol 107:949–957
Hayden MS, Ghosh S (2004) Signaling to NF-kappaB. Genes Dev 18:2195–2224
Hughes G, Murphy MP, Ledgerwood EC (2005) Mitochondrial reactive oxygen species regulate the temporal activation of nuclear factor kappaB to modulate tumor necrosis factor-induced apoptosis: evidence from mitochondria-targeted antioxidants. Biochem J 389:83–89
Jollow DJ, Mitchell JR, Zampaglione N et al (1974) Bromobenzene-induced liver necrosis. Protective role of glutathione and evidence for 3,4-bromobenzene oxide as the hepatotoxic metabolite. Pharmacology 11:151–169
Kim EK, Kwon KB, Han MJ et al (2007) Coptidis rhizoma extract protects against cytokine-induced death of pancreatic beta-cells through suppression of NF-kappaB activation. Exp Mol Med 39:149–159
Kodl CT, Seaquist ER (2008) Cognitive dysfunction and diabetes mellitus. Endocr Rev 29:494–511
Kono Y (1978) Generation of superoxide radical during autoxidation of hydroxylamine and an assay for superoxide dismutase. Arch Biochem Biophys 186:189–195
Kuhad A, Bishnoi M, Tiwari V et al (2009) Suppression of NF-kappabeta signaling pathway by tocotrienol can prevent diabetes associated cognitive deficits. Pharmacol Biochem Behav 92:251–259
Kuhad A, Chopra K (2008) Effect of sesamol on diabetes-associated cognitive decline in rats. Exp Brain Res 185:411–420
Landa P, Kokoska L, Pribylova M et al (2009) In vitro antiinflammatory activity of carvacrol: inhibitory effect on COX-2 catalyzed prostaglandin E(2) biosynthesis. Arch Pharm Res 32:75–78
Mastrocola R, Restivo F, Vercellinatto I et al (2005) Oxidative and nitrosative stress in brain mitochondria of diabetic rats. J Endocrinol 187:37–44
McCrimmon RJ, Ryan CM, Frier BM (2012) Diabetes and cognitive dysfunction. Lancet 379:2291–2299
Mijnhout GS, Scheltens P, Diamant M et al (2006) Diabetic encephalopathy: a concept in need of a definition. Diabetologia 49:1447–1448
Morris RG, Garrud P, Rawlins JN et al (1982) Place navigation impaired in rats with hippocampal lesions. Nature 297:681–683
Nishikawa T, Edelstein D, Du XL et al (2000) Normalizing mitochondrial superoxide production blocks three pathways of hyperglycaemic damage. Nature 404:787–790
Reagan LP, Grillo CA, Piroli GG (2008) The As and Ds of stress: metabolic, morphological, and behavioral consequences. Eur J Pharmacol 585:64–75
Sharma B, Singh N (2011) Behavioral and biochemical investigations to explore pharmacological potential of PPAR-gamma agonists in vascular dementia of diabetic rats. Pharmacol Biochem Behav 100:320–329
Tuzcu M, Baydas G (2006) Effect of melatonin and vitamin E on diabetes-induced learning and memory impairment in rats. Eur J Pharmacol 537:106–110
Umegaki H (2010) Pathophysiology of cognitive dysfunction in older people with type 2 diabetes: vascular changes or neurodegeneration? Age Aging 39:8–10
Waisundara VY, Hsu A, Tan BK et al (2009) Baicalin improves antioxidant status of streptozotocin-induced diabetic Wistar rats. J Agric Food Chem 57:4096–4102
Wessels AM, Scheltens P, Barkhof F et al (2008) Hyperglycemia as a determinant of cognitive decline in patients with type 1 diabetes. Eur J Pharmacol 585:88–96
Wills ED (1966) Mechanisms of lipid peroxide formation in animal tissues. Biochem J 99:667–676
Yu H, Zhang ZL, Chen J et al (2012) Carvacrol, a food-additive, provides neuroprotection on focal cerebral ischemia/reperfusion injury in mice. PLoS One 7:e33584
Conflict of Interest
The authors declare that they have no potential conflict of interest.
Author information
Authors and Affiliations
Corresponding author
Additional information
Highlights
1. Carvacrol evidently improved the blood glucose levels and body weights of diabetic rats.
2. Treatment with carvacrol significantly improved cognitive deficits caused by diabetes.
3. Treatment with carvacrol remarkably suppressed oxidative stress, inflammation, and apoptosis.
Rights and permissions
About this article
Cite this article
Deng, W., Lu, H. & Teng, J. Carvacrol Attenuates Diabetes-Associated Cognitive Deficits in Rats. J Mol Neurosci 51, 813–819 (2013). https://doi.org/10.1007/s12031-013-0069-6
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12031-013-0069-6