Planta Med 2011; 77(18): 1970-1976
DOI: 10.1055/s-0031-1280129
Biological and Pharmacological Activity
Original Papers
© Georg Thieme Verlag KG Stuttgart · New York

Effects of Insulin and St. John's Wort Treatments on Anxiety, Locomotory Activity, Depression, and Active Learning Parameters of Streptozotocin-Diabetic Rats

Özgür Devrim Can1 , Yusuf Öztürk1 , Ümide Demir Özkay1
  • 1Department of Pharmacology, Faculty of Pharmacy, Anadolu University, Eskisehir, Turkey
Further Information

Publication History

received April 4, 2011 revised June 27, 2011

accepted July 1, 2011

Publication Date:
19 August 2011 (online)

Abstract

The aim of this work was to investigate the effects of St. John's Wort (SJW) extract treatment on behavioral changes arising in streptozotocin (STZ)-diabetic rats. Plus-maze, activity cage, modified forced swimming, and active avoidance tests were performed for evaluating exploratory behaviors, spontaneous locomotor activities, depression levels, and learning parameters of animals, respectively. Obtained data exhibited a diabetes mellitus (DM)-induced increase in anxiety and depression levels, decrease in spontaneous locomotor activities, and impairment of learning parameters in rats even in the early stages of the disease. Daily insulin replacement (2 IU/kg/day) could not restore these impaired parameters completely, indicating the need of novel therapeutic approaches. SJW extract (125 and 250 mg/kg) treatments for seven days provided significant improvement in all of the impaired parameters observed in this study, probably due to its antidiabetic and central nervous system (CNS)-related effects.

Based on the findings of the present study, it may be suggested that SJW extracts may be of help to diabetic patients suffering from depressive moods, sleeping disturbances, and cognitive deficits and may provide a new potential alternative for the treatment of psychiatric complications of diabetes.

References

  • 1 World Health Organization .Department of noncommunicable disease surveillance, definition, diagnosis and classification of Diabetes mellitus and its complications. Geneva: World Health Organization; 1999: 1-57
  • 2 Li Z G, Sima A A. C-peptide and central nervous system complications in diabetes.  Exp Diabesity Res. 2004;  5 79-90
  • 3 Linde K. St. John's wort – an overview.  Forsch Komplementmed. 2009;  16 146-155
  • 4 Holsboer-Trachsler E. Phytotherapeutic drugs and sleep.  Schweiz Rundsch Med Prax. 2000;  89 2178-2182
  • 5 Rang H P, Dale M M, Ritterb J M. Pharmacology. London: Churchill Livingstone; 2003: 492-499
  • 6 Kasper S, Caraci F, Forti B, Drago F, Aguglia E. Efficacy and tolerability of Hypericum extract for the treatment of mild to moderate depression.  Eur Neuropsychopharmacol. 2010;  20 747-765
  • 7 Crupi R, Mazzon E, Marino A, La Spada G, Bramanti P, Battaglia F, Cuzzocrea S, Spina E. Hypericum perforatum treatment: effect on behaviour and neurogenesis in a chronic stress model in mice.  BMC Complement Alternat Med. 2011;  11 7
  • 8 Can O D, Öztürk Y, Öztürk N, Sagratini G, Ricciutelli M, Vittori S, Maggi F. Effects of treatment with St. John's wort on blood glucose levels and pain perceptions of streptozotocin-diabetic rats.  Fitoterapia. 2011;  82 576-584
  • 9 Romanovsky D, Cruz N F, Dienel G A, Dobretsov M. Mechanical hyperalgesia correlates with insulin deficiency in normoglycemic streptozotocin-treated rats.  Neurobiol Dis. 2006;  24 384-394
  • 10 Zanoli L P, Rivasi M, Zavatti M, Brusiani F, Baraldi M. New insight in the neuropharmacological activity of Humulus lupulus.  J Ethnopharmacol. 2005;  102 102-106
  • 11 Palenicek T, Votava M, Bubenikova V, Horacek J. Increased sensitivity to the acute effects of MDMA (“ecstasy”) in female rats.  Physiol Behav. 2005;  86 546-553
  • 12 Cryan J F, Markou A, Lucki I. Assessing antidepressant activity in rodents: recent developments and future need.  Trends Pharmacol Sci. 2002;  23 238-245
  • 13 Sanchez D J, Colomina M T, Domingo J L. Effects of vanadium on activity and learning in rats.  Physiol Behav. 1998;  63 345-350
  • 14 Zapata-Sudo G, Mendes T C, Kartnaller M A, Fortes T O, Freitas N F, Kaplan M A, Sudo R T. Sedative and anticonvulsant activities of methanol extract of Dorstenia arifolia in mice.  J Ethnopharmacol. 2010;  130 9-12
  • 15 Fernández S P, Wasowski C, Loscalzo L M, Granger R E, Johnston G A, Paladini A C, Marder M. Central nervous system depressant action of flavonoid glycosides.  Eur J Pharmacol. 2006;  539 168-176
  • 16 Girzu M, Carnat A, Privat A M, Fialip J, Carnat A P, Lamaison J L. Sedative activity in mice of a hydroalcohol extract of Hypericum perforatum L.  Phytother Res. 1997;  11 395-397
  • 17 Butterweck V, Wall A, Lieflander-Wulf U, Winterhoff H, Nahrstedt A. Effects of the total extract and fractions of Hypericum perforatum in animal assays for antidepressant activity.  Pharmacopsychiatry. 1997;  30 117-124
  • 18 Khalifa A E. Hypericum perforatum as a nootropic drug: enhancement of retrieval memory of a passive avoidance conditioning paradigm in mice.  J Ethnopharmacol. 2001;  76 49-57
  • 19 Ramanathan M, Jaiswal A K, Bhattacharya S K. Differential effects of diazepam on anxiety in streptozotocin induced diabetic and non-diabetic rats.  Psychopharmacology. 1998;  135 361-367
  • 20 Hilakivi-Clarke L A, Wozniak K M, Durcan M J, Linnoila M. Behavior of streptozotocin-diabetic mice in tests of exploration, locomotion, anxiety, depression and aggression.  Physiol Behav. 1990;  48 429-433
  • 21 Szkudelski T. The mechanism of alloxan and streptozotocin action in B cells of the rat pancreas.  Physiol Res. 2001;  50 537-546
  • 22 Merali Z, Ahmad Q, Veitch J. Behavioural and neurochemical profile of the spontaneously diabetic Wistar BB rat.  Behav Brain Res. 1988;  29 51-60
  • 23 Howarth F C, Jacobson M, Shafiullah M, Adeghate E. Effects of insulin treatment on heart rhythm, body temperature and physical activity in streptozotocin-induced diabetic rat.  Clin Exp Pharmacol Physiol. 2006;  33 327-331
  • 24 Biessels G J, Kamal A, Urban I J, Spruijt B M, Erkelens D W, Gispen W H. Water maze learning and hippocampal synaptic plasticity in streptozotocin-diabetic rats: effects of insulin treatment.  Brain Res. 1998;  800 125-135
  • 25 Sima A A F, Kamiya H, Li Z G. Insulin, C-peptide, hyperglycemia, and central nervous system complications in diabetes.  Eur J Pharmacol. 2004;  490 187-197
  • 26 Hasanein P, Shahidi S. Effects of Hypericum perforatum extract on diabetes-induced learning and memory impairment in rats.  Phytother Res. 2011;  25 544-549
  • 27 Nassiri-Asl M, Shariati-Rad S, Zamansoltani F. Anticonvulsive effects of intracerebroventricular administration of rutin in rats.  Prog Neuropsychopharmacol Biol Psychiatry. 2008;  32 989-993
  • 28 Fernandes A A, Novelli E L, Okoshi K, Okoshi M P, Di Muzio B P, Guimarães J F, Fernandes Junior A. Influence of rutin treatment on biochemical alterations in experimental diabetes.  Biomed Pharmacother. 2010;  64 214-219
  • 29 Youl E, Bardy G, Magous R, Cros G, Sejalon F, Virsolvy A, Richard S, Quignard J F, Gross R, Petit P, Bataille D, Oiry C. Quercetin potentiates insulin secretion and protects INS-1 pancreatic β-cells against oxidative damage via the ERK1/2 pathway.  Br J Pharmacol. 2010;  161 799-814
  • 30 Anjaneyulu M, Chopra K, Kaur I. Antidepressant activity of quercetin, a bioflavonoid, in streptozotocin-induced diabetic mice.  J Med Food. 2003;  6 391-395
  • 31 Bhutada P, Mundhada Y, Bansod K, Bhutada C, Tawari S, Dixit P, Mundhada D. Ameliorative effect of quercetin on memory dysfunction in streptozotocin-induced diabetic rats.  Neurobiol Learn Mem. 2010;  94 293-302
  • 32 Doris A, Ebmeier K, Shajahan P. Depressive illness.  Lancet. 1999;  354 1369-1375
  • 33 Khoza S, Barner J C. Glucose dysregulation associated with antidepressant agents: an analysis of 17 published case reports.  Int J Clin Pharm. 2011;  33 484-492
  • 34 Derijks H J, Meyboom R H, Heerdink E R, De Koning F H, Janknegt R, Lindquist M, Egberts A C. The association between antidepressant use and disturbances in glucose homeostasis: evidence from spontaneous reports.  Eur J Clin Pharmacol. 2008;  64 531-538

Özgür Devrim Can

Department of Pharmacology
Anadolu University, Faculty of Pharmacy

Tepebaşı

26470 Eskisehir

Turkey

Phone: +90 222 3 35 05 80 ext. 37 49

Fax: +90 222 3 35 07 50

Email: ozgurdt@anadolu.edu.tr