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Alloxan-induced diabetic thermal hyperalgesia, prophylaxis and phytotherapeutic effects of Rheum ribes L. in mouse model

  • Karim RaafatEmail author
  • Maha Aboul-Ela
  • Abdalla El-Lakany
Research Article

Abstract

Rheum ribes L., known as Syrian rhubarb, is used in traditional Lebanese folk medicine for the treatment of diabetes. The present study aims to investigate the activities of R. ribes aqueous extract for glucose homeostasis, in vivo antioxidant and diabetic neuropathy protection in mice. The acute and the subacute effects of various doses of R. ribes on blood glucose and in vivo antioxidant activity utilizing serum catalase level (CAT) were studied in alloxan-diabetic mice. The high doses significantly lowered glucose level and increased serum CAT in alloxan-diabetic mice. Pretreatment with the extract prior to alloxination, protected the mice from acquiring diabetes and diabetic neuropathy. Treatment with the extract for 8 weeks alleviated hyperalgesia in diabetic mice. Our findings provide clinicians with promising drugs intended for the management of the symptoms of diabetic complications. The protective activity of R. ribes against acquiring diabetes and diabetic neuropathy might pave the way for preparing a prophylactic treatment for diabetes risk groups.

Keywords

Rheum ribes L. Diabetes Diabetic neuropathy Alloxan Pain In-vivo antioxidant 

Abbreviations

DM

Diabetes mellitus

RRF

Rutin rich fraction

IP

Intraperitoneal

RP

Reversed phase

DMSO

Dimethyl sulfoxide

LD50

Lethality towards 50 % of a population

ca.

Approximately

R. ribes

Rheum ribes

ROS

Reactive oxygen species

CAT

Catalase

Notes

Acknowledgments

Authors would like to thank the Junior Research Team, Department of Pharmaceutical Sciences, Faculty of Pharmacy, BAU for helping in the methodology preparation.

Conflict of interest

The authors declare that there is no conflict of interest.

References

  1. Al-Azzawie, H.F., and M.S. Alhamdani. 2006. Hypoglycemic and antioxidant effect of oleuropein in alloxan-diabetic rabbits. Life Sciences 78: 1371–1377.PubMedCrossRefGoogle Scholar
  2. Amini, M., and E. Parvaresh. 2009. Prevalence of macro- and microvascular complications among patients with type 2 diabetes in Iran: A systematic review. Diabetes Research and Clinical Practice 83: 18–25.PubMedCrossRefGoogle Scholar
  3. Arulselvan, P., and S.P. Subramanian. 2007. Beneficial effects of Murraya koenigii leaves on antioxidant defense system and ultra structural changes of pancreatic beta-cells in experimental diabetes in rats. Chemico-Biological Interactions 165: 155–164.PubMedCrossRefGoogle Scholar
  4. Bakirel, T., U. Bakirel, O.U. Keles, S.G. Ulgen, and H. Yardibi. 2008. In vivo assessment of antidiabetic and antioxidant activities of rosemary (Rosmarinus officinalis) in alloxan-diabetic rabbits. Journal of Ethnopharmacology 116: 64–73.PubMedCrossRefGoogle Scholar
  5. Chiu, C.J., and A. Taylor. 2011. Dietary hyperglycemia, glycemic index and metabolic retinal diseases. Progress in Retinal and Eye Research 30: 18–53.PubMedCrossRefGoogle Scholar
  6. Edwards, J.L., A.M. Vincent, H.T. Cheng, and E.L. Feldman. 2008. Diabetic neuropathy: Mechanisms to management. Pharmacology & Therapeutics 120: 1–34.CrossRefGoogle Scholar
  7. Harati, Y., C. Gooch, M. Swenson, S.V. Edelman, D. Greene, P. Raskin, P. Donofrio, D. Cornblath, W.H. Olson, and M. Kamin. 2000. Maintenance of the long-term effectiveness of tramadol in treatment of the pain of diabetic neuropathy. Journal of Diabetes and Its Complications 14: 65–70.PubMedCrossRefGoogle Scholar
  8. Kamalakkannan, N., and P.S. Prince. 2006. Antihyperglycaemic and antioxidant effect of rutin, a polyphenolic flavonoid, in streptozotocin-induced diabetic wistar rats. Basic & Clinical Pharmacology & Toxicology 98: 97–103.CrossRefGoogle Scholar
  9. Kamei, J., M. Ohsawa, S. Miyata, K. Endo, and H. Hayakawa. 2008. Effects of cytidine 5′-diphosphocholine (CDP-choline) on the thermal nociceptive threshold in streptozotocin-induced diabetic mice. European Journal of Pharmacology 598: 32–36.PubMedCrossRefGoogle Scholar
  10. Kasabri, V., F.U. Afifi, and I. Hamdan. 2011. In vitro and in vivo acute antihyperglycemic effects of five selected indigenous plants from Jordan used in traditional medicine. Journal of Ethnopharmacology 133: 888–896.PubMedCrossRefGoogle Scholar
  11. King, H., R.E. Aubert, and W.H. Herman. 1998. Global burden of diabetes, 1995–2025: Prevalence, numerical estimates, and projections. Diabetes Care 21: 1414–1431.PubMedCrossRefGoogle Scholar
  12. Lagani, V., L. Koumakis, F. Chiarugi, E. Lakasing, and I. Tsamardinos. 2013. A systematic review of predictive risk models for diabetes complications based on large scale clinical studies. Journal of Diabetes and Its Complications 27: 407–413.PubMedCrossRefGoogle Scholar
  13. Lopez-Alarcon, C., and A. Denicola. 2013. Evaluating the antioxidant capacity of natural products: A review on chemical and cellular-based assays. Analytica Chimica Acta 763: 1–10.PubMedCrossRefGoogle Scholar
  14. Manonmani, G., V. Bhavapriya, S. Kalpana, S. Govindasamy, and T. Apparanantham. 2005. Antioxidant activity of Cassia fistula (Linn.) flowers in alloxan induced diabetic rats. Journal of Ethnopharmacology 97: 39–42.PubMedCrossRefGoogle Scholar
  15. Maritim, A.C., R.A. Sanders, and J.B. Watkins 3rd. 2003. Diabetes, oxidative stress, and antioxidants: A review. Journal of Biochemical and Molecular Toxicology 17: 24–38.PubMedCrossRefGoogle Scholar
  16. Nammi, S., M.K. Boini, S.D. Lodagala, and R.B. Behara. 2003. The juice of fresh leaves of Catharanthus roseus Linn. reduces blood glucose in normal and alloxan diabetic rabbits. BMC Complementary and Alternative Medicine 3: 4.PubMedCentralPubMedCrossRefGoogle Scholar
  17. Naqishbandi, A.M., K. Josefsen, M.E. Pedersen, and A.K. Jäger. 2009. Hypoglycemic activity of Iraqi Rheum ribes root extract. Pharmaceutical Biology 47: 380–383.CrossRefGoogle Scholar
  18. Oktay, M., A. Yildirim, V. Bilaloglu, and I. Gulcin. 2007. Antioxidant activity of different parts of isgin (Rheum ribes L.). Asian Journal of Chemistry 19: 3047–3055.Google Scholar
  19. Özbek, H., E. Ceylan, M. Kara, F. Özgökçe, and M. Koyuncu. 2004a. Hypoglycemic effect of Rheum ribes roots in alloxan induced diabetic and normal mice. Scandinavian Journal of Laboratory Animal Science 31: 113–115.Google Scholar
  20. Özbek, H., E. Ceylan, M. Kara, F. Özgökçe, and M. Koyuncu. 2004b. Hypoglycemic effect of Rheum ribes roots in alloxan induced diabetic and normal mice. Scandinavian Journal of Laboratory Animal Science 31: 113–115.Google Scholar
  21. Ozturk, M., F. Aydogmus-Ozturk, M.E. Duru, and G. Topcu. 2007. Antioxidant activity of stem and root extracts of Rhubarb (Rheum ribes): An edible medicinal plant. Food Chemistry 103: 623–630.CrossRefGoogle Scholar
  22. Punitha, I.S., K. Rajendran, and A. Shirwaikar. 2005. Alcoholic stem extract of Coscinium fenestratum regulates carbohydrate metabolism and improves antioxidant status in streptozotocin-nicotinamide induced diabetic rats. Evidence-Based Complementary and Alternative Medicine 2: 375–381.PubMedCentralPubMedCrossRefGoogle Scholar
  23. Quattrini, C., and S. Tesfaye. 2003. Understanding the impact of painful diabetic neuropathy. Diabetes/Metabolism Research and Reviews 19(Suppl 1): S2–S8.PubMedCrossRefGoogle Scholar
  24. Raafat, K., R. Boukhary, M. Aboul-Ela, and A. El-Lakany. 2013a. Endogenous Lebanese plants treating diabetes and related complications. Natural Products Chemistry & Research 1: 112–120.Google Scholar
  25. Raafat, K., U. Breitinger, L. Mahran, N. Ayoub, and H.-G. Breitinger. 2010. Synergistic inhibition of glycinergic transmission in vitro and in vivo by Flavonoids and strychnine. Toxicological Sciences 118: 171–182.PubMedCrossRefGoogle Scholar
  26. Raafat, K.M., H. Jassar, M. Aboul-Ela, and A. El-Lakany. 2013b. Protective effects of Origanum majorana L. against neurodegeneration: Fingerprinting, isolation and in vivo glycine receptors behavioral model. Inernational Journal of Phytomedicine 5: 46–57.Google Scholar
  27. Rahimi, R., S. Nikfar, B. Larijani, and M. Abdollahi. 2005. A review on the role of antioxidants in the management of diabetes and its complications. Biomedicine & Pharmacotherapy 59: 365–373.CrossRefGoogle Scholar
  28. Reddy, G.B., and N. Dhananjaya. 2000. Chemical investigation of Mycale mytilorum and a study on toxicity and antidiabetic activity of 5-octadecylpyrrole-2-carboxaldehyde. Bioorganic & Medicinal Chemistry 8: 27–36.CrossRefGoogle Scholar
  29. Roy, S., R. Sehgal, B.M. Padhy, and V.L. Kumar. 2005. Antioxidant and protective effect of latex of Calotropis procera against alloxan-induced diabetes in rats. Journal of Ethnopharmacology 102: 470–473.PubMedCrossRefGoogle Scholar
  30. Russell-Jones, D., and R. Khan. 2007. Insulin-associated weight gain in diabetes—Causes, effects and coping strategies. Diabetes, Obesity & Metabolism 9: 799–812.CrossRefGoogle Scholar
  31. Said, G. 2007. Diabetic neuropathy—A review. Nature Clinical Practice Neurology 3: 331–340.PubMedCrossRefGoogle Scholar
  32. Saravanan, R., and L. Pari. 2005a. Antihyperlipidemic and antiperoxidative effect of Diasulin, a polyherbal formulation in alloxan induced hyperglycemic rats. BMC Complementary and Alternative Medicine 5: 1–8.CrossRefGoogle Scholar
  33. Saravanan, R., and L. Pari. 2005b. Antihyperlipidemic and antiperoxidative effect of Diasulin, a polyherbal formulation in alloxan induced hyperglycemic rats. BMC Complementary and Alternative Medicine 5: 14.PubMedCentralPubMedCrossRefGoogle Scholar
  34. Sepici-Dincel, A., S. Acikgoz, C. Cevik, M. Sengelen, and E. Yesilada. 2007. Effects of in vivo antioxidant enzyme activities of myrtle oil in normoglycaemic and alloxan diabetic rabbits. Journal of Ethnopharmacology 110: 498–503.PubMedCrossRefGoogle Scholar
  35. Stanley Mainzen Prince, P., and N. Kamalakkannan. 2006. Rutin improves glucose homeostasis in streptozotocin diabetic tissues by altering glycolytic and gluconeogenic enzymes. Journal of Biochemical and Molecular Toxicology 20: 96–102.PubMedCrossRefGoogle Scholar
  36. Tesfaye, S. 2009. Advances in the management of diabetic peripheral neuropathy. Current Opinion in Supportive and Palliative Care 3: 136–143.PubMedCrossRefGoogle Scholar
  37. Tesfaye, S., A.J. Boulton, P.J. Dyck, R. Freeman, M. Horowitz, P. Kempler, G. Lauria, R.A. Malik, V. Spallone, A. Vinik, L. Bernardi, and P. Valensi. 2010. Diabetic neuropathies: Update on definitions, diagnostic criteria, estimation of severity, and treatments. Diabetes Care 33: 2285–2293.PubMedCentralPubMedCrossRefGoogle Scholar
  38. Tesfaye, S., and D. Selvarajah. 2012. Advances in the epidemiology, pathogenesis and management of diabetic peripheral neuropathy. Diabetes/Metabolism Research and Reviews 28(Suppl 1): 8–14.PubMedCrossRefGoogle Scholar
  39. Tosun, F., and Ç.A. Kizilay. 2003. Anthraquinone and flavonoids from Rheum ribes. Journal of Faculty of Pharmacy of Ankara 32: 31–35Google Scholar
  40. Türkmen, Ö., M. Çirka, and S. Şensoy. 2005. Initial evaluation of a New Edible Wild Rhubarb Species (Rheum ribes L.) with a Modified Weighted Scaling Index method. Pakistan Journal of Biological Sciences 8: 763–765.CrossRefGoogle Scholar
  41. Ueno, Y., Koike, H., Annoh, S., and Nishio, S. 1996. Effects of beraprost sodium, a prostacyclin analogue, on tail flick response in two models of diabetic-neuropathy in rats and its mechanism. Life Science 59: PL105–PL110.Google Scholar
  42. Ulugol, A., C. Oltulu, O. Gunduz, C. Citak, R. Carrara, M.R. Shaqaqi, A.M. Sanchez, and A. Dogrul. 2012. 5-HT7 receptor activation attenuates thermal hyperalgesia in streptozocin-induced diabetic mice. Pharmacology, Biochemistry and Behavior 102: 344–348.PubMedCrossRefGoogle Scholar
  43. Vinik, A.I., V. Bril, P. Kempler, W.J. Litchy, S. Tesfaye, K.L. Price, and E.J. Bastyr III. 2005. Treatment of symptomatic diabetic peripheral neuropathy with the protein kinase C beta-inhibitor ruboxistaurin mesylate during a 1-year, randomized, placebo-controlled, double-blind clinical trial. Clinical Therapeutics 27: 1164–1180.PubMedCrossRefGoogle Scholar
  44. Yasmineh, W.G., T.P. Kaur, B.R. Blazar, and A. Theologides. 1995. Serum catalase as marker of graft-vs-host disease in allogeneic bone marrow transplant recipients: Pilot study. Clinical Chemistry 41: 1574–1580.PubMedGoogle Scholar

Copyright information

© The Pharmaceutical Society of Korea 2014

Authors and Affiliations

  • Karim Raafat
    • 1
    Email author
  • Maha Aboul-Ela
    • 1
  • Abdalla El-Lakany
    • 1
  1. 1.Department of Pharmaceutical Sciences, Faculty of PharmacyBeirut Arab University (BAU)BeirutLebanon

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