title: Synergistic antidiabetic activity of Vernonia amygdalina and Azadirachta indica: biochemical effects and possible mechanism.
abstract: BACKGROUND
  A decoction from a combination of herbs is commonly used in Traditional African Medicine for the management of chronic ailments. In Nigeria, the leaves of Vernonia amygdalina Del. (VA) and Azadirachta indica A. Juss (AI) are used traditionally as a remedy against diabetes mellitus for which empirical evidence attests to its efficacy.
  
  
  OBJECTIVE
  To evaluate the synergistic antidiabetic action of VA and AI, the biochemical effects and possible mechanism in streptozotocin-induced diabetic rat (SDR) models.
  
  
  METHODS
  Ethanolic extracts of VA and AI were co-administered (200 mg/kg, 50:50) to non-diabetic rats (NDRs) and SDRs for 28 days. Blood glucose and body weight were monitored during this period, and at end of treatment, serum glucose, insulin, triiodothyronine (T3), tetraiodothyronine (T4) and α-amylase activity were studied. Glucose and activities of antioxidant enzymes, e.g., catalase (CAT), glutathione peroxidase (GPx) and superoxide dismutase (SOD), were estimated in hepatocytes, along with the impact on the histology of the liver and pancreas. Medium acting insulin, HU (5 IU/kg, s.c.) was used as a positive control.
  
  
  RESULTS
  The study reveals that compared with single extracts, the combined extract (VA/AI) promptly lowered blood glucose and maintained a relatively steady level over the study period, in tandem with HU. During this period, body weight gain successively increased. In SDRs, fasting blood glucose at days 0 and 28 was raised by 4.33 and 3.16 fold, respectively, and the serum glucose was raised by 7.70 fold vs. normal control (P<0.05). The discrepancies in the individual effects of VA and AI on hepatic glucose and α-amylase activity were also restored. In NDRs, VA/AI lowered blood and serum glucose (1.14 and 1.94 fold, respectively), although to a lesser extent when compared with HU. Furthermore, VA/AI was found to lower serum insulin, T3 and T4 by 1.66, 1.57 and 2.16 fold, respectively, in SDR (P<0.05). This was similar to HU, which demonstrated 1.79 and 1.68 fold reduction of insulin and T3, respectively (P<0.05), but had no effect on T4. Conversely, in NDRs, VA/AI caused 1.32, 4.93 and 1.04 fold increase in insulin, T3 and T4, respectively, reciprocal to its effect on blood and serum glucose. Oxidative stress in SDR, characterised by decreased GPx and CAT activities, was ameliorated, as the activities of the enzymes and SOD increased following a 28-day treatment with VA/AI (P<0.05). The features of diabetic pathology, indicated in the histology of the liver and pancreas, were reversed. However, the extent of recovery was partial with VA, better with AI, and distinct and total with VA/AI, compared with a null effect by HU.
  
  
  CONCLUSIONS
  Taken together, our results contribute towards validation of enhanced antidiabetic efficacy of VA and AI when combined. This synergy may be exerted by oxidative stress attenuation, insulin mimetic action and β-cell regeneration.
authors.affiliation: Department of Biochemistry, College of Medical Sciences, University of Calabar, P. M. B. 1115, Calabar, Nigeria. aijustyno@yahoo.com
authors.forename: Item Justin
authors.initials: IJ
authors.lastname: Atangwho
authors.forename: Patrick Ekong
authors.initials: PE
authors.lastname: Ebong
authors.forename: Eyong Ubana
authors.initials: EU
authors.lastname: Eyong
authors.forename: Mohd Zaini
authors.initials: MZ
authors.lastname: Asmawi
authors.forename: Mariam
authors.initials: M
authors.lastname: Ahmad
mesh_terms: D000818:Animals; D031601:Azadirachta; D001786:Blood Glucose / Q000032:analysis; D002374:Catalase / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D004357:Drug Synergism; D005979:Glutathione Peroxidase / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007328:Insulin / Q000097:blood; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D010179:Pancreas / Q000187:drug effects / Q000473:pathology; D008517:Phytotherapy; D018515:Plant Leaves; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000378:metabolism; D013974:Thyroxine / Q000097:blood; D014284:Triiodothyronine / Q000097:blood; D035741:Vernonia; D000516:alpha-Amylases / Q000097:blood
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D014284:Triiodothyronine; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D000516:alpha-Amylases; D013974:Thyroxine