Preventive effects of Salvia officinalis L. against learning and memory deficit induced by diabetes in rats: Possible hypoglycaemic and antioxidant mechanisms

Neurosci Lett. 2016 May 27:622:72-7. doi: 10.1016/j.neulet.2016.04.045. Epub 2016 Apr 22.


Learning and memory impairment occurs in diabetes. Salvia officinalis L. (SO) has been used in Iranian traditional medicine as a remedy against diabetes. We hypothesized that chronic administration of SO (400, 600 and 800mg/kg, p.o.) and its principal constituent, rosmarinic acid, would affect on passive avoidance learning (PAL) and memory in streptozocin-induced diabetic and non-diabetic rats. We also explored hypoglycemic and antioxidant activities of SO as the possible mechanisms. Treatments were begun at the onset of hyperglycemia. PAL was assessed 30days later. Retention test was done 24h after training. At the end, animals were weighed and blood samples were drawn for further analyzing of glucose and oxidant/antioxidant markers. Diabetes induced deficits in acquisition and retrieval processes. SO (600 and 800mg/kg) and rosmarinic acid reversed learning and memory deficits induced by diabetes and improved cognition of healthy rats. While the dose of 400mg/kg had no effect, the higher doses and rosmarinic acid inhibited hyperglycemia and lipid peroxidation as well as enhanced the activity of antioxidant enzymes superoxide dismutase and catalase. SO prevented diabetes-induced acquisition and memory deficits through inhibiting hyperglycemia, lipid peroxidation as well as enhancing antioxidant defense systems. Therefore, SO and its principal constituent rosmarinic acid represent a potential therapeutic option against diabetic memory impairment which deserves consideration and further examination.

Keywords: Diabetes; Hyperglycemia; Learning; Lipid peroxidation; Memory; Salvia officinalis L.

MeSH terms

  • Animals
  • Antioxidants / pharmacology*
  • Antioxidants / therapeutic use
  • Avoidance Learning / drug effects
  • Cinnamates / pharmacology
  • Depsides / pharmacology
  • Diabetes Mellitus, Experimental / drug therapy*
  • Diabetes Mellitus, Experimental / metabolism
  • Diabetes Mellitus, Experimental / psychology
  • Hypoglycemic Agents / pharmacology*
  • Hypoglycemic Agents / therapeutic use
  • Learning Disabilities / drug therapy*
  • Learning Disabilities / psychology
  • Male
  • Memory / drug effects
  • Memory Disorders / drug therapy*
  • Memory Disorders / psychology
  • Oxidative Stress / drug effects
  • Plant Extracts / pharmacology*
  • Plant Extracts / therapeutic use
  • Rats, Wistar
  • Retention, Psychology / drug effects
  • Salvia officinalis / chemistry*


  • Antioxidants
  • Cinnamates
  • Depsides
  • Hypoglycemic Agents
  • Plant Extracts
  • rosmarinic acid