JOURNAL OF MEDICINAL FOOD J Med Food 6 (4) 2003, 391–395 © Mary Ann Liebert, Inc. and Korean Society of Food Science and Nutrition Antidepressant Activity of Quercetin, a Bioflavonoid, in Streptozotocin-Induced Diabetic Mice Muragundla Anjaneyulu, 1 Kanwaljit Chopra, 1 and Indupal Kaur 2 Departments of 1 Pharmacology and 2 Pharmaceutics, University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh, India ABSTRACT Depression is highly prevalent in diabetics and is associated with poor glucose regulation and increased risk of diabetic complications. Identification and effective treatment of comorbid depression are increasingly being considered es- sential components of clinical care of diabetics. In the present study, the antidepressant activity of quercetin (50 and 100 mg/kg, i.p.), a bioflavonoid, was evaluated using the Porsolt forced swimming-induced behavioral despair test in control and 6-week-streptozotocin-induced diabetic mice. The effect of quercetin was compared with that of the classical antidepressants fluoxetine (5 mg/kg, i.p.) and imipramine (15 mg/kg, i.p.). Streptozotocin-induced diabetic mice exhibited prolonged immo- bility duration during the test as compared with age-matched control mice. Quercetin dose-dependently reduced the immo- bility period in diabetic mice, and this effect was comparable to that of fluoxetine (5 mg/kg, i.p.) and imipramine (15 mg/kg, i.p.). Fluoxetine and imipramine significantly lowered the immobility time in naive mice also, but quercetin failed to induce any antidepressant activity in naive mice. The results of our preliminary study indicate that quercetin has the potential to be employed as a therapy for depression associated with diabetes. KEY WORDS:  diabetic depression  fluoxetine  imipramine  quercetin  streptozotocin 391 INTRODUCTION M ENTAL DEPRESSION represents a major public health problem worldwide. According to World Health Or- ganization estimates, 100 million people worldwide suffer from major depression at any given time. Depression is sig- nificantly more prevalent in diabetes, affecting 15–20% of patients with either the insulin-dependent or non–insulin-de- pendent type. 1 Several reports reveal that the presence of di- abetes doubles the odds of comorbid depression. 2 Depres- sion is known to have a profound adverse influence on patients’ quality of life and overall functioning. It has addi- tional relevance in diabetes because of its association with poor glucose control. 3 Recent studies also indicate that de- pression in diabetes is associated with increased occurrence of neuropathy, nephropathy, retinopathy, and macrovascu- lar disease. 4 Reviews on treatment of depression in diabet- ics have revealed that classical antidepressants such as monoamine oxidase (MAO) inhibitors induce hypoglycemia and weight gain, whereas tricyclics lead to hyperglycemia and carbohydrate craving. 5 Thus there is a constant quest to identify newer antidepressants with greater efficacy and fewer side effects to treat diabetic depression. Renewed interest has been observed in recent years on novel multiple activities of flavonoids. Flavonoids are plant phenolic compounds with strong antioxidant properties found in various dietary sources such as tea, onions, broccoli, apples, and green beans. 6 Quercetin (3,5,7,3 9, 49-pentahydroxyflavone) is a widely distributed potent bioflavonoid present in various vegetables and fruits. Ex- tracts of a medicinal plant, Hypericum perforatum (St. John’s wort), are commonly used in many countries for the treatment of mild to moderate forms of depression. 7–9 A re- cent meta-analysis of 23 randomized clinical trials indicated that Hypericum extract was effective and the incidence of side effects was very low as compared with tricyclic anti- depressants and selective serotonin reuptake inhibitors. It has been reported that quercetin inhibits catechol-O-methyl transferase (COMT) and MAO enzymes, 10,11 which are the key enzymes responsible for metabolism of catecholamines in the brain. Thinking on the lines of Hypericum success, the present study was thus designed to evaluate the antidepressant ac- tivity of quercetin in streptozotocin (STZ)-induced diabetic mice. MATERIALS AND METHODS Animals Male Laka mice (weighing 20–30 g) bred in the Animal House Facility of Panjab University were used in the pres- Received 3 June 2003. Accepted 3 July 2003. Address reprint requests to: Dr. Kanwaljit Chopra, Pharmacology Division, University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh-160014, India, E-mail: dr_chopra_k@yahoo.com