Symptoms of sad mood, hopelessness, loss of interest and pleasure, insomnia, feeling of worthlessness and suicidal thoughts indicate depression. 1 It affects more than 280 million people worldwide. 2 Depression may be due to deficiency of monoamine neurotransmitters, dysregulation of HPA (hypothalamic-pituitary-adrenal axis), neuroinflammation and oxidative stress. [3][4][5][6] Continued exposure to stress increases oxidative stress and produced neuroinflammation in brain of humans; which may lead to depression. 7 Chronic unpredictable mild stress (CUMS) is commonly employed model to induce depression in laboratory animals. 8 CUMS leads to anhedonia, increased anxiety-like behavior, and hyperactivity of HPA axis in rodents. 9 The conventional antidepressants presently used to treat depression in allopathic system of medicine have many side effects like body weight gain, sexual dysfunction, sedation, fatigue, etc. 10 Some plants like Hypericum perforatum, Melissa officinalis; bioactive compounds such as crocin, and glycyrrhizic acid, etc. have been reported to alleviate depression in clinical trials. 11-14 Thus, there is strong need for discovering plant-based antidepressants having equal effectiveness to Allopathic medications with no or less side effects. 15 Gentisic acid, also known as 2,5-dihydroxybenzoic acid, is found in citrus fruits (Citrus species), Gentiana species, Vitis vinifera, red sandal wood (Pterocarpus santalinus), Hibiscus rosa-sinensis, Olea europaea, Sesamum indicum, Madagascar rosy periwinkle, avocados, kiwi and apples. [16][17] Gentisic acid has anti-Alzheimer, anti-Parkinsonian, antioxidant, antiinflammatory and cardioprotective properties. [18][19][20][21][22] Since gentisic acid possesses antioxidant and neuroprotective activities, so the current research was intended to study effect of gentisic acid on depressive behavior in normal mice and also stressed mice.
MATERIALS AND METHODS
AnimalsSwiss albino male mice (28-32 g, 2-3 months old) were used in the current research study. Since estrogens possesses antidepressant activity, that is why female mice were excluded. 23 The animals were kept in cages (n = 8 each) in an air-conditioned room (temperature 24-25°C) with twelve hours light and twelve hours dark cycle. The number of mice to be used for research study were approved by Institutional Animals Ethics Committee in the meeting held on March 4, 2020 (IAEC Minutes letter No. IAEC/2020/10-18, dated 04 th March, 2020).
Drugs and chemicalsGentisic acid was procured from Hi-media Laboratories Pvt. Ltd. (Mumbai). It was suspended in 1% w/v carboxy methyl cellulose (CMC). Fluoxetine was purchased from Sigma-Aldrich, St Louis, USA. Fluoxetine was dissolved in normal saline. Other chemicals employed were of analytical grade.
CUMS procedureAccording to Willner et al. (1992) and as followed earlier in our laboratory, "Mice were given variable sequence of following mild unpredictable stressors once a day between 10:30 and 16:00 hr for 21 days: