Original article Antidepressant like effects of hydrolysable tannins of Terminalia catappa leaf extract via modulation of hippocampal plasticity and regulation of monoamine neurotransmitters subjected to chronic mild stress (CMS) Y. Chandrasekhar, E.M. Ramya, K. Navya, G. Phani Kumar*, K.R. Anilakumar Applied Nutrition Division, Defence Food Research Laboratory, DRDO, Mysore 570011, Karnataka, India A R T I C L E I N F O Article history: Received 8 November 2016 Received in revised form 29 November 2016 Accepted 5 December 2016 Keywords: Chronic mild stress Terminalia catappa Hippocampus BDNF Hydrolysable tannins A B S T R A C T Terminalia catappa L. belonging to Combretaceae family is a folk medicine, known for its multiple pharmacological properties, but the neuro-modulatory effect of TC against chronic mild stress was seldom explored. The present study was designed to elucidate potential antidepressant-like effect of Terminalia cattapa (leaf) hydro-alcoholic extract (TC) by using CMS model for a period of 7 weeks. Identification of hydrolysable tannins was done by using LC–MS. After the CMS exposure, mice groups were administered with imipramine (IMP, 10 mg/kg, i.p.) and TC (25, 50 and 100 mg/kg of TC, p.o.). Behavioural paradigms used for the study included forced swimming test (FST), tail suspension test (TST) and sucrose preference test (SPT). After behavioural tests, monoamine neurotransmitter, cortisol, AchE, oxidative stress levels and mRNA expression studies relevant to depression were assessed. TC supplementation significantly reversed CMS induced immobility time in FST and other behavioural paradigms. Moreover, TC administration significantly restored CMS induced changes in concentrations of hippocampal neurotransmitters (5-HT, DA and NE) as well as levels of acetyl cholinesterase, cortisol, monoamine oxidases (MAO-A, MAO-B), BDNF, CREB, and p-CREB. It suggests that TC supplementation could supress stress induced depression by regulating monoamine neurotransmitters, CREB, BDNF, cortisol, AchE level as well as by amelioration of oxidative stress. Hence TC can be used as a complementary medicine against depression-like disorder. © 2016 Elsevier Masson SAS. All rights reserved. 1. Introduction Terminalia catappa Linn (Combretaceae) is also known as Indian almond. The phytochemicals of T. catappa leaf contain chebulagic acid, corilagin, kaempferol, punicalagin, punicalin, quercetin, tercatain, tergallagin, terflavin A, and terflavin B [1]. Early studies indicate that T.catappa has multiple pharmacological properties such are anticancer, wound healing, antidiabetic, anti-inflamma- tory, analgesic, immunomodulatory, hepatoprotective, and aphro- disiac [2]. The leaves of this plant have been used as a folk medicine for treating dermatitis and hepatitis in India and Philippines, but the neuro-modulatory effect of TC against chronic mild stress was seldom explored. Depression is more prevalent in aged people and considered as one of the serious psychiatric disorders [3]. World health organisation (WHO) has revealed that depression is fourth leading cause of disability worldwide and it also predicts that depression will be second leading cause by 2020 [3]. Stress can be characterised by changes in mental status induced by psychologi- cal, physiological or environmental stressors which leading to a state of threatened homeostasis [4]. Chronic mild stress (CMS) is an experimental rodent model aimed at evaluating the progress of stress patho-physiology induced by to mild and unpredictable stressors [5]. CMS model of depression has high validity, since CMS exposed animal exhibits a wide variety of behavioural changes mimicking features of most human depressive states [6,7]. Depressive disorders are generally characterized by hyperactivity of hypothalamic–pituitary–adrenal (HPA) axis and * Corresponding author. E-mail addresses: sekhar268@gmail.com (Y. Chandrasekhar), phani_bot@rediffmail.com (G. Phani Kumar), anilakumarkr@gmail.com (K.R. Anilakumar). http://dx.doi.org/10.1016/j.biopha.2016.12.031 0753-3322/© 2016 Elsevier Masson SAS. All rights reserved. Biomedicine & Pharmacotherapy 86 (2017) 414–425 Available online at ScienceDirect www.sciencedirect.com