Morin mitigates Chronic and Unpredictable Mild Stress-Induced Depression by Regulation of Endoplasmic Reticulum Stress and Brain-Derived Neurotrophic Factor-Mediated Apoptosis

Abstract

According to the report of World Health Organization, it is expected that depression will be one of the major causes for disability and disease in the world, by 2030. Currently used drugs will not be effective to the depressive patients, due to their lower efficiency with side effects. Hence, there is a need to concentrate on natural products to overcome therapeutic hassles. Morin, a bioflavonoid found in fruits, vegetables, some herbs and wine is reported to have an antidepressant-like effect against acute stress conditions. It is reported to possess various pharmacological properties such as antioxidant, anti-diabetic, hepatoprotective, anti-cancer and anti-inflammatory activities. To understand the antidepressant effect of morin against unpredicted chronic mild stress (UCMS), rats were divided into normal, UCMS alone, UCMS and morin (30 & 60 mg/kg) and morin alone (60 mg/kg) groups. Serum corticosterone levels, expression of brain derived neurotrophic factor (BDNF), apoptotic and endoplasmic reticulum (ER) stress related indices were compared among the groups. UCMS alone exposed rats showed less crossings with diminished activities in open field test (OFT), increased serum corticosterone levels and enhanced expression of BDNF signaling and ER stress related markers associated with apoptosis as compared to control. In contrast, morin (60 mg/kg b.w.) cotreatment attenuated UCMS induced abnormalities as compared to UCMS alone exposed animals. The present results indicated the antidepressant-like actions of morin against UCMS in rats were partially due to its anti-apoptotic effects by regulating BDNF/Trk-B and ER stress related markers. Moreover the results of the present study indicated that the morin may act as therapeutic agent for the management of depression alone or with other currently used antidepressants.