Cordia dichotoma Fruits Aqueous Extracts Alleviates Depressive-Like Behavior in a Rat Model via Regulating Serotonergic Neurotransmitters

Depression is a common mental illness caused by the interaction of social, psychological, and physical factors. The number of people suffering from depression is continuously increasing worldwide. However, currently available medications are mostly with unwanted side effects and undesirable pharmacodynamic responses, which usually prompt patients to leave treatment. Cordia dichotoma G.Forst., Boraginaceae, is a medicinal plant that contains rosmarinic acid, which alleviates depressive syndromes and anxiety. This study aims to investigate the antidepressant effects of the aqueous extract of C. dichotoma fruits through observing its impact on changes of depression-like behaviors and the relevant neurotransmitters in a chronic unpredictable mild stress rat model of depression. Rosmarinic acid was quantified by high-performance liquid chromatography. The chronic unpredictable mild stress-induced rats treated with the aqueous extract showed typical anti-depressive-like behavior, including a significant increase in sucrose consumption in the sucrose preference test, a significant reduction in the immobility time both in the open field test and forced swimming test, and an increase in swimming time in the forced swimming test. Besides, LC–MS/MS analysis showed that the serotonin turnover rate (5-HIAA/5-HT) was significantly reduced in frontal cortex, amygdala, hippocampus, and striatum tissue among treated rats. The study provides the first in vivo evidence of possible mechanisms of modulating anti-depressive-like activity through regulating the turnover rate of serotoninergic neurotransmitter via monoamine oxidase inhibition by rosmarinic acid. These findings provide a novel and solid evidence for a new application of the medicinal plant C. dichotoma fruits in combating depression and may open possibilities for developing new antidepressants of plant origin.