Antidepressant-Like Effects of Lindera obtusiloba Extracts on the Immobility Behavior of Rats in the Forced Swim Test
Lindera obtusiloba extracts are commonly used as an alternative medicine due to its numerous health benefits in Korea. However, the antidepressant-like effects of L. obtusiloba extracts have not been fully elucidated. In this study, we aimed to determine whether L. obtusiloba extracts exhibited antidepressant-like activity in rats subjected to forced swim test (FST)-induced depression. Acute treatment of rats with L. obtusiloba extracts (200 mg/kg, p.o.) significantly reduced immobility time
... immobility time and increased swimming time without any significant change in climbing. Rats treated with L. obtusiloba extracts also exhibited a decrease in the limbic hypothalamic-pituitary-adrenal (HPA) axis response to the FST, as indicated by attenuation of the corticosterone response and decreased c-Fos immunoreactivity in the hippocampus CA3 region. In addition, L. obtusiloba extracts, at concentrations that were not affected by cell viability, significantly decreased luciferase activity in response to cortisol in a concentration-dependent manner by the glucocorticoid binding assay in HeLa cells. Our findings suggested that the antidepressant-like effects of L. obtusiloba extracts were likely mediated via the glucocorticoid receptor (GR). Further studies are needed to evaluate the potential of L. obtusiloba extracts as an alternative therapeutic approach for the treatment of depression. Molecules 2016, 21, 277 2 of 10 Recently, many herbal extracts have been shown to have antidepressant-like effects in a variety of animal models. For example, Hypericum perforatum, also known as St. John's wort, is widely used for the treatment of mild to moderate depression  . Panax ginseng, commonly known as Korea Ginseng, has been investigated experimentally and clinically for its stress-attenuating activity [9,10]. Lindera obtusiloba BLUME (Lauraceae), a ubiquitous tree distributed mainly in Southeast Asia has been used in traditional Chinese medicine  . Especially, L. obtusiloba leaf or branch extracts are a remedy that is widely used in Korean traditional medicine for the treatment of liver disease, insomnia, anxiety and for improving blood circulation  . L. obtusiloba has also been reported to possess anti-inflammatory , neuroprotective  , anti-fibrotic  , and anti-hepatotoxic  effects. However, little is known about the antidepressant-like effects of L. obtusiloba extracts, and their efficacy needs to be scientifically evaluated in in vivo experiments. In the present study, the antidepressant-like effects of L. obtusiloba extracts were investigated in response to the forced swim test (FST) in rats. Moreover, to determine the neurobiological effects underlying the antidepressant-like activity of the L. obtusiloba extracts, corticosterone responses and c-Fos immunoreactivity were evaluated in rats exposed to FST. Finally, we also examined the antiglucocorticoid activity of L. obtusiloba extracts using the glucocorticoid binding assay in HeLa cells. Results Effect of L. obtusiloba Extracts on Depressant Behaviors in Response to the FST We examined the antidepressant-like effects of L. obtusiloba extracts in the FST. L. obtusiloba extract treatment in rats reduced the duration of immobility, reducing immobility by a maximum of 35.67% when administered at a dose of 200 mg/kg ( Figure 1A ). L. obtusiloba extracts also significantly increased the swimming time without any significant change in climbing ( Figure 1B ). RU 486 (10 mg/kg), which was used as the positive control, markedly decreased immobility time and increased swimming time in the FST.