Panax ginseng exerts antidepressant-like effects by suppressing neuroinflammatory response and upregulating nuclear factor erythroid 2 related factor 2 signaling in the amygdala.

J Ginseng Res. 2018 Jan;42(1):107-115. doi: 10.1016/j.jgr.2017.04.012. Epub 2017 Apr 29. Choi JH1,2, Lee MJ3, Jang M3, Kim HJ4, Lee S5, Lee SW6, Kim YO6, Cho IH1,2,3,7. Author information 1 Department of Science in Korean Medicine, Graduate School, Kyung Hee University, Seoul, Republic of Korea. 2 Brain Korea 21 Plus Program, Graduate School, Kyung Hee University, Seoul, Republic of Korea. 3 Department of Convergence Medical Science, College of Korean Medicine, Kyung Hee University, Seoul, Republic of Korea. 4 Department of Clinical Pharmacology, College of Medicine, Soonchunhyang University, Cheonan, Republic of Korea. 5 Department of Integrative Plant Science, Chung-Ang University, Anseong, Republic of Korea. 6 Department of Medicinal Crop Research Institute, National Institute of Horticultural and Herbal Science, Rural Development Administration, Eumseong, Republic of Korea. 7 Institute of Korean Medicine, College of Korean Medicine, Kyung Hee University, Seoul, Republic of Korea. Abstract Background: Depression is one of the most commonly diagnosed neuropsychiatric diseases, but the underlying mechanism and medicine are not well-known. Although Panax ginseng has been reported to exert protective effects in various neurological studies, little information is available regarding its antidepressant effects. Methods: Here, we examined the antidepressant effect and underlying mechanism of P. ginseng extract (PGE) in a chronic restraint stress (CRS)-induced depression model in mice. Results: Oral administration of PGE for 14 d decreased immobility (depression-like behaviors) time in forced swim and tail suspended tests after CRS induction, which corresponded with attenuation of the levels of serum adrenocorticotropic hormone and corticosterone, as well as attenuated c-Fos expression in the amygdala. PGE enhanced messenger RNA expression level of brain-derived neurotrophic factor but ameliorated microglial activation and neuroinflammation (the level of messenger RNA and protein expression of cyclooxygenase-2 and inducible nitric oxide synthase) in the amygdala of mice after CRS induction. Interestingly, 14-d treatment with celecoxib, a selective cyclooxygenase-2 inhibitor, and Nω-nitro-L-arginine methyl ester hydrochloride, a selective inducible nitric oxide synthase inhibitor, attenuated depression-like behaviors after CRS induction. Additionally, PGE inhibited the upregulation of the nuclear factor erythroid 2 related factor 2 and heme oxygenase-1 pathways. Conclusion: Taken together, our findings suggest that PGE exerts antidepressant-like effect of CRS-induced depression by antineuroinflammatory and antioxidant (nuclear factor erythroid 2 related factor 2/heme oxygenase-1 activation) activities by inhibiting the hypothalamo-pituitary-adrenal axis mechanism. Further studies are needed to evaluate the potential of components of P. ginseng as an alternative treatment of depression, including clinical trial evaluation. KEYWORDS: Panax ginseng; antineuroinflammation; chronic restraint stress; depression; nuclear factor erythroid 2 related factor 2