Glehnia littoralis Extract Promotes Neurogenesis in the Hippocampal Dentate Gyrus of the Adult Mouse through Increasing Expressions of Brain-Derived Neurotrophic Factor and Tropomyosin-Related Kinase B
Joon Ha Park1, Bich Na Shin2, Ji Hyeon Ahn1, Jeong Hwi Cho2, Tae-Kyeong Lee2, Jae-Chul Lee2, Yong Hwan Jeon3, Il Jun Kang4, Ki-Yeon Yoo5, In Koo Hwang6, Choong Hyun Lee7, Yoo Hun Noh8, Sung-Su Kim8, Moo-Ho Won2, Jong Dai Kim9
1 Department of Biomedical Science and Research Institute for Bioscience and Biotechnology, Hallym University, Chuncheon 24252, Korea
2 Department of Neurobiology, School of Medicine, Kangwon National University, Chuncheon 24341, Korea
3 Department of Radiology, School of Medicine, Kangwon National University, Chuncheon 24341, Korea
4 Department of Food Science and Nutrition, Hallym University, Chuncheon 24252, Korea
5 Department of Oral Anatomy, College of Dentistry and Research Institute of Oral Biology, Gangneung-Wonju National University, Gangneung 25457, Korea
6 Department of Anatomy and Cell Biology, College of Veterinary Medicine, and Research Institute for Veterinary Science, Seoul National University, Seoul 08826, Korea
7 Department of Pharmacy, College of Pharmacy, Dankook University, Cheonan 31116, Korea
8 Famenity Biomedical Research Center, Famenity, Inc., Gyeonggi 13837, Korea
9 Division of Food Biotechnology, School of Biotechnology, Kangwon National University, Chuncheon 24341, Korea
Prof. Jong Dai Kim
Division of Food Biotechnology, School of Biotechnology, Kangwon National University, Chuncheon 24341
Prof. Moo-Ho Won
Department of Neurobiology, School of Medicine, Kangwon National University, Chuncheon 24341
Source of Support: None, Conflict of Interest: None
Background: Glehnia littoralis has been used for traditional Asian medicine, which has diverse therapeutic activities. However, studies regarding neurogenic effects of G. littoralis have not yet been considered. Therefore, in this study, we examined effects of G. littoralis extract on cell proliferation, neuroblast differentiation, and the maturation of newborn neurons in the hippocampus of adult mice.
Methods: A total of 39 male ICR mice (12 weeks old) were randomly assigned to vehicle-treated and 100 and 200 mg/kg G. littoralis extract-treated groups (n = 13 in each group). Vehicle and G. littoralis extract were orally administrated for 28 days. To examine neurogenic effects of G. littoralis extract, we performed immunohistochemistry for 5-bromo-2-deoxyuridine (BrdU, an indicator for cell proliferation) and doublecortin (DCX, an immature neuronal marker) and double immunofluorescence staining for BrdU and neuronal nuclear antigen (NeuN, a mature neuronal marker). In addition, we examined expressional changes of brain-derived neurotrophic factor (BDNF) and its major receptor tropomyosin-related kinase B (TrkB) using Western blotting analysis.
Results: Treatment with 200 mg/kg, not 100 mg/kg, significantly increased number of BrdU-immunoreactive (+) and DCX+ cells (48.0 ± 3.1 and 72.0 ± 3.8 cells/section, respectively) in the subgranular zone (SGZ) of the dentate gyrus (DG) and BrdU+/NeuN+ cells (17.0 ± 1.5 cells/section) in the granule cell layer as well as in the SGZ. In addition, protein levels of BDNF and TrkB (about 232% and 244% of the vehicle-treated group, respectively) were significantly increased in the DG of the mice treated with 200 mg/kg of G. littoralis extract.
Conclusion: G. littoralis extract promots cell proliferation, neuroblast differentiation, and neuronal maturation in the hippocampal DG, and neurogenic effects might be closely related to increases of BDNF and TrkB proteins by G. littoralis extract treatment.