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J Chem Neuroanat. 2019 Jul;98:27-40. doi: 10.1016/j.jchemneu.2019.03.005. Epub 2019 Apr 2.

Improvement in neurogenesis and memory function by administration of Passiflora incarnata L. extract applied to sleep disorder in rodent models.

Author information

1
Department of Biomedical Laboratory Science, College of Medical Sciences, Soonchunhyang University, Asan, 31538, Republic of Korea.
2
Department of Medical Biotechnology, College of Medical Sciences, Soonchunhyang University, Asan, 31538, Republic of Korea.
3
Department of Obstetrics and Gynecology, Soonchunhyang University, College of Medicine, Bucheon, 14584, Republic of Korea.
4
Soonchunhyang Institute of Medi-bio Science, Soonchunhyang University, Cheonan, 31151, Republic of Korea.
5
Department of Anatomy and Cell Biology, College of Veterinary Medicine, Seoul National University, Seoul, Republic of Korea.
6
Department of Health Science, Konyang University, Nonsan, 32992, Republic of Korea.
7
Department of Anatomy, College of Veterinary Medicine, Konkuk University, Seoul, 05030, Republic of Korea.
8
Central Research Institute, Natural F&P Co. Ltd, Yong-In, 16827, Republic of Korea.
9
Laboratory of Developmental Biology and Genomics, College of Veterinary Medicine, Research Institute for Veterinary Science, Seoul National University, Seoul, 08826, Republic of Korea; BK21 Plus Program for Creative Veterinary Science Research, BIO-MAX institute, Interdisciplinary Program for Bioinformatics and Program for Cancer Biology, Seoul National University, Seoul, 08826, Republic of Korea.
10
Laboratory of Developmental Biology and Genomics, College of Veterinary Medicine, Research Institute for Veterinary Science, Seoul National University, Seoul, 08826, Republic of Korea; BK21 Plus Program for Creative Veterinary Science Research, BIO-MAX institute, Interdisciplinary Program for Bioinformatics and Program for Cancer Biology, Seoul National University, Seoul, 08826, Republic of Korea; Korea Mouse Phenotyping Center, Seoul, 08826, Republic of Korea.
11
Department of Biomedical Laboratory Science, College of Medical Sciences, Soonchunhyang University, Asan, 31538, Republic of Korea; Korea Mouse Phenotyping Center, Seoul, 08826, Republic of Korea. Electronic address: admiral96@sch.ac.kr.

Abstract

Recently, there have been reports that chronic insomnia acts as an insult in the brain, causing memory loss through the production of ROS, inflammation, and, Alzheimer's disease if persistent. Insomnia remains the leading cause of sleep disturbance and as such has serious implications for public health. Patients with Alzheimer's disease are also known to suffer from severe sleep disturbance. Meanwhile, vitexin is a key ingredient in Passiflora incarnata L (passion flower, PF) extract, which is known to help with sleep. This medicinal plant has been used as a folk remedy for sedation, anxiety and sleep since centuries ago, but the standardization work has not been done and the extent of the effect has not been clearly demonstrated. For this reason, we tried to test the possibility that repeated administration of PF could improve the memory by promoting hippocampal neurogenesis at the DBA/2 mice known have inherited sleep disorders, as well as preventive effects of Alzheimer's disease. Here, we found that vitexin, which is the main bioactive component of ethanol extracts from leaves and fruits (ratio; 8:2) of PF, confirmed the improvement of neurogenesis (DCX) of DBA/2 mice repeated PF oral administration by immunohistochemistry (IHC) and western blot analysis. PF-treated group showed increased the neurotrophic factor (BDNF) in the hippocampus compared with that of vehicle-treated group, but the inflammation markers Iba-1 (microglial marker) and COX-2 were inconsistent between the groups. However, we found COX-2 signal is essential for hippocampal neurogenesis according to the additional IHC experiments using COX-2 inhibitor and pIkappaB have shown. In addition, although prescription sleeping pills have been reported to show significant changes in appetite and metabolic rate from time to time, no changes in the feeding behavior, body weight, metabolic rate and body composition of the animals were observed by administration of PF. Interestingly, we found that short-term oral administration of PF displayed improved memory according to the water maze test. Quantitative analysis of Tau protein, which is a marker of Alzheimer's disease, was performed in the SD rats and DBA/2 mice by repeated PF oral administration and pTau/Tau values were significantly decreased in PF-treated group than vehicle-treated group. In conclusion, our results suggest that PF lead high hippocampal neurogenesis in the animals even in inherited sleep-disturbed animals. The increased hippocampal neurogenesis functionally enhanced memory and learning functions by repeated PF oral administration. These results identify PF as a potential therapy for enhancing memory functions and prevention of Alzheimer's disease through actions on the hippocampus.

KEYWORDS:

Alzheimer’s disease; Hippocampus; Memory functions; Neurogenesis; Passiflora incarnata L.

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