So Yeon Jo1, In Ho Jung2, Jee Hyun Yi3, Tae Joon Choi4, Seungheon Lee5, Ji Wook Jung6, Jeanho Yun7, Young Choon Lee8, Jong Hoon Ryu9, Dong Hyun Kim10. 1. Department of Biotechnology, College of Natural Resources and Life Science, Dong-A University, Busan 49315, Republic of Korea. Electronic address: csy2863@gmail.com. 2. Department of Life and Nanopharmaceutical Science, Kyung Hee University, Hoeki-dong, Dongdaemoon-Ku, Seoul 02447, Republic of Korea; Daehwa Pharmaceutical Co., Ltd., Seongnam 13488, Republic of Korea. Electronic address: inhojung69@gmail.com. 3. School of Clinical Sciences, Faculty of Medicine and Dentistry, University of Bristol, Bristol, UK. Electronic address: JeeHyun.Yi@bristol.ac.uk. 4. Daehwa Pharmaceutical Co., Ltd., Seongnam 13488, Republic of Korea. Electronic address: cjswoid@gmail.com. 5. Department of Aquatic Biomedical Sciences, School of Marine Biomedical Science, College of Ocean Science, Jeju National University, Jeju 63243, Republic of Korea. Electronic address: slee76@jejunu.ac.kr. 6. Department of Herbal Medicinal Pharmacology, College of Herbal Bio-industry, Daegu Haany University, Kyungsan 38610, Republic of Korea. Electronic address: jwjung@dhu.ac.kr. 7. Department of Biochemistry, College of Medicine, Dong-A University, Busan 607-714, Republic of Korea; Institute of Convergence Bio-Health, Dong-A University, Busan 49315, Republic of Korea. Electronic address: yunj@dau.ac.kr. 8. Department of Medicinal Biotechnology, College of Health Sciences, Dong-A University, Busan 49315, Republic of Korea; Institute of Convergence Bio-Health, Dong-A University, Busan 49315, Republic of Korea. Electronic address: yclee@dau.ac.kr. 9. Department of Life and Nanopharmaceutical Science, Kyung Hee University, Hoeki-dong, Dongdaemoon-Ku, Seoul 02447, Republic of Korea; Department of Oriental Pharmaceutical Science, College of Pharmacy, Kyung Hee University, Seoul 02447, Republic of Korea; Kyung Hee East-West Pharmaceutical Research Institute, College of Pharmacy, Kyung Hee University, Seoul 02447, Republic of Korea. Electronic address: jhryu63@khu.ac.kr. 10. Department of Medicinal Biotechnology, College of Health Sciences, Dong-A University, Busan 49315, Republic of Korea; Institute of Convergence Bio-Health, Dong-A University, Busan 49315, Republic of Korea. Electronic address: mose79@dau.ac.kr.
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE: As the seed of Zizyphus jujuba var. spinosa (Bunge) Hu ex H.F. Chow (Rhamnaceae) has been used to sleep disturbances in traditional Chinese and Korean medicine, many previous studies have focused on its sedative effect. AIM OF THE STUDY: Recently, we reported the neuroprotective effect of the effect of Z. jujuba var. spinosa. However, its effects on synaptic function have not yet been studied. In this project, we examined the action of ethanol extract of the seed of Z. jujuba var. spinosa (DHP1401) on synaptic transmission in the hippocampus. MATERIALS AND METHODS: To investigate the effects of DHP1401, field recordings were conducted using hippocampal slices (400µm). Object recognition test was introduced to examine whether DHP1401 affect normal recognition memory. RESULTS: DHP1401 (50μg/ml) induced a significant increase in synaptic activity in Shaffer collateral pathway in a concentration-dependent manner. This increase of synaptic responses was blocked by NBQX, a broad spectrum α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor antagonist, but not IEM-1460, a Ca2+-permeable AMPAR blocker. Moreover, U0126, a mitogen-activated protein kinase inhibitor, SQ22536, an adenylyl cyclase inhibitor, and PKI, a protein kinase A inhibitor, blocked DHP1401-induced increase in synaptic transmission. Finally, DHP1401 facilitated object recognition memory. CONCLUSIONS: These results suggest that DHP1401 increase synaptic transmission through increase of synaptic AMPAR transmission via MAPK, AC and PAK.
ETHNOPHARMACOLOGICAL RELEVANCE: As the seed of Zizyphus jujuba var. spinosa (Bunge) Hu ex H.F. Chow (Rhamnaceae) has been used to sleep disturbances in traditional Chinese and Korean medicine, many previous studies have focused on its sedative effect. AIM OF THE STUDY: Recently, we reported the neuroprotective effect of the effect of Z. jujuba var. spinosa. However, its effects on synaptic function have not yet been studied. In this project, we examined the action of ethanol extract of the seed of Z. jujuba var. spinosa (DHP1401) on synaptic transmission in the hippocampus. MATERIALS AND METHODS: To investigate the effects of DHP1401, field recordings were conducted using hippocampal slices (400µm). Object recognition test was introduced to examine whether DHP1401 affect normal recognition memory. RESULTS:DHP1401 (50μg/ml) induced a significant increase in synaptic activity in Shaffer collateral pathway in a concentration-dependent manner. This increase of synaptic responses was blocked by NBQX, a broad spectrum α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor antagonist, but not IEM-1460, a Ca2+-permeable AMPAR blocker. Moreover, U0126, a mitogen-activated protein kinase inhibitor, SQ22536, an adenylyl cyclase inhibitor, and PKI, a protein kinase A inhibitor, blocked DHP1401-induced increase in synaptic transmission. Finally, DHP1401 facilitated object recognition memory. CONCLUSIONS: These results suggest that DHP1401 increase synaptic transmission through increase of synaptic AMPAR transmission via MAPK, AC and PAK.
Keywords:
A mitogen-activated protein kinase; Adenylyl cyclase; Protein kinase A; Synaptic transmission; Zizyphus jujuba var. spinose; α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor