We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
Neuroprotection and spatial memory enhancement of four herbal mixture extract in HT22 hippocampal cells and a mouse model of focal cerebral ischemia.
- Authors
Sung Min Ahn; Yu Ri Kim; Ha Neui Kim; Young Whan Choi; Jae Won Lee; Cheol Min Kim; Jin Ung Baek; Hwa Kyoung Shin; Byung Tae Choi
- Abstract
Background: Four traditional Korean medicinal herbs which act in retarding the aging process, Polygonum multiflorum Thunb., Rehmannia glutinosa (Gaertn) Libosch., Polygala tenuifolia Willd., and Acorus gramineus Soland., were prepared by systematic investigation of Dongeuibogam (Treasured Mirror of Eastern Medicine), published in the early 17th century in Korea. This study was performed to evaluate beneficial effects of four herbal mixture extract (PMC-12) on hippocampal neuron and spatial memory. Methods: High performance liquid chromatography (HPLC) analysis was performed for standardization of PMC-12. Cell viability, lactate dehydrogenase, flow cytometry, reactive oxygen species (ROS), and Western blot assays were performed in HT22 hippocampal cells and immunohistochemistry and behavioral tests were performed in a mouse model of focal cerebral ischemia in order to observe alterations of hippocampal cell survival and subsequent memory function. Results: In the HPLC analysis, PMC-12 was standardized to contain 3.09 % 2,3,5,4'-tetrahydroxystilbene-2-O-β-D-glucoside, 0.35 % 3',6-disinapoyl sucrose, and 0.79 % catalpol. In HT22 cells, pretreatment with PMC-12 resulted in significantly reduced glutamate-induced apoptotic cell death. Pretreatment with PMC-12 also resulted in suppression of ROS accumulation in connection with cellular Ca2+ level after exposure to glutamate. Expression levels of phosphorylated p38 mitogen-activated protein kinases (MAPK) and dephosphorylated phosphatidylinositol-3 kinase (PI3K) by glutamate exposure were recovered by pretreatment with either PMC-12 or anti-oxidant N-acetyl-L-cysteine (NAC). Expression levels of mature brain-derived neurotrophic factor (BDNF) and phosphorylated cAMP response element binding protein (CREB) were significantly enhanced by treatment with either PMC-12 or NAC. Combination treatment with PMC-12, NAC, and intracellular Ca2+ inhibitor BAPTA showed similar expression levels. In a mouse model of focal cerebral ischemia, we observed higher expression of mature BDNF and phosphorylation of CREB in the hippocampus and further confirmed improved spatial memory by treatment with PMC-12. Conclusions: Our results suggest that PMC-12 mainly exerted protective effects on hippocampal neurons through suppression of Ca2+-related ROS accumulation and regulation of signaling pathways of p38 MAPK and PI3K associated with mature BDNF expression and CREB phosphorylation and subsequently enhanced spatial memory.
- Subjects
ANIMAL experimentation; APOPTOSIS; FLOW cytometry; FLUORESCENT antibody technique; HIGH performance liquid chromatography; HIPPOCAMPUS (Brain); IMMUNOHISTOCHEMISTRY; MEDICINAL plants; ASIAN medicine; MICE; PHOTOGRAPHY; RESEARCH funding; SPECTROPHOTOMETERS; STATISTICS; WESTERN immunoblotting; PLANT extracts; DATA analysis; REPEATED measures design; NEUROPROTECTIVE agents; IN vitro studies; ONE-way analysis of variance
- Publication
BMC Complementary & Alternative Medicine, 2015, Vol 15, Issue 1, p1
- ISSN
1472-6882
- Publication type
Article
- DOI
10.1186/s12906-015-0741-1