PMID- 25660331 OWN - NLM STAT- MEDLINE DCOM- 20160108 LR - 20191210 IS - 1872-7573 (Electronic) IS - 0378-8741 (Linking) VI - 164 DP - 2015 Apr 22 TI - Protective effects of Bacopa monnieri on ischemia-induced cognitive deficits in mice: the possible contribution of bacopaside I and underlying mechanism. PG - 37-45 LID - S0378-8741(15)00056-2 [pii] LID - 10.1016/j.jep.2015.01.041 [doi] AB - ETHNOPHARMACOLOGICAL RELEVANCE: Bacopa monnieri (L.) Wettst. (BM) is a medicinal plant which has been not only used as a traditional medicine to improve intelligence and memory but also taken as vegetables in Vietnam for a long time. We previously demonstrated that Bacopa monnieri (BM) alcohol extract attenuated olfactory bulbectomy-induced cognitive deficits and the deterioration of septo-hippocampal cholinergic neurons, suggesting the beneficial effects of BM for dementia patients. AIM OF STUDY: The present study was conducted to further clarify the anti-dementia effects of BM, using transient 2 vessels occlusion (T2VO)-induced cognitive deficits in mice, an animal model of vascular dementia, and also to investigate the constituent(s) contributing to the actions of BM, using oxygen- and glucose-deprivation (OGD)-induced hippocampal cell damage as an in vitro model of ischemia. MATERIALS AND METHODS: In the in vivo experiments, T2VO mice were treated daily with a standardized BM extract (50mg/kg, p.o.) 1 week before and continuously 3 days after surgery. In the in vitro experiments, organotypic hippocampal slice cultures (OHSCs) were incubated with triterpenoid saponins from BM (bacosides) or MK-801 1h before and during a 45-min period of OGD. Neuronal cell damage in OHSCs was analyzed by measurement of propidium iodide uptake 24h after OGD. RESULTS: The BM treatment significantly ameliorated T2VO-induced impairments in non-spatial short term memory performance in the object recognition test. Among the bacosides tested in the in vitro experiments using OHSCs, bacopaside I (25 muM) exhibited potent neuroprotective effects against OGD-induced neuronal cell damage. Double staining with TUNEL and PI revealed that OGD caused necrosis and apoptosis and that bacopaside I attenuated the effects of OGD. The neuroprotective effects of bacopaside I were blocked by the PKC inhibitor Ro-31-8220 and PI3K inhibitor LY294002, but not by the ERK inhibitor U0126. OGD reduced the level of phospho-Akt (p-Akt), an anti-apoptotic factor, in OHSCs. This decrease was reversed by bacopaside I. Moreover, the treatment with bacopaside I itself was able to elevate the level of p-Akt in OHSCs. CONCLUSION: These results suggest that BM was beneficial for the prevention of cognitive deficits related to cerebral ischemia and also that bacopaside I, via PKC and PI3K/Akt mechanisms, played a role in the neuroprotective effects of BM observed in the mouse model. CI - Copyright (c) 2015 Elsevier Ireland Ltd. All rights reserved. FAU - Le, Xoan Thi AU - Le XT AD - Institute of Natural Medicine, University of Toyama, 2630 Sugitani, Toyama-shi, Toyama 930-0194, Japan; National Institute of Medicinal Materials, 3B Quang Trung Str., Hoan Kiem Dist., Hanoi, Viet Nam. FAU - Nguyet Pham, Hang Thi AU - Nguyet Pham HT AD - Institute of Natural Medicine, University of Toyama, 2630 Sugitani, Toyama-shi, Toyama 930-0194, Japan; National Institute of Medicinal Materials, 3B Quang Trung Str., Hoan Kiem Dist., Hanoi, Viet Nam. FAU - Van Nguyen, Tai AU - Van Nguyen T AD - National Institute of Medicinal Materials, 3B Quang Trung Str., Hoan Kiem Dist., Hanoi, Viet Nam. FAU - Minh Nguyen, Khoi AU - Minh Nguyen K AD - National Institute of Medicinal Materials, 3B Quang Trung Str., Hoan Kiem Dist., Hanoi, Viet Nam. FAU - Tanaka, Ken AU - Tanaka K AD - Department of Pharmacognosy, College of Pharmaceutical Sciences, Ritsumeikan University, 1-1-1 Nogi-Higashi, Kusatsu-shi, Siga 525-0058, Japan. FAU - Fujiwara, Hironori AU - Fujiwara H AD - Institute of Natural Medicine, University of Toyama, 2630 Sugitani, Toyama-shi, Toyama 930-0194, Japan. FAU - Matsumoto, Kinzo AU - Matsumoto K AD - Institute of Natural Medicine, University of Toyama, 2630 Sugitani, Toyama-shi, Toyama 930-0194, Japan. Electronic address: mkinzo@inm.u-toyama.ac.jp. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20150207 PL - Ireland TA - J Ethnopharmacol JT - Journal of ethnopharmacology JID - 7903310 RN - 0 (Neuroprotective Agents) RN - 0 (Phosphoinositide-3 Kinase Inhibitors) RN - 0 (Plant Extracts) RN - 0 (Saponins) RN - 0 (Triterpenes) RN - 36B8WUA361 (bacopaside I) RN - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) RN - EC 2.7.11.13 (Protein Kinase C) SB - IM MH - Animals MH - *Bacopa MH - Dementia, Vascular/*drug therapy/etiology MH - Hippocampus/drug effects/metabolism/pathology MH - Ischemia/complications MH - Male MH - Mice MH - Neuroprotective Agents/pharmacology/*therapeutic use MH - Phosphatidylinositol 3-Kinases/metabolism MH - Phosphoinositide-3 Kinase Inhibitors MH - Plant Extracts/pharmacology/*therapeutic use MH - Protein Kinase C/antagonists & inhibitors/metabolism MH - Proto-Oncogene Proteins c-akt/metabolism MH - Saponins/pharmacology/therapeutic use MH - Triterpenes/pharmacology/therapeutic use OTO - NOTNLM OT - Bacopa monnieri (L.) Wettst OT - Bacosides OT - Cognitive behavior OT - Ischemia OT - Neuroprotection OT - Organotypic hippocampal slice culture OT - Oxygen and glucose deprivation EDAT- 2015/02/11 06:00 MHDA- 2016/01/09 06:00 CRDT- 2015/02/10 06:00 PHST- 2014/10/29 00:00 [received] PHST- 2015/01/11 00:00 [revised] PHST- 2015/01/14 00:00 [accepted] PHST- 2015/02/10 06:00 [entrez] PHST- 2015/02/11 06:00 [pubmed] PHST- 2016/01/09 06:00 [medline] AID - S0378-8741(15)00056-2 [pii] AID - 10.1016/j.jep.2015.01.041 [doi] PST - ppublish SO - J Ethnopharmacol. 2015 Apr 22;164:37-45. doi: 10.1016/j.jep.2015.01.041. Epub 2015 Feb 7.