title: Protective effects of Bacopa monnieri on ischemia-induced cognitive deficits in mice: the possible contribution of bacopaside I and underlying mechanism.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  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.
  
  
  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 μM) 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.
  
  
  CONCLUSIONS
  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.
authors: 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.
authors: Xoan Thi
authors: XT
authors: Le
authors: 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.
authors: Hang Thi
authors: HT
authors: Nguyet Pham
authors: National Institute of Medicinal Materials, 3B Quang Trung Str., Hoan Kiem Dist., Hanoi, Viet Nam.
authors: Tai
authors: T
authors: Van Nguyen
authors: National Institute of Medicinal Materials, 3B Quang Trung Str., Hoan Kiem Dist., Hanoi, Viet Nam.
authors: Khoi
authors: K
authors: Minh Nguyen
authors: Department of Pharmacognosy, College of Pharmaceutical Sciences, Ritsumeikan University, 1-1-1 Nogi-Higashi, Kusatsu-shi, Siga 525-0058, Japan.
authors: Ken
authors: K
authors: Tanaka
authors: Institute of Natural Medicine, University of Toyama, 2630 Sugitani, Toyama-shi, Toyama 930-0194, Japan.
authors: Hironori
authors: H
authors: Fujiwara
authors: Institute of Natural Medicine, University of Toyama, 2630 Sugitani, Toyama-shi, Toyama 930-0194, Japan. Electronic address: mkinzo@inm.u-toyama.ac.jp.
authors: Kinzo
authors: K
authors: Matsumoto
mesh_terms: D000818:Animals; D034681:Bacopa; D015140:Dementia, Vascular / Q000188:drug therapy* / Q000209:etiology; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D007511:Ischemia / Q000150:complications; D008297:Male; D051379:Mice; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D012503:Saponins / Q000494:pharmacology / Q000627:therapeutic use; D014315:Triterpenes / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D018696:Neuroprotective Agents; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010936:Plant Extracts; D011493:Protein Kinase C; D051057:Proto-Oncogene Proteins c-akt; D012503:Saponins; D014315:Triterpenes; C442170:bacopaside I
keywords: Bacopa monnieri (L.) Wettst; Bacosides; Cognitive behavior; Ischemia; Neuroprotection; Organotypic hippocampal slice culture; Oxygen and glucose deprivation