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  3. Protective effects of Bacopa monnieri on ischemia-induced cognitive deficits in mice: the possible contribution of bacopaside I and underlying mechanism

Protective effects of Bacopa monnieri on ischemia-induced cognitive deficits in mice: the possible contribution of bacopaside I and underlying mechanism

  • J Ethnopharmacol. 2015 Apr 22:164:37-45. doi: 10.1016/j.jep.2015.01.041.
Xoan Thi Le 1,  Hang Thi Nguyet Pham 1,  Tai Van Nguyen 2,  Khoi Minh Nguyen 2,  Ken Tanaka 3,  Hironori Fujiwara 4,  Kinzo Matsumoto 5
Affiliations

Affiliations

  • 1 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.
  • 2 National Institute of Medicinal Materials, 3B Quang Trung Str., Hoan Kiem Dist., Hanoi, Viet Nam.
  • 3 Department of Pharmacognosy, College of Pharmaceutical Sciences, Ritsumeikan University, 1-1-1 Nogi-Higashi, Kusatsu-shi, Siga 525-0058, Japan.
  • 4 Institute of Natural Medicine, University of Toyama, 2630 Sugitani, Toyama-shi, Toyama 930-0194, Japan.
  • 5 Institute of Natural Medicine, University of Toyama, 2630 Sugitani, Toyama-shi, Toyama 930-0194, Japan. Electronic address: [email protected].
PMID: 25660331 DOI: 10.1016/j.jep.2015.01.041
Abstract

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 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.

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.

Keywords

Bacopa monnieri (L.) Wettst; Bacosides; Cognitive behavior; Ischemia; Neuroprotection; Organotypic hippocampal slice culture; Oxygen and glucose deprivation.

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