Xoan Thi Le1, Hang Thi Nguyet Pham1, Tai Van Nguyen2, Khoi Minh Nguyen2, Ken Tanaka3, Hironori Fujiwara4, Kinzo Matsumoto5. 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: mkinzo@inm.u-toyama.ac.jp.
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.
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 dementiapatients. 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 triterpenoidsaponins 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.
Authors: Xoan Thi Le; Hien Thu Nguyen; Tai Van Nguyen; Hang Thi Nguyet Pham; Phuong Thi Nguyen; Khoi Minh Nguyen; Ba Van Nguyen; Kinzo Matsumoto Journal: Evid Based Complement Alternat Med Date: 2021-06-30 Impact factor: 2.629