Anat Cell Biol.  2020 Jun;53(2):216-227. 10.5115/acb.20.011.

Aster ageratoides Turcz. extract attenuates Alzheimer’s disease-associated cognitive deficits and vascular dementia-associated neuronal death

• Jeong JH
• Lee SE
• Lee JH
• Kim HD
• Seo KH
• Kim DH
• Han SY

• KMID: 2503451
• DOI: http://doi.org/10.5115/acb.20.011

Abstract

Dementia is the common neurodegenerative disorder affecting the elderly, with a progressive cognitive decline and memory loss. Since Alzheimer’s disease (AD) and vascular dementia (VD) share key pathologies including oxidative damage, oral supplement of phytochemical medicines, which are well-known for their antioxidant properties, can be a viable therapy for both types of dementia. In this study, the therapeutic potential of the Aster ageratoides extract (AAE), an oriental drug with multiple medicinal properties, was tested on experimental rat models of AD and VD. After confirming the in vitro attenuation of neuronal excitotoxicity by AAE, rats were orally administered with AAE for 7 days and subsequently tested under 2 different experimental paradigms: efficacy screening against #1 AD and #2 VD. For paradigm #1, the rats received intraperitoneal scopolamine and subsequently underwent 3 different behavior tests i.e., the Y-maze, novel object recognition, and passive avoidance tests. For paradigm #2, the rats were operated with the 2-vessel occlusion and hypovolemia (2VO/H) technique, and at postoperative day 7, their hippocampal neuronal viability and the neuroinflammatory changes were quantified. The results showed that the scopolamine-induced impairment of memory performance was significantly improved by AAE intake. Furthermore, while the 2VO/H operation induced marked hippocampal neuronal death and microglial activation, both these effects were significantly attenuated by AAE supplements. Some of the aforementioned effects of AAE intake were dose-dependent. These results provided evidence that AAE supplements can exert anti-AD and -VD efficacies and suggested that AAE might be used as an edible phytotherapeutic for the 2 major types of dementia.

Keyword

Alzheimer disease; Vascular dementia; Aster ageratoides; Neuroinflammation; 2-vessel occlusion

Figure

• 

  Fig. 1 Timelines of the experimental protocols and time-dependent changes in rCBF values during the 2VO/H operation. (A) For experimental paradigm #1, 20 rats (n=5 per group) were pretreated with the vehicle or AAE for 7 days and subsequently treated with scopolamine (i.p.). Using these rats, 3 different behavioral tests were conducted. For experimental paradigm #2, rats (n=5 per group) with the same treatment schedule underwent the 2VO/H surgery, and their brains were obtained for histologic analyses at POD 7. (B) Detailed protocols of 3 behavioral tests. (C) The rCBF values throughout the 2VO/H operation, as detected by a laser-Doppler flowmetry. AAE, Aster ageratoides extract; C-V, cresyl violet; IHC, immunohistochemistry; NORT, novel object recognition test; PAT, passive avoidance test; POD, postoperative day; rCBF, relative cerebral blood flow; Y-MT, Y-maze test; 2VO/H, 2-vessel occlusion and hypovolemia.

• 

  Fig. 2 The effects of AAE on PC12 cell viability in vitro, following glutamate-induced excitotoxicity. (A) Dose-dependent cell viability following a 24 hours challenge with varying concentrations of glutamate. The approximate LD50 value for this cell line after 24 hours of glutamate insult was 50 mM (arrowhead). (B) The effects of 24 hours of co-treatment with AAE (0, 10, 25, and 50 µg/ml) and glutamate (50 mM) on PC12 cell viability. Values are presented as the mean±standard error of the mean (***P<0.001 vs. control; ###P<0.001 vs. the cells treated with only glutamate; δδδP<0.001 vs. the cells co-treated with glutamate and 10 µg/ml AAE). AAE, Aster ageratoides extract; LD50, lethal dose 50.

• 

  Fig. 3 The effects of AAE on memory-related performances in rats with scopolamine-induced amnesia (n=5 per group). The average spontaneous alternation rate (A) and the number of total arm entries for >8 minutes (B) during the Y-maze test. The percentage of time spent exploring the 2 familiar objects during the familiarization session (C), the novel object over the familiar object during the test session (D), and the total distance moved (E) during the novel object recognition test. The step-through latencies (F) and the initial latencies (G) to enter the dark chamber during the test and training sessions, respectively, during the passive avoidance test. Values are presented as the mean±standard error of the mean (***P<0.001 vs. CTRL; #P<0.05 and ###P<0.001 vs. VEH; δP<0.05 vs. AAE-L). AAE, Aster ageratoides extract; AAE-H, high dose of AAE-treated group; AAE-L, low dose of AAE-treated group; CTRL, control group; N.S., statistically not significant; VEH, vehicle-treated group.

• 

  Fig. 4 The effects of AAE on the number of surviving neurons, and the extent of neuroinflammation in the hippocampal CA1 of rats (n=5 per group) at POD 7. A representative cresyl violet-stained image (A) and the graph showing the average number of surviving neurons (B) in the hippocampal CA1. A representative immunohistochemistry image of the hippocampal CA1 using anti-Iba-1 (C) and anti-GFAP (E) and the quantitative graphs (D and F, respectively). The region of interest was within 300 µm in width in the hippocampal CA1 region. Values are presented as the mean±standard error of the mean (**P<0.01 and ***P<0.001 vs. CTRL; #P<0.05 and ###P<0.001 vs. VEH; δP<0.05 and δδδP<0.001 vs. AAE-L). AAE, Aster ageratoides extract; AAE-H, high dose of AAE-treated group; AAE-L, low dose of AAE-treated group; CTRL, control group; GFAP, glial fibrillary acidic protein; N.S., statistically not significant; POD, postoperative day; SO, stratum oriens; SP, stratum pyramidale; SR, stratum radiatum; VEH, vehicle-treated group.

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