Neuroprotective Effects and Mechanism of β-Asarone against Aβ1–42-Induced Injury in Astrocytes

Abstract

Emerging evidence suggests that activated astrocytes play important roles in AD, and β-asarone, a major component of Acorus tatarinowii Schott, was shown to be a potential therapeutic candidate for AD. While our previous study found that β-asarone could improve the cognitive function of rats hippocampally injected with Aβ, the effects of β-asarone on astrocytes remain unclear, and this study aimed to investigate these effects. A rat model of Aβ1–42 (10 μg) was established, and the rats were intragastrically treated with β-asarone at doses of 10, 20, and 30 mg/kg or donepezil at a dose of 0.75 mg/kg. The sham and model groups were intragastrically injected with an equal volume of saline. Animals were sacrificed on the 28th day after administration of the drugs. In addition, a cellular model of Aβ1–42 (1.1 μM, 6 h) was established, and cells were treated with β-asarone at doses of 0, 2.06, 6.17, 18.5, 55.6, and 166.7 μg/mL. β-Asarone improved cognitive impairment, alleviated Aβ deposition and hippocampal damage, and inhibited GFAP, AQP4, IL-1β, and TNF-α expression. These results suggested that β-asarone could alleviate the symptoms of AD by protecting astrocytes, possibly by inhibiting TNF-α and IL-1β secretion and then downregulating AQP4 expression.

The PERK-Dependent Molecular Mechanisms as a Novel Therapeutic Target for Neurodegenerative Diseases

“…Numerous in vivo studies have confirmed the positive effects of application of asarone derivatives, such as αor β-asarone, on cognitive function and alleviation of AD symptoms in animal models [296][297][298]. Anti-amyloidogenic properties of mentioned compounds have also been observed in the PC12 cell line, and likewise an anti-neuroinflammatory effect in BV2 microglial cells [299].…”

Extracts or Active Components from Acorus gramineus Aiton for Cognitive Function Impairment: Preclinical Evidence and Possible Mechanisms

“…Sodium pentobarbital was used to induce anesthesia in 8 studies, and chloral hydrate was used in 2 studies [ 20 , 21 ], 1 study [ 41 ] used phenytoin sodium, 1 study [ 17 ] used CO 2 , and 1 study [ 10 ] used isoflurane, while the remaining 21 studies did not report the type of anesthetics. Cognitive impairment models were induced by lead [ 17 ], noise stress [ 18 ], LPS [ 19 ], amyloid beta 1-42 [ 11 , 21 , 26 , 28 , 29 , 37 , 41 , 46 ], D-gal plus AlCl 3 [ 22 ], scopolamine [ 5 , 24 , 30 , 34 – 36 , 42 , 45 ], ethanol [ 5 , 32 , 34 – 36 ], sodium nitrite [ 5 , 32 ], corticosterone [ 23 ], Ibotenic acid [ 25 ], chronic restraint stress [ 31 ], pentobarbital sodium [ 32 ], D-galactose [ 33 , 38 ], AlCl 3 [ 40 ] , streptozotocin (STZ) [ 43 ], pent ylenetet razol (PTZ) [ 44 ], and NaNO 2 [ 34 – 36 ]. As an intervention, fourteen studies [ 6 , 17 , 20 , 22 , 23 , 26 , 27 , 32 , 35 , 37 , 39 , 41 , 42 , 46 ] used β -asarone, eight studies [ 18 , 19 , 21 , 24 , 33 ...…”

“…The quality scores of the 34 included studies varied from 1/10 to 6/10 with the average of 3.32. One study [ 40 ] got 1 point; 11 studies [ 29 , 31 – 36 , 38 , 39 , 42 , 44 ] got 2 points; 9 studies [ 5 , 6 , 18 , 24 , 25 , 27 , 30 , 43 , 45 ] got 3 points; 4 studies got 4 points; 7 studies got 5 points; and 2 studies [ 20 , 37 ] got 6 points. Thirty-four studies were published.…”

“…Thirty-four studies were published. Sixteen studies described control of temperature [ 6 , 10 , 17 – 26 , 30 , 37 , 41 , 45 ]. Random allocation was declared in 28 studies [ 5 , 6 , 11 , 17 , 19 – 23 , 26 – 28 , 30 – 39 , 41 – 46 ]; 1 study [ 42 ] used random block allocation method, and 2 studies used the method of random digit table [ 34 , 41 ].…”

“…Random allocation was declared in 28 studies [ 5 , 6 , 11 , 17 , 19 – 23 , 26 – 28 , 30 – 39 , 41 – 46 ]; 1 study [ 42 ] used random block allocation method, and 2 studies used the method of random digit table [ 34 , 41 ]. Two studies [ 23 , 37 ] described the use of blinded assessment of outcome. Thirteen studies did not use anesthetics with significant intrinsic neuroprotective activity, and the remaining 21 studies did not report the type of anesthetics [ 5 , 6 , 18 , 19 , 24 , 27 , 30 – 40 , 42 – 45 ].…”