The Mechanism of Memory Enhancement of Acteoside (Verbascoside) in the Senescent Mouse Model Induced by a Combination of d‐gal and AlCl₃

Abstract

Acteoside (verbsacoside), one of the main active phenylethanoid glycosides from Cistanche deserticola, is known to have antioxidant and neuroprotective activity, and herbs containing it are used to enhance memory. However, there is relatively little direct experimental evidence to support the use of acteoside in Alzheimer's disease (AD). The purpose of this study was to elucidate the effects of acteoside in improving learning and memory, using a mouse model of senescence induced by a combination of d-galactose and AlCl3 , and investigate its potential mechanisms compared with the positive controls vitamin E and piracetam. Acteoside was administered intragastrically at doses of 30, 60 and 120 mg/kg/day for 30 days after AD was induced. Memory function was evaluated using a step-down test. The number of neuron was analysed by haematoxylin and eosin staining and the number of Nissl bodies by Nissl staining. The expression of caspase-3 protein in hippocampus was detected by immunohistochemistry and western blot. Nitric oxide and total nitric oxide synthase level in hippocampus were also assessed. Our results showed that the latency of step down was shortened in AD model mice and the number of errors decreased after treatment with all doses of acteoside. Neurons and Nissl bodies in the hippocampus were increased significantly with higher doses (60 and 120 mg/kg/day) of acteoside. The content of nitric oxide, the activity of nitric oxide synthase and the expression of caspase-3 protein were decreased by 120 mg/kg/day acteoside compared with that of the AD model group. Our results support the results obtained previously using the Morris maze test in the same mouse model of senescence, and the use of traditional medicinal herbs containing acteoside for neuroprotection and memory loss.

Phenylethanoid Glycosides: Research Advances in Their Phytochemistry, Pharmacological Activity and Pharmacokinetics

“…The result indicated that 121 could protect SH-SY5Y cells against Aβ [25][26][27][28][29][30][31][32][33][34][35] -induced cell injury by attenuating ROS production and modulating apoptotic signal pathway through Bcl-2 family, cytochrome c, and caspase-3 [65]. Peng et al [66] investigated the effects of 121 in improving learning and memory using a mouse model of senescence induced by a combination of D-galactose and AlCl 3 . Compound 121 was administered intragastrically at doses of 30, 60 and 120 mg/kg/day for 30 days after AD was induced.…”

“…Neurons and Nissl bodies in the hippocampus were increased significantly with higher doses (60 and 120 mg/kg/day) of 121. The content of nitric oxide (NO), the activity of nitric oxide synthase and the expression of caspase-3 protein were decreased by 120 mg/kg/day of 121 compared with that in the AD model group [66]. In a previous study, anti-amnesic activities of 121 using scopolamine-induced amnesic mice with both passive avoidance and Morris water maze test were examined.…”

Acteoside and Isoacteoside Protect Amyloid β Peptide Induced Cytotoxicity, Cognitive Deficit and Neurochemical Disturbances In Vitro and In Vivo

“…Reports have shown that acteoside can alleviate acquired learning disability in mice that is induced by scopolamine [13], and reduce cerebral injury in mice that is induced by d -galactose [14,15]. Acteoside also shortens the escape latency in the Morris water maze (MWM) and reduces the number of retention errors in the step-down test in d -galactose plus AlCl 3 -induced mouse senescence model [16,17]. Acteoside protects neuronal damage caused by Aβ 25-35 in SH-SY5Y neuroblastoma cells [10,18] and inhibits the aggregation of Aβ 1-42 in vitro [19].…”

Protective effects of hydroponic Teucrium polium on hippocampal neurodegeneration in ovariectomized rats

“…Calcineurin selectively enhances L-type Ca(2+) channel activity in hippocampal neurons [37]. The content of nitric oxide, the activity of nitric oxide synthase and the expression of caspase-3 protein were decreased by verbsacoside [38]. This has highlighted a compensatory, neuroprotective role for NO that protects synapses by increasing neuronal excitability (a potential mechanism for augmentation of excitability by nitric oxide is via modulation of voltage-gated potassium channel activity) [39].…”