20(S)-protopanaxatriol (PPT), one of the ginsenosides from Panax ginseng, has been reported to have neuroprotective effects and to improve memory. The present study was designed to investigate the protective effect of PPT on scopolamine-induced cognitive deficits in mice. Male Institute of Cancer Research mice were pretreated with 2 different doses of PPT (20 and 40 μmol/kg) for 27 days by intraperitoneal injection, and scopolamine (0.75 mg/kg) was injected intraperitoneally for 9 days to induce memory impairment. Thirty minutes after the last pretreatment, the locomotor activity was firstly examined to evaluate the motor function of mice. Then, memory-related behaviors were evaluated, and the related mechanism was further researched. It was founded that PPT treatment significantly reversed scopolamine-induced cognitive impairment in the object location recognition experiment, the Morris water maze test, and the passive avoidance task, showing memory-improving effects. PPT also significantly improved cholinergic system reactivity and suppressed oxidative stress, indicated by inhibition of acetylcholinesterase activity, elevation of acetylcholine levels, increasing superoxide dismutase activity and lowering levels of malondialdehyde in the hippocampus. In addition, the expression levels of Egr-1, c-Jun, and cAMP responsive element binding in the hippocampus were significantly elevated by PPT administration. These results suggest that PPT may be a potential drug candidate for the treatment of cognitive deficit in Alzheimer's disease.
In the recent years, interest in soybean as a neuroprotective nutrient in the management of Alzheimer’s disease (AD) has increased and soy isoflavones (SI), as kinds of soybean phytochemicals, are thought to be biologically active components that confer this beneficial effect against neurodegenerative diseases. However, the neuroprotective effect of SI is not well understood. Therefore, the present study (30 days) was conducted to investigate the neuroprotective effects of soy isoflavones (SI) on scopolamine (SCOP)-induced memory impairments in Institute of Cancer Research (ICR) mice (aged 4 weeks) and to elucidate its underlying mechanisms of action. SI (40 mg/kg) administration improved the cognitive performance of SCOP-treated mice in an object location recognition task and the Morris water maze test. SI (40 mg/kg) administration significantly enhanced cholinergic system function and suppressed oxidative stress levels in the hippocampus of SCOP-treated mice. Furthermore, SI (40 mg/kg) treatment markedly upregulated the phosphorylation levels of extracellular signal-regulated kinase (ERK), cAMP response element-binding protein (CREB) and brain-derived neurotrophic factor (BDNF) expression levels in the hippocampus. Taken together, these results demonstrated that soy isoflavones exerted a significant neuroprotective effect on cognitive dysfunctions induced by scopolamine, suggesting that soy isoflavones could be a good candidate for possible treatment of neurodegenerative diseases, such as Alzheimer’s disease (AD).
Rh2 is a rare ginsenoside and there are few reports of its effect on cognition compared with other similar molecules. This study aimed to establish the impact of Rh2 treatment on improving scopolamine (Scop)‐induced memory deficits in mice and illuminate the underlying mechanisms. First, memory‐related behavior was evaluated using two approaches: object location recognition (OLR), based on spontaneous activity, and a Morris water maze (MWM) task, based on an aversive stimulus. Our results suggested that Rh2 treatment effectively increased the discrimination index of the mice in the OLR test. In addition, Rh2 elevated the crossing numbers and decreased the escape latency during the MWM task. Moreover, Rh2 markedly upregulated the phosphorylation of the extracellular signal‐regulated kinase (ERK)‐cAMP response element binding (CREB)‐brain derived neurotrophic factor (BDNF) pathway in the hippocampus. Meanwhile, the administration of Rh2 significantly promoted the cholinergic system and dramatically suppressed oxidative stress in the hippocampus. Taken together, Rh2 exhibited neuroprotective effects against Scop‐induced memory dysfunction in mice. Rh2 activity might be ascribed to several underlying mechanisms, including its effects on modulating the cholinergic transmission, inhibiting oxidative stress and activating the ERK‐CREB‐BDNF signaling pathway. Consequently, the ginsenoside Rh2 might serve as a promising candidate compound for Alzheimer's disease.
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