Saponins from Panax japonicus alleviate HFD-induced impaired behaviors through inhibiting NLRP3 inflammasome to upregulate AMPA receptors.

Obesity is characterized by a condition of low-grade chronic inflammation that facilitates development of numerous comorbidities and dysregulation of brain homeostasis. It is reported that obesity can lead to behavioral alterations such as cognitive decline and depression-like behaviors both in humans and rodents. Saponins from panax japonicus (SPJ) have been reported to exhibit anti-inflammatory action in mouse model of diet-induced obesity. We evaluated the neuroprotection of SPJ on high fat diet (HFD) induced impaired behaviors such as memory deficit and depressive-like behaviors, and explored the underlying mechanisms. 6-week male Balb/c mice were divided into normal control group (NC, 17% total calories from fat), HFD group (60% total calories from fat), and HFD treated with SPJ groups (orally gavaged with dosages of 15 mg/kg and 45 mg/kg), respectively. After treatment for 16 weeks, behavioral tests were performed to evaluate the cognition and depression-like behaviors of the mice. The underling mechanisms of SPJ on HFD-induced impaired behaviors were investigated through histopathological observation, Western blot analysis and immunofluorescence. Our results showed that HFD-fed mice caused behavioral disorders, neuronal degeneration as well as elevated neuroinflammation, which was partly involved in NLRP3 inflammasome that finally resulted in decreased protein levels of AMPA receptors and down-regulated phosphorylated levels of CaMKII and CREB in cortex and hippocampus. All the above changes in cortex and hippocampus induced by HFD were mitigated by SPJ treatment. SPJ treatment alleviated HFD-induced recognitive impairment and depression-like behaviors of mice, which could be partly due to the capacity of SPJ to mitigate neuroinflammation through inhibition of NLRP3 inflammasome and upregulation of AMPA receptors signaling pathway.

[Improved effects of saponins from Panax japonicus on decline of cognitive function in natural aging rats via NLRP3 inflammasome pathway].

The aim of this paper was to investigate the effect of total saponins from Panax japonicus( SPJ) on cognitive decline of natural aging rats and its mechanism. Thirty male SD rats of eighteen month old were randomly divided into three groups: aged group,10 mg·kg~(-1) SPJ-treated group and 30 mg·kg~(-1) SPJ-treated group. The SPJ-treated groups were given SPJ at the dosages of 10 mg·kg~(-1) and 30 mg·kg~(-1),respectively,from the age of 18 to 24 months. Aged group were lavaged the same amount of saline,10 six-month-old rats were used as control group,with 10 rats in each group. The open field test,novel object recognition and Morris water maze were performed to detect the changes of cognitive function in each group. The changes of synaptic transmission of long-term potentiation( LTP) in hippocampal CA1 region were detected by field potential recording. Western blot was used to detect the protein levels of NLRP3,ASC,caspase-1 and the changes of Glu A1,Glu A2,CAMKⅡ,CREB and phosphorylation of CAMKⅡ,CREB in each group.The results showed that SPJ could improve the decline of cognitive function in aging rats,reduce the damage of LTP in the hippocampal CA1 region of aged rats,and decrease the expression of NLRP3,ASC,caspase-1 in aging rats. At the same time,SPJ could enhance the membrane expression of AMPA receptor( Glu A1 and Glu A2),and increase the expression of p-CAMKⅡand p-CREB in aging rats.SPJ could improve cognitive decline of natural aging rats,and its mechanism may be related to regulating NLRP3 inflammasome,thus regulating the membrane expression of AMPA receptor,and enhancing the expression phosphorylation of CAMKⅡ and CREB.