Publications by authors named "Dongfan Wang"

3 Publications

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

Neurochem Int 2021 Sep 12;148:105098. Epub 2021 Jun 12.

Hubei Province Key Laboratory of Occupational Hazard Identification and Control, Wuhan University of Science and Technology, Wuhan, 430065, China; New Medicine Innovation and Development Institute, Department of Pharmacy, College of Medicine, Wuhan University of Science and Technology, Wuhan, 430065, China. Electronic address:

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.
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http://dx.doi.org/10.1016/j.neuint.2021.105098DOI Listing
September 2021

Caloric restriction ameliorates high-fat diet induced cognitive deficits through attenuating neuroinflammation via the TREM2-PI3K/AKT signaling pathway.

Food Funct 2021 Jul 2;12(14):6464-6478. Epub 2021 Jun 2.

College of Medical Science, Three Gorges University, Yichang, Hubei 443002, China.

Prolonged high-fat diet (HFD) feeding impairs cognitive function in rodents. However, the mechanism of caloric restriction (CR) for remedying HFD-induced cognitive dysfunction remains elusive. In the present study, we investigated the effect of CR on HFD-induced cognitive dysfunction and its possible mechanism. BALB/c mice were fed with HFD for 16 weeks and subsequently subjected to CR for 12 weeks. After cognitive function was evaluated by behavioral tests such as Morris water maze and three-chamber paradigm tests, the mice were sacrificed. The prefrontal cortex and hippocampus were rapidly harvested and deposited at -80 °C. The neuroprotective mechanisms of CR on HFD-induced cognitive deficits were evaluated by histopathological and electron microscopy observations, western blotting and immunofluorescence. Compared with the normal control group, HFD mice exhibited obvious cognitive deficits, glucose tolerance impairment, neuronal degeneration and abnormalities of synaptic ultrastructure in the cortex and hippocampus. CR treatment improved cognitive dysfunction and histopathological changes as well as increased the cognition-related protein levels of PSD-95, synaptophysin and BDNF. Meanwhile, HFD increased the protein levels of pro-inflammatory factors including iNOS, COX-2 and IL-1β but decreased the protein levels of anti-inflammatory factors such as CD206, TGF-β, Ym-1 and Arg 1 in the prefrontal cortex and hippocampus, downregulated the protein levels of TREM2 and PI3K and decreased the phosphorylation level of AKT, which can be reversed by CR treatment. Therefore, our results indicated that CR ameliorated cognitive deficits of mice induced by a high-fat diet. The underlying mechanism is associated with the attenuation of the neuroinflammatory response mediated by the TREM2-PI3K/AKT signaling pathway.
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http://dx.doi.org/10.1039/d0fo02946gDOI Listing
July 2021

Panax notoginseng Saponins Attenuate Neuroinflammation through TXNIP-Mediated NLRP3 Inflammasome Activation in Aging Rats.

Curr Pharm Biotechnol 2021 ;22(10):1369-1379

Pharmacy Department, Wuhan University of Science and Technology, Wuhan 430065, China.

Introduction: Microglia-mediated inflammatory responses play a crucial role in aging-related neurodegenerative diseases. The TXNIP/NLRP3 pathway is a key pathway leading to microglial activation. Panax notoginseng Saponins (PNS) have been widely used for the treatment of stroke in China.

Objective: This study evaluates the anti-neuroinflammatory effect of PNS and investigates the mechanism via TXNIP-mediated NLRP3 inflammasome activation in aging rats.

Material And Methods: Eighteen-month-old Sprague-Dawley rats were randomly divided into the aging control group and PNS treated groups (n=15 each group). For PNS-treated groups, rats were administrated food with PNS at the doses of 10 mg/kg and 30 mg/kg for consecutive 6 months until they were 24-month old. Rats from the aging control group were given the same food without PNS. Twomonth- old rats were purchased and given the same food until they were 6-months old as the adult control group (n = 15). Then, the cortex and hippocampus were rapidly harvested and deposited. H&E staining was used to assess histo-morphological changes. Western blotting was carried out to detect the protein expression. Immunofluorescence was employed to measure the co-localization of NLRP3, TXNIP and Iba-1. In vitro model was established by LPS+ATP co-incubation in the BV2 microglia cell line.

Results: Aging rats exhibited increased activation of microglia, accompanied by a high level of IL-1β expression. Meanwhile, aging rats showed enhanced protein expression of TXNIP and NLRP3 related molecules, which co-localized with microglia. PNS treatment effectively reduced the number of degenerated neurons and reversed the activation of the TXNIP/NLRP3 inflammatory pathway. In vitro results showed that PNS up to 100 μg/ml had no significant toxicity on BV2 microglia. PNS (25, 50 μg/ml) effectively reduced the inflammatory response induced by LPS and ATP co-stimulation, thus inhibiting the expression of TXNIP/NLRP3 pathway-related proteins.

Discussion And Conclusion: PNS treatment improved aging-related neuronal damage through inhibiting TXNIP mediated NLRP3 inflammasome activation, which provided a potential target for the treatment of inflammation-related neurodegenerative diseases.
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http://dx.doi.org/10.2174/1389201021999201110204735DOI Listing
January 2021
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