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

[ Vol. 22 , Issue. 10 ]

Author(s):

Zhiyong Zhou, Menghan He, Qingqing Zhao, Dongfan Wang, Changcheng Zhang, Chaoqi Liu, Haixia Zhao, Yaoyan Dun, Yumin He, Chengfu Yuan, Ding Yuan* and Ting Wang*   Pages 1369 - 1379 ( 11 )

Abstract:


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.

Keywords:

Aging, neuroinflammation, Microglia, TXNIP, NLRP3 inflammasome, Saponins from Panax notoginseng.

Affiliation:

Medical College of China Three Gorges University, Yichang 443002, Medical College of China Three Gorges University, Yichang 443002, Medical College of China Three Gorges University, Yichang 443002, Medical College of China Three Gorges University, Yichang 443002, Medical College of China Three Gorges University, Yichang 443002, Medical College of China Three Gorges University, Yichang 443002, Medical College of China Three Gorges University, Yichang 443002, Medical College of China Three Gorges University, Yichang 443002, Medical College of China Three Gorges University, Yichang 443002, Medical College of China Three Gorges University, Yichang 443002, Medical College of China Three Gorges University, Yichang 443002, Pharmacy Department, Wuhan University of Science and Technology, Wuhan 430065



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