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:
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Authors | Zhiyong Zhou, Menghan He, Qingqing Zhao, Dongfan Wang, Changcheng Zhang, Chaoqi Liu, Haixia Zhao, Yaoyan Dun, Yumin He, Chengfu Yuan, Ding Yuan, Ting Wang |
Journal | Current pharmaceutical biotechnology
(Curr Pharm Biotechnol)
Vol. 22
Issue 10
Pg. 1369-1379
( 2021)
ISSN: 1873-4316 [Electronic] Netherlands |
PMID | 33176641
(Publication Type: Journal Article)
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Copyright | Copyright© Bentham Science Publishers; For any queries, please email at [email protected]. |
Chemical References |
- Cell Cycle Proteins
- Inflammasomes
- NLR Family, Pyrin Domain-Containing 3 Protein
- Nlrp3 protein, rat
- Saponins
- TXNIP protein, rat
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Topics |
- Animals
- Cell Cycle Proteins
- Inflammasomes
- NLR Family, Pyrin Domain-Containing 3 Protein
- Panax notoginseng
- Rats
- Rats, Sprague-Dawley
- Saponins
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