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

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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.

Medienart:

E-Artikel

Erscheinungsjahr:

2021

Erschienen:

2021

Enthalten in:

Zur Gesamtaufnahme - volume:22

Enthalten in:

Current pharmaceutical biotechnology - 22(2021), 10 vom: 01., Seite 1369-1379

Sprache:

Englisch

Beteiligte Personen:

Zhou, Zhiyong [VerfasserIn]
He, Menghan [VerfasserIn]
Zhao, Qingqing [VerfasserIn]
Wang, Dongfan [VerfasserIn]
Zhang, Changcheng [VerfasserIn]
Liu, Chaoqi [VerfasserIn]
Zhao, Haixia [VerfasserIn]
Dun, Yaoyan [VerfasserIn]
He, Yumin [VerfasserIn]
Yuan, Chengfu [VerfasserIn]
Yuan, Ding [VerfasserIn]
Wang, Ting [VerfasserIn]

Links:

Volltext

Themen:

Aging
Cell Cycle Proteins
Inflammasomes
Journal Article
Microglia
NLR Family, Pyrin Domain-Containing 3 Protein
NLRP3 inflammasome
Neuroinflammation
Nlrp3 protein, rat
Saponins
Saponins from Panax notoginseng.
TXNIP
TXNIP protein, rat

Anmerkungen:

Date Completed 19.08.2021

Date Revised 19.08.2021

published: Print

Citation Status MEDLINE

doi:

10.2174/1389201021999201110204735

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM31744235X