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 TXNIPmediated
NLRP3 inflammasome activation in aging rats.
Materials 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. Two-month-old rats were purchased and given the same food until 6-month 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 coincubation
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.
Discussion::
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.
Conclusion::
PNS treatment improved aging-related neuronal damage through inhibiting TXNIP mediated NLRP3 inflammasome
activation, which provided a potential target for the treatment of inflammatory-related neurodegenerative diseases.
