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

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 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.

TXNIP Participated in NLRP3-Mediated Inflammation in a Rat Model of Cervical Spondylotic Myelopathy

“… 1 , 26 As is well known, neuroinflammation is strongly associated with activation of the NLRP3 inflammasome. 7 , 11 , 13 , 27 The classical pyroptosis pathway involves formation of the NLRP3 inflammasome, which is comprised of NLRP3, ASC, and pro-caspase-1. After activation, NLRP3 recruits ASC protein, which then recruits the pro-caspase-1 and promotes cleavage to caspase-1, resulting in production and secretion of inflammatory cytokines.…”

Potential benefits of ginseng against COVID-19 by targeting inflammasomes

“…Chikusetsu saponin IVa, a major active triterpenoid saponin in Panax japonicus , inhibited NLRP3 inflammasome activation, hence ameliorating obesity and neuroinflammation in macrophages, adipocytes, primary neurons, and postoperative cognitive dysfunction rats [ 75 , 76 ]. PF11, pseudoginsenoside, in Panax quinquefolius and saponins in Panax notoginseng inhibited NLRP3 inflammasome initiation, attenuating age-related neuroinflammation in macrophages and neurons [ 77 , 78 ].…”

Thioredoxin interacting protein, a key molecular switch between oxidative stress and sterile inflammation in cellular response

“…Later, Zhou et al [ 67 ] found that aging is associated with elevated microglial activation and neuroinflammation along with increased TXNIP/NLRP3 expression in aged rat (24 mo) in comparison with young rats (12 mo). Further, modulating TXNIP-NLRP3 activation with a traditional anti-inflammatory Chinese medicine attenuated age-associated neurodegeneration in aging rats[ 93 ]. Consistently, we recently identified aged-dependent activation of TXNIP-NLRP3 inflammasome in the cortex and hippocampus of brain in both male and female mice[ 94 ].…”