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

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

Volume: 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*Ting Wang*

Affiliation:

• Medical College of China Three Gorges University, Yichang 443002,China

• Pharmacy Department, Wuhan University of Science and Technology, Wuhan 430065,China

Keywords: Aging, neuroinflammation, microglia, TXNIP, NLRP3 inflammasome, saponins from Panax notoginseng.

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.

Cite this article as:

Zhou Zhiyong , He Menghan , Zhao Qingqing , Wang Dongfan , Zhang Changcheng , Liu Chaoqi , Zhao Haixia , Dun Yaoyan , He Yumin , Yuan Chengfu , Yuan Ding *, Wang Ting *, Panax notoginseng Saponins Attenuate Neuroinflammation through TXNIP-Mediated NLRP3 Inflammasome Activation in Aging Rats, Current Pharmaceutical Biotechnology 2021; 22 (10) . https://dx.doi.org/10.2174/1389201021999201110204735