1. Academic Validation
  2. Protective effect of ginsenoside Rh2 against Toxoplasma gondii infection-induced neuronal injury through binding TgCDPK1 and NLRP3 to inhibit microglial NLRP3 inflammasome signaling pathway

Protective effect of ginsenoside Rh2 against Toxoplasma gondii infection-induced neuronal injury through binding TgCDPK1 and NLRP3 to inhibit microglial NLRP3 inflammasome signaling pathway

  • Int Immunopharmacol. 2022 Sep 5;112:109176. doi: 10.1016/j.intimp.2022.109176.
Guang-Nan Jin 1 Jing-Mei Lu 1 Hui-Wen Lan 1 Yu-Nan Lu 1 Xin-Yu Shen 1 Xiang Xu 2 Lian-Xun Piao 3
Affiliations

Affiliations

  • 1 Key Laboratory of Natural Medicines of the Changbai Mountain, Ministry of Education, Molecular Medicine Research Center, College of Pharmacy, Yanbian University, Yanji 133002, Jilin, China.
  • 2 Key Laboratory of Natural Medicines of the Changbai Mountain, Ministry of Education, Molecular Medicine Research Center, College of Pharmacy, Yanbian University, Yanji 133002, Jilin, China. Electronic address: xiangxu@ybu.edu.cn.
  • 3 Key Laboratory of Natural Medicines of the Changbai Mountain, Ministry of Education, Molecular Medicine Research Center, College of Pharmacy, Yanbian University, Yanji 133002, Jilin, China. Electronic address: lxpiao@ybu.edu.cn.
Abstract

Background: Toxoplasma gondii (T. gondii) is a neurotropic obligate intracellular Parasite that can activate microglial and promote neuronal Apoptosis, leading to central nervous system diseases. The NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome signaling complex plays a key role in inducing neuroinflammation. Our previous studies have found that ginsenoside Rh2 (GRh2) inhibits T. gondii infection-induced microglial activation and neuroinflammation by downregulating the Toll-like Receptor 4/nuclear factor-kappa B signaling pathway. However, whether GRh2 reduces T. gondii infection-induced neuronal injury through actions on microglial NLRP3 inflammasome signaling has not yet been clarified.

Methods: In this study, we employed T. gondii RH strain to establish in vitro and in vivo Infection models in BV2 microglia cell line and BALB/c mice. Molecular docking, localized surface plasmon resonance assay, quantitative competitive-PCR, ELISA, western blotting, flow cytometric analysis, and immunofluorescence were performed.

Results: Our results showed that GRh2 alleviated neuropathological damage and neuronal Apoptosis in cortical tissue of T. gondii-infected mice. GRh2 and CY-09 (an inhibitor of NLRP3) exhibited potent anti-T. gondii effects through binding T. gondii calcium-dependent protein kinase 1 (TgCDPK1). GRh2 decreased Iba-1 (a specific microglial marker) and NLRP3 inflammasome signaling pathway-related protein expression by binding NLRP3. Co-culture of microglia/primary cortical neurons revealed that T. gondii-induced microglial activation caused neuronal Apoptosis, but GRh2 reduced this effect, consistent with the effects of CY-09.

Conclusion: Taken together, our results show that GRh2 has a protective effect against T. gondii infection-induced neuronal injury by binding TgCDPK1 and NLRP3 to inhibit NLRP3 inflammasome signaling pathway in microglia.

Keywords

Ginsenoside Rh2; IL-1β; Microglia; NLRP3; Neuron; Toxoplasma gondii.

Figures
Products