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

Jin, Guang-Nan; Lu, Jing-Mei; Lan, Hui-Wen; Lu, Yu-Nan; Shen, Xinyu; Xu, Xiang; Li, Piao

doi:10.1016/j.intimp.2022.109176

Cited by 20 publications

(8 citation statements)

References 65 publications

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“…Since lentinan could decrease cyst burden in the brains of T. gondii -infected mice, we next determined whether lentinan has a direct anti- T. gondii effect or inhibits the proliferation of tachyzoites in BV2 cells according to a previously reported method [ 45 , 46 , 48 , 49 ]. First, we cultivated free tachyzoites of the T. gondii RH strain with different concentrations of lentinan or SD (a classic anti-toxoplasmosis drug used in the clinic).…”

Section: Resultsmentioning

confidence: 99%

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Lentinan has a beneficial effect on cognitive deficits induced by chronic Toxoplasma gondii infection in mice

Liu,

Yan,

Peng

et al. 2023

Parasites Vectors

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Background Toxoplasma gondii (T. gondii) is increasingly considered a risk factor for neurodegenerative diseases. However, there is only limited information on the development of drugs for T. gondii infection. Lentinan from Lentinula edodes is a bioactive ingredient with the potential to enhance anti-infective immunity. The present study aimed to investigate the neuroprotective effect of lentinan on T. gondii-associated cognitive deficits in mice. Methods A chronic T. gondii infection mouse model was established by administering 10 cysts of T. gondii by gavage. Lentinan was intraperitoneally administered 2 weeks before infection. Behavioral tests, RNA sequencing, immunofluorescence, transmission electron microscopy and Golgi-Cox staining were performed to assess the effect of lentinan on cognitive deficits and neuropathology in vivo. In vitro, the direct and indirect effects of lentinan on the proliferation of T. gondii tachyzoites were evaluated in the absence and presence of BV-2 cells, respectively. Results Lentinan prevented T. gondii-induced cognitive deficits and altered the transcriptome profile of genes related to neuroinflammation, microglial activation, synaptic function, neural development and cognitive behavior in the hippocampus of infected mice. Moreover, lentinan reduced the infection-induced accumulation of microglia and downregulated the mRNA expression of proinflammatory cytokines. In addition, the neurite and synaptic ultrastructural damage in the hippocampal CA1 region due to infection was ameliorated by lentinan administration. Lentinan decreased the cyst burden in the brains of infected mice, which was correlated with behavioral performance. In line with this finding, lentinan could significantly inhibit the proliferation of T. gondii tachyzoites in the microglial cell line BV2, although lentinan had no direct inhibitory effect on parasite growth. Conclusions Lentinan prevents cognitive deficits via the improvement of neurite impairment and synaptic loss induced by T. gondii infection, which may be associated with decreased cyst burden in the brain. Overall, our findings indicate that lentinan can ameliorate T. gondii-related neurodegenerative diseases. Graphical Abstract

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Section: Resultsmentioning

confidence: 99%

“…The images were captured using a fluorescence microscope (Eclipse C1, Nikon, Japan). T. gondii tachyzoites were shown colored in green and the nuclei in blue [ 48 , 49 ].…”

Section: Methodsmentioning

confidence: 99%

Lentinan has a beneficial effect on cognitive deficits induced by chronic Toxoplasma gondii infection in mice

Liu,

Yan,

Peng

et al. 2023

Parasites Vectors

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“…GRc regulates FoxO1 phosphorylation by activating PI3K/Akt and inhibits AMPK and FoxO1 acetylation by interacting with SIRT1, and this leads to upregulation of peroxidase under oxidative stress conditions (Kim et al, 2014). GRh2 decreased Iba‐1 and NLRP3 inflammasome signaling pathway‐related protein expression by binding NLRP3 (Jin et al, 2022). The potential protective mechanism of GRh2 is through selective upregulation of PI3K/Akt and inhibition of ERK activation (Hou, Xue, et al, 2018).…”

Section: Potential Mechanisms Of Tcm and Its Major Bioactive Constitu...mentioning

confidence: 99%

Traditional Chinese medicines treat ischemic stroke and their main bioactive constituents and mechanisms

Fan,

Liu,

Liu

et al. 2023

Phytotherapy Research

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Ischemic stroke (IS) remains one of the leading causes of death and disability in humans. Unfortunately, none of the treatments effectively provide functional benefits to patients with IS, although many do so by targeting different aspects of the ischemic cascade response. The advantages of traditional Chinese medicine (TCM) in preventing and treating IS are obvious in terms of early treatment and global coordination. The efficacy of TCM and its bioactive constituents has been scientifically proven over the past decades. Based on clinical trials, this article provides a review of commonly used TCM patent medicines and herbal decoctions indicated for IS. In addition, this paper also reviews the mechanisms of bioactive constituents in TCM for the treatment of IS in recent years, both domestically and internationally. A comprehensive review of preclinical and clinical studies will hopefully provide new ideas to address the threat of IS.

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“…This aids in repairing the neuronal damage caused by Toxoplasma infection. 33 Simultaneously, GRh2 promotes autophagy, inhibits pyroptosis and apoptosis, and reduces oxidative stress levels. 34−36 These findings indicate that GRh2 may have a beneficial effect on secondary damage after SCI.…”

Section: Introductionmentioning

confidence: 99%

Ginsenoside-Rh2 Promotes Functional Recovery after Spinal Cord Injury by Enhancing TFEB-Mediated Autophagy

Liu,

Jiang,

Chen

et al. 2024

J. Agric. Food Chem.

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Background: Following spinal cord injury (SCI), autophagy plays a positive role in neuronal protection, whereas pyroptosis triggers an inflammatory response. Ginsenoside-Rh2 (GRh2), known for its neuroprotective effects, is considered a promising drug. However, the exact molecular mechanisms underlying these protective effects remain unclear. Aim of the Study: Explore the therapeutic value of GRh2 in SCI and its potential mechanisms of action. Materials and Methods: An SCI mouse model was established, followed by random grouping and drug treatments under different conditions. Subsequently, the functional recovery of SCI mice after GRh2 treatment was assessed using hematoxylin and eosin, Masson's trichrome, and Nissl staining, footprint analysis, Basso Mouse Scale scoring, and inclined plane tests. The expression levels of relevant indicators in the mice were detected using Western blotting, immunofluorescence, and a quantitative polymerase chain reaction. Network pharmacology analysis was used to identify the relevant signaling pathways through which GRh2 exerts its therapeutic effects. Results: GRh2 promoted functional recovery after SCI. GRh2 significantly inhibits pyroptosis by enhancing autophagy in SCI mice. Simultaneously, the neuroprotective effect of GRh2, achieved through the inhibition of pyroptosis, is partially reversed by 3-methyladenine, an autophagy inhibitor. Additionally, the increase in autophagy induced by GRh2 is mediated by the promotion of transcription factor EB (TFEB) nuclear translocation and dephosphorylation. Partial attenuation of the protective effects of GRh2 was observed after TFEB knockdown. Additionally, GRh2 can modulate the activity of TFEB in mice post-SCI through the EGFR-MAPK signaling pathway, and NSC228155 (an EGFR activator) can partially reverse the effect of GRh2 on the EGFR-MAPK signaling pathway. Conclusions: GRh2 improves functional recovery after SCI by upregulating TFEB-mediated autophagic flux and inhibiting pyroptosis, indicating its potential clinical applicability.

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

Cited by 20 publications

References 65 publications

Lentinan has a beneficial effect on cognitive deficits induced by chronic Toxoplasma gondii infection in mice

Lentinan has a beneficial effect on cognitive deficits induced by chronic Toxoplasma gondii infection in mice

Traditional Chinese medicines treat ischemic stroke and their main bioactive constituents and mechanisms

Ginsenoside-Rh2 Promotes Functional Recovery after Spinal Cord Injury by Enhancing TFEB-Mediated Autophagy

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