Dataset Information

Ginsenoside Rh2 reduces depression in offspring of mice with maternal toxoplasma infection during pregnancy by inhibiting microglial activation via the HMGB1/TLR4/NF-κB signaling pathway.

ABSTRACT:

Background

Maternal Toxoplasma gondii (T. gondii) infection during pregnancy has been associated with various mental illnesses in the offspring. Ginsenoside Rh2 (GRh2) is a major bioactive compound obtained from ginseng that has an anti-T. gondii effect and attenuates microglial activation through toll-like receptor 4 (TLR4)/nuclear factor-kappa B (NF-κB) signaling pathway. GRh2 also alleviated tumor-associated or lipopolysaccharide-induced depression. However, the effects and potential mechanisms of GRh2 on depression-like behavior in mouse offspring caused by maternal T. gondii infection during pregnancy have not been investigated.

Methods

We examined GRh2 effects on the depression-like behavior in mouse offspring, caused by maternal T. gondii infection during pregnancy, by measuring depression-like behaviors and assaying parameters at the neuronal and molecular level.

Results

We showed that GRh2 significantly improved behavioral measures: sucrose consumption, forced swim time and tail suspended immobility time of their offspring. These corresponded with increased tissue concentrations of 5-hydroxytryptamine and dopamine, and attenuated indoleamine 2,3-dioxygenase or enhanced tyrosine hydroxylase expression in the prefrontal cortex. GRh2 ameliorated neuronal damage in the prefrontal cortex. Molecular docking results revealed that GRh2 binds strongly to both TLR4 and high mobility group box 1 (HMGB1).

Conclusion

This study demonstrated that GRh2 ameliorated the depression-like behavior in mouse offspring of maternal T. gondii infection during pregnancy by attenuating the excessive activation of microglia and neuroinflammation through the HMGB1/TLR4/NF-κB signaling pathway. It suggests that GRh2 could be considered a potential therapy in preventing and treating psychiatric disorders in the offspring mice of mothers with prenatal exposure to T. gondii infection.

SUBMITTER: Xu X

PROVIDER: S-EPMC8753429 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature

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Publications

Ginsenoside Rh2 reduces depression in offspring of mice with maternal toxoplasma infection during pregnancy by inhibiting microglial activation via the HMGB1/TLR4/NF-κB signaling pathway.

Xu Xiang X Lu Yu-Nan YN Cheng Jia-Hui JH Lan Hui-Wen HW Lu Jing-Mei JM Jin Guang-Nan GN Xu Guang-Hua GH Jin Cheng-Hua CH Ma Juan J Piao Hu-Nan HN Jin Xuejun X Piao Lian-Xun LX

Journal of ginseng research 20210428 1

<h4>Background</h4>Maternal <i>Toxoplasma gondii</i> (<i>T. gondii</i>) infection during pregnancy has been associated with various mental illnesses in the offspring. Ginsenoside Rh2 (GRh2) is a major bioactive compound obtained from ginseng that has an anti-<i>T. gondii</i> effect and attenuates microglial activation through toll-like receptor 4 (TLR4)/nuclear factor-kappa B (NF-κB) signaling pathway. GRh2 also alleviated tumor-associated or lipopolysaccharide-induced depression. However, the e ...[more]

PMID: 35035240

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Project description:Acute lung injury (ALI) with uncontrolled inflammatory response has high morbidity and mortality rates in critically ill patients. Pathogen-associated molecular patterns (PAMPs) are involved in the development of uncontrolled inflammatory response injury and associated lethality. In this study, we investigated the inhibit effect of MS19, a microsatellite DNA-derived oligodeoxynucleotide (ODN) with AAAG repeats, on the inflammatory response induced by various PAMPs in vitro and in vivo. In parallel, a microsatellite DNA with AAAC repeats, named as MS19-C, was used as controls. We found that MS19 extensively inhibited the expression of inflammatory cytokines interleukin (IL)-6 and tumor necrosis factor (TNF)-α induced by various PAMPs stimulation, including DNA viruses, RNA viruses, bacterial components lipopolysaccharide (LPS), and curdlan, as well as the dsDNA and dsRNA mimics, in primed bone marrow-derived macrophage (BMDM). Other than various PAMPs, MS19 also demonstrated obvious effects on blocking the high mobility group box1 (HMGB1), a representative damage-associated-molecular pattern (DAMP), nuclear translocation and secretion. With the base substitution from G to C, MS19-C has been proved that it has lost the inhibitory effect. The inhibition is associated with nuclear factor kappa B (NF-κB) signaling but not the mitogen-activated protein kinase (MAPK) transduction. Moreover, MS19 capable of inhibiting the IL-6 and TNF-α production and blocking the HMGB1 nuclear translocation and secretion in LPS-stimulated cells was used to treat mice ALI induced by LPS in vivo. In the ALI mice model, MS19 significantly inhibited the weight loss and displayed the dramatic effect on lessening the ALI by reducing consolidation, hemorrhage, intra-alveolar edema in lungs of the mice. Meanwhile, MS19 could increase the survival rate of ALI by downregulating the inflammation cytokines HMGB1, TNF-a, and IL-6 production in the bronchoalveolar lavage fluid (BALF). The data suggest that MS19 might display its therapeutic role on ALI by inhibiting the HMGB1-TLR4-NF-κB signaling pathway.

Dataset Information

Ginsenoside Rh2 reduces depression in offspring of mice with maternal toxoplasma infection during pregnancy by inhibiting microglial activation via the HMGB1/TLR4/NF-κB signaling pathway.

Background

Methods

Results

Conclusion

Publications

Ginsenoside Rh2 reduces depression in offspring of mice with maternal toxoplasma infection during pregnancy by inhibiting microglial activation via the HMGB1/TLR4/NF-κB signaling pathway.

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