A bioactive gypenoside (GP-14) alleviates neuroinflammation and blood brain barrier (BBB) disruption by inhibiting the NF-κB signaling pathway in a mouse high-altitude cerebral edema (HACE) model

Geng, Yanan; Yang, Jun‐Li; Cheng, Xiang; Han, Ying; Yan, Feng; Wang, Chengbo; Jiang, Xiufang; Meng, Xian‐Hua; Fan, Ming; Zhao, Ming; Zhu, Lijing

doi:10.1016/j.intimp.2022.108675

Cited by 20 publications

(9 citation statements)

References 32 publications

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“…Our previous studies found that GPs had a protective effect on PC12 cells against hypoxia injury and improved spatial memory impairment in mice that had been exposed to hypoxia [ 16 ]. Recently, one of the newly identified bioactive components of GPs, GP-14, was found to inhibit microglial activation, suppress the NF-κB pathway, and prevent pro-inflammatory cytokines from being produced in a mouse high-altitude cerebral edema (HACE) model [ 17 ]. Additionally, GP-14 pretreatment attenuated neuronal injury under hypoxic conditions through the AKT and ERK pathways [ 18 ].…”

Section: Introductionmentioning

confidence: 99%

Gypenoside-14 Reduces Depression via Downregulation of the Nuclear Factor Kappa B (NF-kB) Signaling Pathway on the Lipopolysaccharide (LPS)-Induced Depression Model

et al. 2023

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Neuroinflammation is a common pathogenetic sign of depression and is closely linked to the development of depression. Many clinical anti-inflammatory drugs act as antidepressants by reducing the neuroinflammatory response. Previous research found that gypenosides and their bioactive compound gypenoside-14 (GP-14) had neuroprotective effects against hypoxia-induced injury and reduced neuroinflammation-related high-altitude cerebral edema. Here we investigated the effects of GP-14 on the lipopolysaccharide (LPS)-induced depression-like behavior model. LPS (0.5 mg/kg) was injected into mice intraperitoneally for 7 consecutive days to induce depression-like behavior, which is considered a model for the exacerbation of depression. GP-14 in the amount of 100 mg/kg was simultaneously administered by gavage for 7 days. In the LPS-induced depression model, GP-14 not only attenuated depression-like behavior but also improved the anxiety-like behavior of the mice. Additionally, GP-14 treatment mitigated learning and cognitive decline in depressed mice. ELISA and immunofluorescence staining results revealed that GP-14 inhibited the upregulation of pro-inflammatory cytokines, including tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6), and suppressed the activation of astrocytes induced with LPS, indicating its potent anti-inflammatory effect. GP-14 pretreatment in C8 cells and primary astrocytes can inhibit the activation of the NF-κB signaling pathway and downregulate the levels of pro-inflammatory factors. In summary, our findings showed that GP-14 had significant anti-inflammation and anti-depression properties; thus, GP-14 could be a promising lead compound for treating depression.

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Section: Introductionmentioning

confidence: 99%

Gypenoside-14 Reduces Depression via Downregulation of the Nuclear Factor Kappa B (NF-kB) Signaling Pathway on the Lipopolysaccharide (LPS)-Induced Depression Model

et al. 2023

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“…Our research team has found in previous experiments that GPs and their bioactive compounds can prevent hypoxia‐induced damage through ERK, Akt, and CREB signaling pathways (Wang, Zhao, et al, 2020). In addition, the active compound GP‐14 was also found to have excellent anti‐inflammatory activity and excellent protective effect on high‐altitude cerebral edema model mice induced by hypoxia combined with LPS (Geng et al, 2022). However, the effect of gypenosides on eh hypoxia‐induced injuries remains unknown.…”

Section: Discussionmentioning

confidence: 99%

Gypenosides ( GPs ) alleviates hypoxia‐induced injury in PC12 cells and enhances tolerance to anoxia in C57BL /6 mice

Wang

Zhao

Wang³

et al. 2022

Journal of Food Biochemistry

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Oxygen is a necessary substance for life activities, but reduced oxygen utilization due to high altitude exposure and respiratory dysfunction diseases could lead to pathological changes in the organisms. Herein gypenosides, the active ingredients in the food and medicine resource plant Gynostemma pentaphyllum (Thunb.) Makino were found to alleviate hypoxia‐induced injury in PC12 cells. Moreover, hypoxia induced an increase in Ca2+ and reactive oxygen species content, and such patterns were both significantly reduced by gypenosides treatment. At the same time, gypenosides significantly blocked the decrease of both NO content and mitochondrial membrane potential caused by hypoxia. Furthermore, gypenosides gavage treatment significantly prolonged the survival time of C57BL/6 mice in confinement up to 24.3% and enhanced the locomotor ability of mice. Therefore, gypenosides have good neuroprotective effects and hypoxia tolerance activity and have the prospect of being developed as a preventive and therapeutic drug for hypoxia‐related diseases. Practical applications Gypenosides can enhance tolerance of cells and mice to hypoxia and have the potential to be developed into hypoxia‐resistant health food and drugs.

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“…The pattern recognition receptor TLR4 is expressed in microglia and participates in mediating some components of stress-induced in ammation, including NF-κB and IL-1β [39]. During the in ammatory process, the nuclear translocation of the NF-κB heterodimer is closely related to microglial activation [40]. Moreover, SRC has also been extensively explored in the context of neuroin ammation.…”

Section: Effects Of Mev On the Nf-κb Pathways In Lps-induced Depressi...mentioning

confidence: 99%

Antidepressant-like effect of 5-O-methylvisammioside targeting SRC is accompanied by hippocampal neuroinflammation reduction in lipopolysaccharide-challenged mice

Zhu,

Li,

Cui

2024

Preprint

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5-O-methylvisammioside (MeV), a phenolic compound found in the underground part (radix) Saposhnikovia divaricate (Turcz. ex Ledeb.) Schischk. (Apiaceae) in the early stage, has also been detected in the extract of Eranthis longistipitata(Ranunculaceae) in recent literature. In previous studies, it was discovered to have anti-inflammatory and neuroprotective activities. However, the potential mechanisms of MeV antidepressants remain unclear. In the present study, Network pharmacology was adopted to conduct drug-target networks following obtaining the shared targets between MeV and major depressive disorder (MDD) in multiple databases. The binding ability of the compound to the core target was verified through molecular docking. In addition, the biological processes and signaling pathways involved in the antidepressant effect of MeV by animal experiments. Our results were as follows: i) There were 85 shared targets of MeV & MDD in multiple public databases. The target protein with a higher degree in the protein-protein interaction (PPI) network was Proto-oncogene tyrosine-protein kinase Src (SRC). ii) Gene Ontology analysis showed that MeV treatment of MDD mainly involves the positive regulation of phosphorylation, the response to lipopolysaccharide, and other biological processes. It was closely related to the nuclear factor kappa B (NF-κB) signaling pathway. iii) MeV administration significantly alleviated depression-like behaviors and reduced microgliosis in mice by inhibiting SRC phosphorylation. The antidepressant effects of MeV may be attributed to the NF-κB signaling pathway. The results may contribute to demonstrating the effectiveness of MeV against MDD and facilitate the development of new traditional Chinese medicine ingredients.

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A bioactive gypenoside (GP-14) alleviates neuroinflammation and blood brain barrier (BBB) disruption by inhibiting the NF-κB signaling pathway in a mouse high-altitude cerebral edema (HACE) model

Cited by 20 publications

References 32 publications

Gypenoside-14 Reduces Depression via Downregulation of the Nuclear Factor Kappa B (NF-kB) Signaling Pathway on the Lipopolysaccharide (LPS)-Induced Depression Model

Gypenoside-14 Reduces Depression via Downregulation of the Nuclear Factor Kappa B (NF-kB) Signaling Pathway on the Lipopolysaccharide (LPS)-Induced Depression Model

Gypenosides ( GPs ) alleviates hypoxia‐induced injury in PC12 cells and enhances tolerance to anoxia in C57BL /6 mice

Antidepressant-like effect of 5-O-methylvisammioside targeting SRC is accompanied by hippocampal neuroinflammation reduction in lipopolysaccharide-challenged mice

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