Huanglian-Wendan Decoction Inhibits NF-<i>κ</i>B/NLRP3 Inflammasome Activation in Liver and Brain of Rats Exposed to Chronic Unpredictable Mild Stress

Jia, Ke-Ke; Ding, Hong; Yu, Hanwen; Dong, Tiejun; Pan, Ying; Kong, Ling-Dong

doi:10.1155/2018/3093516

Cited by 33 publications

(17 citation statements)

References 37 publications

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“…Depression has been on the rise in recent years as a result of increases in stress in everyday life. Increasing evidence has indicated that the excessive secretion of proinflammatory cytokines, including MCP-1, IL-1β, IL-6, and TNF-α, results in behavior similar to that of depression [ 28 ]. Here, we also found that MCP-1, IL-1β, IL-6, and TNF-α expression was increased after the induction of depression in both in vivo and in vitro experiments.…”

Section: Discussionmentioning

confidence: 99%

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Adipose-derived mesenchymal stem cells protect against CMS-induced depression-like behaviors in mice via regulating the Nrf2/HO-1 and TLR4/NF-κB signaling pathways

et al. 2019

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Increasing studies show that inflammatory processes may be involved in depressive disorders. Nuclear factor erythroid-2 related factor 2 (Nrf2) modulates tissue microglial M1 phenotypic changes to the M2 phenotype, which is implicated in protection against inflammatory diseases. We have reported that the adipose-derived mesenchymal stem cells (ADSCs) display anti-inflammatory activity. In this study we explored whether the mechanism of anti-inflammatory activity of ADSCs was related to Nrf2. ADSCs were isolated from mouse fat pads and intravenously administered to chronic mild stress (CMS)-exposed C57BL/6 mice at the dose of 1 × 10 6 once a week for 3 weeks. We showed that ADSC administration significantly remedied CMS-induced depressive-like behaviors in sucrose preference test, tail suspension test, and forced swim test accompanied by suppressing microglial activation and the expression of inflammatory factors including MCP-1, TNF-α, IL-1β, and IL-6. Furthermore, ADSC administration promoted both the expression of BDNF and TrkB, and promoted Nrf2/HO-1 signaling but suppressed TLR4/NF-κB signaling in brain tissue. In order to elucidate the role of Nrf2/HO-1 signaling in ADSC-caused neuroprotection, Nrf2-modified ADSCs were cocultured with BV2 microglial cells, then exposed to lipopolysaccharide (LPS). Downregulation of Nrf2 in ADSCs decreased the protective effects of ADSCs against LPS-induced microglial activation and M1 polarization. Nrf2 overexpression in ADSCs markedly suppressed LPS-induced TLR4 and NF-κB expression in microglial cells. These results suggest a possible antidepressive mechanism correlated with microglial polarization for anti-inflammatory agents, which may provide a new microglia-targeted strategy for depression therapy.

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Section: Discussionmentioning

confidence: 99%

“…The tissues were cut coronally into 4-μm slices with a sliding vibratome (CM1900; Leica Microsystems, Wetzlar, Germany). The immunofluorescence and statistical methods were based on previously described methods [ 28 ]. Brains sections that contained the hippocampus were permeabilized with 0.5% Triton X-100 for 10 min.…”

Section: Methodsmentioning

confidence: 99%

Adipose-derived mesenchymal stem cells protect against CMS-induced depression-like behaviors in mice via regulating the Nrf2/HO-1 and TLR4/NF-κB signaling pathways

et al. 2019

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“…Several in vitro and in vivo studies suggested that Andro was able to activate the Wnt/β-Catenin signalling pathway, inducing the transcription of Wnt target genes and inhibiting glycogen synthase kinase3β (GSK3β) by dephosphorylation (Jiang et al, 2015; Tapia-Rojas et al, 2015; Varela-Nallar et al, 2015). Many studies have implicated the role of β-Catenin, GSK3β, NF-κB, and the NLRP3 inflammasome in the pathogenesis of depression, as (1) chronic stress significantly reduced the total and nuclear levels of β-Catenin in the hippocampus of rats (Hui et al, 2018); (2) GSK3β was highly expressed and phosphorylated in the brain of chronically stressed mice, while inhibition of GSK3β led to antidepressant-like actions (Peng et al, 2018); and (3) several antidepressants exerted antidepressant-like effects in mice via the inhibition of NF-κB and the NLRP3 inflammasome (Jia et al, 2018; Song et al, 2018a, 2018b). Therefore, it is possible that these molecules also contribute to the antidepressant-like actions of Andro in mice, and more antagonists/shRNAs will be used in our further study.…”

Section: Discussionmentioning

confidence: 99%

Andrographolide Exerts Significant Antidepressant-Like Effects Involving the Hippocampal BDNF System in Mice

Zhang

Gao

Wang

et al. 2019

International Journal of Neuropsychopharmacology

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Background Major depressive disorder is a worldwide neuropsychiatric disorder associated with various symptoms, but current antidepressants used in clinical practice have various side effects and high failure rates. Andrographolide is the main bioactive ingredient of Andrographis paniculata and exhibits numerous pharmacological actions. This study aimed to evaluate the antidepressant-like effects of andrographolide in male C57BL/6J mice. Methods The antidepressant-like effects of andrographolide in mice were explored in a forced swim test, tail suspension test, and chronic unpredictable mild stress model of depression. Western blotting and immunofluorescence were further performed to assess the effects of chronic unpredictable mild stress and andrographolide on the brain-derived neurotrophic factor signalling cascade and hippocampal neurogenesis. Moreover, a pharmacological inhibitor (K252a) and a lentiviral-short hairpin RNA (LV-TrkB-shRNA) were used to clarify the antidepressant-like mechanism of andrographolide. Results Andrographolide exhibited antidepressant-like potential in the forced swim test and tail suspension test without influencing the locomotor activity of mice. Repeated andrographolide treatment not only produced significant antidepressant-like effects in the chronic unpredictable mild stress model but also prevented the decreasing effects of chronic unpredictable mild stress on hippocampal brain-derived neurotrophic factor signalling and neurogenesis in mice. Importantly, blockade of the hippocampal brain-derived neurotrophic factor system by K252a and TrkB-shRNA fully abolished the antidepressant-like effects of andrographolide in mice. Conclusions Andrographolide exerts antidepressant-like effects in mice via promoting the hippocampal brain-derived neurotrophic factor signalling cascade.

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“…At the same time, confocal microscopy analysis intuitively demonstrated the inhibitory effect of HZTF on ASC dimerization. These results suggested that HZTF may prevent gout by inhibiting NALP3 inflammasome as well as blocking the NF- κ b signaling pathway, which will increase the expression of IL-1 β , IL-6, and TNF- α [49].…”

Section: Discussionmentioning

confidence: 99%

Suppressive Effect of Huzhentongfeng on Experimental Gouty Arthritis: An In Vivo and In Vitro Study

Xue²,

Zhao

et al. 2019

Evidence-Based Complementary and Alternative Medicine

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Background Huzhentongfeng (HZTF) is an extract from four Chinese medical herbs for treating gout. This study aims to evaluate its antigout activity and preliminary explore its mechanism in vivo and in vitro. Methods The rats were intragastrically administered with HZTF for 5 days and then injected 0.1 ml (10 mg) of MSU crystals to their joints for generating a gout model to analyze the paw volume and histopathology of joint synovial tissues of rats with different doses. We also investigated the antioxidant capacity of HZTF in vitro using indication including lipid peroxidation, DPPH·, and ABTS+ radical-scavenging capacity; besides, we used qRT-PCR to measure the effect of HZTF on interleukin (IL)-1β, caspase-1, NLRP3, and NQO1 expression in hydrogen peroxide-stimulated RAW264.7 macrophages and IL-1β, IL-6, and tumor necrosis factor (TNF)-α in MSU crystal-induced THP-1 monocytes. Confocal microscopy analysis was used to observe the dimerization of ASC adapter proteins. In addition, we also established quality standard of HZTF by using the high-performance liquid chromatography (HPLC) method. Results HZTF could significantly suppress the paw swelling and neutrophil infiltration induced by MSU intra-articular injection in rats compared with the control group. HZTF also showed inhibition effects of inflammatory cytokines (IL-1β, IL-6, and TNF-α) secretion at 25.00 and 50.00 μg/ml in MSU-induced THP-1 cells but showed no effects of IL-1β, IL-6, and TNF-α mRNA expression in MSU-induced THP-1 cells. Furthermore, confocal microscopy analysis showed that HZTF could prevent the oligomerization of ASC. Moreover, HZTF also showed effects in cell-free and cell-base tests of antioxidant capacity. Conclusion The results prove that HZTF possessed the potential preventive effect against gout arthritis, and the effect may be attributed to its preventing effect on neutrophil infiltration and proinflammatory cytokines secretion such as IL-1β, IL-6, and TNF-α which were caused by the activation of inflammasome.

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Huanglian-Wendan Decoction Inhibits NF-κB/NLRP3 Inflammasome Activation in Liver and Brain of Rats Exposed to Chronic Unpredictable Mild Stress

Cited by 33 publications

References 37 publications

Adipose-derived mesenchymal stem cells protect against CMS-induced depression-like behaviors in mice via regulating the Nrf2/HO-1 and TLR4/NF-κB signaling pathways

Adipose-derived mesenchymal stem cells protect against CMS-induced depression-like behaviors in mice via regulating the Nrf2/HO-1 and TLR4/NF-κB signaling pathways

Andrographolide Exerts Significant Antidepressant-Like Effects Involving the Hippocampal BDNF System in Mice

Suppressive Effect of Huzhentongfeng on Experimental Gouty Arthritis: An In Vivo and In Vitro Study

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