Hesperidin Alleviates Lipopolysaccharide-Induced Neuroinflammation in Mice by Promoting the miRNA-132 Pathway

Li, Min; Shao, Hu; Zhang, Xia; Qin, Bingyu

doi:10.1007/s10753-016-0402-7

Cited by 41 publications

(18 citation statements)

References 38 publications

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“…Naringin restores the unpredictable chronic stress-induced depressive behavior and decreases serum TNF- α and IL-1 β levels in mice [ 42 ]. Hesperidin shows antidepressant-like effects and reduces prefrontal cortical IL-1 β , IL-6, and TNF- α levels in lipopolysaccharide-treated ICR mice [ 43 ]. Neohesperidin decreases hepatic cyclooxygenase-2 and NF- κ B expression in paraquat-induced acute liver injury of mice [ 44 ].…”

Section: Discussionmentioning

confidence: 99%

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

Jia

Ding

et al. 2018

Mediators of Inflammation

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Depression is a common mental disorder in modern society. A traditional Chinese medicine Huanglian-Wendan decoction with potential anti-inflammation is used as a clinical antidepressant. Our previous study showed central and peripheral inflammatory responses in a rat model of depression developed by chronic unpredictable mild stress (CUMS). Here, we investigated the anti-inflammatory activity and mechanism of Huanglian-Wendan decoction in CUMS rats. LC-MS/MS and HPLC were performed to determine the major compounds in water extract of this decoction. This study showed that Huanglian-Wendan decoction significantly increased sucrose consumption and reduced serum levels of interleukin-1 beta (IL-1β), IL-6, and alanine aminotransferase (ALT) in CUMS rats. Moreover, this decoction inhibited nuclear entry of nuclear factor-kappa B (NF-κB) with the reduction of phosphorylated protein of NF-κB (p-NF-κB) and inhibitor of NF-κB alpha (p-IκBα) and downregulated protein of nod-like receptor family pyrin domain-containing 3 (NLRP3), apoptosis-associated speck-like protein containing CARD (ASC), cysteinyl aspartate-specific proteinase-1 (Caspase-1), and IL-1β in liver and brain regions of CUMS rats. These findings demonstrated that Huanglian-Wendan decoction had antidepressant activity with hepatoprotection in CUMS rats coinciding with its anti-inflammation in both periphery and central. The inhibitory modulation of NF-κB and NLRP3 inflammasome activation by Huanglian-Wendan decoction may mediate its antidepressant action.

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Section: Discussionmentioning

confidence: 99%

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

Jia

Ding

et al. 2018

Mediators of Inflammation

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“…Further studies investigating the therapeutic effects of kososan extract in comparison with existing antidepressant treatments [17] using the CSDS paradigm may be useful in the development of therapeutic strategies. Fourth, the active ingredient(s) of kososan extract particularly associated with the anti-inflammatory benefits and behavioral recovery still remains unclear, although there is some evidence indicating that antidepressant-like effects of apigenin [32] and hesperidin [38] are involved in their anti-inflammatory activities. It has been reported that nobiletin, a polymethoxyflavone in the peels of citrus fruits such as C. unshiu Markovich (a component herb of kososan), rapidly crosses the blood-brain barrier [81, 82] and that it exerts anti-inflammatory effects in response to LPS-stimulated BV-2 and RAW 264.7 cells (murine microglia and macrophage cell lines, respectively) [83–85].…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, our recent study suggests that psychological stress-induced depression-like behaviors in mice were mitigated by treatment with kososan, but not the antidepressant milnacipran [31], a serotonin-noradrenaline reuptake inhibitor. Besides, many rodent studies have shown that some compounds (e.g., apigenin [32, 33], caffeic acid [34], perillaldehyde [35, 36], and rosmarinic acid [37] contained in Perillae Herba; hesperidin [38, 39] and nobiletin [40, 41] contained in Aurantii Nobilis Pericarpium) exert antidepressant-like effects. Although there is increasing evidence for kososan’s therapeutic benefits for depression-like behaviors in preclinical studies, little is known about the efficacy of kososan in the behavioral abnormalities caused by CSDS as an animal model of psychosocial stress.…”

Section: Introductionmentioning

confidence: 99%

Kososan, a Kampo medicine, prevents a social avoidance behavior and attenuates neuroinflammation in socially defeated mice

Ito

Hirose

Ishida

et al. 2017

J Neuroinflammation

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BackgroundKososan, a Kampo (traditional Japanese herbal) medicine, has been used for the therapy of depressive mood in humans. However, evidence for the antidepressant efficacy of kososan and potential mechanisms are lacking. Recently, it has been recognized that stress triggers neuroinflammation and suppresses adult neurogenesis, leading to depression and anxiety. Here, we examined whether kososan extract affected social behavior in mice exposed to chronic social defeat stress (CSDS), an animal model of prolonged psychosocial stress, and neuroinflammation induced by CSDS.MethodsIn the CSDS paradigm, C57BL/6J mice were exposed to 10 min of social defeat stress from an aggressive CD-1 mouse for 10 consecutive days (days 1–10). Kososan extract (1.0 g/kg) was administered orally once daily for 12 days (days 1–12). On day 11, the social avoidance test was performed to examine depressive- and anxious-like behaviors. To characterize the impacts of kososan on neuroinflammation and adult neurogenesis, immunochemical analyses and ex vivo microglial stimulation assay with lipopolysaccharide (LPS) were performed on days 13–15.ResultsOral administration of kososan extract alleviated social avoidance, depression- and anxiety-like behaviors, caused by CSDS exposure. CSDS exposure resulted in neuroinflammation, as indicated by the increased accumulation of microglia, the resident immune cells of the brain, and their activation in the hippocampus, which was reversed to normal levels by treatment with kososan extract. Additionally, in ex vivo studies, CSDS exposure potentiated the microglial pro-inflammatory response to a subsequent LPS challenge, an effect that was also blunted by kososan extract treatment. Indeed, the modulatory effect of kososan extract on neuroinflammation appears to be due to a hippocampal increase in an anti-inflammatory phenotype of microglia while sparing an increased pro-inflammatory phenotype of microglia caused by CSDS. Moreover, reduced adult hippocampal neurogenesis in defeated mice was recovered by kososan extract treatment.ConclusionsOur findings suggest that kososan extract prevents a social avoidant behavior in socially defeated mice that is partially mediated by the downregulation of hippocampal neuroinflammation, presumably by the relative increased anti-inflammatory microglia and regulation of adult hippocampal neurogenesis. Our present study also provides novel evidence for the beneficial effects of kososan on depression/anxiety and the possible underlying mechanisms.Electronic supplementary materialThe online version of this article (doi:10.1186/s12974-017-0876-8) contains supplementary material, which is available to authorized users.

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“…In fact, growing evidence has demonstrated that miR-132 can affect the functions of inflammatory and neurotrophic systems, both of which are implicated in the pathogenesis of depression ( 23 , 24 ). A previous study demonstrated that hesperidin increases miR-132 expression in the prefrontal cortex of lipopolysaccharide-treated mice, suggesting that miR-132 is implicated in the function of hesperidin as an antidepressant ( 25 ). Other studies have speculated that the increased expression of miR-132 may protect the brain by stimulating the synthesis of neurotrophin and by blocking the onset of neuroinflammation ( 26 , 27 ).…”

Section: Introductionmentioning

confidence: 99%

“…It has been reported that the administration of hesperidin can upregulate the expression of miR-132, which is a potential regulator of haematological and neurological expressed 1 (HN1), TGF-β1 and ZEB2 ( 25 , 28 - 30 ). In addition, HN1, TGF-β1 and ZEB2 have been shown to be involved in the pathogenesis of NSCLC ( 31 - 34 ).…”

Section: Introductionmentioning

confidence: 99%

Hesperidin administration suppresses the proliferation of lung cancer cells by promoting apoptosis via targeting the miR‑132/ZEB2 signalling pathway

et al. 2020

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This aim of the present study was to identify the relationship between hesperidin and microRNA (miR)-132, and to study the role of hesperidin and miR-132 in the pathogenesis of non-small cell lung cancer (NSCLC). Computational analysis and luciferase assays were performed to identify the target of miR-132. Subsequently, reverse transcription-quantitative PCR and western blot assays were used to detect the effect of miR-132 and hesperidin on the expression of haematological and neurological expressed 1 (HN1) and zinc finger E-box binding homeobox 2 (ZEB2). Finally, MTT assays and flow cytometry analysis were used to investigate the effect of hesperidin on cell proliferation and apoptosis. ZEB2 was identified as a target gene of miR-132, and transfection with miR-132 mimic reduced the luciferase activity of the wild-type ZEB2 3′-untranslated region (3′-UTR) but not that of the mutant ZEB2 3′-UTR. By contrast, neither transfection with miR-132 mimic nor hesperidin treatment affected HN1 expression. Furthermore, hesperidin evidently inhibited cell proliferation and promoted apoptosis in a dose-dependent manner. Furthermore, the tumour volume in rats transplanted with NSCLC cells and treated with hesperidin was notably smaller compared with that in rats transplanted with NSCLC cells alone, while treatment with hesperidin significantly reduced the colony formation efficiency of NSCLC cells by increasing miR-132 expression and decreasing ZEB2 expression. To the best of our knowledge, the present study demonstrated for the first time that the administration of hesperidin decreased the expression of ZEB2 by upregulating the expression of miR-132, which in turn promoted apoptosis and inhibited the proliferation of NSCLC cells.

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Hesperidin Alleviates Lipopolysaccharide-Induced Neuroinflammation in Mice by Promoting the miRNA-132 Pathway

Cited by 41 publications

References 38 publications

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

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

Kososan, a Kampo medicine, prevents a social avoidance behavior and attenuates neuroinflammation in socially defeated mice

Hesperidin administration suppresses the proliferation of lung cancer cells by promoting apoptosis via targeting the miR‑132/ZEB2 signalling pathway

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