Dataset Information

The Anti-Depressive Effects of Hesperidin and the Relative Mechanisms Based on the NLRP3 Inflammatory Signaling Pathway.

ABSTRACT: There is increasing evidence showing that inflammation is associated with depression in humans. Hesperidin, a natural bioflavonoid, has performed excellent effects on depression. The aim of this research was to investigate the therapeutic e?ect of hesperidin on chronic unpredictable mild stress (CUMS)-induced rats. The sucrose preference test (SPT), forced swimming test (FST), and open ?eld test (OFT) were performed to measure the depression-related symptoms. The enzyme-linked immunosorbent assay (ELISA) was used to determine the concentrations of interleukin (IL)-1?, IL-6, and tumor necrosis factor (TNF)-? in the prefrontal cortex (PFC) of rats and cellular supernatant. PCR and Western blot were used to monitor the differences of NLRP3, caspase-1, ASC activation in the levels of genes and proteins in the PFC of rats and microglia. The activation of microglia was determined using immunofluorescence staining and flow cytometry assay. Our results show that hesperidin treatment signi?cantly relieved depressive like behaviors in CUMS rats. In addition, hesperidin decreased the expression levels of IL-1?, IL-6, TNF-?, NLRP3, caspase-1, and ASC in the PFC and microglia. This study investigated that hesperidin treatment ameliorated CUMS-induced depression by suppressing microglia and inflammation.

SUBMITTER: Xie L

PROVIDER: S-EPMC7456860 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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The Anti-Depressive Effects of Hesperidin and the Relative Mechanisms Based on the NLRP3 Inflammatory Signaling Pathway.

Xie Lulu L Gu Zhimin Z Liu Haizhao H Jia Beitian B Wang Yiyang Y Cao Min M Song Ruiwen R Zhang Zhaiyi Z Bian Yuhong Y

Frontiers in pharmacology 20200814

There is increasing evidence showing that inflammation is associated with depression in humans. Hesperidin, a natural bioflavonoid, has performed excellent effects on depression. The aim of this research was to investigate the therapeutic eﬀect of hesperidin on chronic unpredictable mild stress (CUMS)-induced rats. The sucrose preference test (SPT), forced swimming test (FST), and open ﬁeld test (OFT) were performed to measure the depression-related symptoms. The enzyme-linked immunosorbent assa ...[more]

PMID: 32922291

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Project description:BackgroundSepsis is an excessive inflammatory response to an infection that fails to return to homeostasis. It occurs frequently in patients following a primary infection or injury and is one of the most common causes of mortality in hospitalized patients. However, there is currently no specific and effective therapy for the management of sepsis. Previous findings have suggested that cinnamon and cinnamon extracts have anti-inflammatory and anti-oxidative activities and therefore, may be effective in treating sepsis.MethodsIn the present study, Escherichia coli was injected into mice to induce sepsis. Hematoxylin and eosin staining was used to investigate the influence of cinnamyl alcohol on histological changes including heart, liver, lung, and kidney tissues. Western blotting and real-time polymerase chain reaction (RT-PCR) were applied to measure the levels of NLRP3 inflammasome. The levels of interleukin (IL)-1β and IL-18 in the serum were detected with enzyme-linked immunosorbent assay (ELISA) method.ResultsAdministration of cinnamyl alcohol by gavage effectively reduced the mortality of septic mice (70% survival), compared to untreated septic mice (50% survival). The histological findings indicated that cinnamyl alcohol reduced the inflammatory reaction in the liver, heart, lungs, and kidneys of the septic mice. In the circulatory system, the concentrations of the inflammatory cytokines IL-1β and IL-18 were significantly decreased by cinnamyl alcohol administration compared to the untreated septic group. Western blot analysis and quantitative polymerase chain reaction (qPCR) demonstrated that cinnamyl alcohol decreased the expression of apoptosis-associated speck-like protein containing a C-terminal caspase recruitment domain (ASC), nucleotide-binding oligomerization domain-like receptor 3 (NLRP3), and caspase-1 in the liver, heart, lungs, and kidneys of the mice, suggesting that cinnamyl alcohol alleviated sepsis syndrome via the NLRP3 inflammasome pathway.ConclusionsCinnamyl alcohol may be a novel therapeutic candidate for the treatment of sepsis syndrome.

Project description:Osteoporosis (OP) is distinguished by a reduction in bone mass and degradation of bone micro-structure, frequently resulting in fractures. As the geriatric demographic expands, the incidence of affected individuals progressively rises, thereby exerting a significant impact on the quality of life experienced by individuals. The flavonoid compound hesperidin has been subject to investigation regarding its effects on skeletal health, albeit the precise mechanisms through which it operates remain ambiguous. This study utilized network pharmacology to predict the core targets and signaling pathways implicated in the anti-OP properties of hesperidin. Molecular docking and molecular dynamics simulations were employed to confirm the stability of the interaction between hesperidin and the core targets. The effects of hesperidin on osteoblastic cells MC3T3-E1 were assessed using MTT, ELISA, alkaline phosphatase assay, and RT-qPCR techniques. Furthermore, in vivo experiments were conducted to determine the potential protective effects of hesperidin on zebrafish bone formation and oxidative stress response. The results demonstrate that network pharmacology has identified 10 key target points, significantly enriched in the estrogen signaling pathway. Hesperidin exhibits notable promotion of MC3T3-E1 cell proliferation and significantly enhances ALP activity. ELISA measurements indicate an elevation in NO levels and a reduction in IL-6 and TNF-α. Moreover, RT-qPCR analysis consistently reveals that hesperidin significantly modulates the mRNA levels of ESR1, SRC, AKT1, and NOS3 in MC3T3-E1 cells. Hesperidin promotes osteogenesis and reduces oxidative stress in zebrafish. Additionally, we validate the stable and tight binding of hesperidin with ESR1, SRC, AKT1, and NOS3 through molecular dynamics simulations. In conclusion, our comprehensive analysis provides evidence that hesperidin may exert its effects on alleviating OP through the activation of the estrogen signaling pathway via ESR1. This activation leads to the upregulation of SRC, AKT, and eNOS, resulting in an increase in NO levels. Furthermore, hesperidin promotes osteoblast-mediated bone formation and inhibits pro-inflammatory cytokines, thereby alleviating oxidative stress associated with OP.

Dataset Information

The Anti-Depressive Effects of Hesperidin and the Relative Mechanisms Based on the NLRP3 Inflammatory Signaling Pathway.

Publications

The Anti-Depressive Effects of Hesperidin and the Relative Mechanisms Based on the NLRP3 Inflammatory Signaling Pathway.

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