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黄腐酚通过抑制 NF-κB 信号通路和调节肠道微生物群改善葡聚糖硫酸钠诱导的小鼠结肠炎。

Xanthohumol ameliorates dextran sodium sulfate-induced colitis in mice by inhibiting of NF-κB signaling pathways and modulating intestinal microbiota.

机构信息

Guangdong Provincial Key Laboratory of Veterinary Pharmaceutics Development and Safety Evaluation, College of Veterinary Medicine, South China Agricultural University, Guangzhou, 510642, China.

National Laboratory of Safety Evaluation (Environmental Assessment) of Veterinary Drugs, College of Veterinary Medicine, South China Agricultural University, Guangzhou, 510642, China.

出版信息

Eur J Nutr. 2024 Nov 22;64(1):21. doi: 10.1007/s00394-024-03525-5.

DOI:10.1007/s00394-024-03525-5
PMID:39576384
Abstract

ETHNOPHARMACOLOGICAL RELEVANCE

Xanthohumol (XN), an isoprenylated flavonoid natural product found only in hops, possesses a variety of biological activities such as anticancer, anti-inflammatory, hepatoprotective, and anti-obesity.

AIM OF THE STUDY

The aim of this study was to investigate the effects and mechanisms of XN on the treatment of colitis.

MATERIALS AND METHODS

First, acute colitis was induced by using distilled water containing 3% DSS for 10 consecutive days. The therapeutic efficacy of XN was assessed by an established DSS-induced mouse colitis model. Subsequently, disease activity index (DAI) and colon length of mice were assessed. The health of the intestines was assessed by histopathological analysis. Inflammatory factors, IL-1β, IL-6, and TNF-α, were detected in colon tissues by ELISA.Finally, mouse intestinal contents were extracted and subjected to 16 S rRNA Sequencing, and the gut microbiota was analysed for Alpha-diversity and Beta-diversity.

RESULTS

The results showed that XN ameliorated DSS-induced colitis. Furthermore, XN reduced pro-inflammatory cytokine levels such as IL-1β, IL-6, and TNF-α, as well as inhibited the activation of the TLR4/NF-κB pathway, all of which helped to mitigate the inflammatory response. Finally, we also found that XN alleviated intestinal dysbiosis in colitis mice.

CONCLUSION

In conclusion, our study demonstrated that XN provides protective effects against colitis, and has the potential to be further explored as a lead compound for the treatment of inflammatory bowel disease (IBD).

摘要

民族药理学相关性

黄腐酚(XN)是一种仅在啤酒花中发现的异戊烯基类黄酮天然产物,具有多种生物活性,如抗癌、抗炎、保肝和抗肥胖。

目的

本研究旨在探讨 XN 对结肠炎治疗的作用和机制。

材料和方法

首先,使用含有 3% DSS 的蒸馏水连续 10 天诱导急性结肠炎。通过建立的 DSS 诱导的小鼠结肠炎模型评估 XN 的治疗效果。随后,评估小鼠的疾病活动指数(DAI)和结肠长度。通过组织病理学分析评估肠道健康状况。通过 ELISA 检测结肠组织中炎症因子 IL-1β、IL-6 和 TNF-α 的水平。最后,提取小鼠肠道内容物进行 16S rRNA 测序,并分析肠道微生物群落的 Alpha 多样性和 Beta 多样性。

结果

结果表明,XN 改善了 DSS 诱导的结肠炎。此外,XN 降低了促炎细胞因子水平,如 IL-1β、IL-6 和 TNF-α,并抑制了 TLR4/NF-κB 通路的激活,所有这些都有助于减轻炎症反应。最后,我们还发现 XN 缓解了结肠炎小鼠的肠道菌群失调。

结论

总之,本研究表明 XN 对结肠炎具有保护作用,并有潜力进一步探索作为治疗炎症性肠病(IBD)的先导化合物。

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本文引用的文献

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Front Immunol. 2023 Dec 19;14:1291990. doi: 10.3389/fimmu.2023.1291990. eCollection 2023.
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Xanthohumol ameliorates cardiac injury induced by sepsis in a mice model: role of toll-like receptor 4.黄腐酚改善脓毒症诱导的小鼠心脏损伤: toll 样受体 4 的作用。
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The immunomodulatory effects of probiotics and azithromycin in dextran sodium sulfate-induced ulcerative colitis in rats via TLR4-NF-κB and p38-MAPK pathway.
通过 TLR4-NF-κB 和 p38-MAPK 通路,益生菌和阿奇霉素对葡聚糖硫酸钠诱导的大鼠溃疡性结肠炎的免疫调节作用。
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Geniposidic acid attenuates DSS-induced colitis through inhibiting inflammation and regulating gut microbiota.栀子酸通过抑制炎症反应和调节肠道微生物群缓解 DSS 诱导的结肠炎。
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Berberine a traditional Chinese drug repurposing: Its actions in inflammation-associated ulcerative colitis and cancer therapy.小檗碱:一种传统中药再利用——其在炎症相关溃疡性结肠炎和癌症治疗中的作用。
Front Immunol. 2022 Dec 6;13:1083788. doi: 10.3389/fimmu.2022.1083788. eCollection 2022.
6
Xianglian Pill attenuates ulcerative colitis through TLR4/MyD88/NF-κB signaling pathway.香连丸通过 TLR4/MyD88/NF-κB 信号通路减轻溃疡性结肠炎。
J Ethnopharmacol. 2023 Jan 10;300:115690. doi: 10.1016/j.jep.2022.115690. Epub 2022 Sep 6.
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Smad4-deficient T cells promote colitis-associated colon cancer an IFN-γ-dependent suppression of 15-hydroxyprostaglandin dehydrogenase.Smad4 缺陷型 T 细胞促进结肠炎相关结直肠癌-IFN-γ 依赖性抑制 15-羟基前列腺素脱氢酶。
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