Scutellarin suppresses Mycobacterium tuberculosis-induced pyroptosis in macrophages by inhibiting the HIF-1α-mediated Warburg effect.

IF 7.4 2区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Redox Report Pub Date : 2025-12-01 Epub Date: 2025-10-06 DOI:10.1080/13510002.2025.2565861

Jianchao Wu, Fanglin Liu, Jingjing Shen, Hemin Zhang, Yaqi Liu, Jinxia Sun, Guizhen Yang, Yuejuan Zheng, Xin Jiang

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引用次数: 0

Abstract

Background: Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB), remains a major global health threat due to prolonged treatment and drug-resistant strains. Host-directed therapy (HDT), which modulates host-pathogen interactions, offers potential to shorten treatment and limit resistance. This study investigates the effects of Scutellarin (SCU), a flavonoid from Scutellaria baicalensis, on Mtb-infected macrophages within the HDT framework.

Methods: Anti-pyroptotic and anti-inflammatory effects of SCU were assessed in Mtb-infected THP-1 and J774A.1 macrophages, and in a lipopolysaccharide (LPS)-induced acute lung injury (ALI) mouse model. Mitochondrial function was evaluated by oxygen consumption rate(OCR), membrane potential, and superoxide levels; glycolytic activity was measured by proton efflux rate (GlycoPER). Expression of inflammasome-related markers was analyzed by Western blot, qPCR, ELISA, immunofluorescence, and flow cytometry. The role of hypoxia-inducible factor 1-alpha (HIF-1α) was examined via siRNA knockdown.

Results: SCU inhibited NLRP3 inflammasome activation, reduced IL-1β and IL-18 secretion, and attenuating pyroptosis. It restored mitochondrial integrity by regulating p-DRP1, MFN2, and Cytochrome C expression, and suppressed HIF-1α-mediated glycolytic reprogramming. Silencing of HIF-1α confirmed its role in SCU's mechanism. In vivo, SCU reduced pulmonary inflammation and cytokine release in LPS-induced ALI.

Conclusion: SCU alleviates Mtb-induced pyroptosis and inflammation in macrophages by inhibiting the HIF-1α-mediated Warburg effect.

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黄芩苷通过抑制hif -1α-介导的Warburg效应抑制结核分枝杆菌诱导的巨噬细胞热亡。

背景：结核分枝杆菌（Mtb）是结核病（TB）的病原体，由于长期治疗和耐药菌株，仍然是全球主要的健康威胁。调节宿主-病原体相互作用的宿主定向治疗（HDT）有可能缩短治疗时间并限制耐药性。本研究探讨黄芩黄酮类化合物黄芩苷（Scutellarin， SCU）对HDT框架内感染mtb的巨噬细胞的影响。方法：在mtb感染的THP-1和J774A.1巨噬细胞以及脂多糖（LPS）诱导的急性肺损伤（ALI）小鼠模型中，观察SCU的抗焦亡和抗炎作用。通过耗氧率（OCR）、膜电位和超氧化物水平评估线粒体功能；用质子外排率（GlycoPER）测定糖酵解活性。采用Western blot、qPCR、ELISA、免疫荧光和流式细胞术分析炎性小体相关标志物的表达。低氧诱导因子1- α (HIF-1α)的作用通过siRNA敲低检测。结果：SCU抑制NLRP3炎性体活化，降低IL-1β和IL-18分泌，减轻焦亡。它通过调节p-DRP1、MFN2和细胞色素C的表达来恢复线粒体完整性，并抑制hif -1α介导的糖酵解重编程。HIF-1α的沉默证实了其在SCU机制中的作用。在体内，SCU减少了lps诱导的ALI的肺部炎症和细胞因子释放。结论：SCU通过抑制hif -1α介导的Warburg效应，减轻mmb诱导的巨噬细胞焦亡和炎症。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Redox Report 生物-生化与分子生物学

CiteScore

6.10

自引率

0.00%

发文量

审稿时长

>12 weeks

期刊介绍： Redox Report is a multidisciplinary peer-reviewed open access journal focusing on the role of free radicals, oxidative stress, activated oxygen, perioxidative and redox processes, primarily in the human environment and human pathology. Relevant papers on the animal and plant environment, biology and pathology will also be included. While emphasis is placed upon methodological and intellectual advances underpinned by new data, the journal offers scope for review, hypotheses, critiques and other forms of discussion.