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调节氧化偶氮甲烷诱导的溃疡性结肠炎中的肠道菌群失调和线粒体功能障碍:β-葡聚糖和/或雷公藤红素的修复作用。

Modulating gut dysbiosis and mitochondrial dysfunction in oxazolone-induced ulcerative colitis: the restorative effects of β-glucan and/or celastrol.

机构信息

Medical Biochemistry Department, Faculty of Medicine, Tanta University, Tanta, Egypt.

Pharmacology Department, Faculty of Medicine, Tanta University, Tanta, Egypt.

出版信息

Redox Rep. 2022 Dec;27(1):60-69. doi: 10.1080/13510002.2022.2046425.

Abstract

OBJECTIVES

Microbiome-Mitochondria interaction is gaining a significant attention; thus, studying its mechanism emerges as a must to provide restorative lines in managing diseases. The aim is to study the mechanistic effects of β-Glucan and/or Celastrol in oxazolone-induced ulcerative colitis (UC).

METHODS

75 Wistar rats were allocated into 5 equal groups. Group I: control group. Group II: UC group, Group III: β-Glucan-treated UC group, Group IV: Celastrol-treated UC group & Group V: mutual treatment group. All groups were subjected to the detection of free fatty acid receptor 2 (FFAR-2) and peroxisome proliferator-activated receptor gamma co-activator1α (PGC-1α) mRNA gene expressions. Citrate synthase (CS) activity, mitochondrial membrane potential (MMP), ATP concentration, reactive oxygen species (ROS) were detected. Trimethylamine N-oxide (TMAO) concentration was measured.

RESULTS

After treatment we monitored significant upregulation of FFAR-2 and PGC-1α mRNA expression. Likewise, ATP level and CS activity were significantly increased. On the contrary, there was a significant lessening in ROS and TMAO levels with improvement of MMP.

CONCLUSION

Mutual use of β- Glucan and Celastrol had a greater effect than each alone against UC, which is considered a novel finding highlighting the ameliorative effects of this combined treatment in modulating Microbiome/Mitochondria axis, thus launching promising avenues for UC.

摘要

目的

微生物组-线粒体相互作用正受到越来越多的关注;因此,研究其机制对于提供疾病管理的恢复途径显得尤为必要。本研究旨在探讨β-葡聚糖和/或雷公藤红素在氧化偶氮甲烷诱导的溃疡性结肠炎(UC)中的作用机制。

方法

将 75 只 Wistar 大鼠随机分为 5 组,每组 15 只。第 I 组:对照组。第 II 组:UC 组。第 III 组:β-葡聚糖处理的 UC 组。第 IV 组:雷公藤红素处理的 UC 组。第 V 组:联合治疗组。所有组均检测游离脂肪酸受体 2(FFAR-2)和过氧化物酶体增殖物激活受体γ共激活因子 1α(PGC-1α)mRNA 基因表达。检测柠檬酸合酶(CS)活性、线粒体膜电位(MMP)、ATP 浓度、活性氧(ROS)。测定三甲基胺 N-氧化物(TMAO)浓度。

结果

治疗后,我们监测到 FFAR-2 和 PGC-1α mRNA 表达明显上调。同样,ATP 水平和 CS 活性显著增加。相反,ROS 和 TMAO 水平显著降低,MMP 得到改善。

结论

β-葡聚糖和雷公藤红素的联合使用比单独使用对 UC 有更好的效果,这被认为是一个新的发现,强调了这种联合治疗在调节微生物组/线粒体轴方面的改善作用,为 UC 提供了有前景的途径。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1468/8903761/ba0561b1901b/YRER_A_2046425_F0001_OC.jpg

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