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. 2023 Apr:46:173-188.
doi: 10.1016/j.jare.2022.06.003. Epub 2022 Jun 11.

V体育ios版 - Amelioration of type 2 diabetes by the novel 6, 8-guanidyl luteolin quinone-chromium coordination via biochemical mechanisms and gut microbiota interaction

Xiaodong Ge  1 , Xiaoyu He  2 , Junwei Liu  3 , Feng Zeng  1 , Ligen Chen  3 , Wei Xu  3 , Rong Shao  3 , Ying Huang  1 , Mohamed A Farag  4 , Esra Capanoglu  5 , Hesham R El-Seedi  6 , Chao Zhao  7 , Bin Liu  8
Affiliations

Amelioration of type 2 diabetes by the novel 6, 8-guanidyl luteolin quinone-chromium coordination via biochemical mechanisms and gut microbiota interaction

VSports最新版本 - Xiaodong Ge et al. J Adv Res. 2023 Apr.

Abstract

Introduction: Luteolin is a plant-derived flavonoid that exhibits a broad range of pharmacological activities. Studies on luteolin have mainly focused on its use for hyperlipidaemia prevention, whereas the capacity of the flavonoid to hinder hyperglycaemia development remains underexplored VSports手机版. .

Objectives: To probe the anti-hyperglycemic mechanism of 6,8-guanidyl luteolin quinone-chromium coordination (GLQ. Cr), and to assess its regulatory effect on intestinal microbiota in type 2 diabetes mellitus (T2DM) mice V体育安卓版. .

Methods: High-sucrose/high-fat diet-induced and intraperitoneal injection of streptozotocin was used to develop a T2DM model. Glycometabolism related indicators, histopathology, and gut microbiota composition in caecum samples were evaluated, and RNA sequencing (RNA-seq) of liver samples was conducted V体育ios版. Faecal microbiota transplantation (FMT) was further used to verify the anti-hyperglycemic activity of intestinal microbiota. .

Results: The administration of GLQ. Cr alleviated hyperglycaemia symptoms by improving liver and pancreatic functions and modulating gut microbe communities (Lactobacillus, Alistipes, Parabacteroides, Lachnoclostridium, and Desulfovibrio). RNA-seq analysis showed that GLQ VSports最新版本. Cr mainly affected the peroxisome proliferative activated receptor (PPAR) signalling pathway in order to regulate abnormal glucose metabolism. FMT significantly modulated the abundance of Lactobacillus, Alloprevotella, Alistipes, Bacteroides, Ruminiclostridium, Brevundimonas and Pseudomonas in the caecum to balance blood glucose levels and counteract T2DM mice inflammation. .

Conclusion: GLQ V体育平台登录. Cr improved the abnormal glucose metabolism in T2DM mice by regulating the PPAR signalling pathway and modulating intestinal microbial composition. FMT can improve the intestinal microecology of the recipient and in turn ameliorate the symptoms of T2DM-induced hyperglycaemia. .

Keywords: Anti-hyperglycemic; Faecal microbiota transplantation; Intestinal microbiota; Luteolin; RNA-seq. VSports注册入口.

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"V体育ios版" Conflict of interest statement

Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Figures

None
Graphical abstract
Fig. 1
Fig. 1
The synthetic steps of GLQ.Cr. (A) The mechanism of bromine free radical reaction; (B) The mechanism of palladium acetate catalyzed C-N cross coupling reaction.
Fig. 2
Fig. 2
Changes of mice in different groups during the experimental period. (A) Body weight; (B) FBG; (C) OGTT; (D) AUC; (E) IL-6; (F) IL-10; (G, H) Histopathological analysis of liver (400 × magnification) and caecum (100 × magnification); (I) Immunofluorescence section of pancreas tissue; (J) HOMA-IRI; (K) HOMA-β; and (L) HOMA-ISI. Normal: normal diet; Model: HSHF diet; GLQ: HSHF diet + GLQ (100 mg/kg.d); GLQ.Cr: HSHF diet + GLQ.Cr (100 mg/kg.d); LUT: HSHF diet + Luteolin (100 mg/kg.d); MH: HSHF diet + Metformin hydrochloride (100 mg/kg.d); CrY: HSHF diet + Chromium-enriched yeast (100 mg/kg.d); WK: week. Data are mean ± SD (n = 6). ns: no significant; *p < 0.05 and **p < 0.01 compared with the Normal group; #p < 0.05 and ##p < 0.01 compared with the Model group.
Fig. 3
Fig. 3
Differentially expressed genes (DEGs) in the liver of mice. (A) Statistical map of DEGs between different groups; (B) Volcano map of DEGs between Normal/Model groups; (C) Volcano map of DEGs between GLQ.Cr/Model groups; (D) The GO Terms of DEGs in GLQ.Cr/Model groups; (E) The circos loop graph of KEGG pathway in GLQ.Cr/Model group.
Fig. 4
Fig. 4
(A) Hierarchical clustering analysis calculated using spearman correlation between anti-hyperglycemic correlation parameters and related genes in the four pathways of KEGG. The intensity of the colour represents the degree of association. (B) Visualization of the correlation network according to the partial correlation between the anti-hyperglycemic correlation parameters and genes. (C) qPCR verified the result of RNA-seq. (D) The linear relationship between qPCR and RNA-Seq. (E-F) Immunoblot bands of 5 proteins in each group. (G) Effects of different groups on the protein expression levels of liver genes related to glycometabolism. Quantification of band integrated density values by Image J. All the relative protein expression levels were normalized by β-actin band gray values of their corresponding groups. *p < 0.05 and **p < 0.01 compared with the Normal group; #p < 0.05 and ##p < 0.01 compared with the Model group.
Fig. 5
Fig. 5
Changes in the intestinal microbiota composition of mice caecum contents. Five mice were randomly selected from each group for analysis of caecal microbiota. (A) Composition of intestinal microbiota at the phylum level; (B) The ratio of Firmicutes and Bacteroidetes; (C-G) Five species of bacteria with high abundance at the genus level. *p < 0.05 and **p < 0.01 compared with the Normal group; #p < 0.05 and ##p < 0.01 compared with the Model group. (H) Hierarchical clustering analysis calculated using spearman correlation of anti-hyperglycemic parameters and mice caecum microbiota at the genus level. The intensity of the colour represents the degree of association. (I) Visualization of the correlation network according to the partial correlation between the intestinal microbiota, anti-hyperglycemic correlation parameters, and SCFAs. The node colours including cyan, magenta, and SlateBlue represent the anti-hyperglycemic correlation parameters, SCFA, and intestinal microbiota genus, respectively. The solid red line and dotted black line denote positive and negative correlation, respectively. In addition, line width denotes strength of correlation. Only the significant edges are drawn in the network using the Spearman correlation test (|r|> 0.4, FDR adjusted p < 0.01).
Fig. 6
Fig. 6
Changes of mice in different groups during the FMT experimental period. (A) Schematic diagram of preparation of donor microbiota liquid and transplant of the recipient with faecal microbiota liquid; Boxplots showing change in (B) Body weight; (C) FBG; (D) OGTT; (E) AUC; (F) IL-6; (G) IL-10; (H) HOMA-IRI; (I) HOMA-β; (J) HOMA-ISI. (K, L) Histopathological analysis of liver (400 × magnification) and caecum (100 × magnification); (M) Immunofluorescence section of pancreas tissue. Normal: normal diet; Model: HSHF diet; Recipient: HSHF diet + Fecal microbiota solution (10 mL/kg.d); WK: week. Data are mean ± SD (n = 6). ns: no significant; *p < 0.05 and **p < 0.01 compared with the Normal group; #p < 0.05 and ##p < 0.01 compared with the Model group.
Fig. 7
Fig. 7
Serum and liver biological indicators of mice in each group during the experimental period. (A) Serum TC; (B) Serum TG; (C) Serum LDL-C; (D) Serum HDL-C; (E) Serum GSP; (F) Liver TC; (G) Liver TG; (H) Liver LDL-C; and (I) Liver HDL-C. Effects of short chain fatty acids of faeces in each group during the experimental period. (J) Acetic acid; (K) Propionic acid; (L) Isobutyric acid; (M) Butyric acid; (N) Isovaleric acid and (O) Valeric acid. Data are mean ± SD (n = 6). *p < 0.05 and **p < 0.01 compared with the Normal group; #p < 0.05 and ##p < 0.01 compared with the Model group.
Fig. 8
Fig. 8
Intestinal microbiota composition in mice caecum contents. Five mice were randomly selected from each group for analysis of caecal microbiota. (A) Composition of intestinal microbiota at the phylum level; (B) The ratio of Firmicutes and Bacteroidetes; (C) Abundance of microflora in cecum contents of the donor for FMT(GLQ.Cr) and recipient; (D-J) Seven species of bacteria with high abundance at the genus level; (K) Hierarchical clustering analysis calculated using spearman correlation between anti-hyperglycemic correlation parameters and FMT mice caecum microbiota at the genus level. The intensity of the colour represents the degree of association. *p < 0.05 and **p < 0.01 compared with the Normal group; #p < 0.05 and ##p < 0.01 compared with the Model group.
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