Anti-diabetic effect of baicalein is associated with the modulation of gut microbiota in streptozotocin and high-fat-diet induced diabetic rats

Zhang, Bowei; Sun, Wenlong; Yu, Na; Sun, Jin; Yu, Xiao; Li, Xia; Xing, Yan; Dong, Yanhu; Ding, Qiao; Xiu, Zhilong; B, Ma; Yu, Liyan

doi:10.1016/j.jff.2018.04.070

Cited by 102 publications

(68 citation statements)

References 61 publications

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“…The underlying mechanism by which microbiota affects insulin sensitivity may be metabolic inflammation [12]. The Bacteroidales family S24-7 showed negative correlations to blood glucose, dyslipidemia and inflammation [22,35], and positive correlation to PI3K [36]. Besides, most phyloytpes in Allobaculum and Blautia can produce short-chain fatty acids (SCFAs), which were reported to enter the systemic circulation and be absorbed by muscle cells, and work in alleviating inflammation and promoting insulin sensitivity [37][38][39].…”

Section: Discussionmentioning

confidence: 99%

Antidiabetic Effect of Casein Glycomacropeptide Hydrolysates on High-Fat Diet and STZ-Induced Diabetic Mice via Regulating Insulin Signaling in Skeletal Muscle and Modulating Gut Microbiota

et al. 2020

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This study evaluated the effects and the underlying mechanisms of casein glycomacropeptide hydrolysate (GHP) on high-fat diet-fed and streptozotocin-induced type 2 diabetes (T2D) in C57BL/6J mice. Results showed that 8-week GHP supplementation significantly decreased fasting blood glucose levels, restored insulin production, improved glucose tolerance and insulin tolerance, and alleviated dyslipidemia in T2D mice. In addition, GHP supplementation reduced the concentration of lipopolysaccharides (LPSs) and pro-inflammatory cytokines in serum, which led to reduced systematic inflammation. Furthermore, GHP supplementation increased muscle glycogen content in diabetic mice, which was probably due to the regulation of glycogen synthase kinase 3 beta and glycogen synthase. GHP regulated the insulin receptor substrate-1/phosphatidylinositol 3-kinase/protein kinase B pathway in skeletal muscle, which promoted glucose transporter 4 (GLUT4) translocation. Moreover, GHP modulated the overall structure and diversity of gut microbiota in T2D mice. GHP increased the Bacteroidetes/Firmicutes ratio and the abundance of S24-7, Ruminiclostridium, Blautia and Allobaculum, which might contribute to its antidiabetic effect. Taken together, our findings demonstrate that the antidiabetic effect of GHP may be associated with the recovery of skeletal muscle insulin sensitivity and the regulation of gut microbiota.

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Section: Discussionmentioning

confidence: 99%

Antidiabetic Effect of Casein Glycomacropeptide Hydrolysates on High-Fat Diet and STZ-Induced Diabetic Mice via Regulating Insulin Signaling in Skeletal Muscle and Modulating Gut Microbiota

et al. 2020

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“…Our previous studies showed that baicalein is an α-glycosidase inhibitor and exhibited a synergistic effect with acarbose in improving the postprandial glucose tolerance [19,20]. A subsequent in vivo study by our group showed that 4 weeks of baicalein treatment effectively improved hyperglycemia and regulated the gut microbiota in a rat T2DM model [21]. Besides, the combination of the extract of Oroxylum indicum seeds and baicalein with acarbose decreased the relative risk of progression from prediabetes to diabetes by 75% and 83.3% in vivo, respectively [22,23].…”

Section: Introductionmentioning

confidence: 86%

Baicalein Alleviates Liver Oxidative Stress and Apoptosis Induced by High-Level Glucose through the Activation of the PERK/Nrf2 Signaling Pathway

et al. 2020

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Baicalein, a widely-distributed natural flavonoid, exhibits antioxidative activity in mice with type-2 diabetes. However, the underlying mechanisms remain partially elucidated. In this study, we investigated the effect of baicalein on protein kinase R-like ER kinase (PERK)/nuclear factor erythroid-2-related factor 2 (Nrf2) pathway for the alleviation of oxidative stress and apoptosis. Human liver HL-7702 cells were stimulated with 60.5 mM of glucose to induce oxidative stress and treated with baicalein. The apoptosis was determined by fluorescence microscopy and flow cytometry. The regulation of the PERK/Nrf2 pathway by baicalein was determined by immunoblotting in both HL-7702 cells and liver tissues from diabetic mice. We found that baicalein significantly alleviated the oxidative stress and apoptosis in HL-7702 cells stimulated with glucose. Mechanistic studies showed that baicalein downregulated PERK and upregulated Nrf2, two key proteins involved in endoplasmic reticulum stress, in both HL-7702 cells and liver tissues from diabetic mice receiving baicalein treatment. Furthermore, the subcellular localization of Nrf2 and the regulation of downstream proteins including heme oxygenase-1 and CCAAT-enhancer-binding protein homologous protein (CHOP) by baicalein were also investigated. Our results suggest that the regulation of the PERK/Nrf2 pathway is one of the mechanisms contributing to the bioactivities of baicalein to improve diabetes-associated complications.

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“…32 Purified amplicons were pooled in equimolar concentrations and paired-end sequenced (2 × 300) on an Illumina MiSeq platform (Illumina; San Diego, CA, USA) as per standard protocols of Majorbio Bio-Pharm Technology Co. (Shanghai). soil DNA Kit (Omega Bio-tek; Norcross, GA, USA).…”

Section: High-throughput Sequencingmentioning

confidence: 99%

Phellinus linteus polysaccharide extract improves insulin resistance by regulating gut microbiota composition

Liu

Wang

et al. 2019

FASEB j.

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The hypoglycemic effect of Phellinus linteus polysaccharide extract (PLPE) has been documented in several previous studies, but the functional interactions among PLPE, gut microbiota, and the hypoglycemic effect remain unclear. We examined the regulatory effect of PLPE on gut microbiota, and the molecular mechanism underlying improvement of insulin resistance, using a type 2 diabetic rat model. Here, 24 male Sprague‐Dawley rats were randomly divided into four groups that were subjected to intervention of saline (normal and model control group), metformin (120 mg/kg.bw), and PLPE (600 mg/kg.bw) by oral administration. After 8 weeks of treatment, PLPE increased levels of short‐chain fatty acids (SCFAs) by enhancing abundance of SCFA‐producing bacteria. SCFAs maintained intestinal barrier function and reduced lipopolysaccharides content in blood, thereby helping to reduce systemic inflammation and reverse insulin resistance. Our findings suggest that PLPE (in which polysaccharides are the major component) has potential application as a prebiotic for regulating gut microbiota composition in diabetic patients.

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Anti-diabetic effect of baicalein is associated with the modulation of gut microbiota in streptozotocin and high-fat-diet induced diabetic rats

Cited by 102 publications

References 61 publications

Antidiabetic Effect of Casein Glycomacropeptide Hydrolysates on High-Fat Diet and STZ-Induced Diabetic Mice via Regulating Insulin Signaling in Skeletal Muscle and Modulating Gut Microbiota

Antidiabetic Effect of Casein Glycomacropeptide Hydrolysates on High-Fat Diet and STZ-Induced Diabetic Mice via Regulating Insulin Signaling in Skeletal Muscle and Modulating Gut Microbiota

Baicalein Alleviates Liver Oxidative Stress and Apoptosis Induced by High-Level Glucose through the Activation of the PERK/Nrf2 Signaling Pathway

Phellinus linteus polysaccharide extract improves insulin resistance by regulating gut microbiota composition

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