A polysaccharide extracted from Astragalus membranaceus residue improves cognitive dysfunction by altering gut microbiota in diabetic mice

2019 ◽  
Vol 205 ◽  
pp. 500-512 ◽  
Author(s):  
Yameng Liu ◽  
Wei Liu ◽  
Jing Li ◽  
Shuai Tang ◽  
Majie Wang ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Cognitive Dysfunction ◽  
Astragalus Membranaceus ◽  
Diabetic Mice

Intake of Flavonoids from Astragalus Membranaceus Ameliorated Brain Impairment in Diabetic Mice Via Modulating Brain-Gut Axis

2021 ◽  
Author(s):  
Li Xuling ◽  
Junling Gu ◽  
Zhe Wang ◽  
Jing Lin ◽  
Tingting Zhao ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Brain Damage ◽  
High Fat Diet ◽  
Fasting Blood Glucose ◽  
Synaptic Function ◽  
Astragalus Membranaceus ◽  
Immunological Methods ◽  
Diabetic Mice ◽  
High Fat

Abstract Background: Brain impairment is one of a major complication of diabetes. Dietary flavonoids have been recommended to prevent brain damage. Astragalus membranaceus is a herbal medicine commonly used to relieve the complications of diabetes. Flavonoids is one of the major ingredients of Astragalus membranaceus, but its function and mechanism on diabetic encepholopathy is still unknown.Methods: Type 2 diabetes mellitus (T2DM) model was induced by high fat diet and STZ in C57BL/6J mice, and BEnd.3 and HT22 cell lines were applied in the in vitro study. Quality of flavonoids was evaluated by LC-MS/MS. Differential expressed proteins in the hippocampus were evaluated by proteomics; influence of the flavonoids on composition of gut microbiota was analyzed by metagenomics. Mechanism of the flavonoids on diabetic encepholopathy was analyzed by Q-PCR, Western Blot, and multi-immunological methods et al. Results: We found that flavonoids from Astragalus membranaceus (TFA) significantly ameliorated brain damage by modulating gut-microbiota-brain axis: TFA oral administration decreased fasting blood glucose and food intake, repaired blood brain barrier, protected hippocampus synaptic function; improved hippocampus mitochondrial biosynthesis and energy metabolism; and enriched the intestinal microbiome in high fat diet/STZ-induced diabetic mice. In the in vitro study, we found TFA increased viability of HT22 cells and preserved gut barrier integrity in CaCO2 monocellular layer, and PGC1α/AMPK pathway participated in this process. Conclusion: Our findings demonstrated that flavonoids from Astragalus Membranaceus ameliorated brain impairment via gut-brain axis. Our present study provided an alternative solution on preventing and treating diabetic cognition impairment.

scholarly journals Abnormal gut microbiota composition contributes to cognitive dysfunction in streptozotocin-induced diabetic mice

Aging ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 3262-3279 ◽  
Author(s):  
Fan Yu ◽  
Wei Han ◽  
Gaofeng Zhan ◽  
Shan Li ◽  
Shoukui Xiang ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Cognitive Dysfunction ◽  
Microbiota Composition ◽  
Diabetic Mice ◽  
Gut Microbiota Composition

Lactobacillus casei LC89 exert antidiabetic effects through regulating hepatic glucagon response and gut microbiota in type 2 diabetic mice

2021 ◽  
Author(s):  
Yongli Zhang ◽  
Tao Wu ◽  
Wen Li ◽  
Yunjiao Zhao ◽  
Hairong Long ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Molecular Mechanism ◽  
Lactobacillus Casei ◽  
Diabetic Mice ◽  
Antihyperglycemic Activity ◽  
Underlying Mechanisms ◽  
Type 2 Diabetic ◽  
Antidiabetic Effects

Previous study suggests Lactobacillus casei exhibit antihyperglycemic activity, however, the molecular mechanism has rarely been elucidated. Here, the anti-diabetic effects and underlying mechanisms of Lactobacillus casei LC89 were investigated in...

scholarly journals Clostridial Butyrate Biosynthesis Enzymes Are Significantly Depleted in the Gut Microbiota of Nonobese Diabetic Mice

mSphere ◽  
2018 ◽  
Vol 3 (5) ◽  
Author(s):  
Alessandro Tanca ◽  
Antonio Palomba ◽  
Cristina Fraumene ◽  
Valeria Manghina ◽  
Michael Silverman ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Intestinal Microbiota ◽  
Time Window ◽  
High Resolution Mass Spectrometry ◽  
Nod Mice ◽  
16S Rrna Gene Sequencing ◽  
Rrna Gene ◽  
Diabetic Mice ◽  
Nonobese Diabetic ◽  
Nonobese Diabetic Mice

ABSTRACT Increasing evidence suggests that the intestinal microbiota is involved in the pathogenesis of type 1 diabetes (T1D). Here we sought to determine which gut microbial taxa and functions vary between nonobese diabetic (NOD) mice and genetically modified NOD mice protected from T1D (Eα16/NOD) at 10 weeks of age in the time window between insulitis development and T1D onset. The gut microbiota of NOD mice were investigated by analyzing stool samples with a metaproteogenomic approach, comprising both 16S rRNA gene sequencing and microbial proteome profiling through high-resolution mass spectrometry. A depletion of Firmicutes (particularly, several members of Lachnospiraceae) in the NOD gut microbiota was observed compared to the level in the Eα16/NOD mice microbiota. Moreover, the analysis of proteins actively produced by the gut microbiota revealed different profiles between NOD and Eα16/NOD mice, with the production of butyrate biosynthesis enzymes being significantly reduced in diabetic mice. Our results support a model for gut microbiota influence on T1D development involving bacterium-produced metabolites as butyrate. IMPORTANCE Alterations of the gut microbiota early in age have been hypothesized to impact T1D autoimmune pathogenesis. In the NOD mouse model, protection from T1D has been found to operate via modulation of the composition of the intestinal microbiota during a critical early window of ontogeny, although little is known about microbiota functions related to T1D development. Here, we show which gut microbial functions are specifically associated with protection from T1D in the time window between insulitis development and T1D onset. In particular, we describe that production of butyrate biosynthesis enzymes is significantly reduced in NOD mice, supporting the hypothesis that modulating the gut microbiota butyrate production may influence T1D development.

scholarly journals Severe Hypoglycemia Contributing to Cognitive Dysfunction in Diabetic Mice is Associated with Pericyte and Blood–Brain Barrier Dysfunction

2021 ◽  
Author(s):  
Lu Lin ◽  
Lishan Huang ◽  
Lijing Wang ◽  
Yubin Wu ◽  
Zhou Chen ◽  
...  
Keyword(s):  
Cognitive Function ◽  
Cognitive Dysfunction ◽  
Blood Brain Barrier ◽  
Severe Hypoglycemia ◽  
Brain Barrier ◽  
Blue Staining ◽  
Diabetic Patients ◽  
Inflammatory Factor ◽  
Diabetic Mice ◽  
Blood Brain

Abstract Background: Severe hypoglycemia can cause cognitive impairment in diabetic patients, but the underlying molecular mechanism remains unclear.Objective: To assess the effect of severe hypoglycemia on cognitive function in diabetic mice to clarify the relationship between the mechanism and dysfunction of pericytes and the blood–brain barrier (BBB).Method: We established type 1 diabetes mellitus in 80 male C57BL/6J mice by intraperitoneal injection of streptozotocin (180 mg/kg). Further abdominal injection of short-acting insulin induced severe hypoglycemia. The mice were divided into normal, diabetes, and diabetic + severe hypoglycemia groups, and their blood glucose and general weight index were examined. Pericyte and BBB morphology and function were detected by histological and western blot analyses, BBB permeability was detected by Evans blue staining, and cognitive function was detected with the Morris water maze.Results: Severe hypoglycemia aggravated the histological damage, BBB damage, brain edema, and pericyte loss in the diabetic mice. It also reduced the expression of the BBB tight junction proteins occludin and claudin-5, the expression of the pericyte-specific markers PDGFR-β (platelet-derived growth factor receptor-β) and α-SMA, and increased the expression of the inflammatory factor MMP9. At the same time, diabetic mice with severe hypoglycemia had significantly reduced cognitive function.Conclusion: Severe hypoglycemia leads to cognitive dysfunction in diabetic mice, and its possible mechanism is related to pericyte dysfunction and BBB destruction.

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