Asperuloside Improves Obesity and Type 2 Diabetes through Modulation of Gut Microbiota and Metabolic Signaling

Nakamura, Anna; Yokoyama, Yoko; Tanaka, Kazuki; Benegiamo, Giorgia; Hirayama, Akiyoshi; Zhu, Qi; Kitamura, Naho; Sugizaki, Taichi; Morimoto, Kohkichi; Itoh, Hiroshi; Fukuda, Shinji; Auwerx, Johan; Tsubota, Kazuo; Watanabe, Mitsuhiro

doi:10.1016/j.isci.2020.101522

Cited by 27 publications

(15 citation statements)

References 37 publications

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“…Intestinal dysbiosis in T2DM was characterized previously as an increase in genus of Bacteroides spp., Parabacteroides, Clostridium spp ., as well as an increase in phylum of Proteobacteria and Firmicutes/Bacteroidetes ratio. [ 8,50–52 ] Similar signatures were manifested in our microbiome data from the T2DM mice by 16S rRNA amplicon sequencing (Figure 8). Microbiome‐related strategies to ameliorate gut barrier disruption involve the microbiome‐altering interventions such as probiotics, postbiotics, and prebiotics including dietary fiber, alkaloid berberine, oligofructose, curcumin, and grape polyphenols.…”

Section: Discussionsupporting

confidence: 76%

Urolithin A Attenuates Diabetes‐Associated Cognitive Impairment by Ameliorating Intestinal Barrier Dysfunction via N‐glycan Biosynthesis Pathway

Xiao

Bian

et al. 2022

Molecular Nutrition Food Res

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Scope This study aims to investigate the effect of Urolithin A (UA) on diabetes‐associated cognitive impairment in type 2 diabetes mellitus (T2DM) mouse model induced by high‐fat diet (HFD) and streptozotocin (STZ). Methods and Results The UA‐treated T2DM mice display an attenuated cognitive impairment as well as reduced levels of metabolic endotoxemia and proinflammatory cytokines in serum. A systemic restraint of gut/brain inflammation in UA‐treated T2DM mice is also observed as the downregulation of TLR4 and Myd88 in colon along with the inhibition of GFAP, Iba‐1, NLRP3, and inflammation‐related genes in brain. Moreover, UA ameliorates gut barrier dysfunction by upregulating tight‐junction proteins levels. Furthermore, UA restores the hyperglycemia‐mediated downregulation of genes involved in N‐glycan biosynthesis both in vivo and in vitro, which plays a crucial role in barrier integrity. Although UA shares similar beneficial effects on diabetes with metformin, unlike metformin, the effect of UA is independent of gut microbiome and short chain fatty acids. Taken together, these data suggest that feeding UA can attenuate diabetes‐associated cognitive impairment by ameliorating systemic inflammation and intestinal barrier dysfunction via N‐glycan biosynthesis pathway. The study implies UA as a potential novel pharmaceutic target for diabetes therapy via manipulating gut‐brain axis and N‐glycan metabolism.

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Section: Discussionsupporting

confidence: 76%

Urolithin A Attenuates Diabetes‐Associated Cognitive Impairment by Ameliorating Intestinal Barrier Dysfunction via N‐glycan Biosynthesis Pathway

Xiao

Bian

et al. 2022

Molecular Nutrition Food Res

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“…[4][5][6] Recent studies have shown that there is a close interaction between obesity, diabetes, and gut microbiota disorder. [7][8][9][10][11] Disordered gut microbiota seems to affect the host's metabolism by using nutrients and metabolites, increasing the sensitivity to metabolic disorders, such as insulin resistance and metabolic syndrome. 12,13 There are pieces of evidence showing that the composition of the adult gut microbiota between those diabetic patients and control groups had significant differences, 14,15 and indicating that the composition of gut microbiota may affect the energy intake and utilization, intestinal permeability, transport rate, mucosal immunity, and systemic inflammation.…”

Section: Introductionmentioning

confidence: 99%

Nutritional Effects of the Enteral Nutritional Formula on Regulation of Gut Microbiota and Metabolic Level in Type 2 Diabetes Mellitus Mice

Wei¹,

Jia²,

Xue³

et al. 2021

DMSO

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Purpose Due to the adverse effects of antidiabetic drugs, nowadays, nutraceuticals have been of much interest to investigators. Therefore, the present study aimed to explore the potential effects of enteral nutritional (EN) formulas on the gut microbiota and metabolic regulation of type 2 diabetes mellitus (T2DM) mice and compare the differences between whey protein and soy protein. Methods EN formulas made of whey protein or soy protein were administered for five weeks and then mice tissue samples were obtained to examine the metabolic parameters and histopathology of the pancreas, liver, jejunum and colon. 16S rRNA V3-V4 region gene sequencing was used to analyze the changes in the gut microbiota. Results After the five-week intervention, the alpha diversity had recovered slightly, and the soy protein group (SPG) achieved a better effect than the whey protein group (LPG). The overall composition of gut microbiota was regulated. The abundance of Bacteroidetes and TM7 had raised significantly and the abundance of Firmicutes and Deferribacteres had declined after treatment, with no significant difference between the LPG and SPG. The types of beneficial bacteria were increased at the genus and species level. The level of hexokinase (HK) and pyruvate kinase (PK) had significantly recovered and inhibited the level of α-glucosidase. In addition, the EN formulas treatment reduced the levels of inflammatory factor (TNF-α) in liver and muscle. The level of glucose transporter type 2 (GLUT-2) levels in the liver and intestine also significantly increased. Moreover, the metabolism regulation of the SPG was better than that of the LPG. The EN formulas treatment improved the pancreas, liver, jejunum and colon histology. Conclusion The EN formulas regulated the overall structure of the gut microbiota and improved the metabolic level in streptozotocin/high-fat diet (STZ/HFD) diabetic mice. Therefore, EN formula may potentially become an effective nutritional adjunctive therapy for T2DM.

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“…11-keto-β-boswellic acid is a triterpenoid found in Boswellia serrata and has potential therapeutic efficacy against several chronic inflammatory diseases and neurodegenerative diseases [ 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 ]. Asperuloside, which is classified under the category of iridoid glycosides, has potential for the treatment of obesity, inflammatory diseases, cancer, bacterial infection, and renal fibrosis [ 61 , 62 , 63 , 64 , 65 , 66 ]. Echinatin, as a bioactive flavonoid of Glycyrrhiza plants, displays antioxidant and anti-inflammatory activities [ 36 , 67 , 68 ].…”

Section: Discussionmentioning

confidence: 99%

Identification of Novel Cannabinoid CB2 Receptor Agonists from Botanical Compounds and Preliminary Evaluation of Their Anti-Osteoporotic Effects

Cheng

Zhou

et al. 2022

Molecules

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As cannabinoid CB2 receptors (CB2R) possess various pharmacological effects—including anti-epilepsy, analgesia, anti-inflammation, anti-fibrosis, and regulation of bone metabolism—without the psychoactive side effects induced by cannabinoid CB1R activation, they have become the focus of research and development of new target drugs in recent years. The present study was intended to (1) establish a double luciferase screening system for a CB2R modulator; (2) validate the agonistic activities of the screened compounds on CB2R by determining cAMP accumulation using HEK293 cells that are stably expressing CB2R; (3) predict the binding affinity between ligands and CB2 receptors and characterize the binding modes using molecular docking; (4) analyze the CB2 receptors–ligand complex stability, conformational behavior, and interaction using molecular dynamics; and (5) evaluate the regulatory effects of the screened compounds on bone metabolism in osteoblasts and osteoclasts. The results demonstrated that the screening system had good stability and was able to screen cannabinoid CB2R modulators from botanical compounds. Altogether, nine CB2R agonists were identified by screening from 69 botanical compounds, and these CB2R agonists exhibited remarkable inhibitory effects on cAMP accumulation and good affinity to CB2R, as evidenced by the molecular docking and molecular dynamics. Five of the nine CB2R agonists could stimulate osteoblastic bone formation and inhibit osteoclastic bone resorption. All these findings may provide useful clues for the development of novel anti-osteoporotic drugs and help elucidate the mechanism underlying the biological activities of CB2R agonists identified from the botanical materials.

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Asperuloside Improves Obesity and Type 2 Diabetes through Modulation of Gut Microbiota and Metabolic Signaling

Cited by 27 publications

References 37 publications

Urolithin A Attenuates Diabetes‐Associated Cognitive Impairment by Ameliorating Intestinal Barrier Dysfunction via N‐glycan Biosynthesis Pathway

Urolithin A Attenuates Diabetes‐Associated Cognitive Impairment by Ameliorating Intestinal Barrier Dysfunction via N‐glycan Biosynthesis Pathway

Nutritional Effects of the Enteral Nutritional Formula on Regulation of Gut Microbiota and Metabolic Level in Type 2 Diabetes Mellitus Mice

Identification of Novel Cannabinoid CB2 Receptor Agonists from Botanical Compounds and Preliminary Evaluation of Their Anti-Osteoporotic Effects

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