Vaccarin enhances intestinal barrier function in type 2 diabetic mice

Sun, Jiangnan; Yu, Xiaoyi; Hou, Bao; Ai, Min; Qi, Mengting; Ma, Xinyu; Cai, Mingjie; Gao, Min; Cai, Weiwei; Ni, Lulu; Xu, Fei; Zhou, Yuetao; Qiu, Ling

doi:10.1016/j.ejphar.2021.174375

Cited by 16 publications

(14 citation statements)

References 61 publications

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“…In addition, Bifidobacterium , a popular intestinal probiotic, can reduce the gastrointestinal dysfunction [ 40 ]. Bacteroides enhance the differentiation of goblet cells, leading to an increase in the number of goblet cells and mucin gene expression in the colon of gnotobiotic rats [ 41 ]. It has been discovered that Prevotella is essential for maintaining the gut barrier and ameliorating intestinal inflammation.…”

Section: Discussionmentioning

confidence: 99%

Surfactin Mitigates a High-Fat Diet and Streptozotocin-Induced Type 2 Diabetes through Improving Pancreatic Dysfunction and Inhibiting Inflammatory Response

Chen

Zhao

et al. 2022

IJMS

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Surfactin from Bacillus amyloliquefaciens fmb50 was utilized to treat mice with type 2 diabetes (T2DM) induced by a high-fat diet/streptozotocin (HFD/STZ). Our group’s earlier research indicated that surfactin could lower blood glucose and mitigate liver dysfunction to further improve HFD/STZ-induced T2DM through modulating intestinal microbiota. Thus, we further investigated the effects of surfactin on the pancreas and colon in mice with T2DM to elucidate the detailed mechanism. In the present study, mice with HFD/STZ-induced T2DM had their pancreatic and colon inflammation, oxidative stress, and endoplasmic reticulum stress (ERS) reduced when given oral surfactin at a dose of 80 mg/kg body weight. According to further research, surfactin also improved glucose metabolism by activating the phosphatidylinositol kinase (PI3K)/protein kinase B (Akt) signaling pathway, further protecting islets β-cell, promoting insulin secretion, inhibiting glucagon release and mitigating pancreas dysfunction. Additionally, after surfactin treatment, the colon levels of the tight junction proteins Occludin and Claudin-1 of T2DM mice were considerably increased by 130.64% and by 36.40%, respectively. These findings revealed that surfactin not only ameliorated HFD/STZ-induced pancreas inflammation and dysfunction and preserved intestinal barrier dysfunction and gut microbiota homeostasis but also enhanced insulin sensitivity and glucose homeostasis in T2DM mice. Finally, in the further experiment, we were able to demonstrate that early surfactin intervention might delay the development of T2DM caused by HFD/STZ, according to critical biochemical parameters in serum.

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Section: Discussionmentioning

confidence: 99%

Surfactin Mitigates a High-Fat Diet and Streptozotocin-Induced Type 2 Diabetes through Improving Pancreatic Dysfunction and Inhibiting Inflammatory Response

Chen

Zhao

et al. 2022

IJMS

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“…Vaccarin is an active monomer of saponaria vaccaria, an ancient Chinese medicine. Previous studies have proved that vaccarin shows the potential function in a variety of complications caused by diabetes, including macrovascular disease ( Xie, Cai et al, 2015 ; Qiu, Du et al, 2016 ; Sun, Cai et al, 2017 ; Zhu, Lei et al, 2018 ; Lei, Gong et al, 2019 ; Xu, Liu et al, 2019 ; Hou, Cai et al, 2020 ; Hou, Qi et al, 2020 ; Liu, Sun et al, 2020 ; Sun, Yu et al, 2021 ). However, the effect of vaccarin on alleviating endothelial inflammatory injury in T2DM and the molecular mechanism has not been elucidated.…”

Section: Discussionmentioning

confidence: 99%

“…The cells were cultured at 37°C in a humidified incubator of 5% CO 2 and 95% air. After reaching 70% confluence ( Xu, Liu et al, 2019 ), HUVEC cells were exposed to HG (35 mM) for 24h, then to 5 µM vaccarin or 20 µM metformin ( Raj, Natarajan et al, 2021 ) (Solarbio, Beijing, China) 16 h. Vaccarin was purchased from Shanghai Shifeng Technology (Shanghai, China) ( Sun, Yu et al, 2021 ), purity >98%, the molecular formula is C 32 H 38 O 19 , and molecular mass is 726.63 g/mol.…”

Section: Methodsmentioning

confidence: 99%

“…Aortic tissue was fixed with 4% paraformaldehyde and embedded in paraffin. The sections were stained with hematoxylin-eosin (H&E) (Solarbio, Beijing, China) ( Sun, Yu et al, 2021 ) and then observed by optical microscope (Nikon, Japan).…”

Section: Methodsmentioning

confidence: 99%

“…Vaccarin (VAC), a flavonoid monomer which contains twelve phenolic hydroxyl groups ( Figure 1 ), is extracted from Vaccaria segetalis seeds ( Hou et al, 2020 ; Hou et al, 2020 ). Vaccarin has a wide range of biological effects, including endothelial cell injury prevention, angiogenesis promotion, wound healing, and liver protection ( Sun, Yu et al, 2021 ). Previous studies have shown that vaccarin can participate in FGF-2 mediated fibroblast growth factor receptor 1 (FGFR-1) induced angiogenesis in vitro and in vivo ( Sun, Cai et al, 2017 ).…”

Section: Introductionmentioning

confidence: 99%

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Vaccarin alleviates endothelial inflammatory injury in diabetes by mediating miR-570-3p/HDAC1 pathway

Zhu

et al. 2022

Front. Pharmacol.

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Vaccarin is a flavonoid glycoside, which has a variety of pharmacological properties and plays a protective role in diabetes and its complications, but its mechanism is unclear. In this study, we aim to investigate whether histone deacetylase 1(HDAC1), a gene that plays a pivotal role in regulating eukaryotic gene expression, is the target of miR-570-3p in diabetic vascular endothelium, and the potential molecular mechanism of vaccarin regulating endothelial inflammatory injury through miR-570-3p/HDAC1 pathway. The HFD and streptozotocin (STZ) induced diabetes mice model, a classical type 2 diabetic model, was established. The aorta of diabetic mice displayed a decrease of miR-570-3p, the elevation of HDAC1, and inflammatory injury, which were alleviated by vaccarin. Next, we employed the role of vaccarin in regulating endothelial cells miR-570-3p and HDAC1 under hyperglycemia conditions in vitro. We discovered that overexpression of HDAC1 counteracted the inhibitory effect of vaccarin on inflammatory injury in human umbilical vein endothelial cells (HUVECs). Manipulation of miRNA levels in HUVECs was achieved by transfecting cells with miR-570-3p mimic and inhibitor. Overexpression of miR-570-3p could decrease the expression of downstream components of HDAC1 including TNF-α, IL-1β, and malondialdehyde, while increasing GSH-Px activity in HUVECs under hyperglycemic conditions. Nevertheless, such phenomenon was completely reversed by miR-570-3p inhibitor, and administration of miR-570-3p inhibitor could block the inhibition of vaccarin on HDAC1 and inflammatory injury. Luciferase reporter assay confirmed the 3′- UTR of the HDAC1 gene was a direct target of miR-570-3p. In summary, our findings suggest that vaccarin alleviates endothelial inflammatory injury in diabetes by mediating miR-570-3p/HDAC1 pathway. Our study provides a new pathogenic link between deregulation of miRNA expression in the vascular endothelium of diabetes and inflammatory injury and provides new ideas, insights, and choices for the scope of application and medicinal value of vaccarin and some potential biomarkers or targets in diabetic endothelial dysfunction and vascular complications.

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Berberine alleviates intestinal barrier dysfunction in glucolipid metabolism disorder hamsters by modulating gut microbiota and gut‐microbiota‐related tryptophan metabolites

et al. 2022

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BACKGROUND: Barberry plants can be considered as useful additives and functional compounds in various industries, especially in the food industry. Berberine (BBR), the most important functional compound in the barberry roots, has recently been used to treat obesity, diabetes, and atherosclerosis. Gut microbiota and the intestinal barrier play an important role in the development of glucolipid metabolism disorders (GLMDs). However, the association of gut microbiota metabolism disorder and the intestinal barrier dysfunction effect of BBR in GLMDs remains elusive. RESULTS:The results showed that administration of BBR could increase the number of colonic glands and goblet cell mucus secretion, improve the intestinal barrier function, and reduce the serum glycolipid level in GLMD hamsters. Interestingly, BBR was metabolized into 12 metabolites by gut microbiota, and the main metabolic pathways were oxidation, demethylation, and hydrogenation. In addition, BBR significantly improved the species diversity and uniformity of gut microbiota and promoted the proliferation of beneficial microbiota. Furthermore, the levels of tryptophan metabolites, such as indole, indole-3-acetamide, indole-3-acetaldehyde, indole-3-pyruvic acid, and indole-3-acetic acid were significantly altered by BBR. Both the intestinal tight junction proteins and intestinal immune factors were altered by BBR.CONCLUSION: BBR could alleviate intestinal barrier dysfunction of GLMDs by modulating gut microbiota and gut-microbiotarelated tryptophan metabolites, which may be one of the pharmacological mechanisms for the treatment of GLMDs.

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Vaccarin enhances intestinal barrier function in type 2 diabetic mice

Cited by 16 publications

References 61 publications

Surfactin Mitigates a High-Fat Diet and Streptozotocin-Induced Type 2 Diabetes through Improving Pancreatic Dysfunction and Inhibiting Inflammatory Response

Surfactin Mitigates a High-Fat Diet and Streptozotocin-Induced Type 2 Diabetes through Improving Pancreatic Dysfunction and Inhibiting Inflammatory Response

Vaccarin alleviates endothelial inflammatory injury in diabetes by mediating miR-570-3p/HDAC1 pathway

Berberine alleviates intestinal barrier dysfunction in glucolipid metabolism disorder hamsters by modulating gut microbiota and gut‐microbiota‐related tryptophan metabolites

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