Butyrolactone‐I, an efficient α‐glucosidase inhibitor, improves type 2 diabetes with potent TNF‐α–lowering properties through modulating gut microbiota in db/db mice

Abstract

The aim of this study was to evaluate the effects of butyrolactone‐I (A6) on type 2 diabetes (T2D) in db/db mice because A6 was found to inhibit α‐glucosidase activities and TNF‐α release, which were associated with improving T2D. Male db/db mice were divided into 6 groups and given an equivalent volume of olive oil, acarbose, or different doses of A6 for 4 wk (n = 8/group). In this study, 11 butenolide derivatives were screened for their α‐glucosidase and TNF‐α suppressive activity in vitro. A6, an efficient α‐glucosidase inhibitor, exerts hypoglycemic and multiple activities in reducing weight, improving glucose tolerance and insulin resistance, increasing short‐chain fatty acid (SCFA) levels, activating SCFA‐induced increases in glucagon‐like peptide 1 and peroxisome proliferator‐activated receptor‐γ expression, enhancing intestinal mucosal barrier function and mitigating endoxemia in db/db mice. These effects may result from mediation of gut microbiota by A6. Meanwhile, A6, with potent TNF‐α–lowering properties, was demonstrated to have multiple salutary effects with excellent structural stability and long‐term safety in vivo. A6, an effective α‐glucosidase inhibitor with high security and stability, exerted potent antidiabetic effects in vivo. Furthermore, the modulation of gut microbiota of A6 was demonstrated to be one of the mechanisms contributing to anti‐inflammation properties and improving endoxemia. Our work confirms that the compound A6 is a prospective drug candidate for T2D.—Wu, W., Liu, L., Zhu, H., Sun, Y., Wu, Y., Liao, H., Gui, Y., Li, L., Liu, L., Sun, F., Lin, H. Butyrolactone‐I, an efficient α‐glucosidase inhibitor, improves type 2 diabetes with potent TNF‐α–lowering properties through modulating gut microbiota in db/db mice. FASEB J. 33, 12616–12629 (2019). http://www.fasebj.org

Coral-Derived Endophytic Fungal Product, Butyrolactone-I, Alleviates Lps Induced Intestinal Epithelial Cell Inflammatory Response Through TLR4/NF-κB and MAPK Signaling Pathways: An in vitro and in vivo Studies

“…However, BTL-1 has different activities in the IBD mouse model, which inhibits the phosphorylation of ERK and P38, thus downregulating the expression of TNF-α. Our results are consistent with the results of related literature in inhibiting the expression of TNF-α in mice (46).…”

Improvement of intestinal barrier function, gut microbiota, and metabolic endotoxemia in type 2 diabetes rats by curcumin

“…Lipopolysaccharide (LPS) in the blood circulation forms a complex with CD14 of monocyte macrophages, which is recognized by toll-like receptor 4 (TLR4) on the surface of immune cells. They could activate nuclear transcription factors through myeloid differentiation molecule 88 (MyD88) [ 3 ] and promote the synthesis and secretion of many inflammatory factors including tumor necrosis factor α, interferon γ, and interleukin-6, which may further affect the insulin resistance and T2DM [ 4 ].…”

Alpha-Glucosidase Inhibitor Voglibose Suppresses Azoxymethane-Induced Colonic Preneoplastic Lesions in Diabetic and Obese Mice

“…In addition, AGIs are reported to increase the levels of butyrate, which is associated with the inhibited growth of transformed cells in the colorectal mucosa [17] and the inhibition of the production and activity of bile acids, particularly secondary bile acids, which are said to have carcinogenic effects owing to weak acidification of the intestinal environment. Moreover, many studies have indicated the links between gut microbiota and CRC development [44], and recent investigations have shown that AGI may attenuate inflammation and ameliorate DM through modulating intestinal microbiota [45,46]. Those effects of AGIs might be associated with suppression of CRC development, although bile acid metabolism or alteration of gut microbiota were not examined in this study.…”