Daphnetin ameliorates experimental colitis by modulating microbiota composition and T _reg /T _h 17 balance

Abstract

Inflammatory bowel diseases (IBDs) are characterized by chronic pathologies associated with extensive gut dysbiosis and intestinal inflammation. Hence, endeavors to improve the inflammatory pathology by manipulating gut microbiota are ongoing. Daphnetin (DAPH) is a coumarin derivative extracted from Daphne odora var with anti‐inflammatory and immune‐regulatory properties that has been widely used in treating inflammatory disorders. Herein, we showed that DAPH remarkably alleviated experimental colitis by reducing colonic inflammation, improving colonic integrity, and reestablishing immune and metabolic homeostasis in the inflicted intestines. Our analysis showed that DAPH modified the composition of gut microbiota and altered the metabolic profiles in dextran sulfate sodium–treated mice. In particular, this agent significantly elevated the abundance of short‐chain fatty acid (SCFA)–producing gut microbiota, causatively related with the enhanced development of Treg cells and the reduced proinflammatory Th17 cell differentiation. More critically, the protective effect of DAPH was shown to be transmissible among colitic mice through cohousing or fecal microbiota transplantation, further substantiating the importance of SCFA‐producing gut microbiota in DAPH action. We thus for the first time reveal the potential of DAPH in resetting the gut microbiome and reestablishing immune homeostasis in colitic mice, which may have clinical implications for treating IBD.—Ji, J., Ge, X., Chen, Y., Zhu, B., Wu, Q., Zhang, J., Shan, J., Cheng, H., Shi, L. Daphnetin ameliorates experimental colitis by modulating microbiota composition and Treg/Th17 balance. FASEB J. 33,9308–9322 (2019). http://www.fasebj.org

Protective effects of tuna meat oligopeptides (TMOP) supplementation on hyperuricemia and associated renal inflammation mediated by gut microbiota

“…Hyperuricemic mice received gut microbiota via transplants from the control, model, or TMOP groups to further substantiate whether the beneficial effects of TMOP were mediated by gut microbiota. FMT-LD-TMOP alleviated hyperuricemia and renal inflammation phenotypes, consistent with other studies on obesity, colitis, etc,, 30,41 and the beneficial effects were characterized by the reversal in uric acid metabolism and pro-inflammatory cytokine release, and inhibition of the NLRP3 inflammasome and TLR4/NF-κB signaling pathways activations (Figure 7). Meanwhile, FMT-LD-TMOP mice exhibited repaired gut intestinal integrity and increased SCFA productions, similar as the corresponding diet-treated mice (LD-TMOP group) ( Figure 8A-F).…”

Protective effect of bergapten in acetic acid-induced colitis in rats

“…Maduzia et al., (2020) [ 51 ], in their study also showed a similar protective effect exhibited by warfarin treatment before the induction of acute pancreatitis in the model employed in the study. Anti-inflammatory, protective and therapeutic effects have been observed in other studies on colons on the administration of coumarins such as daphnetin [ 52 ], 4-methylesculin [ 53 ], or osthole [ 54 ]. Although studies have not been done on the anticoagulant effect of bergapten, results from these experiments conducted indicate that possible, anti-inflammatory action shown by bergapten may be due to its possible anticoagulant activity.…”

Daphnetin suppresses experimental abdominal aortic aneurysms in mice via inhibition of aortic mural inflammation

“…Furthermore, Liu et al (26) reported that DAP has protective effects on severe acute pancreatitis in a rat model by inhibiting the expression of inflammatory cytokines. Ji et al (32) demonstrated that DAP ameliorates experimental colitis by modulating microbiota composition and the Treg/Th17 balance. Currently, an increasing number of studies have demonstrated that DAP serves a crucial role in the prevention and treatment of inflammation-related diseases due to its powerful anti-inflammatory activities (33)(34)(35).…”

“…Liu et al (26) reported that DAP has some protective effects on severe acute pancreatitis in a rat model by inhibiting the expression of inflammatory cytokines. Subsequently, DAP was found to prevent and treat numerous diseases, including cerebral ischaemia/reperfusion injury, rheumatoid arthritis, colitis and endotoxin-induced lung injury, due to its powerful anti-inflammatory activities (24,(27)(28)(29)(30)(31)(32). At present, DAP is an anti-inflammatory agent used in some inflammation-related diseases (33)(34)(35).…”