Astragalin Attenuates Dextran Sulfate Sodium (DSS)-Induced Acute Experimental Colitis by Alleviating Gut Microbiota Dysbiosis and Inhibiting NF-κB Activation in Mice

Abstract

With the ulcerative colitis (UC) incidence increasing worldwide, it is of great importance to prevent and treat UC. However, efficient treatment options for UC are relatively limited. Due to the potentially serious adverse effects of existing drugs, there is an increasing demand for alternative candidate resources derived from natural and functional foods. Astragalin (AG) is a type of anti-inflammatory flavonoid, with Moringa oleifera and Cassia alata being its main sources. In this study, we investigated the therapeutic effects of AG on mice with dextran sulfate sodium (DSS)-induced colitis. Our results suggested that AG treatment reduced weight loss and the disease activity index (DAI), prevented colon shortening and alleviated colonic tissue damage. AG treatment reduced the expression of pro-inflammatory cytokines and related mRNAs (such as TNF-α, IL-6, and IL-1β), inhibited colonic infiltration by macrophages and neutrophils, ameliorated metabolic endotoxemia, and improved intestinal mucosal barrier function (increased expression levels of mRNAs such as ZO-1, occludin, and Muc2). Western blot analysis revealed that AG downregulated the NF-κB signaling pathway. Moreover, AG treatment partially reversed the alterations in the gut microbiota in colitis mice, mainly by increasing the abundance of potentially beneficial bacteria (such as Ruminococcaceae) and decreasing the abundance of potentially harmful bacteria (such as Escherichia-Shigella). Ruminococcaceae and Enterobacteriaceae (Escherichia-Shigella) were thought to be the key groups affected by AG to improve UC. Therefore, AG might exert a good anti-UC effect through microbiota/LPS/TLR4/NF-kB-related pathways in mice. The results of this study reveal the anti-inflammatory effect and mechanism of AG and provide an important reference for studying the mechanisms of natural flavonoids involved in preventing inflammation-driven diseases.

Ficus pandurata Hance Inhibits Ulcerative Colitis and Colitis‐Associated Secondary Liver Damage of Mice by Enhancing Antioxidation Activity

“…Lipopolysaccharide is an endotoxin derived from gram-negative bacteria, penetrating the gut mucosa only in trace amounts in normal physiological status, while in pathological status, it can increase the levels of proinflammatory cytokines by stimulating toll-like receptors such as TLR4 [ 25 , 58 ]. Once TLR4 is activated by LPS, the cell signal transduction would be triggered, and the downstream target genes MyD88 and NF- κ B would be activated, thereby promoting the development of inflammation, such as the formation of pro-IL-18 [ 59 ]. Meanwhile, the NLRP3 inflammasome and oxygen free radicals promoted the maturation of pro-IL-1 β and pro-IL-18 and then augmented the production of proinflammatory cytokines [ 60 ].…”

Astragalin Inhibits the Proliferation and Migration of Human Colon Cancer HCT116 Cells by Regulating the NF-κB Signaling Pathway

“…Furthermore, studies have shown that astragalin at a dose of 25–75 mg/kg had a significant inhibitory effect on LPS-induced inflammatory response ( Soromou et al, 2012 ). Our previous research also found that astragalin at a dose of 50–100 mg/kg had a significant inhibitory on effect on DSS-induced ulcerative colitis by regulating gut microbiota and NF-κB pathway ( Peng et al, 2020 ), and there was no apparent toxic effect on mice in this range of doses. In this study, we also found that astragalin had a significant inhibitory effect on different kinds of human colon cancer (HCT116, LoVo, SW620, SW480, Caco2), especially in HCT116 cells, and did not impart any toxicity toward normal human colon epithelial cell lines NCM460.…”

GB1a Ameliorates Ulcerative Colitis via Regulation of the NF-κB and Nrf2 Signaling Pathways in an Experimental Model

“…A major feature of UC is the development of severe inflammation in response to impaired immune responses in which NF-κB signaling pathways play a central role ( 57 , 58 ). The release of related inflammatory cytokines and pro-inflammatory mediators after activation of the NF-κB pathway plays a crucial role in UC.…”