Exploring the Mechanism of Indigo Naturalis in the Treatment of Ulcerative Colitis Based on TLR4/MyD88/NF-κB Signaling Pathway and Gut Microbiota

Abstract

Background: Clinical trials have proven that indigo naturalis is a candidate drug for treating ulcerative colitis (UC), but its therapeutic mechanism is still unclear.Purpose: This study aimed to evaluate the protective effect and mechanism of indigo naturalis to treat mice with dextran sulfate sodium (DSS)-induced UC.Methods: DSS-induced UC mice were treated with indigo naturalis (200 mg/kg), indigo (4.76 mg/kg), and indirubin (0.78 mg/kg) for 1 week. The anti-UC mechanism of indigo naturalis was studied by pathological section, inflammatory factor, western blot, and 16S rRNA sequencing.Results: According to body weight change, disease activity index, and colon length, indigo naturalis had the strongest anti DSS-induced UC effect, followed by indirubin and indigo. Pathological section showed that indigo naturalis, indigo, and indirubin could reduce the infiltration of inflammatory cells, increase the secretion of intestinal mucus, and repair the intestinal mucosa. Indigo naturalis, indigo, and indirubin could reduce IL-1β,IL-6, and TNF-α by inhibiting TLR4/MyD88/NF-κB signal transduction. Indigo naturalis and indigo could also reduce IgA and IgG both in serum and colon tissue. In addition, indigo naturalis, indigo, and indirubin could adjust the gut microbiota structure of DSS-induced UC mice, reducing the ratio of Firmicutes/Bacteroidetes and increasing the abundance of probiotics.Conclusion: Indigo and indirubin are one of the main anti-UC components of indigo naturalis. INN could regulate intestinal flora, reduce inflammation, repair intestinal mucosa, and improve the physiological status of DSS-induced UC mice and its anti-UC mechanism may be involved in inhibiting TLR4/MyD88/NF-κB signal transduction.

Dexmedetomidine alleviates intestinal barrier dysfunction and inflammatory response in mice via suppressing TLR4/MyD88/NF-κB signaling in an experimental model of ulcerative colitis

“…Eriodictyol treatment alleviates TNBS-induced colon inflammation and intestinal tissue damage in rats by inactivating the TLR4/NF-κB signaling [61]. Indigo and indirubin repair intestinal mucosa, reduce inflammation, regulate intestinal flora, and ameliorate physiological symptoms of DSSinduced colitis in mice via repressing TLR4/MyD88/NF-κB signal transduction [62]. In our study, DSS exposure elevated the levels of TLR4, MyD88, p-p65 and p-IκBα in colon tissues.…”

Polyphenolic Extracts of Coffee Cherry Husks Alleviated Colitis-Induced Neural Inflammation via NF-κB Signaling Regulation and Gut Microbiota Modification

“…34 Abnormal activation of the TLR4/ MyD88/NF-κB signaling pathway in colonic mucosa of UC patients causes persistent aggravation of intestinal inflammation and becomes targets for drug therapy in UC patients. 35 The regulation of the TLR4/MyD88/NF-κB pathway by polyphenols has been reported previously. Xue et al have reported that EGCG, a constituent of tea polyphenols, mitigates DSS-induced colitis through the TLR4/MyD88/ NF-κB signaling pathway in rats.…”

“…Toll-like receptors (TLRs) play a key role in nonspecific or innate immune defense, and activation of the TLR4/MyD88/NF-κB signaling pathway led to the expression of inflammatory factors, such as TNF-α and IL-1β . Abnormal activation of the TLR4/MyD88/NF-κB signaling pathway in colonic mucosa of UC patients causes persistent aggravation of intestinal inflammation and becomes targets for drug therapy in UC patients . The regulation of the TLR4/MyD88/NF-κB pathway by polyphenols has been reported previously.…”

Tonifying-Qi-and-Detoxification Decoction attenuated injuries of colon and lung tissues in ulcerative colitis rat model via regulating NF-κB and p38MAPK pathway

“…NF-κB has been shown to be activated in UC, which can stimulate the secretion of multiple inflammatory cytokines to form an inflammatory cascade (26). Suppression of NF-κB was demonstrated to slow UC development (27), while activation was verified to promote UC progression (28). Previous literatures reported that some components of TQDD exerted excellent anti-inflammatory activity via regulating NF-κB pathway (29,30).…”