Methyl Gallate Alleviates Acute Ulcerative Colitis by Modulating Gut Microbiota and Inhibiting TLR4/NF-κB Pathway

Abstract

Ulcerative colitis (UC) is a complex immune-mediated inflammatory disease. In recent years, the incidence of UC has increased rapidly, however, its exact etiology and mechanism are still unclear. Based on the definite anti-inflammatory and antibacterial activities of Sanguisorba officinalis L., we studied its monomer, methyl gallate (MG). In this study, we employed flow cytometry and detected nitric oxide production, finding MG regulated macrophage polarization and inhibited the expression of proinflammatory cytokines in vitro. MG also exhibited anti-inflammatory activity accompanying with ameliorating body weight loss, improving colon length and histological damage in dextran sulfate sodium-induced UC mice. Meanwhile, transcription sequencing and 16S rRNA sequencing analyzed the key signaling pathways and changes in the gut microbiota of MG for UC treatment, proving that MG could alleviate inflammation by regulating the TLR4/NF-κB pathway in vivo and in vitro. Additionally, MG altered the diversity and composition of the gut microbiota and changed the abundance of metabolic products. In conclusion, our results are the first to demonstrate that MG has obvious therapeutic effects against acute UC, which is related to macrophage polarization, improved intestinal flora dysbiosis and inhibition of TLR4/NF-κB signaling pathway, and MG may be a promising therapeutic agent for UC treatment.

Margaritaria nobilis L.f. (Phyllanthaceae) Ethanolic Extract: Low Acute Oral Toxicity and Antinociceptive Activity

“…Oxidative stress and inflammation are closely related, as the overproduction of reactive oxygen and nitrogen species intrinsically participates in the cellular and humoral response, also influencing the inflammatory mechanisms of pain [ 30 ]. Furthermore, ellagic acid, gallic acid, methyl gallate, p -coumaric acid, quercetin 3-O-xyloside, quercetin, and kaempferol have also demonstrated important anti-inflammatory activity, related to the suppression of synthesis and release of pro-inflammatory cytokines (e.g., IL-1β, IL-6, IL-17, TNFα, INFγ) and elevation of anti-inflammatory cytokines (e.g., IL-4, IL-10) and to the reduction in expression and activity of pro-inflammatory enzymes (e.g., COX-2, iNOS) and mediators (e.g., PGE2, NO), in addition to the ability to modulate nuclear factor kB (NF-kB), a key element in the inflammatory response regulation, attributed to p -coumaric acid [ 30 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 ].…”

“…On this aspect, the metabolic annotation has expedited the clarification of the chemical-pharmacological signature of complex matrices, without ignoring the unequivocal identification that may allow bioactivity of greater magnitudes [14]. Thus, because some of these compounds are structural scaffolds for promising pharmacological segments, we contend that they may explain the observed activities interactively, such as gallic acid derivatives (1), quercetin O-glycosylated derivatives (40), and similar compounds (10, 14, 15, 21, 26, 28, 29, and 41), kaempferol (42) and its glycosylated derivatives, ellagitannins (analogs of 5-7, 17, 31, 38, and 48), and gallotannins (analogs of 8, 23, and 32).…”

Der Große Wiesenknopf Sanguisorba officinalis L.

“…In diesem Zusammenhang sind Untersuchungen zur Beeinflussung des Mikrobioms bei Patienten mit Colitis ulcerosa durch Polyphenole und Methylgallat aus dem Extrakt von S. officinalis interessant. Neben einer partiellen Aufhebung der Dysbiose wurde eine Änderung der Makrophagenpolarisation im Sinne einer Entzündungshemmung beobachtet, die auf die Blockade des TLR4/NFκBSignalwegs zurückgeführt wurde [13]. Dieser Signalweg kann offensichtlich auch durch Triterpenglykoside aus der Droge moduliert werden [14], sodass beim Einsatz von Drogenextrakten auf additive und/ oder synergistische Effekte bei der Modulation der Immun antwort ausgegangen werden kann.…”

Potential application mechanism of traditional Chinese medicine in treating immune checkpoint inhibitor-induced colitis

“…Sanguisorba officinalis L. (SOL), known for its potent anti-inflammatory effects, contains a component called Methyl gallate (MG) that exhibits efficient anti-UC efficacy. A study has revealed that MG can effectively prompt the polarization of macrophages from M1 to M2 and inhibit the release of inflammatory cytokines ( 52 ).…”