Asiaticoside ameliorates DSS-induced colitis in mice by inhibiting inflammatory response, protecting intestinal barrier and regulating intestinal microecology.

Ulcerative colitis (UC) is one of the most prevalent inflammatory bowel diseases and poses a serious threat to human health. Currently, safe and effective preventive measures are unavailable. In this study, the protective effects of asiaticoside (AS) on dextran sodium sulfate (DSS)-induced colitis in mice and the underlying molecular mechanism were investigated. In this experiment, colitis was induced in mice with DSS. Subsequently, the role of AS in colitis and its underlying mechanisms were examined using H&E staining, immunofluorescence staining, western blot, Elisa, FMT, and other assays. The results showed that AS significantly attenuated the related symptoms of DSS-induced colitis in mice. In addition, AS inhibited the activation of signaling pathways TLR4/NF-κB and MAPK reduced the release of inflammatory factors, thereby attenuating the inflammatory response in mice. AS administration also restored the permeability of the intestinal barrier by increasing the levels of tight junction-associated proteins (claudin-3, occludin, and ZO-1). In addition, AS rebalanced the intestinal flora of DSS-treated mice by increasing the diversity of the flora. AS can alleviate DSS-induced ulcerative colitis in mice by maintaining the intestinal barrier, thus inhibiting the signaling pathways TLR4/NF-κB and MAPK activation, reducing the release of inflammatory factors, and regulating intestinal microecology.

Fufangxiaopi formula alleviates DSS-induced colitis in mice by inhibiting inflammatory reaction, protecting intestinal barrier and regulating intestinal microecology.

ETHNOPHARMACOLOGICAL RELEVANCE: Fufangxiaopi Formula (FF) is a modified form of Sishen Wan, traditionally used for treating diarrhea. The application of FF for treating ulcerative colitis (UC) has achieved desirable outcomes in clinical settings. However, the underlying mechanism of the effect of FF on UC is yet to be determined. AIM OF STUDY: This study aimed to evaluate the protective effect and underlying mechanism of FF on mice with dextran sodium sulfate (DSS)-induced colitis. MATERIALS AND METHODS: In vivo, the efficacy of FF on the symptoms associated with DSS-induced colitis in mice was clarified by observing the body weight change, colon length, DAI score, and H&E staining. The release of inflammatory mediators in mouse colon tissues was detected by ELISA and MPO, and the contents of TLR4/NF-κB signaling pathway and MAPK signaling pathway-related proteins, as well as intestinal barrier-related proteins, were detected in mouse colon tissues by western blot method. Changes in the content of barrier proteins in mouse colon tissues were detected by immunofluorescence. 16S rRNA sequencing and FMT were performed to clarify the effects of FF on intestinal flora. In vitro, the effect of FF-containing serum on LPS-induced inflammatory mediator release from RAW264.7 cells were detected by qRT-PCR. The contents of TLR4/NF The effects of FF-containing serum on B signaling pathway and MAPK signaling pathway related proteins in RAW264.7 cells and intestinal barrier related proteins in Caco-2 cells were detected by western blot. The effects of FF-containing serum on LPS-induced nuclear translocation of p65 protein in RAW264.7 cells and barrier-associated protein in Caco-2 cells were detected by immunofluorescence. RESULTS: In vivo studies showed that FF could significantly alleviate the symptoms of UC, including reducing colon length, weight loss, clinical score, and colon tissue injury in mice. FF could significantly reduce the secretion of proinflammatory cytokines by suppressing the activation of the TLR4/NF-κB and MAPK signaling pathways. Moreover, FF could protect the integrity of intestinal barriers by significantly increasing claudin-3, occludin, and ZO-1 expression levels. 16S rRNA sequencing and FMT elucidate that FF can alleviate symptoms associated with colitis in mice by interfering with intestinal flora. In vitro studies showed that FF drug-containing serum could significantly inhibit proinflammatory responses and attenuate the secretion of iNOS, IL-1ß, TNF-α, IL-6, and COX-2 by suppressing the activation of TLR4/NF-κB and MAPK signaling pathways in RAW264.7 cells. Furthermore, FF could protect the Caco-2 cell epithelial barrier. CONCLUSION: FF could alleviate DSS-induced colitis in mice by maintaining the intestinal barrier, inhibiting the activation of TLR4/NF-κB and MAPK signaling pathways, reducing the release of proinflammatory factors, and regulating intestinal microecology.

Natural Polyphenols for Treatment of Colorectal Cancer.

Colorectal cancer (CRC) is a prevalent and serious gastrointestinal malignancy with high mortality and morbidity. Chemoprevention refers to a newly emerged strategy that uses drugs with chemopreventive properties to promote antioxidation, regulate cancer cell cycle, suppress proliferation, and induce cellular apoptosis, so as to improve cancer treatment outcomes. Natural polyphenols are currently recognized as a class of chemopreventive agents that have shown remarkable anticarcinogenic properties. Numerous in vitro and in vivo studies have elucidated the anti-CRC mechanisms of natural polyphenols, such as regulation of various molecular and signaling pathways. Natural polyphenols are also reportedly capable of modulating the gut microbiota and cancer stem cells (CSCs) to suppress tumor formation and progression. Combined use of different natural polyphenols is recommended due to their low bioavailability and instability, and combination treatment can exert synergistical effects, reduce side effects, and avoid drug resistance in CRC treatment. In summary, the application of polyphenols in the chemoprevention and treatment of CRC is promising. Further clinical evaluation of their effectiveness is warranted and anticipated.

Protective Effect of Prim-O-Glucosylcimifugin on Ulcerative Colitis and Its Mechanism.

Intestinal epithelial immune dysfunction or imbalance in the homeostasis of intestinal flora can lead to the occurrence or exacerbation of ulcerative colitis (UC). Prim-O-glucosylcimifugin (POG) is an extract of Chinese traditional medicine (TCM) Saposhnikov, which has analgesic, anti-inflammatory, and antioxidant effects. The present work discussed how the POG alternated ulcerative colitis (UC) along with its underlying mechanism. This was clarified by performing animal studies in a mice model, wherein UC was induced by dextran sulfate sodium (DSS). In vivo studies have found that POG increased clinical score, colonic length, and weight of mice in the ulcerative colitis model. It repaired the pathological injury of an intestinal mucosa within mice while inhibiting the inflammatory factor levels such as IL-1ß, TNF-α, and IL-6. Meanwhile, by16SrDNA sequencing analysis, it was found that POG regulated the richness of intestinal microbiota structure and repaired the intestinal immune barrier by upregulating the expression levels of tight junction proteins Occludin, Claudin-3, and ZO-1. To further confirm the above results, we found in in vitro studies that POG also protected lipopolysaccharide- (LPS-) induced RAW264.7 cells. POG dramatically suppressed inflammatory factor production (including TNF-α, IL-1ß, and IL-6) within LPS-treated RAW264.7 cells by inhibiting the activation of ERK1/2, AKT, JNK1/2, IκB-α, P38, and P65 phosphorylation. In conclusion, POG plays a protective role against UC by inhibiting the activation of pro-inflammatory signaling pathways MAPK, AKT, and NF-κB; repairing the integrity of the intestinal barrier; and regulating the diversity and abundance of intestinal flora.

Therapeutic Mechanism and Effect of Camptothecin on Dextran Sodium Sulfate-Induced Ulcerative Colitis in Mice.

Camptothecin (CPT) is a cytotoxic quinoline alkaloid isolated from the bark and branches of the Chinese tree Camptotheca acuminata. CPT inhibits topoisomerase I. It possesses various antitumor activities and is mainly used in the treatment of colon, ovarian, liver, and bone cancers as well as leukemia. CPT inhibits the expressions of inflammatory genes and can prevent death from chronic inflammation. Therefore, we investigated the effect of CPT treatment in ulcerative colitis (UC) using DSS-induced UC mouse model; after that, we explored its potential mechanisms. Here, we found that CPT exerted protection on DSS-induced UC in rats. In addition, the administration prominently reduced the disease activity index as well as colon length of the model rats and remarkably reduced the inflammatory cytokines. Further, CPT significantly reduced several vital proinflammatory proteins in LPS-induced RAW264.7 cells. In summary, our findings demonstrate that CPT is hopefully to act as a therapeutic agent for UC.

The protective effect and mechanism of pedunculoside on DSS (dextran sulfate sodium) induced ulcerative colitis in mice.

Pedunculoside (PE) is derived from the bark of iron holly, a member of the holly family. Previous studies have shown that PE has anti-inflammatory, antitumor, antiviral, cholesterol-lowering and blood-pressure-lowering effects. In this study, we aimed to investigate the effects of PE on ulcerative colitis and to explore its potential mechanisms. We treated a mouse model of ulcerative colitis induced by DSS (dextran sulfate sodium) with PE. The results showed that PE had an obvious effect on DSS-induced ulcerative colitis. PE significantly improved the colon length and clinical score in mice, and significantly inhibited the production of inflammatory cytokines. In the LPS-induced inflammatory response of RAW264.7 macrophages, we also found that PE significantly inhibited the phosphorylation of AKT, ERK1/2, JNK1/2, P65, and P38 to reduce the production of IL-1ß, IL-6, TNF-α, COX-2, and iNOS. Furthermore, PE suppressed the LPS-induced transcriptional activities of nuclear factor P65 as well as the phosphorylation of P65. In addition, we also studied the effect of PE on LPS induced AKT/NF-κB and MAPK signaling pathways with primary peritoneal macrophages. In summary, PE has a beneficial effect on ulcerative colitis, and may be a potential natural product in the treatment of ulcerative colitis.