RESUMO
Ulcerative Colitis (UC) is a chronic inflammatory disease of the intestinal tract with unknown definitive etiology. Polysaccharides are among the most important active components of Abelmoschi Corolla, exhibitings various pharmacological activities such as antioxidation and immunomodulation. However, no studies have yet reported the application of Abelmoschi Corolla Polysaccharides (ACP) in treating UC. This study aims to highlight the therapeutic efficacy of ACP in UC and reveal the underlying mechanism. The potential therapeutic effect is initially verified using a dextran sodium sulfate (DSS)-induced colitis model. 16S rRNA sequencing is performed using feces samples and untargeted metabolomics using serum samples to further reveal that ACP reprograms the dysbiosis triggered by UC progression, increases the abundance of Bacteroides spp., Blautia spp., and Parabacteroides spp. at the genus level and enriches the serum concentration of 7-ketodeoxycholic acid (7-KDA). Furthermore, using the FXR-/- mouse model, it is revealed that Farnesoid X Receptor (FXR) is a key target for ACP and the metabolite 7-KDA to block STAT3 phosphorylation by repairing the intestinal barrier to attenuate UC. Taken together, this work highlights the therapeutic potential of ACP against UC, mainly exerting its effects via modulating gut microbiota and regulating the FXR/STAT3 signaling pathway.
Assuntos
Abelmoschus , Microbioma Gastrointestinal , Polissacarídeos , Receptores Citoplasmáticos e Nucleares , Fator de Transcrição STAT3 , Transdução de Sinais , Animais , Microbioma Gastrointestinal/efeitos dos fármacos , Fator de Transcrição STAT3/metabolismo , Polissacarídeos/farmacologia , Polissacarídeos/química , Transdução de Sinais/efeitos dos fármacos , Camundongos , Receptores Citoplasmáticos e Nucleares/metabolismo , Abelmoschus/química , Sulfato de Dextrana , Modelos Animais de Doenças , Masculino , Colite/tratamento farmacológico , Colite/metabolismo , Colite/induzido quimicamente , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/metabolismo , Colite Ulcerativa/microbiologia , Camundongos Endogâmicos C57BLRESUMO
Longstranded noncoding RNAs (lncRNAs) are RNAs that consist of >200 nucleotides. The majority of lncRNAs do not encode proteins but have been revealed to mediate a variety of important physiological functions. AntisenselncRNAs (ASlncRNAs) are transcribed from the opposite strand of a protein or nonprotein coding gene as part of the antisense strand of the coding gene. ASlncRNAs can serve an important role in the tumorigenesis, prognosis, metastasis and drug resistance of a number of malignancies. This has been reported to be exerted through various mechanisms, such as endogenous competition, promoter interactions, direct interactions with mRNAs, acting as 'scaffolds' to regulate mRNA halflife, interactions with 5untranslated regions and regulation of sense mRNAs. ASlncRNAs have been found to either inhibit or promote tumor aggressiveness by regulating cell proliferation, energy metabolism, inflammation, inflammatorycarcinoma transformation, invasion, migration and angiogenesis. In addition, accumulating evidence has documented that ASlncRNAs can regulate tumor therapy resistance. Therefore, targeting aberrantly expressed ASlncRNAs for cancer treatment may prove to be a promising approach to reverse therapy resistance. In the present review, research advances on the role of ASlncRNAs in tumor occurrence and development were summarized, with the aim of providing novel ideas for further research in this field.