RESUMO
Background: Ulcerative colitis (UC) is an immune-mediated inflammatory disease that can lead to persistent damage and even cancer without any intervention. Conventional treatments can alleviate UC symptoms but are costly and even cause various side effects. Tauroursodeoxycholic acid (TUDCA), a secondary bile acid derivative, possesses anti-inflammatory and cytoprotective properties for various diseases, but its potential therapeutic benefits in UC have not been fully explored. Methods: Mice were subjected to colitis induction using 3% dextran sulfate sodium (DSS). The therapeutic effect of TUDCA was evaluated by body weight loss, disease activity index (DAI), colon length, and spleen weight ratio. Tissue pathology was assessed using H&E staining, while the levels of pro-inflammatory and anti-inflammatory cytokines in colonic tissue were quantified via enzyme-linked immunosorbent assay (ELISA). Tight junction proteins were detected by immunoblotting and intestinal permeability was assessed using fluorescein isothiocyanate (FITC)-dextran. Moreover, the gut microbiota was profiled using high-throughput sequencing of the 16S rDNA gene. Results: TUDCA alleviated the colitis in mice, involving reduced DAI, attenuated colon and spleen enlargement, ameliorated histopathological lesions, and normalized the levels of pro-inflammatory and anti-inflammatory cytokines. Furthermore, TUDCA treatment inhibited the downregulation of intestinal barrier proteins including ZO-1 and occludin, thus reducing intestinal permeability. The analysis of gut microbiota suggested that TUDCA modulated the dysbiosis in mice with colitis, especially for the remarkable rise in Akkermansia Conclusion: TUDCA exerted a therapeutic efficacy in DSS-induced colitis by reducing intestinal inflammation, protecting intestinal barrier integrity, and restoring gut microbiota balance. Significance Statement This study demonstrates the potential therapeutic benefits of Tauroursodeoxycholic acid (TUDCA) in ulcerative colitis (UC). TUDCA effectively alleviated colitis symptoms in mice, including reducing inflammation, restoring intestinal barrier integrity and the dysbiosis of gut microbiota. This work highlights the promising role of TUDCA as a potentially alternative treatment, offering new insights into managing this debilitating condition.
RESUMO
BACKGROUND: Tea (Camellia sinensis) has a rich history and is widely consumed across many countries, and is categorized into green tea, white tea, oolong tea, yellow tea, black tea, and dark tea based on the level of fermentation. Based on a review of previous literature, the commonly recognized bioactive substances in tea include tea polyphenols, amino acids, polysaccharides, alkaloids, terpenoids, macro minerals, trace elements, and vitamins, which have been known to have various potential health benefits, such as anticancer, antioxidant, anti-inflammatory, anti-diabetes, and anti-obesity properties, cardiovascular protection, immune regulation, and control of the intestinal microbiota. Most studies have only pointed out the characteristics of tea's bioactivities, so a comprehensive summary of the pharmacological characteristics and mechanisms of tea's bioactivities and their use risks are vital. AIM OF REVIEW: This paper aims to summarize tea's bioactive substances of tea and their pharmacological characteristics and mechanisms, providing a scientific basis for the application of bioactive substances in tea and outlining future research directions for the study of bioactive substances in tea. KEY SCIENTIFIC CONCEPTS OF REVIEW: This review summarizes the main biologically active substances, pharmacological effects, and mechanisms and discusses the potential risks. It may help researchers grasp more comprehensive progress in the study of tea bioactive substances to further promote the application of tea as a natural bioactive substance in the medical field.
RESUMO
BACKGROUND: Ulcerative colitis (UC) is an inflammatory disease of the colon that is characterized by mucosal ulcers. Given its increasing prevalence worldwide, it is imperative to develop safe and effective drugs for treating UC. Emodin, a natural anthraquinone derivative present in various medicinal herbs, has demonstrated therapeutic effects against UC. However, low bioavailability due to poor water solubility limits its clinical applications. METHODS: Emodin-borate nanoparticles (EmB) were synthesized to improve drug solubility, and they modified with oligomeric mannitol into microgels (EmB-MO) for targeted delivery to intestinal macrophages that express mannose receptors. UC was induced in a mouse model using dextran sulfate sodium (DSS), and different drug formulations were administered to the mice via drinking water. The levels of inflammation-related factors in the colon tissues and fecal matter were measured using enzyme-linked immunosorbent assay. Intestinal permeability was evaluated using fluorescein isothiocyanate dextran. HE staining, in vivo imaging, real-time PCR, and western blotting were performed to assess intestinal barrier dysfunction. RESULTS: Both EmB and EmB-MO markedly alleviated the symptoms of UC, including body weight loss, stool inconsistency, and bloody stools and restored the levels of pro- and anti-inflammatory cytokines. However, the therapeutic effects of EmB-MO on the macroscopic and immunological indices were stronger than those of EmB and similar to those of 5-aminosalicylic acid. Furthermore, EmB-MO selectively accumulated in the inflamed colon epithelium and restored the levels of the gut barrier proteins such as ZO-1 and Occludin. CONCLUSIONS: EmB-MO encapsulation significantly improved water solubility, which translated to greater therapeutic effects on the immune balance and gut barrier function in mice with DSS-induced UC. Our findings provide novel insights into developing emodin-derived drugs for the management of UC.
RESUMO
New types of antidiabetic agents are continually needed with diabetes becoming the epidemic in the world. Indole alkaloids play an important role in natural products owing to their variable structures and versatile biological activities like anticonvulsant, anti-inflammatory, antidiabetic, antimicrobial, and anticancer activities, which are a promising source of novel antidiabetic drugs discovery. The synthesized indole derivatives possess similar properties to natural indole alkaloids. In the last two decades, more and more indole derivatives have been designed and synthesized for searching their bioactivities. This present review describes comprehensive structures of indole compounds with the potential antidiabetic activity including natural indole alkaloids and the synthetic indole derivatives based on the structure classification, summarizes their approaches isolated from natural sources or by synthetic methods, and discusses the antidiabetic effects and the mechanisms of action. Furthermore, this review also provides briefly synthetic procedures of some important indole derivatives.
