Abstract
This study systematically evaluated the effect of Forsythia suspensa extract on dextran sodium sulfate (DSS)-induced ulcerative colitis (UC) and determined its mechanism of action. The results showed that Forsythia suspensa extract significantly inhibited DSS-induced UC in mice. In vivo mechanistic studies revealed that Forsythia suspensa extract relieved the symptoms of colitis by enhancing antioxidant activity and inhibiting pyroptosis. Further in vitro experiments on the mechanism of Forsythia suspensa showed that it reduced the level of reactive oxygen species (ROS) in J774A.1 cells. We found that Forsythia suspensa extract enhanced cellular antioxidation activity and inhibited pyroptosis. After silencing NLRP3, it was found to play an important role in pyroptosis. In addition, after Nrf2 was silenced, the inhibitory effect of Forsythia suspensa extract on cell pyroptosis was eliminated, indicating an interaction between Nrf2 and NLRP3. Metabonomics revealed that Forsythia suspensa extract significantly improved metabolic function in colitis mice by reversing the abnormal changes in the levels of 9 metabolites. The main metabolic pathways involved were glutathione metabolism, aminoacyl-tRNA biosynthesis and linoleic acid metabolism. In conclusion, we found that Forsythia suspensa extract significantly alleviated DSS-induced UC injury through the Nrf2-NLRP3 pathway and relieved metabolic dysfunction.
Highlights
Ulcerative colitis (UC) is a common nonspecific inflammatory disease characterized by chronic inflammation and ulcers in the lining of the rectum and colon
The results showed that Forsythia suspensa extract promoted the gene expression of HO-1, J774A.1 cells, weNQO1, usedNrf2 a cell pyroptosis model
The results showed that glutathione metabolism, aminoacyl-tRNA biosynthesis, and linoleic acid metabolism are potentially targeted by Forsythia suspensa extract in the treatment of UC in mice (Figure 13)
Summary
Ulcerative colitis (UC) is a common nonspecific inflammatory disease characterized by chronic inflammation and ulcers in the lining of the rectum and colon. The clinical manifestations include pain, weight loss, bloody stools and intestinal mucosal ulcers [1,2]. The development of UC involves many factors, such as microenvironmental factors, genetic factors, an abnormal immune response, and destruction of the colonic barrier [3,4]. Pyroptosis is a form of programmed cell death. Excessive release of IL-1β during pyroptosis can lead to severe acute and chronic inflammatory diseases [5]. Many studies have found that inhibiting pyroptosis signalling can alleviate experimental colitis. Cholecalciferol cholesterol emulsion alleviates the damage caused by experimental colitis by inhibiting pyroptosis [6]. Knockdown of Gasdermin E (GSDME) can attenuate ATP-induced pyroptosis in mouse macrophages [7]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
