Sinapic Acid Attenuates Chronic DSS-Induced Intestinal Fibrosis in C57BL/6J Mice by Modulating NLRP3 Inflammasome Activation and the Autophagy Pathway.
Wan-Ying LiJun-Yang LiuZi-Xian WangKe-Ying WangChun-Xiang HuangWen HeJia-Le SongPublished in: ACS omega (2023)
Ulcerative colitis (UC) is a chronic gastrointestinal disease that results from repeated inflammation and serious complications. Sinapic acid (SA) is a hydroxycinnamic acid present in a variety of plants that has antioxidant, anti-inflammatory, anticancer, and other protective effects. This study investigated the antifibrotic effect of SA on chronic colitis induced by dextran sulfate sodium salt (DSS) in mice. We observed that SA could significantly reduce clinical symptoms (such as improved body weight loss, increased colon length, and decreased disease activity index score) and pathological changes in mice with chronic colitis. SA supplementation has been demonstrated to repair intestinal mucosal barrier function and maintain epithelial homeostasis by inhibiting activation of the NLRP3 inflammasome and decreasing the expression of IL-6, TNF-α, IL-17A, IL-18, and IL-1β. Furthermore, SA could induce the expression of antioxidant enzymes ( Cat , Sod1 , Sod2 , Mgst1 ) by activating the Nrf2/keap1 pathway, thus improving antioxidant capacity. Additionally, SA could increase the protein expression of downstream LC3-II/LC3-I and Beclin1 and induce autophagy by regulating the AMPK-Akt/mTOR signaling pathway, thereby reducing the production of intestinal fibrosis-associated proteins Collagen-I and α-SMA. These findings suggest that SA can enhance intestinal antioxidant enzymes, reduce oxidative stress, expedite intestinal epithelial repair, and promote autophagy, thereby ameliorating DSS-induced colitis and intestinal fibrosis.
Keyphrases
- oxidative stress
- signaling pathway
- nlrp inflammasome
- diabetic rats
- ulcerative colitis
- anti inflammatory
- disease activity
- rheumatoid arthritis
- induced apoptosis
- pi k akt
- cell death
- poor prognosis
- weight loss
- dna damage
- epithelial mesenchymal transition
- cell proliferation
- endoplasmic reticulum stress
- systemic lupus erythematosus
- type diabetes
- bariatric surgery
- mass spectrometry
- high resolution
- small molecule
- adipose tissue
- simultaneous determination
- roux en y gastric bypass
- insulin resistance
- metabolic syndrome
- risk factors
- heat shock
- depressive symptoms
- binding protein
- liver fibrosis
- gastric bypass
- stress induced