Sinapic Acid Attenuates Chronic DSS-Induced Intestinal Fibrosis in C57BL/6J Mice by Modulating NLRP3 Inflammasome Activation and the Autophagy Pathway

Abstract

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, antiinflammatory, 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.

Li-Hong Tang alleviates dextran sodium sulfate-induced colitis by regulating NRF2/HO-1 signaling pathway and gut microbiota

“…Oxidative stress is closely intertwined with the inflammatory response in the pathogenesis and progression of UC. When cells undergo oxidative stress, the resulting cellular damage promotes and prolongs the inflammatory process ( Li et al, 2024 ). MPO is prevalent in neutrophils and is a prominent candidate for promoting oxidative tissue damage during inflammation ( Nadel et al, 2023 ).…”

Sinapic acid modulates oxidative stress and metabolic disturbances to attenuate ovarian fibrosis in letrozole‐induced polycystic ovary syndrome SD rats

“…Sinapic acid (SA) is a well‐known polyphenol found in several herbs (such as borage, sage, mace, and rosemary), fruits (such as strawberries, lemons, blueberries, kiwi, plums, cherries, and apples), cereals (oats), and some vegetables (such as kale, broccoli, and turnips) in the Brassicaceae family (Bin Jardan et al., 2020 ; Zare et al., 2015 ). Some pharmacological investigations have reported that SA has antioxidant, antianxiety, anticolitis, anticancer cell growth, intestinal barrier maintenance, anti‐inflammatory, immunomodulatory, antifibrotic (liver and lung), antihypertensive, and antimicrobial activities and improves lipid metabolism (Jabbar et al., 2023 ; Lan et al., 2021 ; Li et al., 2023 ; Qian et al., 2020 ; Wang et al., 2022 ; Zhao et al., 2021 ). This study intends to assess SA's impact on ovarian fibrosis in rats with PCOS, as the efficacy of SA in preventing ovarian fibrosis has not yet been explored.…”

Pharmacological Activities and Molecular Mechanisms of Sinapic Acid in Neurological Disorders

“…Sinapic acid (SA), 3,5-dimethoxy-4-hydroxycinnamic acid, belongs to the phenylpropanoid family and is commonly found in the human diet (Figure ). It is present in various plant sources such as cereals, nuts like hazelnuts, seed oils, mustard, and rapeseeds, as well as in fruits like oranges, grapefruits, and berries, exhibiting antioxidant properties (Table ).…”