Silybum marianum seeds mitigate pro-inflammatory functions of human neutrophils and alleviate ulcerative colitis in rats

Pro-inflammatory signaling targets and free radicals contribute to the occurrence of ulcerative colitis (UC). Chemical drugs can reduce the UC, whereas their side effects limit their applications. Currently, plant remedies present a promising field for pharmaceutical research. Our study aims to screen bioactive compounds in the aqueous extract from Silybum marianum seeds (AESS) and determine its effect on neutrophil pro-inflammatory functions and colitis. The phytochemical profile and antioxidant potential of AESS were investigated. Human neutrophils were used to assess AESS cytotoxicity and its effects on oxygen-free radicals using chemiluminescence. The western blot was used to evaluate the degranulation mechanism. Furthermore, azurophilic granules, xanthine-xanthine oxidase (X-XO), and horseradish peroxidase (HRP) were used to examine the AESS effects on myeloperoxidase (MPO), superoxide anion (O₂^–.) and hydrogen peroxide (H₂O₂). For the UC, rats were given oral (p.o.) doses of AESS and sulfasalazine (SSZ) for one week before colitis induction, then histological structure and inflammatory and oxidative markers were examined. Findings showed that AESS exhibited antioxidant capacities due to its flavonoids and mainly their flavonolignans, such as silychristin, silydianin, and silibinin A and silibinin B. Myeloperoxidase and HRP activities demonstrated that AESS decreased total oxygen radicals, H₂O₂ and hypochlorous acid (HOCl), and modulated neutrophil degranulation. AESS (100 and 1000 mg/kg, p.o.) prevents the rise of tumor necrosis factor-α (TNF-α) and interleukin (IL)-1β and preserves the microstructure of the colon and its redox status during the UC. Flavonolignans of AESS possess anti-inflammatory and antioxidant potentials, making it a safe candidate to prevent inflammation.