Fenofibrate as an Adjunct Therapy for Ulcerative Colitis: Targeting Inflammation via SIRT1, NLRP3, and AMPK Pathways:...

Ulcerative colitis (UC) is an idiopathic chronic inflammation of colonic and rectal mucosa. The peroxisome proliferator-activated receptor α (PPARα) has been identified as having protective effects in UC.

The study aimed to investigate the efficacy of fenofibrate, a PPARα agonist, in UC.

A total of 70 patients with mild to moderate UC were allocated randomly and assigned to two groups (n = 35 each) from Gastroenterology Department, Faculty of Medicine, Menoufia University. The mesalamine group received a placebo along with 1 g of mesalamine three times daily, while the fenofibrate group received 1 g of mesalamine three times and fenofibrate 160 mg once daily. The study duration was for six months. A gastroenterologist assessed patients by non-invasive Partial Mayo Score (PMS) and the Inflammatory Bowel Disease Questionnaire (IBDQ) to evaluate clinical response and remission. The serum levels of silent information regulator 1 (SIRT1), NOD-like receptor protein 3 (NLRP3), and adenosine monophosphate activated protein kinase (AMPK), as well as fecal calprotectin levels were examined to determine the biological effect of fenofibrate.

After treatment, the fenofibrate group showed statistically significant reductions in PMS (p = 0.044) and improved digestive domain of IBDQ (p = 0.023). Additionally, there were significant decreases in serum NLRP3 (p = 0.041) and fecal calprotectin (p = 0.035), along with significant increases in SIRT1 (p = 0.002) and AMPK (p = 0.0003). The fenofibrate group also had higher response and remission rates compared to the mesalamine group.

Fenofibrate may be a promising adjunct for improving clinical outcomes, quality of life, and modulating inflammation in mild to moderate patients with UC.

NCT05781698.