Fenofibrate as an Adjunct Therapy for Ulcerative Colitis: Targeting Inflammation via SIRT1, NLRP3, and AMPK Pathways: A Randomized Controlled Pilot Study.

IF 4.7 2区医学 Q1 CHEMISTRY, MEDICINAL Drug Design, Development and Therapy Pub Date : 2024-11-16 eCollection Date: 2024-01-01 DOI:10.2147/DDDT.S490772

Sumaiah J Alarfaj, Mostafa M Bahaa, Thanaa A Elmasry, Eman I Elberri, Eman El-Khateeb, Amir O Hamouda, Muhammed M Salahuddin, Marwa Kamal, Abdel-Naser Abdel-Atty Gadallah, Nashwa Eltantawy, Mohamed Yasser, Walaa A Negm, Manal A Hamouda, Amsha S Alsegiani, Sarah Alrubia, Mamdouh Eldesoqui, Mahmoud S Abdallah

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Abstract

Background: 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.

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

Methods: 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.

Results: 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.

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

Trial registration identifier: NCT05781698.

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非诺贝特作为溃疡性结肠炎的辅助疗法：通过 SIRT1、NLRP3 和 AMPK 通路靶向炎症：一项随机对照试验研究。

背景：溃疡性结肠炎（UC溃疡性结肠炎（UC）是结肠和直肠粘膜的一种特发性慢性炎症。目的：本研究旨在探讨 PPARα 激动剂非诺贝特对 UC 的疗效：梅努菲亚大学医学院消化内科共随机分配了70名轻中度UC患者，并将其分为两组（每组35人）。美沙拉明组在服用安慰剂的同时服用 1 克美沙拉明，每日三次；非诺贝特组服用 1 克美沙拉明，每日三次，同时服用 160 毫克非诺贝特，每日一次。研究为期六个月。胃肠病专家通过无创部分梅奥评分（PMS）和炎症性肠病问卷（IBDQ）对患者进行评估，以评价临床反应和缓解情况。为了确定非诺贝特的生物效应，还检测了血清中沉默信息调节因子1（SIRT1）、NOD样受体蛋白3（NLRP3）和单磷酸腺苷激活蛋白激酶（AMPK）的水平以及粪钙蛋白的水平：结果：治疗后，非诺贝特组的 PMS（p = 0.044）明显减少，IBDQ 消化域（p = 0.023）也有所改善。此外，血清 NLRP3（p = 0.041）和粪便钙蛋白（p = 0.035）明显下降，SIRT1（p = 0.002）和 AMPK（p = 0.0003）明显增加。与美沙拉明组相比，非诺贝特组的反应率和缓解率也更高：结论：非诺贝特可能是改善轻中度UC患者临床疗效、生活质量和调节炎症的有效辅助药物：NCT05781698。

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来源期刊

Drug Design, Development and Therapy CHEMISTRY, MEDICINAL-PHARMACOLOGY & PHARMACY

CiteScore

9.00

自引率

0.00%

发文量

382

审稿时长

>12 weeks

期刊介绍： Drug Design, Development and Therapy is an international, peer-reviewed, open access journal that spans the spectrum of drug design, discovery and development through to clinical applications. The journal is characterized by the rapid reporting of high-quality original research, reviews, expert opinions, commentary and clinical studies in all therapeutic areas. Specific topics covered by the journal include: Drug target identification and validation Phenotypic screening and target deconvolution Biochemical analyses of drug targets and their pathways New methods or relevant applications in molecular/drug design and computer-aided drug discovery* Design, synthesis, and biological evaluation of novel biologically active compounds (including diagnostics or chemical probes) Structural or molecular biological studies elucidating molecular recognition processes Fragment-based drug discovery Pharmaceutical/red biotechnology Isolation, structural characterization, (bio)synthesis, bioengineering and pharmacological evaluation of natural products** Distribution, pharmacokinetics and metabolic transformations of drugs or biologically active compounds in drug development Drug delivery and formulation (design and characterization of dosage forms, release mechanisms and in vivo testing) Preclinical development studies Translational animal models Mechanisms of action and signalling pathways Toxicology Gene therapy, cell therapy and immunotherapy Personalized medicine and pharmacogenomics Clinical drug evaluation Patient safety and sustained use of medicines.