在临床前结肠炎模型中补充褪黑素:关于炎症、氧化应激和结肠修复的系统综述和剂量反应荟萃分析

IF 2.4 Q3 NUTRITION & DIETETICS PharmaNutrition Pub Date : 2024-10-08 DOI:10.1016/j.phanu.2024.100414
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引用次数: 0

摘要

背景溃疡性结肠炎(UC)是炎症性肠病(IBD)的一种自身免疫形式,会导致结肠慢性炎症。现有的治疗方法往往效果不佳,因此需要替代或辅助疗法。褪黑素以其抗氧化和抗炎作用而闻名,在这方面大有可为。因此,本研究对临床前模型进行了剂量反应荟萃分析和系统综述,以评估褪黑激素对 UC 的有效性。方法在 PubMed、Scopus、Embase 和 Web of Science 中进行了广泛的检索,遵守了 SYRCLE 的偏倚风险指南,并在 PROSPERO(CRD42024511595)上进行了注册。随机效应模型计算了疾病活动指数、炎症标志物和抗氧化防御能力的标准平均差(SMD)和95%置信区间(CI)。研究发现,褪黑素能明显降低溃疡指数(SMD = -3.19)和丙二醛水平(SMD = -2.31)。它还明显抑制了主要的促炎介质,包括TNF-α(SMD =-1.14)、IL-6(SMD =-1.44)、IL-1β(SMD =-1.63)和IL-17(SMD =-1.77),同时提高了抗氧化防御能力,特别是谷胱甘肽水平(SMD = 2.80)。此外,褪黑素还能有效调节关键的炎症调节因子,包括核因子卡巴B(SMD =-1.97)和环氧化酶-2(SMD =-1.34)。结论褪黑素在临床前 UC 模型中显示出显著的抗炎、抗氧化和组织修复功效,支持临床试验以确认其治疗潜力和最佳剂量。
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Melatonin supplementation in preclinical colitis models: A systematic review and dose-response meta-analysis on inflammation, oxidative stress, and colon repair

Background

Ulcerative colitis (UC), an autoimmune form of inflammatory bowel disease (IBD), leads to chronic inflammation of the colon. Existing treatments often fall short, highlighting the need for alternative or supplementary therapies. Melatonin, known for its antioxidant and anti-inflammatory effects, shows promise in this context. Thus, this study conducts a dose-response meta-analysis and systematic review of preclinical models to evaluate melatonin's effectiveness in UC.

Methods

Extensive searches in PubMed, Scopus, Embase, and Web of Science were performed, adhering to SYRCLE’s risk of bias guidelines, and registered with PROSPERO (CRD42024511595). Random-effects models calculated standard mean differences (SMD) and 95 % confidence intervals (CI) for disease activity indices, inflammatory markers, and antioxidant defenses.

Results

Out of 860 screened records, 72 studies met the inclusion criteria. Melatonin was found to significantly lower the ulcer index (SMD = −3.19) and malondialdehyde levels (SMD = −2.31). It also notably suppressed key pro-inflammatory mediators, including TNF-α (SMD = −1.14), IL-6 (SMD = −1.44), IL-1β (SMD = −1.63) and IL-17 (SMD = −1.77), while enhancing antioxidant defenses, particularly glutathione levels (SMD = 2.80). Furthermore, melatonin effectively modulated critical inflammatory regulators including nuclear factor kappa B (SMD = −1.97) and cyclooxygenase-2 (SMD = −1.34). The optimal therapeutic dose was identified as up to 10 mg/kg, with the highest efficacy observed via intraperitoneal and intracolonic administration routes.

Conclusion

Melatonin showed significant anti-inflammatory, antioxidant and tissue-repairing benefits in preclinical UC models, supporting clinical trials to confirm its therapeutic potential and optimal dosing.
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来源期刊
PharmaNutrition
PharmaNutrition Agricultural and Biological Sciences-Food Science
CiteScore
5.70
自引率
3.10%
发文量
33
审稿时长
12 days
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