Evaluating natural bioactive chronobiotics in a C. elegans circadian disruption system induced by light-temperature entrainment.

IF 8.3 1区 医学 Q1 CHEMISTRY, MEDICINAL
Phytomedicine Pub Date : 2026-06-01 Epub Date: 2026-03-27 DOI:10.1016/j.phymed.2026.158129
Yiwen Guo, Tao Zhang, Ying Xu, Ming Chang, Ruijie Liu
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引用次数: 0

Abstract

Background: The prevalence of circadian rhythm disruption (CRD) is increasing due to the worsening light pollution, rising societal stress, and globalized lifestyles. Long-term CRD can cause significant physiological changes and raise the risk of various health disorders. Natural bioactive compounds (NBC) are showing promise as novel circadian modulators because they can precisely target core clock networks, be administered flexibly, and have multi-target effects, requiring efficient screening models.

Purpose: The objective of this study was to establish and characterize a CRD model in C. elegans and to explore its applicability for evaluating the chronobiotic potential of NBCs.

Methods: A synchronized light-temperature perturbation protocol was used to induce a stable CRD state in C. elegans. The model's validity was rigorously assessed by monitoring locomotor behavioral rhythms and quantifying transcriptional changes in core clock genes. Rhythm integrity and periodicity were analyzed using the Biodare2 platform. The restorative effects of administered nine NBCs were evaluated through this integrated behavioral, physiological, and molecular framework.

Results: The environmental perturbation successfully recapitulated key features of human CRD, leading to markedly disturbed behavioral rhythms and altered expression of core clock genes. The model showed good reproducibility and proved suitable for compound evaluation. Several chronobiotic compounds, including nobiletin, serotonin, N-acetylserotonin, melatonin, catechin, and capsaicin, alleviated CRD-associated phenotypes to varying degrees, demonstrating the model's utility for investigating the circadian regulatory effects of NBCs.

Conclusion: Our multidimensional analysis in C. elegans reveals that natural bioactive compounds can modulate CRD, offering new perspectives on the therapeutic potential of plant-derived chronobiotics.

评估秀丽隐杆线虫在光温诱导的昼夜节律中断系统中的天然生物活性计时生物。
背景:由于光污染的恶化、社会压力的增加和全球化的生活方式,昼夜节律紊乱(CRD)的患病率正在增加。长期CRD可引起显著的生理变化,并增加各种健康障碍的风险。天然生物活性化合物(NBC)作为一种新型的昼夜节律调节剂正显示出前景,因为它们可以精确地靶向核心时钟网络,灵活地给药,具有多靶点效应,需要有效的筛选模型。目的:建立秀丽隐杆线虫的CRD模型并对其进行表征,探讨该模型在评价NBCs时生潜能方面的适用性。方法:采用同步光温扰动法诱导秀丽隐杆线虫进入稳定的CRD状态。通过监测运动行为节律和量化核心时钟基因的转录变化,严格评估了模型的有效性。使用Biodare2平台分析节律完整性和周期性。通过这种综合的行为、生理和分子框架来评估给予的9种nbc的恢复效果。结果:环境扰动成功再现了人类CRD的关键特征,导致行为节律明显紊乱,核心时钟基因表达改变。该模型重现性好,适用于复方评价。几种时间生物化合物,包括nobiletin、5 -羟色胺、n -乙酰5 -羟色胺、褪黑素、儿茶素和辣椒素,在不同程度上缓解了crd相关的表型,证明了该模型在研究nbc的昼夜节律调节作用方面的实用性。结论:我们对秀丽隐杆线虫的多维分析揭示了天然生物活性化合物可以调节CRD,为植物源性时间生物制剂的治疗潜力提供了新的视角。
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来源期刊
Phytomedicine
Phytomedicine 医学-药学
CiteScore
10.30
自引率
5.10%
发文量
670
审稿时长
91 days
期刊介绍: Phytomedicine is a therapy-oriented journal that publishes innovative studies on the efficacy, safety, quality, and mechanisms of action of specified plant extracts, phytopharmaceuticals, and their isolated constituents. This includes clinical, pharmacological, pharmacokinetic, and toxicological studies of herbal medicinal products, preparations, and purified compounds with defined and consistent quality, ensuring reproducible pharmacological activity. Founded in 1994, Phytomedicine aims to focus and stimulate research in this field and establish internationally accepted scientific standards for pharmacological studies, proof of clinical efficacy, and safety of phytomedicines.
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