ArticleInternational journal of molecular sciences2019
Coordinate Regulation of Cholesterol and Bile Acid Metabolism by the Clock Modifier Nobiletin in Metabolically Challenged Old Mice.
Article in International journal of molecular sciences, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
25 citing papers in PubMed, 1 synthesis or guideline pooled it, 41 citations in OpenAlex.
- Citrus Flavonoids as Promising Phytochemicals Targeting Diabetes and Related Complications: A Systematic Review of In Vitro and In Vivo Studies.Nutrients · 2020Pooled it
- Cryptochrome Loss Drives COPD-like Lung Pathology through Disrupted Alveolar Epithelial Proliferation and Immune Homeostasis.bioRxiv : the preprint server for biology · 2026Article
- TCM-Driven Circadian Modulation in Cancer: Engineering Spatiotemporal Drug Delivery for Precision Oncology.International journal of nanomedicine · 2026Review
- Potential and Mechanism of Nobiletin in Diabetes Mellitus and Associated Complications.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Nobiletin from citrus peel: a promising therapeutic agent for liver disease-pharmacological characteristics, mechanisms, and potential applications.Frontiers in pharmacology · 2024Review
- Circadian regulation of liver metabolism: experimental approaches in human, rodent, and cellular models.American journal of physiology. Cell physiology · 2023Review
- The Circadian Nobiletin-ROR Axis Suppresses Adipogenic Differentiation and IκBα/NF-κB Signaling in Adipocytes.Nutrients · 2023Article
- Circadian regulation of cardiac muscle function and protein degradation.Chronobiology international · 2023Article
- A Narrative Review of the Effects of Citrus Peels and Extracts on Human Brain Health and Metabolism.Nutrients · 2022Review
- ROR activation by Nobiletin enhances antitumor efficacy via suppression of IκB/NF-κB signaling in triple-negative breast cancer.Cell death & disease · 2022Article
- Dietary Phytochemicals that Can Extend Longevity by Regulation of Metabolism.Plant foods for human nutrition (Dordrecht, Netherlands) · 2022Review
- The clock modulator Nobiletin mitigates astrogliosis-associated neuroinflammation and disease hallmarks in an Alzheimer's disease model.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2022Article
- Dietary Supplements and Natural Products: An Update on Their Clinical Effectiveness and Molecular Mechanisms of Action During Accelerated Biological Aging.Frontiers in genetics · 2022Review
- Circadian stabilization loop: the regulatory hub and therapeutic target promoting circadian resilience and physiological health.F1000Research · 2022Review
- Circadian Rhythms, Disease and Chronotherapy.Journal of biological rhythms · 2021Review
- Efficacy of nobiletin in improving hypercholesterolemia and nonalcoholic fatty liver disease in high-cholesterol diet-fed mice.Nutrition research and practice · 2021Article
- Effects of the Clock Modulator Nobiletin on Circadian Rhythms and Pathophysiology in Female Mice of an Alzheimer's Disease Model.Biomolecules · 2021Article
- Clock-Modulating Activities of the Anti-Arrhythmic Drug Moricizine.Clocks & sleep · 2021Article
- Beneficial Effects of Citrus-Derived Polymethoxylated Flavones for Central Nervous System Disorders.Nutrients · 2021Review
- Recent advances in modulators of circadian rhythms: an update and perspective.Journal of enzyme inhibition and medicinal chemistry · 2020Review
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
Cholesterol and bile acid (BA) homeostasis plays a central role in systemic metabolism. Accumulating evidence suggests a key regulatory function of the circadian clock, our biological timer, in lipid metabolism, particularly cholesterol and bile acid flux. Previously, we showed that Nobiletin (NOB), a natural compound targeting the ROR (Retinoic acid receptor-related orphan receptor) nuclear receptors in the circadian oscillator, strongly protects lipid homeostasis, including normal serum cholesterol levels in high-fat (HF) fed mice at both young and old ages. In this study, we further examined the role of NOB in cholesterol metabolism in HF-fed aged mice, and found that NOB lowered the serum LDL/VLDL cholesterol levels and consequently the LDL/HDL ratio. BA levels in the serum were markedly reduced in the HF.NOB group, and examination of additional hepatic markers further indicate a protective role of NOB in the liver. At the molecular level, whereas HF feeding downregulated hepatic expression of several ROR target genes involved in bile acid synthesis, NOB treatment (HF.NOB) was able to rescue it. In accordance, fecal BA excretion was enhanced by NOB, and microbial 16S sequencing revealed alteration of several taxa known to be involved in secondary BA production in the gut. Together, these results demonstrate concerted effects of the clock-modulating compound NOB in cholesterol and BA metabolism, suggesting pharmacological manipulation of the clock as a novel therapeutic strategy against metabolic disorders and age-related decline.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.