ArticleNutrition & metabolism2015
Ammonia-lowering activities and carbamoyl phosphate synthetase 1 (Cps1) induction mechanism of a natural flavonoid.
Article in Nutrition & metabolism, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 36 citations in OpenAlex.
- CPS1: a multipurpose mitochondrial enzyme, bile protein, acute liver injury biomarker, and cytokine.Gut · 2026Review
- Cryptochrome Loss Drives COPD-like Lung Pathology through Disrupted Alveolar Epithelial Proliferation and Immune Homeostasis.bioRxiv : the preprint server for biology · 2026Article
- Effect of the Citrus Flavone Nobiletin on Circadian Rhythms and Metabolic Syndrome.Molecules (Basel, Switzerland) · 2022Review
- 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
- 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
- Circadian stabilization loop: the regulatory hub and therapeutic target promoting circadian resilience and physiological health.F1000Research · 2022Review
- Effects of the Clock Modulator Nobiletin on Circadian Rhythms and Pathophysiology in Female Mice of an Alzheimer's Disease Model.Biomolecules · 2021Article
- Nobiletin: Targeting the Circadian Network to Promote Bioenergetics and Healthy Aging.Biochemistry. Biokhimiia · 2020Review
- CPS1: Looking at an ancient enzyme in a modern light.Molecular genetics and metabolism · 2020Review
- Nobiletin inhibits cell growth through restraining aerobic glycolysis via PKA-CREB pathway in oral squamous cell carcinoma.Food science & nutrition · 2020Article
- SWI/SNF complex subunit BAF60a represses hepatic ureagenesis through a crosstalk between YB-1 and PGC-1α.Molecular metabolism · 2020Article
- Cardiolipin Synthesis in Skeletal Muscle Is Rhythmic and Modifiable by Age and Diet.Oxidative medicine and cellular longevity · 2020Article
- Coordinate Regulation of Cholesterol and Bile Acid Metabolism by the Clock Modifier Nobiletin in Metabolically Challenged Old Mice.International journal of molecular sciences · 2019Article
- Nobiletin fortifies mitochondrial respiration in skeletal muscle to promote healthy aging against metabolic challenge.Nature communications · 2019Article
- Effects of a high protein diet and liver disease in an in silico model of human ammonia metabolism.Theoretical biology & medical modelling · 2019Article
- Two novel CPS1 mutations in a case of carbamoyl phosphate synthetase 1 deficiency causing hyperammonemia and leukodystrophy.Journal of clinical laboratory analysis · 2018Article
- Development and Therapeutic Potential of Small-Molecule Modulators of Circadian Systems.Annual review of pharmacology and toxicology · 2018Review
- Article
- A Filtration-based Method of Preparing High-quality Nuclei from Cross-linked Skeletal Muscle for Chromatin Immunoprecipitation.Journal of visualized experiments : JoVE · 2017Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
objectiveAmmonia detoxification is essential for physiological well-being, and the urea cycle in liver plays a predominant role in ammonia disposal. Nobiletin (NOB), a natural dietary flavonoid, is known to exhibit various physiological efficacies. In the current study, we investigated a potential role of NOB in ammonia control and the underlying cellular mechanism. MATERIALS/
methodsC57BL/6 mice were fed with regular chow (RC), high-fat (HFD) or high-protein diet (HPD) and treated with either vehicle or NOB. Serum and/or urine levels of ammonia and urea were measured. Liver expression of genes encoding urea cycle enzymes and C/EBP transcription factors was determined over the circadian cycle. Luciferase reporter assays were carried out to investigate function of CCAAT consensus elements on the carbamoyl phosphate synthetase (Cps1) gene promoter. A circadian clock-deficient mouse mutant, Clock (Δ19/Δ19) , was utilized to examine a requisite role of the circadian clock in mediating NOB induction of Cps1.
resultsNOB was able to lower serum ammonia levels in mice fed with RC, HFD or HPD. Compared with RC, HFD repressed the mRNA and protein expression of Cps1, encoding the rate-limiting enzyme of the urea cycle. Interestingly, NOB rescued CPS1 protein levels under the HFD condition via induction of the transcription factors C/EBPα and C/EBPβ. Expression of other urea cycle genes was also decreased by HFD relative to RC and again restored by NOB to varying degrees, which, in conjunction with Cps1 promoter reporter analysis, suggested a C/EBP-dependent mechanism for the co-induction of urea cycle genes by NOB. In comparison, HPD markedly increased CPS1 levels relative to RC, yet NOB did not further enrich CPS1 to a significant extent. Using the circadian mouse mutant Clock (Δ19/Δ19) , we also showed that a functional circadian clock, known to modulate C/EBP and CPS1 expression, was required for NOB induction of CPS1 under the HFD condition.
conclusionNOB, a dietary flavonoid, exhibits a broad activity in ammonia control across varying diets, and regulates urea cycle function via C/EBP-and clock-dependent regulatory mechanisms.
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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.