Identification of Functional Food Factors as β2-Adrenergic Receptor Agonists and Their Potential Roles in Skeletal Muscle
Open accessAbstract
Maintaining skeletal muscle functions by controlling muscle metabolism is of utmost importance. β2-Adrenergic receptor (β2-AR), which is expressed in skeletal muscle, is a member of the G-protein-coupled receptor family that plays a critical role in the maintenance of muscle mass. In the present study, using luciferase reporter assays in β2-AR-expressing HEK293 cells, we discovered several food factors that exhibited agonistic activity at mouse or human β2-AR. Osthole, gramine, and hordenine were identified as both mouse and human β2-AR agonists, whereas berberine was identified as a mouse β2-AR agonist only. Additionally, intramuscular injection of gramine or hordenine in mice facilitated gene expression of several cAMP response element binding protein targets, which is thought to result in increased skeletal muscle protein synthesis. This study provides evidence that several food factors might exert potential health effects on skeletal muscle by enhancing cAMP signaling through the activation of β2-AR.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Hordenine is an agonist of mouse β2-AR in a dose-dependent manner: little or no effect at 10 μM, a twofold increase in luciferase activity at 30 μM, and a more than sevenfold increase at 100 μM.
“They found hordenine to be an agonist of mouse β2-AR in a dose-dependent manner, with little to no effect with 10 μM, a twofold increase in luciferase activity compared to control with 30 μM of hordenine, and a significant more than sevenfold increase at 100 μM of hordenine.”
Hordenine at 100 μM is an agonist of human β2-AR in HEK293 cells.
“Regarding HEK293 cells expressing human β2-AR, hordenine at 100 μM was also confirmed as an agonist of the receptor.”
Hordenine is a β2-AR agonist in mice skeletal muscle.
“Hordenine was reported as a β2-AR agonist in mice skeletal muscle by Chikazawa and Sato in 2018.”
In mice injected with hordenine (20 mg/kg) in quadriceps, Nr4A1 and PGC-1α4 mRNA levels increased compared to control, suggesting a potential role in muscle hypertrophic gene expression and positive skeletal muscle function.
“RT-PCR was performed on the muscle extracts, and nuclear receptor-4A1 (Nr4A1) and PPAR coactivator 1 alpha 4 (PGC-1α4) mRNA levels were increased when compared to the control, suggesting a potential role of hordenine in muscle hypertrophic gene expression and positive skeletal muscle function.”
Cites
Thomas, D. R. (2007) · Clinical Nutrition · doi:10.1016/j.clnu.2007.03.008 · Cited by 521 · see citing works
Yimlamai, T., Dodd, S. L., Borst, S. E., & Park, S. (2005) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00448.2004 · Cited by 115 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Boucher, R., Germain, H., & Desgagné-Penix, I. (2025) · Plants · doi:10.3390/plants14091372 · Cited by 23 · see citing works
- Authors
- CHIKAZAWA, M., & SATO, R.
- Affiliations
- The University of Tokyo (JP)
- Japan Agency for Medical Research and Development (JP)
- Venue
- Journal of Nutritional Science and Vitaminology
- Published
- 2018
- Volume
- 64
- Issue
- 1
- Pages
- 68-74
- ISSN
- 0301-4800 (ISSN-L)
- 1881-7742
- OpenAlex
- W2789966694
- Cited by
- 8
- References
- 2
- Citations by year
- 2025: 3 · 2023: 1 · 2021: 1 · 2020: 1 · 2019: 2
- FWCI
- 0.36
- Type
- journal article
- Language
- en
- Open access
- diamond
- doi.org
- Locations
- Journal of Nutritional Science and Vitaminology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Japan Agency for Medical Research and Development (CREST, 16gm0910008h0001)
- Ministry of Education, Culture, Sports, Science and Technology (15H05781, 17K15267, CREST)
- Japan Society for the Promotion of Science (15H05781, 17K15267)
- Core Research for Evolutional Science and Technology (16gm0910008h0001)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Life Sciences › Agricultural and Biological Sciences › Animal Science and Zoology › Pharmacological Effects and Assays
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Keywords
- beta2-adrenergic receptor, skeletal muscle, osthole, gramine, hordenine, berberine, cAMP signaling, muscle protein synthesis, muscle mass, G protein-coupled receptors
- MeSH terms
- Cyclic AMP, Alkaloids, Animals, Coumarins, Gene Expression Regulation, Humans, Injections, Intramuscular, Male, Mice, Inbred C57BL, Tyramine, Receptors, Adrenergic, beta-2, Muscle, Skeletal, Indole Alkaloids, CREB-Binding Protein, Mice, Functional Food, HEK293 Cells, Adrenergic beta-2 Receptor Agonists
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
