The DOI matches its Crossref record; 47 of the 48 references it cites were found in a registry or an index.
Flavonoid Apigenin Is an Inhibitor of the NAD+ase CD38
Open accessAbstract
Metabolic syndrome is a growing health problem worldwide. It is therefore imperative to develop new strategies to treat this pathology. In the past years, the manipulation of NAD+ metabolism has emerged as a plausible strategy to ameliorate metabolic syndrome. In particular, an increase in cellular NAD+ levels has beneficial effects, likely because of the activation of sirtuins. Previously, we reported that CD38 is the primary NAD+ase in mammals. Moreover, CD38 knockout mice have higher NAD+ levels and are protected against obesity and metabolic syndrome. Here, we show that CD38 regulates global protein acetylation through changes in NAD+ levels and sirtuin activity. In addition, we characterize two CD38 inhibitors: quercetin and apigenin. We show that pharmacological inhibition of CD38 results in higher intracellular NAD+ levels and that treatment of cell cultures with apigenin decreases global acetylation as well as the acetylation of p53 and RelA-p65. Finally, apigenin administration to obese mice increases NAD+ levels, decreases global protein acetylation, and improves several aspects of glucose and lipid homeostasis. Our results show that CD38 is a novel pharmacological target to treat metabolic diseases via NAD+-dependent pathways.
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“For example, apigenin, a naturally occurring flavonoid, enhances NAD+ levels in human cells and mouse liver tissue, and improves glucose and lipid homeostasis in mouse models of obesity226.”
From NAD+ metabolism and its roles in cellular processes during ageing (2021) · cites this paper as [226]
In the citing paper
“For example, apigenin, a naturally occurring flavonoid, enhances NAD+ levels in human cells and mouse liver tissue, and improves glucose and lipid homeostasis in mouse models of obesity226.”
From NAD+ metabolism and its roles in cellular processes during ageing (2021) · cites this paper as [226]
In the citing paper
“have been implicated in the regulation of chromosomal integrity, DNA damage repair, metabolism, aging, health span, and longevity”
From A Potent and Specific CD38 Inhibitor Ameliorates Age-Related Metabolic Dysfunction by Reversing Tissue NAD+ Decline (2018) · cites this paper as Escande et al., 2013
In the citing paper
“Sirtuins are enzymes that remove specific covalent modification in lysine residues, such as acetylation, malonylation, and succinylation, in several proteins”
From A Potent and Specific CD38 Inhibitor Ameliorates Age-Related Metabolic Dysfunction by Reversing Tissue NAD+ Decline (2018) · cites this paper as Escande et al., 2013
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Metadata
- Authors
- Escande, C., Nin, V., Price, N. L., Capellini, V., Gomes, A. P., Barbosa, M. T., O’Neil, L., White, T. A., Sinclair, D. A., & Chini, E. N.
- Affiliations
- Mayo Clinic (US)
- Department of Anesthesiology and Kogod Aging Center Mayo Clinic, Rochester, Minnesota
- Harvard University (US)
- Corresponding author
- Chini, Eduardo N.
- ORCID
- Venue
- Diabetes
- Publisher
- American Diabetes Association
- Published
- 2013-03-14
- Volume
- 62
- Issue
- 4
- Pages
- 1084-1093
- ISSN
- 0012-1797 (ISSN-L)
- 1939-327X
- PMC
- PMC3609577
- OpenAlex
- W2112866277
- Cited by
- 332
- References
- 48
- Citations by year
- 2026: 27 · 2025: 20 · 2024: 30 · 2023: 17 · 2022: 37 · 2021: 38 · 2020: 33 · 2019: 23 · 2018: 31 · 2017: 25 · 2016: 17 · 2015: 18 · 2014: 11 · 2013: 5
- FWCI
- 5.35
- Type
- journal article
- Language
- en
- Update notices
- correction (2014-04-01)
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Diabetes (publishedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
- Funders
- National Institute on Aging (R37AG028730, T32AG000222)
- National Institute of Diabetes and Digestive and Kidney Diseases (P30DK050456, R01DK084055)
- Topics
- Health Sciences › Medicine › Geriatrics and Gerontology › Sirtuins and Resveratrol in Medicine
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Natural Antidiabetic Agents Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Biochemical and Molecular Research
- Keywords
- apigenin, CD38, NAD+ metabolism, sirtuins, protein acetylation, quercetin, metabolic syndrome, obesity, p53 acetylation, glucose homeostasis, lipid homeostasis, flavonoids, CD38 inhibitors
- MeSH terms
- Animals, Gene Expression Regulation, Humans, Mice, Inbred C57BL, NAD, Obesity, Quercetin, Random Allocation, Molecular Structure, Mice, Knockout, Metabolic Syndrome, Cell Line, Tumor, Apigenin, Mice, ADP-ribosyl Cyclase 1, Sirtuin 1
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