Pharmacokinetics, Pharmacodynamics, and PKPD Modeling of Curcumin in Regulating Antioxidant and Epigenetic Gene Expression in Healthy Human Volunteers
Mol Pharm.2019;16(5):1881-1889. DOI: 10.1021/acs.molpharmaceut.8b01246
| Epigenetic modification is a regulation, primarily constitutes processes like DNA methylation, histone modifications, and alteration in microRNA (miRNA) which leads altered gene expression without any change in the DNA sequence. Studies have shown that it is important mechanism by which dietary components can selectively activate or inactivate gene expression. Curcumin has been recently shown to induce epigenetic changes leading to beneficial expression of genes related to antioxidants and inflammation. Many studies concern the low bioavailability of curcuminoids. |
Objective:
To describe the acute pharmacokinetics and pharmacodynamics (PK/PD) of curcumin in normal, healthy human volunteers.
Methods:
Twelve volunteers received a 4 g dose of curcumin capsules with a standard breakfast. Plasma samples were collected at specified time points and analyzed for curcumin and its glucuronide levels. RNA was extracted from leukocytes and analyzed for expression of select antioxidant and epigenetic histone deacetylase (HDAC) genes. Pharmacodynamics marker antioxidant genes NRF2, HO-1, and NQO1 and epigenetic genes HDAC1, HDAC2, HDAC3, and HDAC4 were quantified by qPCR.
Results:
Conclusion
Bioavailability of the parent curcumin compound is low, and oral administration of curcumin can still deliver detectable levels of curcumin glucuronide metabolite. Though at low detectability, curcumin elicits antioxidant and epigenetic effects which could contribute to the overall health beneficial effects of curcumin.