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:

  • Plasma levels of parent curcumin were below the detection limit by HPLC-ITMS/MS/MS. However, curcumin-O-glucuronide (COG), a major metabolite of curcumin, was detected as soon as 30 min.
  • Increased the gene expression of antioxidant genes NRF2, HO-1, and NQO1 and suppressed epigenetic genes HDAC1, HDAC2, HDAC3, and HDAC4.

 

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.

 

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