Impact of Chrysin on Vitamin D and Bone Health - Preclinical Studies

Abstract Vitamin D deficiency is an endemic problem existing worldwide. Although several strategies were established to enhance vitamin D3 levels, studies specifically focussing inhibition of vitamin D metabolism which may prolong the availability of active vitamin D in pathological conditions are less explored. Studies also suggest that higher doses of vitamin D3 fail to achieve optimum vitamin D levels. In this context, we focussed on the enzyme CYP3A4 which promotes inactivation of active vitamin D. The current study was aimed to decipher the impact of chrysin, a proven CYP3A4 inhibitor as an intervention and its effects in combination with low dose vitamin D3 (40 IU) and bone health in vitamin D deficiency condition. The in-vivo activity of chrysin was evaluated on female Wistar albino rats fed with a vitamin D deficient diet to attain vitamin D deficiency for 28 days. Chrysin was given alone and in combination with calcium carbonate (CaCO3) and/or vitamin D3. All the therapeutic interventions were assessed for serum 25-OH-D3 by LC-MS, biochemical, urinary, and bone parameters. Animals treated with chrysin alone and in combination with low dose vitamin D3 and/or CaCO3 showed an eminent rise in serum 25-OH-D3 levels along with increased serum biochemical parameters. On contrary, a significant decrease in the urinary parameters followed by beneficial effects on bone parameters was noticed in contrast with the vitamin D deficient diet group. Our findings revealed that although chrysin alone showed a notable effect on 25-OH-D3 and osseous tissue, comparatively it showed intensified therapeutic effect in combination with vitamin D3 and CaCO3 which can be employed as a cost-effective option to improve bone health. Graphical Abstractbiorxiv;2020.11.19.390757v1/UFIG1F1ufig1