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

Kasarla, S. S.; Dodoala, S.; Sampathi, S.; Talluri, N. K.

2020-11-20 pharmacology and toxicology
10.1101/2020.11.19.390757 bioRxiv
Show 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 Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=165 SRC="FIGDIR/small/390757v1_ufig1.gif" ALT="Figure 1"> View larger version (41K): org.highwire.dtl.DTLVardef@10769corg.highwire.dtl.DTLVardef@db1157org.highwire.dtl.DTLVardef@4f7694org.highwire.dtl.DTLVardef@f20f88_HPS_FORMAT_FIGEXP M_FIG C_FIG

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