Targeted delivery of 1,25-dihydroxyvitamin D3 to colon tissue and identification of a major 1,25-dihydroxyvitamin D3 glycoside from Solanum glaucophyllum plant leaves

Abstract

Leaves of the Solanum glaucophyllum (Sg) plant, indigenous to South America, have long been known for their calcinogenic toxicity in ruminant animals. It was determined the leaves contained glycosidic derivatives of 1,25-dihydroxyvitamin D3 (1,25D3) and liberation of the free hormone by rumen bacterial populations elicited a hypercalcemic response. Our interest in the leaves is predicated on the concept that the glycoside forms of 1,25D3 would target release of the active hormone in the lower gut of non-ruminant mammals. This would provide a means of delivering 1,25D3 directly to the colon, where the hormone has been shown to have beneficial effects in models of inflammatory bowel disease (IBD) and colon cancer. We fed mice for 10 days with variable amounts of Sg leaf. Feeding 7-333 ug leaf/day produced no changes in plasma Ca2+ and 1,25D3 concentrations, and only at > 1000 ug leaf/day did these values become significantly elevated compared to controls. Gene expression studies from colon tissue indicated a linear relationship between the amount of leaf consumed and expression of the Cyp24a1 gene. In contrast, Cyp24a1 gene expression in the duodenums and ileums of these mice was unchanged compared to controls. One of the major 1,25D3-glycosides was isolated from leaves following extraction and purification by Sep-Pak cartridges and HPLC fractionation. Ultraviolet absorbance was consistent with modification of the 1-hydroxyl group, and positive ion ESI mass spectrometry indicated a diglycoside of 1,25D3. 2-Dimensional NMR analyses were carried out and established the C1 proton of the A-ring was interacting with a C1’ sugar proton, while the C3 proton of the A-ring was linked with a second C1’ sugar proton. The structure of the isolated compound is therefore consistent with a beta-linked 1,3-diglycoside of 1,25D3. Thus, Sg leaf administered to mice at up to 333 ug/day can elicit colon-specific enhancement of Cyp24a1 gene expression without inducing hypercalcemia, and the 1,3-diglycoside is one of the major forms of 1,25D3 found in the leaf.

Plant Oils as Potential Sources of Vitamin D

“…Yellow oat grass ( Trisetum flavescens ) is well described for its capability to synthesize bioactive vitamin D. It contains vitamin D glycosides which can be hydrolyzed in the gut or by the gastrointestinal microflora to the biologically active 1,25-dihydroxyvitamin D ( 6 – 8 ). Other so-called calcinogenic plants that contain active vitamin D forms are Solanum malacoxylon, Cestrum diurnum , and Nierembergia veitchii of the Solanaceae family ( 6 – 8 ). These plants are presumed to cause calcinosis in grazing animals due to the hypercalcemic effect of toxic 1,25-dihydroxyvitamin D levels ( 9 ).…”

Bone traits and gastrointestinal tract parameters of piglets fed cholecalciferol and 1,25-dihydroxycholecalciferol glycoside

“…The main pharmacokinetic difference between the 1,25(OH) 2 D 3 glycoside and the synthetic 1,25(OH) 2 D 3 is the absorption speed, since the glycosidic form needs to be broken down to be absorbed. This mechanism causes a delay in absorption and a lower metabolic plasma peak and, consequently, a longer biological half-life, presenting a lower risk of toxicity (Zimmerman et al, 2015;Mathis et al, 2016).…”