1,25-Dihydroxyvitamin D3-glycoside of herbal origin exhibits delayed release pharmacokinetics when compared to its synthetic counterpart

Bachmann, H.; Offord‐Cavin, Elizabeth; Phothirath, Phoukham; Horcajada, Marie‐Noëlle; Romeis, Peter; Mathis, Georg A.

doi:10.1016/j.jsbmb.2012.09.016

Cited by 17 publications

(9 citation statements)

References 6 publications

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“…However, the leaf reportedly contains multiple forms of 1,25D 3 -glycosides [36], so we set about to begin identification of the vitamin D glycosides present in leaf extracts. Previous work in the field by Wassermann [37], and in our laboratory, revealed the 1,25D 3 activity in Sg leaf tissue consisted of water-extractable, neutral glycosides of 1,25D 3 .…”

Section: Resultsmentioning

confidence: 99%

“…Other glycoside forms of vitamin D have also been found in Sg , including 25D 3 and vitamin D 3 itself, but they are much less abundant, and are less important than glycosides of 1,25D 3 with regards to the hypercalcemic activity of the plant [43, 44]. Substantial evidence documents that the plant and/or plant extracts are active in monogastrics, and if given in high amounts can serve as a means of increasing plasma 1,25D 3 concentrations [34, 36, 45-50]. There is also an isolated report where the leaf was administered to a handful of human patients with renal failure as a source of 1,25D 3 to prevent secondary renal hyperparathyroidism [51].…”

Section: Disucussionmentioning

confidence: 99%

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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

Zimmerman

Koszewski

Hoy

et al. 2015

The Journal of Steroid Biochemistry and Molecular Biology

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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.

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Section: Resultsmentioning

confidence: 99%

Section: Disucussionmentioning

confidence: 99%

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

Zimmerman

Koszewski

Hoy

et al. 2015

The Journal of Steroid Biochemistry and Molecular Biology

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“…Glycoside conjugation to hydroxy groups of the aglycone occurs at C1, C3 and C25. The molecular distribution of glycosyl moieties has been found to be 1-12 hexose units per aglycone; a mono-glycoside as well as di-and tri-glycosides have been identified (Bachmann et al, 2013). The structural formula of glycosides of 1,25(OH) 2 D 3 is shown in Figure 2.…”

Section: Active Substance(s)mentioning

confidence: 98%

Scientific Opinion on the safety ofSolanum glaucophyllumstandardised leaves as feed material

Feed¹

2015

EFSA Journal

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Solanum glaucophyllum standardised leaves (PAN) is a mixture of irradiated Solanum glaucophyllum ground leaves and wheat middlings to ensure a concentration of minimum 10 mg glycosylated 1,25-dihydroxycholecalciferol/kg feedingstuff. Glycosylation of the vitamin molecule affected biopotency in poultry and rats, but not in ruminants. Up to 1 000 mg PAN/kg complete diet was considered safe for chickens and piglets. PAN concentrations meeting the chicken's requirement for vitamin D in diets without supplemental vitamin D 3 could not be established. No evidence for an improvement of zootechnical parameters by PAN in diets already supplemented with vitamin D 3 was provided for chickens, laying hens and piglets. In dairy cows, PAN had the potential to be efficacious in the prevention of milk fever. However, a feeding regime ensuring its safe use at efficacious doses has not yet been established. No data on safety and efficacy of PAN for other animal species and categories were provided. A water-soluble extract of Solanum glaucophyllum was not genotoxic. A no observed adverse effect level could be not derived from sub-acute toxicity studies in rabbits. A benchmark dose lower confidence limit (BMDL 05 ) based on an increase in plasma calcium in a 28-day repeat dose rat study corresponded to 2 900-3 500 mg PAN/kg diet. Maternal toxicity and fetotoxicity were observed in rats and rabbits at all extract doses tested. An overall safe dose of PAN was not identified from the available toxicological data in laboratory animals. Since PAN did not increase the concentration of 1,25-dihydroxycholecalciferol in animal tissues, the use of PAN in animal nutrition is safe for consumers. Inhalation of PAN could be hazardous. PAN was not irritant to skin and eyes and unlikely to cause skin sensitisation. Considering the content of 1,25-dihydroxycholecalciferol in PAN its use in animal nutrition would not pose a risk to the environment. SUMMARYFollowing a request from the European Commission, the Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) was asked to deliver a scientific opinion on the safety of leaves of Solanum glaucophyllum (SG) as feed material. The scientific opinion should cover, in particular, the content of glycosides of 1,25-dihydroxycholecalciferol in the ground leaves and the supply with and the physiology of vitamin D in the target species.In the view of the EFSA FEEDAP Panel, Solanum glaucophyllum standardised leaves (PAN) was a compound feed. It consisted of a mixture of irradiated Solanum glaucophyllum ground leaves and wheat middlings to ensure a concentration of minimum 10 mg glycosylated 1,25-dihydroxycholecalciferol (1,25(OH) 2 D 3 )/kg feedingstuff.Glycosylation of the vitamin molecule affected biopotency in poultry and rats, but not in ruminants.The species-related differences in biopotency of glycosylated 1,25(OH) 2 D 3 prevented the setting of a universal vitamin D bioequivalence of PAN in terms of international units.Based on the limited number of endpoints, up to 1 000 mg...

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“…Glycoside conjugates of 25OHD3 and 1,25(OH) 2 D3 are present in plant species in addition to their unconjugated forms . De‐glycosylation occurs by β‐glycosidase enzymes in the intestinal wall so that only the free form is absorbed . The relative abundance and ratio of free to glycosylated vitamin D form depend on the type of plant species …”

Section: Vitamin D Conjugationmentioning

confidence: 99%

The vitamin D metabolome: An update on analysis and function

Jenkinson

2019

Cell Biochemistry & Function

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Current understanding of vitamin D tends to be focussed on the measurement of the major circulating form 25‐hydroxyvitamin D3 (25OHD3) and its conversion to the active hormonal form, 1α,25‐dihydroxyvitamin D3 (1α,25(OH)2D3) via the enzyme 25‐hydroxyvitamin D‐1α‐hydroxylase (CYP27B1). However, whilst these metabolites form the endocrine backbone of vitamin D physiology, it is important to recognise that there are other metabolic and catabolic pathways that are now recognised as being crucially important to vitamin D function. These pathways include C3‐epimerization, CYP24A1 hydroxylase, CYP11A1 alternative metabolism of vitamin D3, and phase II metabolism. Endogenous metabolites beyond 25OHD3 are usually present at low endogenous levels and may only be functional in specific target tissues rather than in the general circulation. However, the technologies available to measure these metabolites have also improved, so that measurement of alternative vitamin D metabolic pathways may become more routine in the near future. The aim of this review is to provide a comprehensive overview of the various pathways of vitamin D metabolism, as well as describe the analytical techniques currently available to measure these vitamin D metabolites.

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1,25-Dihydroxyvitamin D3-glycoside of herbal origin exhibits delayed release pharmacokinetics when compared to its synthetic counterpart

Cited by 17 publications

References 6 publications

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

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

Scientific Opinion on the safety ofSolanum glaucophyllumstandardised leaves as feed material

The vitamin D metabolome: An update on analysis and function

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