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Constitutional flavonoids derived from Epimedium dose-dependently reduce incidence of steroid-associated osteonecrosis not via direct action by themselves on potential cellular targets.

Zhang G, Wang XL, Sheng H, Xie XH, He YX, Yao XS, Li ZR, Lee KM, He W, Leung KS, Qin L - PLoS ONE (2009)

Bottom Line: However, there are no clinically employed agents capable of simultaneously targeting these two key pathogenic events.The present experimental study demonstrated that constitutional flavonoid glycosides derived from herb Epimedium (EF, composed of seven flavonoid compounds with common stem nuclear) exerted dose-dependent effect on inhibition of both thrombosis and lipid-deposition and accordingly reducing incidence of steroid-associated ON in rabbits, which was not via direct action by themselves rather by their common metabolite on potential cellular targets involved in the two pathogenic pathways.The underlying mechanism could be explained by counteracting endothelium injury and excessive adipogenesis.

View Article: PubMed Central - PubMed

Affiliation: Musculoskeletal Research Laboratory, Department of Orthopaedics & Traumatology, The Chinese University of Hong Kong, Hong Kong, China.

ABSTRACT
Intravascular-thrombosis and extravascular-lipid-deposit are the two key pathogenic events considered to interrupt intraosseous blood supply during development of steroid-associated osteonecrosis (ON). However, there are no clinically employed agents capable of simultaneously targeting these two key pathogenic events. The present experimental study demonstrated that constitutional flavonoid glycosides derived from herb Epimedium (EF, composed of seven flavonoid compounds with common stem nuclear) exerted dose-dependent effect on inhibition of both thrombosis and lipid-deposition and accordingly reducing incidence of steroid-associated ON in rabbits, which was not via direct action by themselves rather by their common metabolite on potential cellular targets involved in the two pathogenic pathways. The underlying mechanism could be explained by counteracting endothelium injury and excessive adipogenesis. These findings encourage designing clinical trials to investigate potential of EF in prevention of steroid-associated ON.

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A total ion chromatogram in full scan mode generated by HPLC/UV/MS/MS.(A)∼(B) Compared with the blank sera, a peak shown in 38.1 min in the sera from L-EF, M-EF and H-EF group. (C) HPLC profile of standard Icaritin. (D) 391 (m/z [M+Na]+) for Icaritin selected for the subsequent selected ion chromatography (SIC), with a peak at 38.1 min. (E) The +MS showed the mass weight by 391 ion (m/z [M+Na]+) and the absence of 56 exhibited the existence of prenyl in the +MS2 chromatography. (F) Epimedium-derived flavonoids with common stem nuclei intestinally metabolized to Icaritin.
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pone-0006419-g004: A total ion chromatogram in full scan mode generated by HPLC/UV/MS/MS.(A)∼(B) Compared with the blank sera, a peak shown in 38.1 min in the sera from L-EF, M-EF and H-EF group. (C) HPLC profile of standard Icaritin. (D) 391 (m/z [M+Na]+) for Icaritin selected for the subsequent selected ion chromatography (SIC), with a peak at 38.1 min. (E) The +MS showed the mass weight by 391 ion (m/z [M+Na]+) and the absence of 56 exhibited the existence of prenyl in the +MS2 chromatography. (F) Epimedium-derived flavonoids with common stem nuclei intestinally metabolized to Icaritin.

Mentions: A total ion chromatogram in full scan mode was generated by HPLC/UV/MS/MS. Compared with the blank sera from the CON group, it was obviously that there was a peak in 38.1 min in the sera from three EF groups (Figure 4A∼B), which was structurally identified as Icaritin with the following steps. 1) Under the same mobile phase elution, the standard Icaritin was also washed out with the same retention time (Figure 4C); 2) 391 (m/z [M+Na]+) for Icaritin was selected for the subsequent selected ion chromatography (SIC), and a peak at 38.1 min was also present (Figure 4D); 3) Further, the +MS showed the mass weight by 391 ion (m/z [M+Na]+) and the absence of 56 exhibited the existence of prenyl in the +MS2 chromatography (Figure 4E), which firmly confirmed the structure of Icaritin. In addition, those seven flavonoid compounds were found not only absent in the HPLC profiles, but also not shown in the SIC profiles according to their mass weight.


Constitutional flavonoids derived from Epimedium dose-dependently reduce incidence of steroid-associated osteonecrosis not via direct action by themselves on potential cellular targets.

Zhang G, Wang XL, Sheng H, Xie XH, He YX, Yao XS, Li ZR, Lee KM, He W, Leung KS, Qin L - PLoS ONE (2009)

A total ion chromatogram in full scan mode generated by HPLC/UV/MS/MS.(A)∼(B) Compared with the blank sera, a peak shown in 38.1 min in the sera from L-EF, M-EF and H-EF group. (C) HPLC profile of standard Icaritin. (D) 391 (m/z [M+Na]+) for Icaritin selected for the subsequent selected ion chromatography (SIC), with a peak at 38.1 min. (E) The +MS showed the mass weight by 391 ion (m/z [M+Na]+) and the absence of 56 exhibited the existence of prenyl in the +MS2 chromatography. (F) Epimedium-derived flavonoids with common stem nuclei intestinally metabolized to Icaritin.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2713419&req=5

pone-0006419-g004: A total ion chromatogram in full scan mode generated by HPLC/UV/MS/MS.(A)∼(B) Compared with the blank sera, a peak shown in 38.1 min in the sera from L-EF, M-EF and H-EF group. (C) HPLC profile of standard Icaritin. (D) 391 (m/z [M+Na]+) for Icaritin selected for the subsequent selected ion chromatography (SIC), with a peak at 38.1 min. (E) The +MS showed the mass weight by 391 ion (m/z [M+Na]+) and the absence of 56 exhibited the existence of prenyl in the +MS2 chromatography. (F) Epimedium-derived flavonoids with common stem nuclei intestinally metabolized to Icaritin.
Mentions: A total ion chromatogram in full scan mode was generated by HPLC/UV/MS/MS. Compared with the blank sera from the CON group, it was obviously that there was a peak in 38.1 min in the sera from three EF groups (Figure 4A∼B), which was structurally identified as Icaritin with the following steps. 1) Under the same mobile phase elution, the standard Icaritin was also washed out with the same retention time (Figure 4C); 2) 391 (m/z [M+Na]+) for Icaritin was selected for the subsequent selected ion chromatography (SIC), and a peak at 38.1 min was also present (Figure 4D); 3) Further, the +MS showed the mass weight by 391 ion (m/z [M+Na]+) and the absence of 56 exhibited the existence of prenyl in the +MS2 chromatography (Figure 4E), which firmly confirmed the structure of Icaritin. In addition, those seven flavonoid compounds were found not only absent in the HPLC profiles, but also not shown in the SIC profiles according to their mass weight.

Bottom Line: However, there are no clinically employed agents capable of simultaneously targeting these two key pathogenic events.The present experimental study demonstrated that constitutional flavonoid glycosides derived from herb Epimedium (EF, composed of seven flavonoid compounds with common stem nuclear) exerted dose-dependent effect on inhibition of both thrombosis and lipid-deposition and accordingly reducing incidence of steroid-associated ON in rabbits, which was not via direct action by themselves rather by their common metabolite on potential cellular targets involved in the two pathogenic pathways.The underlying mechanism could be explained by counteracting endothelium injury and excessive adipogenesis.

View Article: PubMed Central - PubMed

Affiliation: Musculoskeletal Research Laboratory, Department of Orthopaedics & Traumatology, The Chinese University of Hong Kong, Hong Kong, China.

ABSTRACT
Intravascular-thrombosis and extravascular-lipid-deposit are the two key pathogenic events considered to interrupt intraosseous blood supply during development of steroid-associated osteonecrosis (ON). However, there are no clinically employed agents capable of simultaneously targeting these two key pathogenic events. The present experimental study demonstrated that constitutional flavonoid glycosides derived from herb Epimedium (EF, composed of seven flavonoid compounds with common stem nuclear) exerted dose-dependent effect on inhibition of both thrombosis and lipid-deposition and accordingly reducing incidence of steroid-associated ON in rabbits, which was not via direct action by themselves rather by their common metabolite on potential cellular targets involved in the two pathogenic pathways. The underlying mechanism could be explained by counteracting endothelium injury and excessive adipogenesis. These findings encourage designing clinical trials to investigate potential of EF in prevention of steroid-associated ON.

Show MeSH
Related in: MedlinePlus