Limits...
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.

Show MeSH

Related in: MedlinePlus

Hematology/cytology/MRI data analysis.There was no significant change from baseline in ALT (A) and AST (B) when compared to the CON group. Significantly increased TM (C) from baseline in the CON group was attenuated in the L-EF group or prevented in both the M-EF and H-EF group at week 1 post induction, and adipocyte positive colonies (D) in the CON group were attenuated in the L-EF group or prevented in both the M-EF and H-EF group after induction. In addition, the significantly decreased PEP (E) from baseline in the CON group was attenuated in the L-EF group or prevented in both the M-EF and H-EF group at week 1 post induction. Note: * P<0.05 for comparison with CON; # P<0.05 for comparison with baseline. • CON group; ⧫ L-EF group; ▪ M-EF group; ▴ H-EF group.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC2713419&req=5

pone-0006419-g002: Hematology/cytology/MRI data analysis.There was no significant change from baseline in ALT (A) and AST (B) when compared to the CON group. Significantly increased TM (C) from baseline in the CON group was attenuated in the L-EF group or prevented in both the M-EF and H-EF group at week 1 post induction, and adipocyte positive colonies (D) in the CON group were attenuated in the L-EF group or prevented in both the M-EF and H-EF group after induction. In addition, the significantly decreased PEP (E) from baseline in the CON group was attenuated in the L-EF group or prevented in both the M-EF and H-EF group at week 1 post induction. Note: * P<0.05 for comparison with CON; # P<0.05 for comparison with baseline. • CON group; ⧫ L-EF group; ▪ M-EF group; ▴ H-EF group.

Mentions: Neither organ bleeding nor death was found in any group throughout the experimental period. Either ALT or AST, the index of hepatocyte injury, did not significantly change from baseline among all the groups except moderate increase at 1 week in the CON group throughout the experimental period (Figure 2A–B). ON lesion was not found until week 2 post induction in each group. ON lesion was histopathologically characterized with trabecular bone containing considerable empty lacunae (Figure 3A, 3B and 3C). The ON Incidence was 93% (15/16) in the CON group, 56% (9/16) in the L-EF group, 13% (2/16) in the M-EF group and 6% (1/16) in the H-EF group, respectively. Fisher's exact probability test showed that the ON incidence in the L-EF, M-EF and H-EF group was significantly lower than that in the CON group (P<0.05 for all). The ON Incidence in the M-EF and H-EF group was significantly lower than that in the L-EF group (P<0.05 for both), whereas no difference in the ON Incidence was found between the M-EF and H-EF group (P>0.05). There was no significant difference in the ON Extent among the CON group (2.8±0.8), L-EF group (2.5±0.6), M-EF group (2.4±0.7) and H-EF group (2.6±0.5) (Figure 3D and 3E).


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)

Hematology/cytology/MRI data analysis.There was no significant change from baseline in ALT (A) and AST (B) when compared to the CON group. Significantly increased TM (C) from baseline in the CON group was attenuated in the L-EF group or prevented in both the M-EF and H-EF group at week 1 post induction, and adipocyte positive colonies (D) in the CON group were attenuated in the L-EF group or prevented in both the M-EF and H-EF group after induction. In addition, the significantly decreased PEP (E) from baseline in the CON group was attenuated in the L-EF group or prevented in both the M-EF and H-EF group at week 1 post induction. Note: * P<0.05 for comparison with CON; # P<0.05 for comparison with baseline. • CON group; ⧫ L-EF group; ▪ M-EF group; ▴ H-EF group.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0006419-g002: Hematology/cytology/MRI data analysis.There was no significant change from baseline in ALT (A) and AST (B) when compared to the CON group. Significantly increased TM (C) from baseline in the CON group was attenuated in the L-EF group or prevented in both the M-EF and H-EF group at week 1 post induction, and adipocyte positive colonies (D) in the CON group were attenuated in the L-EF group or prevented in both the M-EF and H-EF group after induction. In addition, the significantly decreased PEP (E) from baseline in the CON group was attenuated in the L-EF group or prevented in both the M-EF and H-EF group at week 1 post induction. Note: * P<0.05 for comparison with CON; # P<0.05 for comparison with baseline. • CON group; ⧫ L-EF group; ▪ M-EF group; ▴ H-EF group.
Mentions: Neither organ bleeding nor death was found in any group throughout the experimental period. Either ALT or AST, the index of hepatocyte injury, did not significantly change from baseline among all the groups except moderate increase at 1 week in the CON group throughout the experimental period (Figure 2A–B). ON lesion was not found until week 2 post induction in each group. ON lesion was histopathologically characterized with trabecular bone containing considerable empty lacunae (Figure 3A, 3B and 3C). The ON Incidence was 93% (15/16) in the CON group, 56% (9/16) in the L-EF group, 13% (2/16) in the M-EF group and 6% (1/16) in the H-EF group, respectively. Fisher's exact probability test showed that the ON incidence in the L-EF, M-EF and H-EF group was significantly lower than that in the CON group (P<0.05 for all). The ON Incidence in the M-EF and H-EF group was significantly lower than that in the L-EF group (P<0.05 for both), whereas no difference in the ON Incidence was found between the M-EF and H-EF group (P>0.05). There was no significant difference in the ON Extent among the CON group (2.8±0.8), L-EF group (2.5±0.6), M-EF group (2.4±0.7) and H-EF group (2.6±0.5) (Figure 3D and 3E).

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