The anti-angiogenic herbal composition Ob-X inhibits adipose tissue growth in obese mice.
OBJECTIVE
The growth and development of adipose tissue are thought to be associated with angiogenesis and extracellular matrix remodeling. As the composition of the herbal extract called Ob-X has been shown to have both anti-angiogenic and matrix metalloproteinase (MMP)-inhibiting activities, we hypothesized that growth of adipose tissue can be regulated by Ob-X.


METHODS
The effects of Ob-X on angiogenesis and extracellular matrix remodeling were measured using in vitro and ex vivo assays. The effects of Ob-X on adipose tissue growth were investigated in nutritionally obese mice.


RESULTS
Ob-X inhibited angiogenesis in a dose-dependent manner in the human umbilical vein endothelial cell tube formation assay in vitro and the rat aortic ring assay ex vivo. Ob-X also suppressed MMP activity in vitro. Administration of Ob-X to high fat diet-induced obese mice produced significant reductions in body weight gain and adipose tissue mass compared with control. The mass of both visceral (VSC) and subcutaneous (SC) fat was reduced in Ob-X-treated mice. The size of adipocytes in VSC and SC adipose tissues was also significantly reduced in Ob-X-treated mice. Ob-X treatment decreased the blood vessel density and MMP activity in VSC adipose tissues of nutritionally obese mice. Ob-X reduced mRNA levels of angiogenic factors (VEGF-A and FGF-2) and MMPs (MMP-2 and MMP-9), whereas it increased mRNA levels of angiogenic inhibitors (TSP-1, TIMP-1 and TIMP-2) in SC and VSC adipose tissues of nutritionally obese mice.


CONCLUSIONS
Ob-X, which has anti-angiogenic and MMP-inhibitory activities, reduces adipose tissue mass in nutritionally induced obese mice, providing evidence that adipose tissue growth and development may be prevented by inhibiting angiogenesis. In addition, these data suggest that regulation of adipose tissue growth by inhibiting angiogenesis may alter the expression of genes involved in angiogenesis and the MMP system.
Kim
M-Y
MY
AngioLab, Inc, Daejeon, Korea. mykim@angio-lab.co.kr
Park
B Y
BY
Lee
H S
HS
Park
E K
EK
Hahm
J C
JC
Lee
J
J
Hong
Y
Y
Choi
S
S
Park
D
D
Lee
H
H
Yoon
M
M
D017667:Adipocytes / Q000166:cytology / Q000187:drug effects*; D000273:Adipose Tissue / Q000098:blood supply / Q000187:drug effects* / Q000254:growth & development; D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D015151:Immunoblotting; D061965:Matrix Metalloproteinase Inhibitors; D031334:Melissa; D051379:Mice; D008820:Mice, Obese; D031625:Morus; D008517:Phytotherapy / Q000379:methods; D010936:Plant Extracts / Q000494:pharmacology*; D051381:Rats
D020533:Angiogenesis Inhibitors; D061965:Matrix Metalloproteinase Inhibitors; D010936:Plant Extracts