Inhibitory effect of atractylenolide I on angiogenesis in chronic inflammation in vivo and in vitro.
Angiogenesis is involved in the pathology of chronic inflammatory diseases. Application of anti-angiogenic strategies is beneficial in the treatment of inflammatory disorders. Atractylenolide I is an anti-inflammation agent. To further investigate the anti-angiogenesis mechanism of atractylenolide I in cell and mice based on inflammation model, the vascular index and microvessel outgrowth were measured by using the Freunds complete adjuvant (FCA) induced mouse air pouch model as well as the mice aortic ring co-cultured with peritoneal macrophages model. The ID(50) values of atractylenolide I were 15.15 mg/kg and 3.89 microg/ml for inhibiting the vascular index in vivo and microvessel outgrowth in vitro, respectively. Atractylenolide I could dose-dependently inhibit the production of nitric oxide (NO), tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), interleukin-6 (IL-6), vascular endothelial growth factor (VEGF) and placenta growth factor (PlGF) activity in the flute of mouse air pouch and the peritoneal macrophages stimulated by lipopolysaccharide (LPS). Atractylenolide I displayed a potent inhibitory effect on angiogenesis by a set of down-regulatory actions of NO, TNF-alpha, IL-1beta, IL-6, VEGF and PlGF in chronic inflammation.
School of Medicine, Xi'an Jiaotong University, Xi'an 710061, PR China.
Changhe
C
Wang
Haijie
H
Duan
Langchong
L
He
D020533:Angiogenesis Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000494:pharmacology*; D001011:Aorta / Q000166:cytology; D002908:Chronic Disease; D018920:Coculture Techniques; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects; D004730:Endothelium, Vascular / Q000166:cytology; D005260:Female; D007249:Inflammation / Q000378:metabolism / Q000473:pathology; D020128:Inhibitory Concentration 50; D053583:Interleukin-1beta / Q000037:antagonists & inhibitors; D007783:Lactones / Q000737:chemistry / Q000494:pharmacology*; D017737:Macrophages, Peritoneal / Q000166:cytology / Q000187:drug effects; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D055806:Microvessels / Q000187:drug effects; D015394:Molecular Structure; D009389:Neovascularization, Pathologic / Q000188:drug therapy*; D009569:Nitric Oxide / Q000037:antagonists & inhibitors; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors; D000072483:Placenta Growth Factor; D011257:Pregnancy Proteins / Q000037:antagonists & inhibitors; D012717:Sesquiterpenes / Q000737:chemistry / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors; D000093242:Interleukin-6 Inhibitors
D020533:Angiogenesis Inhibitors; D000893:Anti-Inflammatory Agents; D053583:Interleukin-1beta; D007783:Lactones; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; D000072483:Placenta Growth Factor; D011257:Pregnancy Proteins; D012717:Sesquiterpenes; D014409:Tumor Necrosis Factor-alpha; D042461:Vascular Endothelial Growth Factor A; D000093242:Interleukin-6 Inhibitors; C000608037:Pgf protein, mouse; C424804:atractylenolide I