Flavonoids from Inula britannica L. inhibit injury-induced neointimal formation by suppressing oxidative-stress generation.
OBJECTIVE
We aimed to investigate whether and how the total flavonoid extracts (TFE) from Inula britannica L. block neointimal hyperplasia induced by balloon injury in rats.


METHODS
Rats were administered orally TFE doses of 12.5, 25 and 50 mg/kg/d by gastric gavage from 3 days before balloon injury to 14 days after the injury. The ratio of intima (I) to media (M) thickness (I/M) in carotid arteries was examined by morphological analyses. The MDA content and SOD activity in plasma were measured. The O(2)(-) production in vascular tissues was detected in situ. The expression of p47(phox) in carotid arteries was analyzed by Western blot analysis and immunohistochemistry.


RESULTS
The rats treated with TFE 50 mg/kg/d showed a reduction in neointimal hyperplasia, and the ratio of I/M of balloon injured-carotid arteries was significantly reduced by over 70% after TFE treatment, compared with the injured group. The inhibitory effect of TFE on neointimal hyperplasia was almost consistent with that of atorvastatin, a positive control. The plasma SOD activity was obviously increased by TFE treatment (P<0.01), while plasma MDA production was markedly decreased by TFE treatment (P<0.05). On day 14 after balloon injury, the carotid arteries showed an increase in O(2)(-) production that was most evident in the neointimal and medial layer of the vessel. Thus, TFE significantly inhibited injury-induced O(2)(-) production and p47(phox) expression in carotid arteries.


CONCLUSIONS
Our results suggest that TFE inhibit the neointimal hyperplasia after balloon injury, at least partly, by suppressing oxidative-stress generation.
Zhang
Hong-Bing
HB
Department of Biochemistry and Molecular Biology, Institute of Basic Medicine, Hebei Medical University, Shijiazhuang, PR China.
Wen
Jin-Kun
JK
Wang
Yan-Yan
YY
Zheng
Bin
B
Han
Mei
M
D000818:Animals; D020212:Carotid Artery Injuries / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002404:Catheterization; D004195:Disease Models, Animal; D004365:Drugs, Chinese Herbal / Q000737:chemistry / Q000627:therapeutic use*; D005419:Flavonoids / Q000737:chemistry / Q000627:therapeutic use*; D006965:Hyperplasia / Q000188:drug therapy*; D038143:Inula / Q000737:chemistry; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D008840:Microfilament Proteins / Q000378:metabolism; D015394:Molecular Structure; D009124:Muscle Proteins / Q000378:metabolism; D019255:NADPH Oxidases / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000097:blood; D000072105:Superoxide Dismutase-1; D017539:Tunica Intima / Q000187:drug effects / Q000293:injuries / Q000473:pathology
D004365:Drugs, Chinese Herbal; D005419:Flavonoids; D008840:Microfilament Proteins; D009124:Muscle Proteins; C051615:transgelin; D008315:Malondialdehyde; C000606292:Sod1 protein, rat; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; D019255:NADPH Oxidases; C060505:neutrophil cytosolic factor 1