Total Flavonoids of Fructus Chorspondiatis inhibits collagen synthesis of cultured rat cardiac fibroblasts induced by angiotensin II: correlated with NO/cGMP signaling pathway.
OBJECTIVE
To investigate the molecular mechanism of Total Flavonoids of Fructus Chorspondiatis (TFFC) on preventing cardiac fibroblasts collagen synthesis induced by angiotensin II.


METHODS
Collagen synthesis was determined by measuring (3)H-proline incorporation cardiac fibroblasts and hydroxyproline content in the culture mediums. The expression of collagen types I and III mRNA and protein was measured by RT-PCR and western blot, respectively. NO level in the culture medium was measured by the Griess reagent. NOS level in the culture medium was measured by chemical colorimetric method. The cellular concentration of cyclic GMP (cGMP) was measured by radioimmunoassay.


RESULTS
TFFC (25, 50, and 100mg/L) inhibited collagen synthesis in cardiac fibroblasts in a dose-dependent manner compared with angiotensin II group (P<0.01), and the inhibitory effects were blocked by pretreatment with NG-nitro-L-arginine methyl ester (L-NAME) and 1H-[1,2,4]-oxadiazole-[4,3-a]-quinoxalin-1-one (ODQ). TFFC increased nitric oxide (NO) and nitric oxide synthase (NOS) levels in the culture medium, increased intracellular cGMP level in cardiac fibroblasts, decreased collagen types I and III protein level in cardiac fibroblasts. The mRNA expression of collagen type I and III was suppressed by TFFC.


CONCLUSIONS
These results suggested that TFFC inhibited collagen synthesis induced by angiotensin II in cardiac fibroblasts, and the inhibitory effect might associate with the activation of the NO/cGMP signaling pathway.
Department of Cardiovascular Disease, Traditional Chinese-Mongolian Hospital of Inner Mongolia Autonomous Region, Hohhot 010020, China. yangyumin331@126.com
Yumin
Y
Yang
Xiaohui
X
Gao
Xiaoling
X
Wang
Liang
L
Su
Huihui
H
Xing
D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D002478:Cells, Cultured; D024042:Collagen Type I / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D024061:Collagen Type III / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D006152:Cyclic GMP / Q000378:metabolism*; D004365:Drugs, Chinese Herbal / Q000737:chemistry; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism; D005419:Flavonoids / Q000494:pharmacology*; D006909:Hydroxyproline / Q000494:pharmacology; D008297:Male; D009206:Myocardium / Q000166:cytology / Q000378:metabolism; D058628:Myofibroblasts / Q000187:drug effects* / Q000378:metabolism; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D010936:Plant Extracts / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects
D024042:Collagen Type I; D024061:Collagen Type III; D004365:Drugs, Chinese Herbal; D005419:Flavonoids; D010936:Plant Extracts; D012333:RNA, Messenger; D000804:Angiotensin II; D009569:Nitric Oxide; D006152:Cyclic GMP; D006909:Hydroxyproline; D019331:NG-Nitroarginine Methyl Ester