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题目:: Actein activates stress- and statin-associated responses and is bioavailable in Sprague-Dawley rats.
作者:: Einbond(Linda Saxe),Soffritti(Morando),Esposti(Davide Degli),Park(Taesik),Cruz(Erica),Su(Tao),Wu(Hsan-Au),Wang(Xiaomei),Zhang(Yu-Jing),Ham(Justin),Goldberg(Ira J),Kronenberg(Fredi),Vladimirova(Antoaneta)
状态:: 发布时间2009-06-16 , 更新时间 2015-06-15
期刊:: Fundam Clin Pharmacol
摘要:: The purpose of this study was to assess in rats the pharmacological parameters and effects on gene expression in the liver of the triterpene glycoside actein. Actein, an active component from the herb black cohosh, has been shown to inhibit the proliferation of human breast cancer cells. To conduct our assessment, we determined the molecular effects of actein on livers from Sprague-Dawley rats treated with actein at 35.7 mg/kg for 6 and 24 h. Chemogenomic analyses indicated that actein elicited stress and statin-associated responses in the liver; actein altered expression of cholesterol and fatty acid biosynthetic genes, p53 pathway genes, CCND1 and ID3. Real-time RT-PCR validated that actein induced three time-dependent patterns of gene expression in the liver: (i) a decrease followed by a significant increase of HMGCS1, HMGCR, HSD17B7, NQO1, S100A9; (ii) a progressive increase of BZRP and CYP7A1 and (iii) a significant increase followed by a decrease of CCND1 and ID3. Consistent with actein's statin- and stress-associated responses, actein reduced free fatty acid and cholesterol content in the liver by 0.6-fold at 24 h and inhibited the growth of human HepG2 liver cancer cells. To determine the bioavailability of actein, we collected serum samples for pharmacokinetic analysis at various times up to 24 h. The serum level of actein peaked at 2.4 microg/mL at 6 h. Actein's ability to alter pathways involved in lipid disorders and carcinogenesis may make it a new agent for preventing and treating these major disorders.
语言:: eng
DOI:: 10.1111/j.1472-8206.2009.00673.x

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