Actein activates stress‐ and statin‐associated responses and is bioavailable in Sprague‐Dawley rats

Abstract

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.

Terpenoids as potential chemopreventive and therapeutic agents in liver cancer

“…Recent studies indicate that black cohosh may have chemopreventive and chemotherapeutic potential [73,74] . Actein was found to inhibit the growth of p53-positive HepG2 cells with an IC50 value of 27 μg/mL [75] . Ardisiacrispin (A+B), a triterpenoid saponin mixture in the fixed proportion 2:1 of ardisiacrispin A and ardisiacrispin B, is derived from Ardisia crenata.…”

“…10-50 μmol/L Huang et al [72] Triterpenes Actein Inhibited the growth of p53-positive HepG2 cells 27 μg/mL [IC50] Einbond et al [75] Ardisiacrispin (A+B)…”

Need of an Ancient Roots to Modern Medicine in the Treatment of Cancer- A review

“…Thymoquinone, the active component of Nigella sativa, targets various signalling pathways involved in the process of carcinogenesis, thus suggesting its possible role in cancer therapy [101]. Actein, the active component of Actaea racemosa inhibits the proliferation of human breast cancer and liver cancer cells and thus show antitumor potential [102]. Allium sativum contains sulfur compounds which show chemopreventive activity [103].…”

Phytochemical importance of medicinal plants as potential sources of anticancer agents

“…Actein alters the expression of cholesterol and fatty acid biosynthetic genes, p53 pathway genes, CCND1, and ID3. Actein-induced inhibition of growth of human HepG2 liver cancer cells is because of the reduced free fatty acid and cholesterol levels in the liver (Einbonda et al, 2009). …”