|Virol J. 2015 Mar 1;12(1):35. |
|Formononetin inhibits enterovirus 71 replication by regulating COX- 2/PGE2 expression.[Pubmed: 25890183]|
|The activation of ERK, p38 and JNK signal cascade in host cells has been demonstrated to up-regulate of enterovirus 71 (EV71)-induced cyclooxygenase-2 (COX-2)/ prostaglandins E2 (PGE₂) expression which is essential for viral replication. So, we want to know whether a compound can inhibit EV71 infection by suppressing COX-2/PGE₂ expression.
METHODS AND RESULTS:
The antiviral effect of Formononetin was determined by cytopathic effect (CPE) assay and the time course assays. The influence of Formononetin for EV71 replication was determined by immunofluorescence assay, western blotting assay and qRT-PCR assay. The mechanism of the antiviral activity of Formononetin was determined by western blotting assay and ELISA assay.
Formononetin could reduce EV71 RNA and protein synthesis in a dose-dependent manner. The time course assays showed that Formononetin displayed significant antiviral activity both before (24 or 12 h) and after (0-6 h) EV71 inoculation in SK-N-SH cells. Formononetin was also able to prevent EV71-induced cytopathic effect (CPE) and suppress the activation of ERK, p38 and JNK signal pathways. Furthermore, Formononetin could suppress the EV71-induced COX-2/PGE₂ expression. Also, Formononetin exhibited similar antiviral activities against other members of Picornaviridae including coxsackievirus B2 (CVB2), coxsackievirus B3 (CVB3) and coxsackievirus B6 (CVB6).
Formononetin could inhibit EV71-induced COX-2 expression and PGE₂ production via MAPKs pathway including ERK, p38 and JNK. Formononetin exhibited antiviral activities against some members of Picornaviridae. These findings suggest that Formononetin could be a potential lead or supplement for the development of new anti-EV71 agents in the future.
|Mol Carcinog. 2016 Mar;55(3):312-9. |
|Formononetin promotes proliferation that involves a feedback loop of microRNA-375 and estrogen receptor alpha in estrogen receptor-positive cells.[Pubmed: 25663261]|
|Formononetin is an O-methylated isoflavone that is isolated from the root of Astragalus membranaceus, and it has antitumorigenic effects. Our previous studies found that Formononetin triggered growth-inhibitory and apoptotic activities in MCF-7 breast cancer cells.
METHODS AND RESULTS:
To further investigate the potential effect of Formononetin in promoting cell proliferation in estrogen receptor (ER)-positive cells, we used in vivo and in vitro studies to elucidate the possible mechanism. ERα-positive cells (HUVEC, MCF-7) were treated with Formononetin. The CCK8 assay, Hoechst 33258, and flow cytometry were used to assess cell proliferation and apoptosis. mRNA levels of ERα, Bcl-2, and miR-375 were quantified using real-time polymerase chain reaction. ERα, p-Akt, and Bcl-2 expression was determined using Western blot. Compared with the control, low Formononetin concentrations (2-6 μM) stimulated ERα-positive cell proliferation (HUVEC, MCF-7). The more sensitive HUVEC cells were used to study the relevant signaling pathway. After treatment with Formononetin, ERα, miR-375, p-Akt, and Bcl-2 expression was significantly upregulated. The proliferative effect of Formononetin was also blocked by a miR-375 inhibitor or raloxifene pretreatment. Additionally, in the in vivo studies, uterine weight in ovariectomized mice treated with Formononetin increased significantly, but the weight dramatically decreased with raloxifene or miR-375 inhibitor pretreatment before Formononetin.
This study demonstrated that Formononetin promoted ERα-positive cell proliferation through miR-375 activation and this mechanism is possibly involving in a miR-375 and ERα feedback loop.
|J Nutr Biochem. 2010 Jul;21(7):613-20. |
|Formononetin, an isoflavone, relaxes rat isolated aorta through endothelium-dependent and endothelium-independent pathways.[Pubmed: 19570671 ]|
|We evaluated the vasorelaxation effects of Formononetin, an isoflavone/phytoestrogen found abundantly in Astragalus mongholicus Bunge, on rat isolated aorta and the underlying mechanisms involved.
METHODS AND RESULTS:
Cumulative administration of Formononetin, genistein, daidzein and biochanin A relaxed phenylephrine-preconstricted aorta. Formononetin and biochanin A caused a similar magnitude of relaxation whereas daidzein was least potent. Mechanical removal of endothelium, L-NAME (100 microM) and methylene blue (10 microM) suppressed Formononetin-induced relaxation. Formononetin increased endothelial nitric oxide (NO) synthase (eNOS), but not inducible NO synthase, activity with an up-regulation of eNOS mRNA and p-eNOS(Ser1177) protein expression. In endothelium-denuded preparations, Formononetin-induced vasorelaxation was significantly reduced by glibenclamide (3 microM) and iberiotoxin (100 nM), and a combination of glibenclamide (3 microM) plus iberiotoxin (100 nM) abolished the relaxation. In contrast, Formononetin-elicited endothelium-independent relaxation was not altered by ICI 182,780 (10 microM, an estrogen receptor (ER alpha/ER beta) antagonist) or mifepristone (10 microM, a progesterone receptor antagonist). In single aortic smooth muscle cells, Formononetin caused opening of iberiotoxin-sensitive Ca(2+)-activated K(+) (BK(Ca)) channels and glibenclamide-sensitive adenosine triphosphate (ATP)-dependent K(+) (K(ATP)) channels.
Thus, our results suggest that Formononetin caused vascular relaxation via endothelium/NO-dependent mechanism and endothelium-independent mechanism which involves the activation of BK(Ca) and K(ATP) channels.
|Cell Physiol Biochem. 2014;34(4):1351-8. |
|Formononetin promotes cell cycle arrest via downregulation of Akt/Cyclin D1/CDK4 in human prostate cancer cells.[Pubmed: 25301361]|
|Formononetin is an O-methylated isoflavone isolated from the root of Astragalus membranaceus. It has already been reported that Formononetin could inhibit cell proliferation and induce cell apoptosis in several cancers, including prostate cancer. This study aimed to further investigate whether cell cycle arrest is involved in Formononetin-mediated antitumor effect in human prostate cancer cells, along with the underlying molecular mechanism. |
METHODS AND RESULTS:
Human prostate cancer cells PC-3 and DU145 were respectively treated with various concentrations of Formononetin. The inhibitory effect of Formononetin on proliferation of prostate cancer cells was determined using MTT assays and flow cytometry. Next, Formononetin-induced alterations in cyclin D1, CDK4 and Akt expression in PC-3 cells were detected by real-time PCR and western blot. Formononetin dose-dependently inhibited prostate cancer cell proliferation via the induction of cell cycle arrest at G0/G1 phase in vitro, which was more evident in PC-3 cells. Meanwhile, concomitant with reduced phosphorylation of Akt in PC-3 cells, Formononetin remarkably downregulated expression levels of cyclin D1 and CDK4 in a dose-dependent manner. More interestingly, in the in vivo studies, Formononetin showed a noticeable inhibition of tumor growth in recipient mice.
Formononetin could exhibit inhibitory activity against human prostate cancer cells in vivo and in vitro, which is associated with G1 cell cycle arrest by inactivation of Akt/cyclin D1/CDK4. Therefore, Formononetin may be used as a candidate agent for clinical treatment of prostate cancer in the future.