Research on Formononetin

Formononetin is an O-methylated isoflavon, an active constituent of the Chinese herb Astragali Radix, has been reported to have beneficial effects for Alzheimer's disease (AD). It is a kind of off-white powders, he Molecular Formula is C16H12O4, Molecular Weight is 268.27. We should store it in a cool, dry place and in a tightly closed container. The CAS Registry Number of Formononetin is 485-72-3.

Formononetin is found in a number of plants and herbs like the red clover. Along with other phytoestrogens, it predominantly occurs in leguminous plants and Fabaceae, particularly in beans, such as green beans, lima beans, soy and many others, as the free aglycone or in form of its glucoside ononin.It can also be found in Maackia amurensis cell cultures.

The present study shows that formononetin(CAS NO:485-72-3) increases soluble-AβPPαsecretion and thus protects human-AβPP Swedish mutation cell from hypoxia-induced apoptosis. Using hypoxic N2a-AβPP cell as an in vitro model of AD-like pathology, we confirmed that regular treatment with formononetin could have neuroprotective effects, followed respectively by reduced caspase 3 activity and increased cell viability. 

Strikingly, our data revealed that the caspase 3-blocking effect of formononetin was largely mediated by stimulation of α-secretase cleavage of AβPP, and increasing the secretion of its soluble form, sAβPPα. Moreover, the protective effect of formononetin was totally inhibited by TAPI-2, an α-secretase complex inhibitor, suggesting the role of the sAβPPαpathway in the neuroprotective response to formononetin. 

We also found that the stimulative effect of formononetin onα-secretase activity was mainly conducted by upregulating ADAM10 expression at the transcriptional level. Altogether, our study provides novel insights into how formononetin mediates stimulation of the ADAM10-sAβPPα pathway and exerts a neuronal protective effect.

Formononetin and equol, a secondary metabolite of formononetin, have been reported to be responsible for reproductive dysfunction and infertility in ruminants. The hormonal effects of formononetin may have a possible influence on breast cancer risk in mice, since it has been reported that formononetin supported mammary gland, pro-liferation, enhanced mammary estrogen receptor expres-sion, and increased circulating prolactin level in an estrogen-deficient murine model. However, ER binding of formonetin has much lower affinity than daidzein and equol, which are metabolites of formononetin.

Equol was proposed to be the major active phytoestrogen found in sheep and cattle that consumed alfalfa or clover. Aglycone and conjugated forms of formononetin, daidzein, and equol have also been detected in bovine blood plasma and urine from cows fed a diet containing daidzein and formononetin.

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