Formononetin, J1 and J2 have different effects on endothelial cells via EWSAT1‐TRAF6 and its downstream pathway

Abstract

Formononetin is a natural isoflavone compound found mainly in Chinese herbal medicines such as astragalus and red clover. It is considered to be a typical phytooestrogen. In our previous experiments, it was found that formononetin has a two‐way regulatory effect on endothelial cells (ECs): low concentrations promote the proliferation of ECs and high concentrations have an inhibitory effect. To find a specific mechanism of action and provide a better clinical effect, we performed a structural transformation of formononetin and selected better medicinal properties for formononetin modifier J1 and J2 from a variety of modified constructs. The MTT assay measured the effects of drugs on human umbilical vein endothelial cell (HUVEC) activity. Scratch and transwell experiments validated the effects of the drugs on HUVEC migration and invasion. An in vivo assessment effect of the drugs on ovariectomized rats. Long‐chain non‐coding RNA for EWSAT1, which is abnormally highly expressed in HUVEC, was screened by gene chip, and the effect of the drug on its expression was detected by PCR after the drug was applied. The downstream factors and their pathways were analysed, and the changes in the protein levels after drug treatment were evaluated by Western blot. In conclusion, the mechanism of action of formononetin, J1 and J2 on ECs may be through EWSAT1‐TRAF6 and its downstream pathways.

Silicon-substituted calcium phosphate promotes osteogenic-angiogenic coupling by activating the TLR4/PI3K/AKT signaling axis

“…The process of osteogenic differentiation and angiogenesis is extremely complex, and multiple cytokines and signaling pathways have been shown to be involved. 48,49 I t is reported that the signal pathways involved in the process of osteogenic differentiation include Smad signal pathway, Wnt signal pathway and PI3K/AKT signal pathway and so on. 50 In the meantime, the involvement of PI3K/AKT signaling pathway, Notch signaling pathway and Shh signaling pathway in angiogenesis has also been indicated by several studies.…”

Therapeutic targets of formononetin for treating prostate cancer at the single-cell level

“…So, targeting ER could be an option for discovery of novel compound for treating prostate cancer. Formononetin, a natural isoflavone phytoestrogen, was mainly extracted from the Chinese herbs Astragalus membranaceus and Red Clover [ 12 ]. Formononetin exhibits estrogen-like effects through its interaction with ER, especially ERβ [ 13 ].…”

Potential Therapeutic Targets of Formononetin, a Type of Methoxylated Isoflavone, and Its Role in Cancer Therapy through the Modulation of Signal Transduction Pathways

“…Formononetin, a methoxylated isoflavone (7-hydroxy-3-(4-methoxypheny)-4H-1benzopyran-4-one) (Figure 1), is a chief ingredient isolated from red clover as well as the Chinese plant Astragalus membranaceus [3], and it belongs to the isoflavonoid group of phytoestrogens [4,5]. The role of formononetin has been described in different cancers through the regulation of different cellular processes and molecular signaling pathways.…”