Using high-throughput screening, we discovered that soybean isoflavone genistein (GEN) is a novel CB1 receptor antagonist that does not cross the blood-brain barrier, thereby avoiding CNS effects and psychiatric side effects. We further enhanced the water solubility and oral bioavailability of GEN through microbial fermentation. This strategy has been patented and can be used to treat cardiovascular diseases and has therapeutic potential for other diseases related to abnormal CB1 activation.

Developing CB1 receptor antagonists without psychiatric side effects is an unmet medical need. We discovered that Genistein (GEN) is a novel CB1 antagonist that neither crosses the blood-brain barrier nor causes psychiatric side effects. Through microbial fermentation, GEN was converted into Genistein-7-O-Phosphate (GEN-7P), exhibiting a 100,000-fold increase in water solubility and 83% intestinal permeability, significantly enhancing the oral bioavailability of GEN.

Our team has experience in fermentation and natural product development. We have analyzed the isoflavone content of Taiwanese soybeans and established a complete supply chain. Through microbial fermentation, we significantly increased the water solubility, intestinal permeability, and bioavailability of GEN. The strategy has been patented, strains deposited, and the GEN derivatives have been approved by the U.S. FDA NDI, which will facilitate subsequent clinical development and application.