Tectoridin Derived from Puerariae Flos Alleviates Acute Ethanol-Induced Ataxia in Rats by Targeting the Adenosine A1 Receptor via Its Aglycone.

As ingredients in vegetables, tea, and jelly, Puerariae Flos can relieve the discomfort caused by excessive ethanol intake. Here, we integrated liquid chromatography, gas chromatography, and in vivo microdialysis to explore the active components and mechanisms underlying Puerariae Flos-mediated attenuation of acute ethanol intoxication. Results demonstrate that Puerariae Flos flavonoid extract (PFF) and its active constituent tectoridin significantly enhance motor coordination in ethanol-exposed rats without altering the ethanol concentrations in blood or cerebellum. Notably, tectorigenin, a metabolite of tectoridin, crossed the blood-brain barrier (BBB) and exerted antiataxic effects by targeting adenosine A1 receptor (A1AR), as confirmed by molecular docking, cellular thermal shift assay (CETSA), drug affinity responsive target stability (DARTS) assay, and GloSensor assay. We conclude that tectoridin in Puerariae Flos functions primarily via its metabolite tectorigenin, which targets cerebellar A1AR to alleviate ethanol-induced acute ataxia. This work provides novel mechanistic insight into Puerariae Flos for combating acute ethanol poisoning.