Kurarinone, a Lavandulyl Flavanone from <i>Sophora flavescens</i>, Inhibits T-type Calcium Channels and Exerts Analgesic Effects in a Mouse Model of Inflammatory Pain

Kurarinone, the major lavandulyl flavanone identified in the roots of Sophora flavescens, has been reported to have different channel and transporter activity modulation capacities; nevertheless, its ability to block T-type channels and inflammatory pain activity have not been fully investigated. In this work, we used the whole-cell patch clamp technique to examine the ability of kurarinone to block T-type calcium channels. Kurarinone acted as a nonselective T-type channel antagonist that inhibited Cav3.2 channels expressed in tsA-201 cells with an IC50 of 1.1 ± 0.3 μM and blocked native T-type channels in mouse dorsal root ganglion neurons. Transiently expressed Cav2.2 channels were also blocked. Molecular docking analysis predicted that the phenyl ring, lavandulyl, and hydroxyl groups of kurarinone interact directly with the pore domains of all three T-type calcium channels via hydrogen and hydrophobic interactions. Kurarinone administered intraperitoneally (10 mg/kg/i.p.) significantly inhibited phase II of formalin-induced nocifensive responses in mice. Furthermore, kurarinone reduced thermal hyperalgesia and mechanical hypersensitivity in mice injected with Complete Freund’s adjuvant (CFA) into the hind paw in an inflammatory pain mouse model. Taken together, our findings indicate that kurarinone has analgesic activity through blocking calcium channels.