Discovery of maslinic acid being a Nav1.7 inhibitor with analgesic efficacy in rodent pain models

Abstract

AbstractBackground Voltage gated sodium channels are essential for the generation of exceptional pain signals after peripheral nerve injury. Among them, voltage-gated sodium (Nav) subtype Nav1.7 is a powerful target for a broad range of pain conditions. Maslinic acid, one of the most common pentacyclic triterpenes widely distributed in medicinal plants, showed pharmacologic safety and potent pharmacological action. Herein, we present maslinic acid (MA) as an inhibitor of Nav1.7 with analgesic efficacy in rodent pain models. Methods We first explored the target of maslinic acid using the CMap method and patch clamp recording. Maslin acid and its inactive analogue (oleanolic acid as negative controls) was used to culture MCF-7 cells. Then, we performed RNA-seq of the cultured MCF-7 cells and analyzed the transcriptome data. The differential genes were identified and used as an input for CMap. The CMap result was further confirmed by patch clamp recording. Results The CMap result suggested that maslinic acid was an agonist of Nav channels. Further whole cell patch-clamp experiments revealed that maslinic acid inhibited the Nav1.7 channel with an IC50value of 6.1 µM. Conclusion Maslinic acid showed a potent analgesic effect in two rodent models of formaldehyde and acid-induced pain. Our findings show novel insights into the new target of maslinic acid in complex neurological disorders. Maslinic acid targeting Nav1.7 is a new analgesic lead.