Joannesia princeps Vell. inhibits purinergic P2Y receptors and presents antinociceptive and anti-inflammatory effects.

P2Y2, P2Y4, and P2Y6 are purinergic receptors physiologically activated by uridine nucleotides. These metabotropic Gq-coupled receptors induce intracellular calcium mobilization and are expressed in various cell types, particularly leukocytes. Their activation triggers proinflammatory responses, playing a critical role in the progression of inflammatory diseases, nociception, and cancer. However, the absence of selective antagonists limits their clinical application, encouraging the search for novel compounds. In this study, we investigated the antagonistic effects of dichloromethane-methanol (DCM-MeOH) and ethanolic (EtOH) extracts from the branches and leaves of Joannesia princeps Vell. Using calcium measurement techniques, we demonstrated that the extracts, particularly those from branches, inhibit calcium responses mediated by P2Y receptors, suggesting potential selectivity. Importantly, this inhibitory activity was not attributed to a quenching effect. Additionally, cell viability was evaluated after 1 and 24 h of extract treatment using the MTT assay, which confirmed that the extracts did not induce cell death. Furthermore, we examined the analgesic and anti-inflammatory properties of J. princeps branch extract, which could be related to P2Y receptor activation. In formalin-induced nociception and paw edema models in Swiss mice, the EtOH branch extract significantly reduced pain-related behaviors and alleviated paw edema. These findings highlight the potential of J. princeps branch extract as a uridine-activated P2Y receptor antagonist, offering promising therapeutic applications for inflammation and pain management.