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Background: Senecio scandens Buch.-Ham ( S. scandens ) belongs to the Compositae family. As a Traditional Chinese medicine, S. scandens has been used in China to treat conjunctivitis, mastitis and vaginitis, it also has the function of antibacterial and relieving itching., Methods: Water extract of S. scandens (WSS) was prepared and its quality was controlled by HPLC. The antipruritic effects of WSS were evaluated by itch behavioral experiments. The oxazolone and compound 48/80 were induced to mice scratch behavior, scratch was recorded 30 min after sensitization. The relationship between the antipruritic mechanism and MrgprB2 on mast cell was studied by using mast cell-deficient Kit (W-sh) "Sash" mice and MrgprB2 -/- mice. The mast cells were observed by toluidine blue staining. In vitro, the effects of WSS on MrgprB2 were studied by calcium imaging; The whole-cell patch clamp method recorded the MrgprB2 mediate voltage-dependent currents in mast cells., Results: The content of rutin (0.012%) and hyperin (0.014%) in the WSS were determined. WSS could ameliorate the pruritus induced by Oxazolone (inhibition was 41.19%, p = 0.004) and compound 48/80 (inhibition was 50.29%, p = 0.001). Meanwhile, WSS could reduce the number of mast cells in mice skin tissue with allergic contact dermatitis (ACD) ( p = 0.002) or compound 48/80 ( p = 0.013). In addition, WSS could inhibit the calcium influx (1 mg/mL: p = 0.001, 3 mg/mL: p < 0.0001) and the voltage-dependent currents induced by activation of MrgprB2 on mast cell. WSS also attenuated the calcium influx induced by compound 48/80 in HEK293 cells overexpressing MrgprB2/X2., Conclusion: These results showed that WSS could ameliorate pruritus by inhibiting MrgprB2 receptor on mast cells., Competing Interests: The authors declare that there are no conflicts of interest in this work., (© 2022 Ye et al.)

Background: Mast cells are well known for their role in inflammatory pain. P2X7 receptor (P2X7R) has attracted much attention due to its prominent role in inflammatory diseases. Salicylates are commonly used anti-inflammatory and analgesic drugs. Until now, little has been known about whether P2X7R in mast cells is involved in inflammatory pain and whether it is a potential target for salicylates., Methods: First, the expression of P2X receptors in mouse peritoneal mast cells was detected by using RT-PCR, immunofluorescence, calcium imaging and electrophysiological technique. In addition, the functions of P2X receptors, especially P2X7R, in mast cells were studied by using QPCR, ELISA and behavioral tests. Furthermore, P2X7R was used as a target to screen for some anti-inflammatory monomers that could inhibit its activity. At last, the effect of salicylic acid (SA) and aspirin (ASA) on the activity of P2X7R was studied by using calcium imaging, electrophysiological technique, ELISA, real-time PCR, behavioral tests, immunofluorescence and molecular docking., Results: We found that P2X1, P2X3, P2X4 and P2X7 receptors were expressed in mouse peritoneal mast cells. The functions of different P2X receptors were various. Activation of P2X7R in mouse mast cells induced the release of inflammatory mediators, such as histamine, IL-1β, and CCL3. In addition, inflammation pain induced by high concentrations of ATP could be alleviated by P2X7R blockers or mast cell defects. Interestingly, SA or ASA could reduce high concentrations of ATP-induced inward current, P2X7R upregulation, mediators release, and inflammatory pain. SA or ASA also inhibited the inward current evoked by P2X7R agonist, BZATP. Molecular docking showed that SA or ASA had affinity for the cytoplasmic GDP-binding region of P2X7R., Conclusion: P2X7R in mast cells was involved in inflammation pain by releasing inflammatory mediators, and P2X7R might be a potential target for SA and ASA analgesia., Competing Interests: The authors declare that they have no competing interests., (© 2021 Jiang et al.)