Study On The Antipruritic Mechanism Of Paeonol

Chronic pruritus is a refractory disease which is extremely difficult to cure.It can seriously damage health and affect normal life.So far,the research on pruritus is not thorough enough,so there is no effective drug and reasonable scheme to treat pruritus in clinic.Through literature review,we found that paeonol,a traditional Chinese medicine,has a good inhibitory effect on chronic pruritus(psoriasis).Paeonol is derived from the dry root bark of Ranunculaceae plant Peony.Existing studies have confirmed that paeonol has a variety of pharmacological functions and health effects,but the mechanism of its antipruritic effect is still unclear.The purpose of this study was to explore the anti-pruritus mechanism of Paeonol in the treatment of pruritus,and to provide new ideas for clarifying the formation mechanism of pruritus and the development of new anti-pruritus drugs.To investigate whether paeonol can inhibit histamine-mediated itching and non-histamine-mediated itching,we used histamine-induced acute itching model in mice,chloroquine-induced acute itching model in mice and acetone-diethyl ether-water(AEW)induced chronic itching model in mice to verify.Specific methods are as follows:(1)Acute itching model of mice was established by chloroquine(CQ)and histamine(Histamine),and xerodermia model of mice was established by acetone-diethyl ether-water(AEW).(2)To explore the antipruritic effect of paeonol by skin morphology(3)To detect the expression of cytokines in Elisa serum and skin.(4)RT-PCR was used to detect the expression of cytokines in skin and dorsal root ganglion(DRG).(5)Calcium imaging was used to study the inhibition of TRP channel by paeonol.Through behavioral statistics,it was found that paeonol could not reduce the number of scratches in acute itching model(CQ,Histamine)mice,but paeonol could effectively reduce the number of scratches in chronic itching model(AEW)mice with concentration-dependent characteristics.Paeonol significantly improved the skin damage of AEW mice,and paeonol could reduce the levels of IL-4,IL-6,IL-1beta and other cytokines in serum of AEW mice.At the gene level,paeonol can reduce the levels of TRPA1,TRPV1 transient ion channels and inflammatory factors in DRG.Paeonol has the same effect as TRPA1 specific agonist AITC on TRPA1 activation,but has no effect on TRPV1 activation and inhibition,and no effect on TRPM8 activation.Paeonol can effectively inhibit the chronic pruritus caused by AEW,and effectively inhibit the thickness of cuticle and reduce the number of mast cells.Paeonol can inhibit the content of inflammatory factors in serum and achieve anti-inflammatory effect.To explore the itching factors in DRG,we found that paeonol could significantly inhibit the expression of itching molecules in dorsal root ganglion and inflammatory factors in skin.Calcium imaging showed that paeonol could activate TRPA1 pathway,which verified the anti-itching effect of paeonol.Paeonol inhibits AEW-induced pruritus in mice,one of its mechanisms is by controlling the activity of TRPA1 and inhibiting the expression of Th1/Th2 inflammatory cells.This discovery will help to develop new antipruritic drugs in clinic.It provides a new idea for the mechanism of pruritus.