Anti-anaphylactic potential of benzoylpaeoniflorin through inhibiting HDC and MAPKs from Paeonia lactiflora

Guided by cell-based anti-anaphylactic assay, eighteen cage-like monoterpenoid glycosides ( 1 − 18 ) were obtained from the bioactive fraction of P. lactiflora extract. Among these, compounds 1 , 5 , 6 , 11 , 12 , 15 , and 17 significantly reduced the release rate of β-HEX and HIS without or with less cytotoxicity. Furthermore, the most potent inhibitor benzoylpaeoniflorin ( 5 ) was selected as the prioritized compound for the study of action of mechanism, and its anti-anaphylactic activity was medicated by dual-inhibiting HDC and MAPK signal pathway. Moreover, molecular docking simulation explained that benzoylpaeoniflorin ( 5 ) blocked the conversion of L-histidine to HIS by occupying the HDC active site. Finally, in vivo on PCA using BALB/c mice, benzoylpaeoniflorin ( 5 ) suppressed the IgE-mediated PCA reaction in antigen-challenged mice. These findings indicated that cage-like monoterpenoid glycosides, especially benzoylpaeoniflorin ( 5 ), mainly contribute to the anti-anaphylactic activity of P. lactiflora by dual-inhibiting HDC and MAPK signal pathway. Therefore, benzoylpaeoniflorin ( 5 ) may be considered as a novel drug candidate for the treatment of anaphylactic diseases.