Abstract:
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.