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...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 ofβ-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.展开更多
基金This work was supported by the National Natural Science Foundation of China(Nos:81773996,81773589,500101135,and 81522050)Beijing Natural Science Foundation(No.JQ18026).
文摘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 ofβ-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.
