Objective:To investigate the anti-anaphylactic,anti-inflammatory and membrane stabilizing properties of plumerianine(compound 1)isolated from the root bark of Plumeria acuifolia Poir.Methods:The anti-anaphylactic acti...Objective:To investigate the anti-anaphylactic,anti-inflammatory and membrane stabilizing properties of plumerianine(compound 1)isolated from the root bark of Plumeria acuifolia Poir.Methods:The anti-anaphylactic activity of compound 1(10,25 and 50 mg/kg)was studied by using models such as passive cutaneous anaphylaxis,passive paw anaphylaxis and its antiinflammatory activity against carrageenin induced paw edema and cotton pellet granuloma in albino rats was also investigated using ketotifen and indomethacin as reference drugs.Results:A dose-dependent beneficial effect was observed on leakage of evans blue dye in skin challenged with antigen and on paw anaphylaxis induced by antiserum.The compound 1 also exhibited significant(P<0.01)inhibition of rat paw edema and granuloma tissue formation,including significant protection of RBC against the haemolytic effect of hypotonic solution,an indication of membrane-stabilizing activity.Conclusions:Anti-anaphylactic activity of compound 1 may be possibly due to inhibition of the release of various inflammatory mediators.Anti-inflammatory activity of compound may be related to the inhibition of the early phase and late phase of inflammatory events.展开更多
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
文摘Objective:To investigate the anti-anaphylactic,anti-inflammatory and membrane stabilizing properties of plumerianine(compound 1)isolated from the root bark of Plumeria acuifolia Poir.Methods:The anti-anaphylactic activity of compound 1(10,25 and 50 mg/kg)was studied by using models such as passive cutaneous anaphylaxis,passive paw anaphylaxis and its antiinflammatory activity against carrageenin induced paw edema and cotton pellet granuloma in albino rats was also investigated using ketotifen and indomethacin as reference drugs.Results:A dose-dependent beneficial effect was observed on leakage of evans blue dye in skin challenged with antigen and on paw anaphylaxis induced by antiserum.The compound 1 also exhibited significant(P<0.01)inhibition of rat paw edema and granuloma tissue formation,including significant protection of RBC against the haemolytic effect of hypotonic solution,an indication of membrane-stabilizing activity.Conclusions:Anti-anaphylactic activity of compound 1 may be possibly due to inhibition of the release of various inflammatory mediators.Anti-inflammatory activity of compound may be related to the inhibition of the early phase and late phase of inflammatory events.
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.
