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.
Subject(s)
Animals , Mice , Glucosides , Mice, Inbred BALB C , Molecular Docking Simulation , Monoterpenes , Paeonia , Plant RootsABSTRACT
Antiallergic activity of Aristolochia bracteolata was evaluated by using compound 48/80 induced anaphylaxis, dermatitis rhinitis and pruritis, as a preclinical model for acute phase of hypersensitivity reactions. The late phase hypersensitivity was evidenced by considering toluidine diisocyanate induced volume of bronchoalveolar fluid secretion and its inhibition. The possible antiallergic mechanism was evaluated by using compound 48/80 induced mast cell activation and estimated serum nitric oxide (NO), rat peritoneal fluid NO, bronchoalveolar fluid NO and blood histamine levels. The present study implied that the chloroform extract of Aristolochia bracteolata had potent and significant inhibitory effect on compound 48/80 induced pruritis and dermatitis activity in Swiss albino mice. It showed significant effect in toluidine diisocyanate induced rhinitis in swiss albino mice. Mast cell membrane stabilization activity was also observed in compound 48/80 induced mast cell activation. A significant reduction was observed in serum nitrate levels, rat peritoneal fluid nitrate levels and BAL nitrate levels. The extract was also found to possess significant inhibitory effect on blood histamine levels. It could be concluded that chloroform extract of A. bracteata possess potent antiallergic activity, possibly through mast cell membrane stabilization, inhibiting NO and histamine pathway.
ABSTRACT
?-caryophyllene was one of the effective antiasthmatic principles of essential oil of Artemisia argyi, by way of structural modification to form ?-caryophyllene alcohol. P-caryophyllene alcohol could protect acetylcholine and histamine-induced asthma in guinea pig, and the effect was longer than 4h. It had relaxant effect on isolated guinea pig tra.cheal smooth muscle prepareations, and the pD2 values was 4.36 + 0.37. The drug not only significantly inhibited antigen induced release of SRS-A in the lung fragments of sensitized guinea pig( ID50 23mg/L ), but also inhibited SRS-A induced contraction of the guinea pig ileum(ID50 18mg/L). In addition, P-caryophyllene alcohol had antitussive and expectora'at actions. These results show that p-caryophyllene alcohol is a new antiathmatic drug.