Effects of dihydrocubebin, a lignan isolated from Indonesian plant Piper cubeba, on the histamine release from rat mast cells

The fruits of Piper cubeba L. are used traditionally to treat respiratory disorders in Indonesia. In order to determine the compounds responsible for this activity, the fruits were extracted with nhexane followed by ethanol to give n-hexane and ethanol extracts. Based on tracheospasmolytic assay on these two extracts, the n-hexane extract was more active to inhibit trachea contraction than that of ethanol extract. Upon bioassay guided isolation of the n-hexane extract, a tracheospasmolytic active compound was isolated and identified as dihydrocubebin [(3,4),(3’,4’)-bis-methylenedioxy9,9’dihydroxylignan] (1). Compound 1 was tested further for its ability to inhibit histamine released from mast cells, using rat basophilic leukemia (RBL-2H3) cell line and rat peritoneal mast cells RPMCs) as models; and DNP 24 -BSA, thapsigargin, ionomycin, compound 48/80 and PMA were used as inducers for histamine released from mast cell. The test result showed that 1 inhibited histamine release from RBL-2H3 cells induced by DNP 24 -BSA, thapsigargin and ionomycin. In addition, 1 suppressed histamine release from RPMC induced by either thapsigargin or ionomycin. However, 1 did not inhibit histamine release from RPMC induced by either compound 48/80 or combination PMA-sub optimum dose of ionomycin. Therefore, it was concluded that the inhibitory effects of 1 on the histamine released from mast cells may involve mechanisms related to intracellular Ca2+ signaling events or downstream processes of intracellular Ca2+ signaling in mast cells.