23-24-dihydrocucurbitacin-b and Edema

Wilbrandia ebracteata (WE), a Brazilian medicinal plant used in folk medicine for the treatment of rheumatic diseases, displays anti-inflammatory properties and constitutes a rich source of cucurbitacins and cucurbitacin-related compounds. The current study investigated the potential anti-inflammatory properties of Dihydrocucurbitacin B (DHCB), a cucurbitacin-derived compound isolated from roots of WE, in some in vivo and in vitro experimental models. Intraperitoneal treatment of mice with DHCB reduced both carrageenan-induced paw edema (0.3, 1 and 3 mg/kg caused inhibitions of 26, 44 and 56 % at 2 h after stimulation, respectively) and pleurisy (10 mg/kg inhibited leukocyte numbers and LTB(4) levels in the pleural fluid by 51 and 75% at 6 h after cavity challenge, respectively). In vitro, DHCB (up to 10 microg/mL) failed to modify LTB(4) production by human neutrophils or PGE(2) production by COS-7 cells transfected with COX-1, but PGE(2) production by COX-2 transfected COS-7 cells was markedly inhibited (by 72%). The levels of COX-1 or COX-2 proteins in IL-1alpha-stimulated NIH3T3 cells were unaffected by DHCB. The results corroborate the potential anti-inflammatory properties ascribed to W. ebracteata Cogn. in folk medicine and suggest that they might be attributed, at least in part, to the capacity of one of this plants main constituents, DHCB, to inhibit COX-2 activity (but not its expression) during inflammation.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Carrageenan; Chlorocebus aethiops; COS Cells; Cucurbitaceae; Cyclooxygenase 1; Cyclooxygenase 2 Inhibitors; Cyclooxygenase Inhibitors; Dinoprostone; Edema; Humans; Leukotriene B4; Male; Methylene Chloride; Mice; Neutrophils; NIH 3T3 Cells; Plant Roots; Pleurisy; Solvents; Triterpenes

Fractionation of an anti-inflammatory extract from Cayaponia tayuya roots yielded two active compounds, identified as 23,24-dihydrocucurbitacin B (1) and cucurbitacin R (2). Both were evaluated for their anti-inflammatory activity on several experimental models of pain and inflammation. In addition, their cytotoxicity and effects on leukotriene B4 (LTB4) formation were evaluated in rat polymorphonuclear leukocytes. Both compounds showed activity in the following models: carrageenan-induced mouse paw oedema (1, 4 mg/kg p.o., 46% inhibition at 3 h), phospholipase A2-induced mouse paw oedema (2, 3 mg/kg i.p., 61% inhibition at 60 min), serotonin-induced mouse paw oedema (1 and 2, 0.5 mg/kg s.c., 73% and 79% inhibition, respectively), 12- O-tetradecanoylphorbol 13-acetate (TPA)-induced acute ear oedema (2, 36% inhibition at 4 mg/kg p.o., and 87% inhibition at 0.1 mg/ear topically). The compounds were also active against the inflammation induced by repeated application of TPA on mouse ears, affecting both the oedema itself (1 and 2 at 0.1 mg/ear, 44% and 56% inhibition, respectively) as well as cell infiltration (68% and 69%, respectively). The activity of both compounds against oedema induced by serotonin was not modified by the glucocorticoid receptor antagonist mifepristone; however, the protein synthesis inhibitor cycloheximide abolished the anti-inflammatory response in both cases. Neither compound modified the production of LTB4 in rat polymorphonuclear leukocytes, nor did they exhibit analgesic properties at the dose assayed.

Topics: Administration, Cutaneous; Administration, Oral; Animals; Anti-Inflammatory Agents, Non-Steroidal; Carrageenan; Cucurbitaceae; Cucurbitacins; Dose-Response Relationship, Drug; Edema; Female; Leukocytes; Leukotriene B4; Mice; Pain; Phospholipases A; Phospholipases A2; Phytotherapy; Plant Extracts; Plant Roots; Rats; Rats, Wistar; Tetradecanoylphorbol Acetate; Triterpenes