Anti-Inflammatory Activity of Two Cucurbitacins Isolated from Cayaponia tayuya Roots

Abstract

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.

Cayaponia tayuya - Cucurbitaceae - 23,24-dihydrocucurbitacin B - cucurbitacin R - anti-inflammatory activity

References

• 1 Dos Santos R I, Dos Santos M A, Schenkel E P. Analysis of the plant drug Wilbrandia ebracteata (Cogn) Cogn.  Int J Pharmacog. 1996;  26 335-41
• 2 Bauer R, Berganza L H, Seligmann O, Wagner H. Cucurbitacins and flavone C-glycosides from Cayaponia tayuya .  Phytochemistry. 1985;  24 1587-91
• 3 Ríos J L, Giner R M, Jiménez M J, Wickman G, Hancke J L. A study on the anti-inflammatory activity of Cayaponia tayuya root.  Fitoterapia. 1990;  61 275-8
• 4 Musza L L, Speight P, McElhiney S, Barrow C J, Gillum A M, Cooper R, Killar L M. Cucurbitacins, cell adhesion inhibitors from Conobea scoparioides .  J Nat Prod. 1994;  57 1498-502
• 5 Oh H, Mun Y J, Im S J, Lee S Y, Song H J, Lee H S, Woo W H. Cucurbitacins from Trichosanthes kirilowii as the inhibitory components on tyrosinase activity and melanin synthesis of B16/F10 melanoma cells.  Planta Med. 2002;  68 832-3
• 6 Bauer R, Wagner H. Cucurbitacin-haltige Drogen.  Dtsch Apoth Ztg. 1983;  123 1313-21
• 7 Yesilada E, Tanaka S, Sezik E, Tabata M. Isolation of an anti-inflammatory principle from the fruit juice of Ecballium elaterium .  J Nat Prod. 1988;  51 504-8
• 8 Yesilada E, Ustun O, Sezik E, Takaishi Y, Ono Y, Honda G. Inhibitory effects of Turkish folk remedies on inflammatory cytokines: interleukin-1α, interleukin-1β and tumor necrosis factor α.  J Ethnopharmacol. 1997;  58 59-73
• 9 Yesilada E, Tanaka S, Tabata M, Sezik E. Anti-inflammatory effects of the fruit juice of Ecballium elaterium on edemas in mice.  Phytother Res. 1989;  3 75-6
• 10 Peters R R, Saleh T F, Lora M, Patry C, de Brum-Fernandes A J, Farias M R, Ribeiro-do-Valle R M. Anti-inflammatory effects of the products from Wilbrandia ebracteata on carrageenan-induced pleurisy in mice.  Life Sci. 1999;  64 2429-37
• 11 Giner R M, Villalba M L, Recio M C, Máñez S, Cerdá-Nicolás M, Ríos J L. Anti-inflammatory glycoterpenoids from Scrophularia auriculata .  Eur J Pharmacol. 2000;  389 243-52
• 12 Giner-Larza E M, Máñez S, Recio M C, Giner R M, Prieto J M, Cerdá-Nicolás M, Ríos J L. Oleanonic acid, a 3-oxotriterpene from Pistacia, inhibits leukotriene synthesis and has anti-inflammatory activity.  Eur J Pharmacol. 2001;  428 137-43
• 13 Leech M, Hutchinson P, Holdsworth S R, Morand E F. Endogenous glucocorticoids modulate neutrophil migration and synovial P-selectin but not neutrophil phagocytic or oxidative function in experimental arthritis.  Clin Exp Immunol. 1998;  112 383-8
• 14 Sugishita E, Amagaya S, Ogihara Y. Studies on the mechanism of anti-inflammatory activities of papyriogenin A and C.  J Pharm Dyn. 1983;  6 287-94
• 15 Atta-ur-Rahman , Choudhary M I, Thomsen W J. Bioassay techniques for drug development. Harwood Academic Publishers Amsterdam; 2001: p. 100
• 16 Che C T, Phoebe Jr C H, Kinghorn A D, Farnsworth N R. High-field ¹H-NMR spectral analysis of some cucurbitacins.  J Nat Prod. 1985;  48 429-34
• 17 Jacobs H, Singh T, Reynolds W F, McLean S. Isolation and ¹³C-NMR assignments of cucurbitacins from Cayaponia angustiloba, Cayaponia racemosa, and Gurania subumbellata .  J Nat Prod. 1990;  53 1600-5
• 18 Recio M C, Giner R M, Máñez S, Ríos J L. Investigations on the steroidal anti-inflammatory activity of triterpenoids from Diospyros leucomelas .  Planta Med. 1995;  61 9-12
• 19 Peters R R, Farias M R, Ribeiro-do-Valle R M. Anti-inflammatory and analgesic effects of cucurbitacins from Wilbrandia ebracteata .  Planta Med. 1997;  63 525-8
• 20 Ukiya M, Akihisa T, Yasukawa K, Tokuda H, Toriumi M, Koike K, Kimura Y, Nikaido T, Aoi W, Nishino H, Takido M. Anti-inflammatory and anti-tumor-promoting effects of cucurbitane glycosides from the roots of Bryonia dioica .  J Nat Prod. 2002;  65 179-83
• 21 Miró M. Cucurbitacins and their pharmacological effects.  Phytother Res. 1995;  9 159-68
• 22 Panossian A, Gabrielian E, Wagner H. On the mechanism of action of plant adaptogens with particular reference to cucurbitacin R diglucoside.  Phytomedicine. 1999;  6 147-55
• 23 Jayaprakasam B, Seeram N P, Nair M G. Anticancer and anti-inflammatory activities of cucurbitacins from Cucurbita andreana .  Cancer Lett. 2003;  189 11-6
• 24 Park C S, Lim K J, Baek S H, Sohn H O, Lee D W, Yun H Y, Baek K J, Lee H S, Kwon N S. 23,24-Dihydrocucurbitacin D inhibits nitric oxide generation from murine macrophages by blocking nuclear factor-κB activation.  FASEB J. 2001;  15 A197