Planta Med 2007; 73 - P_045
DOI: 10.1055/s-2007-986827

Steroids from Vernonia nigritiana Oliv. & Hiern. with topical anti-inflammatory activity

S Sosa 1, N De Tommasi 2, G Cioffi 2, I Merfort 3, R Della Loggia 1, A Tubaro 1
  • 1Dipartimento dei Materiali e delle Risorse Naturali, Università di Trieste, Via A. Valerio 6, 34127, Trieste, Italia
  • 2Dipartimento di Scienze Farmaceutiche, Università di Salerno, Via Ponte Don Melillo, 84084, Fisciano, Salerno, Italia
  • 3Lehrstuhl für Pharmazeutische Biologie und Biotechnologie, Universität Freiburg, Stefan-Meier-Straße 19, 79104 Freiburg, Germany

Vernonia nigritiana Oliv. & Hiern. (Asteraceae) is a widely distributed plant of West Africa where is traditionally used against dermatoses, digestive insufficiency, fever, rheumatism and headache [1]. Previous studies revealed a topical anti-inflammatory activity of a chloroform extract from the aerial parts of V. nigritiana, containing stigmastane-type steroids [2]. Continuing the investigation of V. nigritiana constituents, nine polyhydroxylated stigmasterol glycosides (1-9) and six (10-15) polyhydroxylated stigmastanes having a Δ7(8), 9(11), 24(28) -steroid cyclic system, were isolated. Their structure was elucidated by NMR, 1D-TOCSY, 2D-HOHAHA, COSY-DQF, HSQC, HMBC, 1D-ROESY and 1D-NOESY. The molecular formula of the compounds was confirmed by MS analysis.

All the compounds were screened for their topical anti-inflammatory activity as inhibition of the Croton oil-induced ear oedema in mice [3]. Each compound provoked a significant oedema reduction, the most active being compounds 1 and 12 (ID50=0.10 and 0.21µmol/cm2, respectively). Their effect was only two and five fold lower than that of the steroidal drug hydrocortisone (ID50=0.04µmol/cm2). Compounds 2-11 and 13-15 provoked inhibitions in the range of 31–83% at the highest dose (0.5µmol/cm2). As reference, the parent compounds stigmasterol and stigmastanol (0.5µmol/cm2) were inactive. To clarify a possible mechanism of action, these compounds were evaluated for their ability to inhibit NF-κB, a transcription factor regulating the expression of inflammatory macromolecules. Studies, carried out in an electrophoretic mobility shift assay [4], showed a complete NF-κB inhibition induced by compounds 1 and 5 (50µM), and a slight inhibition for compounds 6 (50µM) and 8 (20–100µM).

References: [1] Igile, G. et al. (1995) J. Nat. Prod. 58: 1438–1443. [2] Cioffi G. et al. (2001) International Symposium of the Phytochemical Society of Europe. Lausanne, 12th-14th September 2001. [3] Tubaro A. et al. (1985) Agents Actions 17: 317–319. [4] Lyss G. et al. (1997) Biol. Chem. 378: 951–961.