Eur J Pharmacol. 2003 Feb; 461(1): 53-61.

Assessment of the anti-inflammatory activity and free radical scavenger activity of tiliroside.

Sala A, Recio MC, Schinella GR, MÃ¡Ã±ez S, Giner RM, CerdÃ¡-NicolÃ¡s M, RosÃ JL.

Departament de Farmacologia, Facultat de FarmÃ cia, Universitat de ValÃ¨ncia, Av. Vicent AndrÃ©s EstellÃ©s s/n, 46100 Burjassot, Spain.

Three flavonoids, gnaphaliin, pinocembrin and tiliroside, isolated from Helichrysum italicum, were studied in vitro for their antioxidant and/or scavenger properties and in vivo in different models of inflammation. In vitro tests included lipid peroxidation in rat liver microsomes, superoxide radical generation in the xanthine/xanthine oxidase system and the reduction of the stable radical 1,1-diphenyl-2-pycryl-hydrazyl (DPPH). Acute inflammation was induced by application of 12-O-tetradecanoylphorbol 13-acetate (TPA) to the mouse ear or by subcutaneous injection of phospholipase A(2) or serotonin in the mouse paw. Eczema provoked on the mouse ear by repeated administration of TPA was selected as a model of chronic inflammation. The flavonoids were assayed against sheep red blood cell-induced mouse paw oedema as a model of delayed-type hypersensitivity reaction. The most active compound, both in vitro and in vivo, was tiliroside. It significantly inhibited enzymatic and non-enzymatic lipid peroxidation (IC(50)=12.6 and 28 microM, respectively). It had scavenger properties (IC(50)=21.3 microM) and very potent antioxidant activity in the DPPH test (IC(50)=6 microM). In vivo, tiliroside significantly inhibited the mouse paw oedema induced by phospholipase A(2)(ED(50)=35.6 mg/kg) and the mouse ear inflammation induced by TPA (ED(50)=357 microg/ear). Pinocembrin was the only flavonoid that exhibited anti-inflammatory activity in the sheep red blood cell-induced delayed-type hypersensitivity reaction. However, only tiliroside significantly reduced the oedema and leukocyte infiltration induced by TPA. As in the case of other flavonoids, the anti-inflammatory activity of tiliroside could be based on its antioxidant properties, although other mechanisms are probably involved.