Assessment of the anti-inflammatory activity and free radical scavenger activity of tiliroside.
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.
Sala
Araceli
A
Departament de Farmacologia, Facultat de Farmàcia, Universitat de València, Av. Vicent Andrés Estellés s/n, 46100 Burjassot, Spain.
Recio
M Carmen
MC
Schinella
Guillermo R
GR
Máñez
Salvador
S
Giner
Rosa M
RM
Cerdá-Nicolás
Miguel
M
Rosí
José Luis
JL
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000302:isolation & purification / Q000627:therapeutic use*; D001578:Benzopyrans / Q000737:chemistry / Q000302:isolation & purification / Q000627:therapeutic use*; D001713:Biphenyl Compounds / Q000737:chemistry; D005260:Female; D044950:Flavanones; D005419:Flavonoids / Q000737:chemistry / Q000302:isolation & purification / Q000627:therapeutic use; D016166:Free Radical Scavengers / Q000737:chemistry / Q000302:isolation & purification / Q000627:therapeutic use*; D036562:Helichrysum / Q000737:chemistry; D006801:Humans; D006834:Hydrazines / Q000737:chemistry; D006968:Hypersensitivity, Delayed / Q000188:drug therapy; D066298:In Vitro Techniques; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy; D007962:Leukocytes / Q000187:drug effects / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D051379:Mice; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism; D009195:Peroxidase / Q000378:metabolism; D008517:Phytotherapy; D010851:Picrates; D010936:Plant Extracts / Q000737:chemistry / Q000302:isolation & purification / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D012756:Sheep; D013481:Superoxides / Q000378:metabolism
D000893:Anti-Inflammatory Agents; D001578:Benzopyrans; D001713:Biphenyl Compounds; D044950:Flavanones; D005419:Flavonoids; D016166:Free Radical Scavengers; D006834:Hydrazines; D010851:Picrates; D010936:Plant Extracts; C121845:gnaphalin; D013481:Superoxides; C052083:tiliroside; C016063:pinocembrin; C004931:1,1-diphenyl-2-picrylhydrazyl; D009195:Peroxidase