Background and purpose:In the present paper we studied the effect of shikonin on ear oedema induced by 12-Otetradecanoylphorbol-13-acetate (TPA), and determined the mechanisms through which shikonin might exert its topical anti-inflammatory action. Experimental approach: Acute ear oedema was induced in mice by topical application of TPA. The in vitro assays used macrophages RAW 264.7 cells stimulated with lipopolysaccharide. Cyclooxygenase-2, inducible nitric oxide synthase, protein kinase Ca, extracellular signal-regulated protein kinase (ERK), phosphorylated ERK (pERK), c-Jun N-terminal kinase (JNK), pJNK, p38, p-p38, p65, p-p65, inhibitor protein of nuclear factor-kB (NF-kB) (IkBa) and pIkBa were measured by Western blotting, activation and binding of NF-kB to DNA was detected by reporter gene and electrophoretic mobility shift assay, respectively, and NF-kB p65 localization was detected by immunocytochemistry. Key results: Shikonin reduced the oedema (inhibitory dose 50 = 1.0 mg per ear), the expression of cyclooxygenase-2 (70%) and of inducible nitric oxide synthase (100%) in vivo. It significantly decreased TPA-induced translocation of protein kinase Ca, the phosphorylation and activation of ERK, the nuclear translocation of NF-kB and the TPA-induced NF-kB-DNA-binding activity in mouse skin. Moreover, in RAW 264.7 cells, shikonin significantly inhibited the binding of NF-kB to DNA in a dose-dependent manner and the nuclear translocation of p65. Conclusions and implications: Shikonin exerted its topical anti-inflammatory action by interfering with the degradation of IkBa, thus inhibiting the activation of NF-kB.
The present paper reports the results of the methanol extract of Haplophyllum hispanicum Spach on single or repeated local 12-O-tetradecanoylphorbol acetate (TPÄ ) administration and in the oxazolone-induced contact-delayed hypersensitivity mouse ear edemas. Two topi cal anti-inflammatory aryl naphthalide lignans were isolated from the active fractions of the methanol extract. They were identified by spectroscopic methods, including 13C NMR and heteronuclear multiple bond correlation (H M B C ), as diphyllin acetyl apioside and tubercu latin. The former was the most active on acute TPA edema with a ID 5 0 of 0.27 |a,mol/ear.
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