The potential of Triptolide as effective topical anti-inflammatory agent

Abstract

Inflammation is one of the characteristics in the psoriasis and the key in the therapy. The 5-lipoxygenase product, leukotriene B4 (LTB4), has been demonstrated to induce the key features associated with an acute inflammatory reaction including psoriasis. In the production of LTB4, there are two key enzymes, the upper one is 5-lipoxygenase, the other one is leukotriene A4 (LT A4) hydrolase. The purpose of the present study was to investigate some anti-inflammatory and anti-proliferative compounds, anthralin (ATL), Cyclosporin A (CyA), tretinoin (RA), clobetasol propionate (CP), methotrexate (MTX) and triptolide(TO), for their capacity to regulate 5-LO of circulating leukocyte and LTA4 hydrolase of cultured human epidermal cells. For 5-LO assay, leukocytes were incubated with ATL, CyA, RA, CP, MTX or TO, then 5-HETE and LTB4 formation were determined by RT-HPLC to estimate 5-LO activity or 5-LO mRNA was determined by RT-PCR to evaluate 5-LO content on transcriptional level. For LTA4 hydrolase assay, epidermal cell COLO 16 was incubated with ATL, CyA, RA, CP, MTX or TO, then LTB4 formation was determined by RT-HPLC to estimate LTA4 hydrolase activity or LTA4 hydrolase mRNA was determined by RT-PCR to evaluate LTA4 hydrolase content on transcriptional level. The results showed that ATL, CyA, RA and TO could inhibit 5-LO activity of circulating leukocyte in a dose-dependent way while no compounds influenced 5-LO content on transcriptional level. TO could inhibit LTA4 hydrolase activity in COLO 16 cell line while ATL could downregulate mRNA expression of LTA4 hydrolase in a dose-dependent pattern. The other compounds had no influence on LTA4 hydrolase at transcriptional level. In short, TO inhibits not only 5-LO also LTA4 hydrolase as well as ALT which is very effective in treating psoriasis as topical application. This study has indirectly proved the key role of LTA4 hydrolase in the pathological mechanism of psoriasis. And it also provides experimental data to support the LTA4 hydrolase as the therapeutic target of inflammatory agents and give a good future to triptolide as topic antipsoriatic drug.