9-Deoxymuzigadial, a Sesquiterpene Isolated From Drimys brasiliensis (Winteraceae), Displays Reduced Cytotoxicity In Vitro and Modulates Leukocyte Activity and Fibrogenesis In Vivo

Abstract

The aims of this study were to investigate in vitro cytotoxic potential and the effects of daily administration during the inflammatory response induced by sponge implants in mice of the sesquiterpene 9-deoxymuzigadial (9-DOM), isolated from Drimys brasiliensis (Winteraceae). Initially, 9-DOM showed no cytotoxic activity in RAW264.7 macrophages. In implants treated with 0.1 µg of 9-DOM, a reduction in macrophage activity and in the average number of mast cells were observed. In addition, a pro-fibrogenic effect was observed, with an increase in the synthesis and deposition of collagen, particularly thinner collagen fibers. None of the doses evaluated were able to alter the parameters associated with angiogenesis assessed. Although initial, the data demonstrates the low toxicity of 9-DOM and its possible therapeutic application in situations where exacerbated inflammation and low collagen synthesis and deposition can compromise tissue repair.