Sesquiterpene Polygodial from Drimys brasiliensis (Winteraceae) Down-Regulates Implant-Induced Inflammation and Fibrogenesis in Mice

Abstract

Drimys brasiliensis (Winteraceae) has been investigated in traditional medicine for its anti-inflammatory properties to treat gastric ulcers and allergic and respiratory system diseases as well as for cancer treatment. In this work, we investigate the ability of the sesquiterpene polygodial, isolated from D. brasiliensis stem barks, to modulate the chronic inflammatory response induced by polyester-polyurethane sponge implants in C57BL/6J mice. Daily treatment with polygodial inhibited the macrophage content in the implants as determined by the activity of the N-acetyl-β-d-glucosaminidase enzyme as well as decreased the levels of CXCL1/KC and CCL2/JE/MCP-1 pro-inflammatory chemokines and the presence of mast cells along the formed fibrovascular tissue. Similarly, the deposition of a new extracellular matrix (total collagen and type I and III collagen fibers) as well as the production of the TGF-β1 cytokine were attenuated in implants treated with polygodial, showing for the first time its antifibrogenic capacity. The hemoglobin content, the number of newly formed vessels, and the levels of VEGF cytokine, which were used as parameters for the assessment of the neovascularization of the implants, did not change after treatment with polygodial. The anti-inflammatory and antifibrogenic effects of polygodial over the components of the granulation tissue induced by the sponge implant indicate a therapeutic potential for the treatment of inflammatory diseases associated with the development of fibrovascular tissue.

An In Vivo Assessment of the Effect of Hexane Extract from Endlicheria paniculata Branches and Its Main Compound, Methyldehydrodieugenol B, on Murine Sponge-Induced Inflammation

“…The implants (n = 6 for each group, Table S3 ) were excised carefully, fixed in methacarn (60% MeOH, 30% CHCl 3 , 10% acetic acid, v / v ) at 4 °C for 24 h, and embedded in paraffin. The analyses were performed as described in previous studies [ 42 , 43 ]. Briefly, twenty-five sequential fields were captured from the histological sections (5 µm) and stained with hematoxylin and eosin (H and E) or toluidine blue using a LEICA ICC50 microcamera.…”

Wound healing activity of the hydroethanolic extract of the leaves of Maytenus ilicifolia Mart. Ex Reis

“…Histological sections were stained with 0.25% Toluidine Blue in a MacIlvaine pH 4.0 to determine the number of mast cells. 29 Ten areas of the wound were analyzed per animal. Photomicrographs were obtained with 400X magnification (40X objective) in Leica Microscope ICC50 (Leica Microsystems).…”

“…The slides obtained were stained with Sirius Red for quantification of total collagen and type I and III collagen. 29 , 35 , 36 For total collagen quantification, photomicrographs were obtained with 200X magnification (20X objective) in Nikon TS 100 microscope with Optcam microcamera system. For collagen I and III quantification, a polarization filter was used.…”