α-zingiberene, a sesquiterpene from essential oil from leaves of Casearia sylvestris, suppresses inflammatory angiogenesis and stimulates collagen deposition in subcutaneous implants in mice.

α-zingiberene is a phytochemical of the sesquiterpenes class, the major constituent of the essential oil from the leaves of Casearia sylvestris, a plant widely used in traditional medicine for the treatment of inflammatory diseases, tumours, and bacterial infections. In the present study, we evaluated the effects of daily administration of α-zingiberene (0.01, 0.1 and 1 µg diluted in 10 µl of 0.5% DMSO) on the inflammatory, angiogenic, and fibrogenic components, induced by subcutaneous sponge implants in an animal model. Treatment with sesquiterpene resulted in a reduction in macrophage activation, as well as in mean blood vessels and in the activity of metalloproteinases 2 and 9. Furthermore, it resulted in an increase in collagen deposition near the implants. These results show the therapeutic potential of α-zingiberene in the treatment of pathologies, in which processes such as inflammation and angiogenesis are exacerbated, or even for the treatment of chronic wounds.

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

BACKGROUND AND AIM: Maytenus ilicifolia has analgesic, healing, antioxidant and anti-inflammatory properties. This study evaluated effect of the hydroalcoholic extract of M. ilicifolia leaves on skin wound repair. EXPERIMENTAL PROCEDURE: Wounds were induced on mice and treated with the extract. The treatment was performed daily, until day 7 after wound induction. Wound closure was measured and the features of the repaired tissue were investigated, including mast cell quantification, neutrophil and macrophage activities, collagen deposition, angiogenesis, and pro-metalloproteases and metalloproteases 2 and 9 activity (pro-MMPs and MMPs). RESULTS AND CONCLUSION: The M. ilicifolia extract accelerated the closure of wounds. The extract at a concentration of 4% was found to be effective, presenting anti-inflammatory effects and hemoglobin increased, along with increased soluble, total and type III collagens in the wound. In addition, there was an increase in pro-MMP9 and MMP9 activity after day 7th of treatment. The phenolic compounds and tannins present in this plant could be associated with the anti-inflammatory and healing activities observed in this study. Therefore, the ability to modulate essential parameters for accelerated and adequate healing as shown here suggests that the use of standardised extracts of M. ilicifolia and its fractions enriched in polyphenols may represent a therapeutic strategy for the treatment of wounds.

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

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-ß-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-ß1 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.

DisBa-01 inhibits angiogenesis, inflammation and fibrogenesis of sponge-induced-fibrovascular tissue in mice.

Integrins are involved in a number of physio-pathological processes including wound healing, chronic inflammation and neoplasias. Blocking its activity is potentially of therapeutic value in these conditions. We investigated whether DisBa-01, a recombinant His-tag RGD-disintegrin from Bothrops alternatus snake venom, could modulate key events (inflammatory cell recruitment/activation, neovascularization and extracellular matrix deposition) of the proliferative fibrovascular tissue induced by polyether polyurethane sponge implants in mice. The hemoglobin content (µg/mg wet tissue), blood flow measurements (laser Doppler perfusion imaging) and number of vessels in the implants, used as indices of vascularization, showed that the disintegrin dose-dependently reduced angiogenesis in the implants relative to the Saline-treated group. DisBa-01 inhibited neutrophil and macrophage content as determined by the myeloperoxidase (MPO) and N-acetyl-ß-D-glucosaminidase (NAG) activities, respectively. Similarly, down regulation of the fibrogenic component studied (collagen deposition) was observed in DisBa-01-treated implants. VEGF, bFGF, TNF-α, CXCL1 and CCL2 levels were also decreased by the disintegrin. The inhibitory effect of this αvß3-blocking disintegrin on the angiogenic, inflammatory, and fibrogenic components of the fibrovascular tissue induced by the synthetic matrix extends the range of DisBa-01 actions and may indicate its therapeutic potential in controlling angiogenesis in fibroproliferative diseases.

Alterations of antioxidant biomarkers and type I collagen deposition in the parotid gland of streptozotocin-induced diabetic rats.

BACKGROUND AND OBJECTIVE: Acarbose is a competitive inhibitor of intestinal alpha-glycosidases that slows the breakdown of sucrose and starch, thereby reducing glucose and fructose absorption. The aim of this study was to evaluate the effect of acarbose treatment on antioxidant parameters and deposition of type I collagen in the parotid glands of diabetic rats. METHODS: Diabetes mellitus was induced by intravenous injection of streptozotocin, and rats were divided into four groups: non-diabetic (NDM), diabetic (DM), diabetic treated with 25mg/kg acarbose (DMA) and non-diabetic treated with acarbose (NDMA). Changes in enzymatic antioxidant systems, such as the activity of SOD and GPx enzymes, were evaluated, and the specific staining pattern of the type I collagen fibres was investigated in the rat parotid glands. RESULTS: The DM group presented high levels of SOD and GPx enzymes, which were reduced by acarbose treatment. Tissue damage, which was indicated by an increased MDA concentration in the parotid glands of rats in the DM group, was also reversed in the DMA group. Moreover, type I collagen fibres from DM rats were more intensely stained than those of NDM rats. Acarbose treatment was effective in decreasing collagen deposition, which was shown by a decrease in staining intensity of approximately 25%. CONCLUSIONS: These results suggest that the diabetic state influences the type I collagen concentration in the parotid glands of rats. In addition, acarbose treatment was helpful in preventing the deposition of such fibres, as well the increase in oxidative stress induced by hyperglycemia.