New insights into the roles of myofibroblasts and innervation during skin healing and innovative therapies to improve scar innervation.

During the resolution phase of normal skin wound healing, there is a considerable loss of various cell types, including myofibroblasts by apoptosis. Inappropriate delay of apoptosis, and thus increased survival of myofibroblasts, may be a factor leading to pathologies and excessive scarring. Considerable data now clearly suggest that innervation plays a major role in wound healing, including the modulation of fibroblast cellular activity. An abnormal level of neuromediators is implicated not only in the development of chronic wounds but also in excessive scar formation. Understanding interactions between neuromediators and myofibroblasts, allowing normal reinnervation and having adequate levels of neuromediators during the healing process are clearly important to avoid the appearance of pathological healing or fibrosis/scarring. The aim of this review was first to discuss the mechanisms leading to normal or excessive scarring and then to present the roles of innervation during wound healing. Finally, the latest therapeutic strategies to help wound repair and reinnervation after skin damage will be introduced. Advantages and limitations in the use of neuropeptides, growth factors and biomaterials will be discussed as well as the most recent studies on electrostimulation and the potential of targeting resident skin mesenchymal stem cells.

Antioxidant and anti-inflammatory effects of Ruta chalepensis L. extracts on LPS-stimulated RAW 264.7 cells.

Ruta chalepensis L. is used in the traditional herbal treatment of various diseases. The aim of this work is to investigate the effect of different extracts of R. chalepensis L. on inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) gene expressions and their antioxidant capacity on murine RAW 264.7 macrophage challenged with lipopolysaccharide (LPS). In fact, this study shows that the ethanol and ethyl acetate extracts of R. chalepensis L. considerably decreased the nitric oxide (NO) production in murine RAW 264.7 macrophages stimulated with lipopolysaccharide. Thus, the treatment with both extracts significantly suppressed the levels of iNOS and COX-2 gene expressions through the inhibition of the nuclear factor-κB (NF-κB) activation. The preincubation of RAW 264.7 cells with various concentrations of ethanol and ethyl acetate extracts decreased the production of thiobarbituric acid-reactive substances (TBARS) in a dose-dependent manner. It also increased the activities of antioxidative enzymes, including superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) in LPS-stimulated macrophages, compared to those in the cells treated only with LPS. Besides, the (1)H NMR spectra of both extracts have demonstrated the presence of aromatic signals, thus confirming the existence of phenolic compounds such as flavonoids and polyphenols. So, the ethanol and ethyl acetate extracts of R. chalepensis L. have been shown to possess enough antioxidant and anti-inflammatory activities to prevent LPS-induced oxidative stress and inflammation in RAW 264.7 macrophages.

Effects of sangre de drago in an in vitro model of cutaneous neurogenic inflammation.

Sangre de drago (SD) is a viscous bright red resin collected from Croton lechleri trees that grow in the South American jungle. This sap is used extensively in the native pharmacopoeia to treat skin disorders. Its effectiveness as an inhibitor of neurogenic inflammation has been recently demonstrated. To understand the underlying mechanisms of these effects, we examined the ability of SD to reduce substance P (SP) release in an in vitro model of cutaneous neurogenic inflammation (CNI). This model is based on an enzyme immunoassay of SP (an inducer of CNI) in a porcine co-culture of dorsal root ganglion neurons and keratinocytes. After incubation with different concentrations of SD, we noted an immediate and significant dose-dependent decrease in basal SP release, with average values of 32% at 1% SD (v/v) and 26% at 0.1% (v/v). On the other hand, pretreatment (72 or 1 h) of the co-culture with 1% SD (v/v) was sufficient to induce a 111% (72 h) or 65% (1 h) inhibition of capsaicin-induced SP release, while 0.1% SD (v/v) triggered a 109% (72 h) or 30% (1 h) inhibition. We conclude that sangre de drago is a potent inhibitor of CNI through direct inhibition of neuropeptide release by sensory afferent nerves.