RESUMEN
Wound healing is a public health concern. Licorice gained a great attention for its antioxidant and anti-inflammatory properties which expand its valuable effects as a herbal medicine. In this study, we pointed out to the wound healing potential and the mechanism by which licorice alcoholic extract can modulate cutaneous wound healing through immune, antioxidant, histopathological, immunohistochemical (IHC) and molecular studies. 24 Wister rats were assigned into 3 groups (n = 8 each); control group, topical and oral supplied groups. Licorice extract administration significantly increased total and differential leucocyte counts, phagocytic activity of neutrophils, antioxidant biomarkers as superoxide dismutase (SOD), glutathione peroxidase activities (GPx) and reduced glutathione (GSH) content with a notable reduction in oxidative stress marker malondialdehyde (MDA). Moreover, histopathological findings detected complete re-epithelialization with increasing collagen synthesis while IHC results revealed a significant enhancement in the expression of α-SMA, PDGFR-α, FGFR1 and Cytokeratin 14 in licorice treated groups compared with the control group. Licorice extract supplementation accelerated wound healing by increasing angiogenesis and collagen deposition through up-regulation of bFGF, VEGF and TGF-ß gene expression levels compared with the control group. UPLC-PDA-MS/MS aided to authenticate the studied Glycyrrihza species and recognized 101 potential constituents that may be responsible for licorice-exhibited potentials. Based on our observations we concluded that licorice enhanced cutaneous wound healing via its free radical-scavenging potential, potent antioxidant activities, and anti-inflammatory actions. Therefore, licorice could be used as a potential alternative therapy for wound injury which could overcome the associated limitations of modern therapeutic products.
Asunto(s)
Inductores de la Angiogénesis/farmacología , Antiinflamatorios/farmacología , Antioxidantes/farmacología , Glycyrrhiza , Fitoquímicos/farmacología , Extractos Vegetales/farmacología , Piel/efectos de los fármacos , Cicatrización de Heridas/efectos de los fármacos , Heridas Penetrantes/tratamiento farmacológico , Inductores de la Angiogénesis/aislamiento & purificación , Proteínas Angiogénicas/genética , Proteínas Angiogénicas/metabolismo , Animales , Antiinflamatorios/aislamiento & purificación , Antioxidantes/aislamiento & purificación , Modelos Animales de Enfermedad , Regulación de la Expresión Génica , Glycyrrhiza/química , Mediadores de Inflamación/metabolismo , Masculino , Neovascularización Fisiológica/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Fitoquímicos/aislamiento & purificación , Extractos Vegetales/aislamiento & purificación , Ratas Wistar , Especies Reactivas de Oxígeno/metabolismo , Piel/lesiones , Piel/metabolismo , Piel/patología , Heridas Penetrantes/genética , Heridas Penetrantes/metabolismo , Heridas Penetrantes/patologíaRESUMEN
The larvae of Lucilia sericata have been used for centuries as medicinal maggots in the healing of wounds. The present study aimed to screen potential microRNAs related to ES-induced wound healing in rat skin wounds and to investigate the potential mechanisms contributing to accelerated wound healing. Healthy, male, 12 weeks old Wistar albino rats weighing 250-300 g were supplied by the Animal Experimental Center. All animal studies were performed in accordance with the NIH Guide for the Care and Use of Laboratory Animals. Wistar albino rats were treated by ES after post wounding and the differentially expressed miRNAs in wound biopsies were screened by microarray analysis at the end of treatments for 4,7 and 10 days. In addition, bioinformatics approaches were used to identify the potential target genes of differentially expressed miRNAs and the functions of their target genes. We found a significant up-regulation of rno-miR-99a* and rno-mir-877 in response to ES treatment. Further investigation of rno-miR-99a* and rno-mir-877 and their target genes (TGFa, TNF, TAGLN, MAPK1, MMP-9) implicated in present study could provide new insight for an understanding lead to the development of new treatment strategies. The identified miRNAs can be new biomarkers for ES- induced wound healing.
Asunto(s)
Secreciones Corporales/química , Terapias Complementarias/métodos , MicroARNs/genética , Cicatrización de Heridas/genética , Heridas Penetrantes/terapia , Animales , Secreciones Corporales/metabolismo , Biología Computacional/métodos , Dípteros/química , Dípteros/fisiología , Perfilación de la Expresión Génica , Regulación de la Expresión Génica , Larva/química , Larva/fisiología , Masculino , Metaloproteinasa 9 de la Matriz/genética , Metaloproteinasa 9 de la Matriz/metabolismo , MicroARNs/metabolismo , Proteínas de Microfilamentos/genética , Proteínas de Microfilamentos/metabolismo , Proteína Quinasa 1 Activada por Mitógenos/genética , Proteína Quinasa 1 Activada por Mitógenos/metabolismo , Proteínas Musculares/genética , Proteínas Musculares/metabolismo , Ratas , Ratas Wistar , Factor de Crecimiento Transformador alfa/genética , Factor de Crecimiento Transformador alfa/metabolismo , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/metabolismo , Heridas Penetrantes/genética , Heridas Penetrantes/patologíaRESUMEN
Despite the large use of the Plantago major and Siparuna guianensis in traditional medicine, there are no studies demonstrating the effectiveness from extracts of these plants in the healing process by the present methodology. This study reported the effects and toxicity of the P. major and S. guianensis extracts in the wound healing compared with a commercial product used in Brazil by macroscopic and microscopic analysis. Following injury in cervical dorsal area of the mice, the extract from P. major and S. guianensis and ointment was applied after an injury in cervical dorsal area of the mice. Wound healing rates were calculated at 4, 9, 15 and 21 d after the wounding, and tissues were obtained on the ninth day for histological analysis. Moreover, mutagenic assay of extracts was performed. Mutagenicity studies carried out with plant extracts showed not mutagenic with or without metabolic activations. Reduction of the wound area occurred earlier in mice treated with P. major and control treatment. On the 15th day, the complete wound closure occurred in P. major-treated wounds. Throughout ointment and S. guianensis treatment it was not observed the wound closured. Microscopic analyses of the wound, on the ninth day, showed the more efficient formation of the neoepithelium and skin appendages in animals treated with S. guianensis and P. major, while ointment treatment presented no re-epithelialization and absent skin appendages in wound. Thus, P. major extract showed good effects on wound healing processes rendering it a promising candidate for the treatment of wounds what also justified its traditional usage in wound treatment.