RESUMEN
Coffea canephora plant stem cells can have bioactive compounds with tissue repairing and anti-inflammatory action. This study aimed to develop a liposomal stem cell extract formulation obtained from the leaves of C. canephora (LSCECC) and to investigate its capacity to contribute to the dynamic mechanisms of tissue repair. The liposome cream was developed and characterized through the dynamic light scattering technique, atomic force microscopy, and transmission electron microscopy. The excisional full-thickness skin wound model was used and daily topically treated with the LSCECC formulation or vehicle control. On days 2, 7, 14, and 21 after wounding, five rats from each group were euthanized and the rates of wound closure and re-epithelialization were evaluated using biochemical and histological tests. LSCECC resulted in faster re-epithelialization exhibiting a significant reduction in wound area of 36.4, 42.4, and 87.5% after 7, 10, and 14 days, respectively, when compared to vehicle control. LSCECC treated wounds exhibited an increase in granular tissue and a proper inflammatory response mediated by the reduction of pro-inflammatory cytokines like TNF-α and IL-6 and an increase of IL-10. Furthermore, wounds treated with LSCECC showed an increase in the deposition and organization of collagen fibers at the wound site and improved scar tissue quality due to the increase in transforming growth factor-beta and vascular endothelial growth factor. Our data showed that LSCECC improves wound healing, the formation of extracellular matrix, modulates inflammatory response, and promotes neovascularization being consider a promising bioactive extract to promote and support healthy skin. The graphical presents the action of LSCECC in all four phases of wound healing and tissue repair. The LSCECC can reduce the inflammatory infiltrate in the inflammatory phase by decreasing the pro-inflammatory cytokines like IL-6 and TNF-α, in addition to maintaining this modulation through lesser activation and recruitment of macrophages. The LSCECC can also increase the release of IL-10, an anti-inflammatory cytokine, decreasing local edema. The increase in VEGF provides neovascularization and the supply of nutrients to newly repaired tissue. Finally, signaling via TGF-ß increases the production and organization of collagen fibers in the remodeling phase.
Asunto(s)
Coffea , Interleucina-10 , Ratas , Animales , Interleucina-10/metabolismo , Coffea/metabolismo , Extractos Celulares , Factor de Necrosis Tumoral alfa/metabolismo , Interleucina-6/metabolismo , Factor A de Crecimiento Endotelial Vascular , Liposomas/metabolismo , Cicatrización de Heridas/fisiología , Piel/patología , Citocinas/metabolismo , Antiinflamatorios/farmacología , Colágeno/metabolismoRESUMEN
The benefits of kefir consumption are partially due to the rich composition of bioactive molecules released from its fermentation. Angiotensin-converting enzyme (ACE) inhibitors are bioactive molecules with potential use in the treatment or prevention of hypertension, heart failure, and myocardial infarction. Here, the in vivo actions of the Kef-1 peptide, an ACE inhibitor derived from kefir, were evaluated in an angiotensin II-dependent hypertension model. The Kef-1 peptide showed a potential anti-hypertensive effect. Additionally, Kef-1 exhibited systemic antioxidant and anti-inflammatory activities. In smooth muscle cells (SMCs), the Kef-1 peptide decreased ROS production through the reduced participation of NADPH oxidase and mitochondria. The aorta of 2K1C mice treated with Kef-1 showed lesser wall-thickening and partial restoration of the endothelial structure. In conclusion, these novel findings highlight the in vivo biological potential of this peptide demonstrating that Kef-1 may be a relevant nutraceutical treatment for cardiovascular diseases.
Asunto(s)
Inhibidores de la Enzima Convertidora de Angiotensina/farmacología , Inflamación/metabolismo , Kéfir , Estrés Oxidativo/efectos de los fármacos , Péptidos/farmacología , Animales , Antihipertensivos/farmacología , Aorta/efectos de los fármacos , Aorta/patología , Células Cultivadas , Masculino , Ratones , Ratones Endogámicos C57BL , Miocitos del Músculo Liso/citologíaRESUMEN
Sildenafil (SIL) has potential as an interesting gastroprotective drug. However, the pathways of its protective effect still needs to be clarified, and its use as a potential gastroprotective agent validated. This study aims to evaluate the effects of SIL via modulation of oxidative stress in a NSAID-induced gastric lesion model. Male Swiss mice were divided into six groups: control (CON, water), nonsteroidal anti-inflammatory drug (NSAID, water), proton pump inhibitor (PPI, 30 mg/kg of lansoprazole), SIL 5 (5 mg/kg), SIL 25 (25 mg/kg) and SIL 50 (50 mg/kg). The animals were treated by gavage (a single dose) after 24 hours of fasting, and gastric lesions were performed after 30 minutes, with indomethacin (40 mg/kg, by gavage). After 6h, the animals were killed and the stomach was removed to evaluate reactive oxygen species (ROS) production, oxidation of macromolecules, quantification of antioxidant enzymes, DNA fragmentation, apoptosis and macroscopic and histologic analysis of gastric lesions. SIL exerts a dose-dependent gastroprotective effect against NSAID-induced mucosal injury, also reducing cytoplasmic levels of ROS and consequent oxidative damage to macromolecules. In addition, SIL increases nitric oxide bioavailability, antioxidant enzymes and gastric cellular viability, as well as restoring important factors involved in gastroprotection. Our results demonstrate that different doses of SIL prevent indomethacin-induced gastric ulcer in mice via different, but complementary antioxidant, antigenotoxic and antiapoptotic mechanisms.
Asunto(s)
Antioxidantes , Úlcera Gástrica , Animales , Antiinflamatorios no Esteroideos , Masculino , Ratones , Citrato de SildenafilRESUMEN
This work aimed to evaluate the in vivo capacity of a vegetable oil blend formulation (VOB) developed to accelerate cutaneous wound closure. Total thickness wounds were punctured on the skin on the back side of each animal and topically treated with the VOB formulation, Dersani® ointment or the vehicle control. After 2, 7, 14, 21 days post-wounding, five animals from each group were euthanized, and the rates of wound closure and re-epithelialization were evaluated. The wounds were harvested for histological and biochemical analysis. VOB resulted in faster and greater re-epithelialization in the in vivo excisional wounds, exhibiting significant wound area reduction of 8.9, 8.0, 35.1, 45.2 and 47.0% after 2, 5, 10, 14 and 21 days post-wounding, respectively, when compared with the vehicle control. Histological and biochemical analyses showed that the VOB-treated wounds exhibited a significant increase of granular tissue and controlled inflammatory response by modulation of the release of pro-inflammatory cytokines TNF-α, IL-6 and IL-1. Moreover, VOB-treated wounds showed a significant and concrete increase in the deposition and organisation of collagen fibres in the wound site and improved the quality of the scar tissue. Altogether, these data revealed that VOB accelerates wound healing processes and might be beneficial for treating wound disorders.