OBJECTIVE: The present study evaluates the anti-inflammatory effect of the quinoline alkaloid skimmianine (SKM), isolated from Ruta graveolens L., against carrageenan-induced acute inflammation. METHODS: SKM at a dose of 5.0 mg/kg body weight was found to be the minimal concentration for maximal edema inhibition. Carrageenan suspension was administered into the sub-plantar tissue of the right hind paw 1 h after SKM and diclofenac (20 mg/kg) administration (i.p.). Paw edema was determined 3 h after carrageenan administration. The rats were then killed and mRNA expressions of TNF-α and IL-6, levels of PGE2 and TBARS, activities of COX-2, 5-LOX, SOD, catalase, glutathione peroxidase (GPx) and myeloperoxidase (MPO) and the level of nitrite were measured. RESULTS: SKM treatment resulted in a decrease in the mRNA levels of TNF-α and IL-6, which are upstream events of the inflammatory cascade. The levels of PGE2 and NO and the activities of COX-2 and 5-LOX were also significantly reduced after SKM treatment. Neutrophil infiltration, lipid peroxidation and associated oxidative stress in the paw tissue were reduced following SKM treatment. CONCLUSION: These results support the anti-inflammatory properties of skimmianine and its multi-targeted mechanism of action, suggesting its potential therapeutic efficacy in various inflammatory diseases.
OBJECTIVE: The present study evaluates the anti-inflammatory effect of the quinoline alkaloid skimmianine (SKM), isolated from Ruta graveolens L., against carrageenan-induced acute inflammation. METHODS:SKM at a dose of 5.0 mg/kg body weight was found to be the minimal concentration for maximal edema inhibition. Carrageenan suspension was administered into the sub-plantar tissue of the right hind paw 1 h after SKM and diclofenac (20 mg/kg) administration (i.p.). Paw edema was determined 3 h after carrageenan administration. The rats were then killed and mRNA expressions of TNF-α and IL-6, levels of PGE2 and TBARS, activities of COX-2, 5-LOX, SOD, catalase, glutathione peroxidase (GPx) and myeloperoxidase (MPO) and the level of nitrite were measured. RESULTS:SKM treatment resulted in a decrease in the mRNA levels of TNF-α and IL-6, which are upstream events of the inflammatory cascade. The levels of PGE2 and NO and the activities of COX-2 and 5-LOX were also significantly reduced after SKM treatment. Neutrophil infiltration, lipid peroxidation and associated oxidative stress in the paw tissue were reduced following SKM treatment. CONCLUSION: These results support the anti-inflammatory properties of skimmianine and its multi-targeted mechanism of action, suggesting its potential therapeutic efficacy in various inflammatory diseases.
Authors: Carolina de la Guardia; David E Stephens; Hang T Dang; Mario Quijada; Oleg V Larionov; Ricardo Lleonart Journal: Molecules Date: 2018-03-16 Impact factor: 4.411