OBJECTIVE AND DESIGN: We have investigated the mechanisms of action of aethiopinone, an anti-inflammatory compound from Salvia aethiopis L. roots. MATERIAL AND SUBJECTS: Human neutrophils from healthy volunteers and murine peritoneal macrophages. Swiss mice were randomly divided into groups of six animals. TREATMENT: Test compounds were applied topically in the mouse ear oedema test. In the air pouch, mice received aethiopinone (0.001-0.5 pmol/pouch or 12.5-50 mg/kg p.o.). METHODS: LTB4 production was assayed in human neutrophils and COX-2 and iNOS activities in murine macrophages. Air pouches were induced subcutaneously in mice and injected with zymosan on the day six. Mouse ear oedema was induced by arachidonic acid. Dunnett's t-test was employed for statistical analysis. RESULTS: We have observed potent inhibitory effects on human neutrophil LTB4 production without effects on COX or NOS activities. Aethiopinone is an in vitro inhibitor of 5-LO from human neutrophils (IC50 = 0.11 microM). In addition, aethiopinone reduced leukocyte accumulation and showed in vivo inhibitory activity on this enzyme. CONCLUSIONS: Our results indicate that inhibition of 5-LO could participate in the anti-inflammatory properties of this natural product.
OBJECTIVE AND DESIGN: We have investigated the mechanisms of action of aethiopinone, an anti-inflammatory compound from Salvia aethiopis L. roots. MATERIAL AND SUBJECTS:Human neutrophils from healthy volunteers and murine peritoneal macrophages. Swiss mice were randomly divided into groups of six animals. TREATMENT: Test compounds were applied topically in the mouseear oedema test. In the air pouch, mice received aethiopinone (0.001-0.5 pmol/pouch or 12.5-50 mg/kg p.o.). METHODS: LTB4 production was assayed in human neutrophils and COX-2 and iNOS activities in murine macrophages. Air pouches were induced subcutaneously in mice and injected with zymosan on the day six. Mouseear oedema was induced by arachidonic acid. Dunnett's t-test was employed for statistical analysis. RESULTS: We have observed potent inhibitory effects on human neutrophil LTB4 production without effects on COX or NOS activities. Aethiopinone is an in vitro inhibitor of 5-LO from human neutrophils (IC50 = 0.11 microM). In addition, aethiopinone reduced leukocyte accumulation and showed in vivo inhibitory activity on this enzyme. CONCLUSIONS: Our results indicate that inhibition of 5-LO could participate in the anti-inflammatory properties of this natural product.
Authors: Victor Kenyon; Ganesha Rai; Ajit Jadhav; Lena Schultz; Michelle Armstrong; J Brian Jameson; Steven Perry; Netra Joshi; James M Bougie; William Leister; David A Taylor-Fishwick; Jerry L Nadler; Michael Holinstat; Anton Simeonov; David J Maloney; Theodore R Holman Journal: J Med Chem Date: 2011-07-08 Impact factor: 7.446
Authors: Maria Carla Marcotullio; Federica Messina; Massimo Curini; Antonio Macchiarulo; Marco Cellanetti; Donata Ricci; Laura Giamperi; Anahi Bucchini; Alba Minelli; Anna Lisa Mierla; Ilaria Bellezza Journal: Molecules Date: 2011-12-14 Impact factor: 4.411