7-Epiclusianone, the Natural Prenylated Benzophenone, Inhibits Superoxide Anions in the Neutrophil Respiratory Burst

Abstract

Despite defenses by polymorphonuclear neutrophils in the host against invading agents, overproduction of oxidant species by phagocytes can lead to damage in the surrounding tissues. Several benzophenones have been shown to possess anti-inflammatory properties. The effect of the natural benzophenone 7-epiclusianone isolated from leaves of Garcinia brasiliensis was investigated by using in vitro antioxidant and ex vivo anti-inflammatory assays, focusing on the neutrophil respiratory burst and on the biochemical pathways involved. The bioactive extract, 7-epiclusianone, showed low in vitro antioxidant activity as evaluated by the 2,2-diphenyl-1-picrylhydrazyl free radical scavenging assay, the reducing power test, or the chelating power assay. However, the benzophenone displayed potent activity in the ex vivo model of the neutrophil respiratory burst, inhibiting the generation of superoxide anions in a dose-dependent manner. When the respiratory burst was triggered by N-formyl-methionyl-leucyl-phenylalanine, a chemotactic peptide, the 50% effective concentration (EC(50)) was 41.18 μg/10(7) cells. When phagocytes were stimulated directly through protein kinase C via phorbol, the EC(50) was 34.3 μg/10(6) cells. The results indicated that 7-epiclusianone was able to down-regulate inflammatory phagocyte superoxide anion release through a mechanism controlled by tyrosine protein phosphorylation and by a direct stimulation of protein kinase C. These findings could lead to new therapeutic approaches for inflammation management and the development of new drugs.

Antiproliferative Activity and Antioxidant Potential of Extracts of Garcinia gardneriana

“…The observed results, showing the presence in both fruits and leaves of flavonoids, biflavonoids, catechins, xanthones, and others, corroborate the importance of phenolic compounds as promising active components. For several of the compounds found in the extracts of fruits and leaves, studies have attributed the following bioactive potentials: Antioxidant [33][34][35], antiproliferative, and apoptotic [36,37].…”

“…The ethanolic extracts were dissolved in methanol to obtain a concentration of 0.5 mg/solids/mL −1 and then analyzed. The total amount of phenols in each extract was quantified using a standard curve prepared with gallic acid and expressed as gallic acid equivalent (GAE) [37].…”

Antioxidant, cytotoxic and antimutagenic activities of 7-epi-clusianone obtained from pericarp of Garcinia brasiliensis

“…In this context, it is not always noted that antioxidant values are determinants of the antimutagenic potential of products. A study by Santa-Cecília et al (2012) with MI has shown that, even as low antioxidant activity, the MI was able to down regulate inflammatory phagocyte superoxide anion release through a mechanism controlled by protein tyrosine phosphorylation and by the direct stimulation of the protein kinase C.…”

Anticancer activity of 7-epiclusianone, a benzophenone from Garcinia brasiliensis, in glioblastoma

“…7-epiclusianone has shown important biological effects including anti-inflammatory [ 7 , 8 ], antinociceptive [ 7 , 9 ], antimicrobial [ 10 , 11 ], antispasmodic [ 12 ], antianaphylactic [ 13 ] and antiprotozoal activities [ 14 ]. On the other hand, the potential anticancer and apoptotic effect is underexplored.…”