Abstract
In this study, we aimed to evaluate the immunomodulatory effects of crude leaf extracts from Piper gaudichaudianum Kunth, P. arboreum Aub., P. umbellata L., P. fuligineum Kunth, and Peperomia obtusifolia A. Dietr. on an in vitro model of inflammatory response. The crude extracts were previously obtained by maceration of the leaves. The half-maximal inhibitory concentration was determined by the MTT assay using human peripheral blood mononuclear cells. Human monocytes were simultaneously challenged with each crude extract and lipopolysaccharide (LPS), the major component of the outer membrane of Gram-negative bacteria, to induce a strong inflammatory response. After 24 h of incubation, cell-free supernatants were used for evaluating the mediators involved in inflammation: H2O2, TNF-α, IL-8, IL-6, IL-1β, IL-10, IL-12, FGF-b, and TGF-β1. We also compared the results with the effects of ketoprofen, a well-known anti-inflammatory drug. The P. gaudichaudianum crude extract downmodulated the production of H2O2, IL-1β, IL-6, IL-8, and TGF-β1 by LPS-stimulated monocytes; P. arboreum, IL-1β, IL-6, IL-8, and TNF-α; P. umbellata and P. fuligineum, H2O2, IL-1β, IL-6, IL-8, IL-10, and TNF-α; and P. obtusifolia, H2O2, IL-6, IL-8, IL-10, and TNF-α. In general, the crude leaf extracts amplified the anti-inflammatory response when compared with ketoprofen, particularly reducing the production of IL-8, a mediator involved in neutrophil recruitment during tissue damage. Thus, the crude leaf extracts of P. gaudichaudianum, P. arboreum, P. umbellata, P. fuligineum, and Peperomia obtusifolia elicited an anti-inflammatory response against LPS-challenged monocytes. These findings show the anti-inflammatory properties of these crude leaf extracts and offer new perspectives for their use in the treatment of inflammatory diseases.
Highlights
The family Piperaceae comprises pantropical herbal plants, widely distributed in Latin America, from Mexico to the southwest of Argentina [1,2,3]
To evaluate the effects of crude leaf extract on an inflammatory milieu, we first evaluated the influence of each crude extract on human monocytes without an inflammatory stimulus, i.e., we verified if the crude extracts triggered any alteration in monocyte activity at baseline condition, and we compared the effects of the crude extracts with those of ketoprofen
To the best of our knowledge, we demonstrated for the first time, in this study, that all of the evaluated crude leaf extracts induced anti-inflammatory activity that was more potent than that of ketoprofen
Summary
The family Piperaceae comprises pantropical herbal plants, widely distributed in Latin America, from Mexico to the southwest of Argentina [1,2,3]. The potent inhibitory effect of kavalactones in P. fuligineum against hepatitis C virus replication was recently described [30] Their potential anti-inflammatory and anxiolytic properties were described [31]. The accumulation of prenylated chromenes and chromanes with potent trypanocidal activity against the Y-strain of Trypanosoma cruzi was observed in P. gaudichaudianum and Peperomia obtusifolia [18,20,21]. Chemical studies with P. gaudichaudianum demonstrated the presence of gaudichaudianic acid, a prenylated chromene that is a major secondary metabolite in leaves and roots of this species [18,19]. The unusual presence of two natural isomeric forms of gaudichaudianic acid [(+)-S and (-)-R] was observed during the isolation of such compounds, as well as their synergistic effect, with the racemic mixture being the most active in trypanocidal assays [20]
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