Crude leaf extracts of Piperaceae species downmodulate inflammatory responses by human monocytes.

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-1ß, IL-10, IL-12, FGF-b, and TGF-ß1. 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-1ß, IL-6, IL-8, and TGF-ß1 by LPS-stimulated monocytes; P. arboreum, IL-1ß, IL-6, IL-8, and TNF-α; P. umbellata and P. fuligineum, H2O2, IL-1ß, 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.

Phenolic compounds alone or in combination may be involved in propolis effects on human monocytes.

OBJECTIVES: Propolis is a natural product with a complex chemical composition. Its isolated compounds exert biological activities; however, its synergistic effects are unknown. The involvement of phenolic acids (caffeic - Caf, dihydrocinnamic - Cin and p-coumaric - Cou) alone or in combination was investigated in the action of propolis in human monocytes. METHODS: Cell viability was analysed by MTT assay; TNF-α, IL-6 and IL-10 production by enzyme-linked immunosorbent assay (ELISA); cell markers expression by flow cytometry; colony-forming units were counted to assess the microbicidal activity; and H2 O2 production was analysed by colorimetric assay. KEY FINDINGS: Treatments did not affect monocytes viability. Propolis and combinations containing Caf enhanced TNF-α production by resting cells. Propolis, Cin, Cou and Caf + Cin stimulated IL-6 production. All treatments upregulated IL-10. In LPS-stimulated cells, treatments downregulated IL-6 and maintained TNF-α and IL-10 production. A lower TLR-2 expression was seen than propolis. Caf + Cin enhanced TLR-4 expression. Propolis, Caf and Caf + Cin stimulated H2 O2 production, whereas propolis, Cin, Cou, and Caf + Cin + Cou induced a higher fungicidal activity. Cin and Cin + Cou increased the bactericidal activity of human monocytes. CONCLUSION: Propolis activated human monocytes, and acids were involved differently in propolis activity.

Immunomodulatory/anti-inflammatory effects of a propolis-containing mouthwash on human monocytes.

Propolis is a bee product used in folk medicine to improve health and prevent inflammatory diseases. It has attracted the attention of researchers from the odontological field lately, reducing inflammation resulting from surgical procedures and as an antimicrobial agent in the control of bacterial plaque. Thus far, no side-effects that might compromise oral health have been observed. Chlorhexidine is an antimicrobial agent widely used as an antiseptic, but side-effects restrict its use. This work investigated the effects of an odontological product containing propolis in combination with chlorhexidine in lower concentrations on human monocytes. Cell marker expression, the nuclear factor kappa B (NF-κB) signaling pathway, the production of pro- and anti-inflammatory cytokines, and the bactericidal activity of these cells against Streptococcus mutans were evaluated. Data showed that the combination of propolis and chlorhexidine may favor the recognition of antigens by monocytes, slightly activates the NF-κB signaling pathway, and increases the bactericidal activity of human monocytes against S. mutans Also, the combination played a role in anti-inflammatory cytokine production, which can be beneficial in the treatment of periodontal diseases. These results may have implications for the development of odontological products with immunomodulatory/anti-inflammatory action, and may have further-reaching implications for the pharmaceutical industry.

Cinnamic Acid is partially involved in propolis immunomodulatory action on human monocytes.

Propolis is a beehive product used in traditional medicine due to its biological properties. It shows a complex chemical composition including phenolics, such as cinnamic acid (Ci). The mechanisms of action of propolis have been the subject of research recently; however, the involvement of Ci on propolis activity was not investigated on immune cells. Ci effects were evaluated on human monocytes, assessing the expression of Toll-like receptors (TLRs), HLA-DR, and CD80. Cytokine production (TNF- α and IL-10) and the fungicidal activity of monocytes were evaluated as well. Data showed that Ci downregulated TLR-2, HLA-DR, and CD80 and upregulated TLR-4 expression by human monocytes. High concentrations of Ci inhibited both TNF- α and IL-10 production, whereas the same concentrations induced a higher fungicidal activity against Candida albicans. TNF- α and IL-10 production was decreased by blocking TLR-4, while the fungicidal activity of monocytes was not affected by blocking TLRs. These results suggest that Ci modulated antigen receptors, cytokine production, and the fungicidal activity of human monocytes depending on concentration, and TLR-4 may be involved in its mechanism of action. Ci seemed to be partially involved in propolis activities.