Brazilian red propolis exerts a cytotoxic action against prostate cancer cells and upregulates human monocyte functions.

Different propolis samples can be obtained in Brazil, such as green, brown and red. Studies related to Brazilian red propolis (BRP) have increased in the last few years, so the aim of this study was to investigate its effects on the prostate cell lines LNCaP and PC-3 and on human monocytes. BRP chemical composition was analyzed by HPLC-DAD, the viability of monocyte and cancer cell by MTT assay. Cytokine production (TNF-α, IL-1ß, IL-6, IL-10) by monocytes was quantitated by ELISA, the expression of cell markers (TLR-2, TLR-4, HLA-DR, CD80) and reactive oxygen species by flow cytometry. The candidacidal activity and the effects of supernatant of treated monocytes on tumor cells were assessed. BRP affected LNCaP viability after 48 and 72 h, while PC-3 cells were more resistant over time. BRP upregulated CD80 and HLA-DR expression, and stimulated TNF-α, IL-6 and IL-10 production. BRP enhanced the fungicidal activity of monocytes, displayed an antioxidant action and the supernatant of BRP-treated monocytes diminished LNCaP viability. In the search for new immunomodulatory and antitumoral agents, BRP exerted a selective cytotoxic activity on prostate cancer cells and an immunomodulatory action, suggesting its potential for clinical trials with oncological patients and for the discovery of new immunomodulatory and antitumor drugs.

Brazilian green propolis: A novel tool to improve the cytotoxic and immunomodulatory action of docetaxel on MCF-7 breast cancer cells and on women monocyte.

Docetaxel (DTX) is used against breast cancer despite its side effects such as toxicity and immunosuppression. Here we investigated the cytotoxic and immunomodulatory effects of the ethanol solution extract of propolis (EEP) in combination with DTX on MCF-7 breast cancer cells and on women's monocyte. The cytotoxic potential of EEP + DTX was assessed by MTT assay and the type of tumor cell death was evaluated by flow cytometry. The effects of EEP + DTX on the migration and invasion of MCF-7 cells were analyzed. Cytokine production by monocytes was assessed by ELISA and the expression of cell surface markers was evaluated by flow cytometry. We also assessed the fungicidal activity of monocytes against Candida albicans and the generation of reactive oxygen species (ROS). Finally, the impact of the supernatants of treated monocytes in the viability, migration, and invasiveness of tumor cells was assessed. EEP enhanced the cytotoxicity of DTX alone against MCF-7 cells by inducing necrosis and inhibiting their migratory ability. EEP + DTX exerted no cytotoxic effects on monocytes and stimulated HLA-DR expression, TNF-α, and IL-6 production, exerted an immunorestorative action in the fungicidal activity, and reduced the oxidative stress. Our findings have practical implications and reveal new insights for complementary medicine.

Propolis antiviral and immunomodulatory activity: a review and perspectives for COVID-19 treatment.

OBJECTIVES: Viral outbreaks are a frequent concern for humans. A great variety of drugs has been used to treat viral diseases, which are not always safe and effective and may induce adverse effects, indicating the need for new antiviral drugs extracted from natural sources. Propolis is a bee-made product exhibiting many biological properties. An overview of viruses, antiviral immunity, propolis safety and its immunomodulatory and antiviral action is reported, as well as perspectives for coronavirus disease 2019 (COVID-19) treatment. PubMed platform was used for data collection, searching for the keywords "propolis", "virus", "antiviral", "antimicrobial" and "coronavirus". KEY FINDINGS: Propolis is safe and exerts antiviral and immunomodulatory activity; however, clinical trials should investigate its effects on individuals with viral diseases, in combination or not with antiviral drugs or vaccines. SUMMARY: Regarding COVID-19, the effects of propolis should be investigated directly on the virus in vitro or on infected individuals alone or in combination with antiviral drugs, due to its immunomodulatory and anti-inflammatory action. Propolis administration simultaneously with vaccines should be analyzed, due to its adjuvant properties, to enhance the individuals' immune response. The search for therapeutic targets may be useful to find out how propolis can help to control COVID-19.

The chemical composition and events related to the cytotoxic effects of propolis on osteosarcoma cells: A comparative assessment of Colombian samples.

Osteosarcoma (OSA) is a type of bone cancer showing an aggressive biological behavior with metastatic progression. Because propolis potential for the development of new antitumoral drugs has been indicated, we evaluated the chemical composition of Colombian propolis samples and the mechanisms involved in their cytotoxic effects on OSA cells. The chemical composition was analyzed by GC-MS and the DPPH free radical scavenging activity was measured. Cluster and principal components analysis were used to establish an association with their inhibitory concentration 50% (IC50 ). Cell viability was analyzed by MTT assay; apoptosis was determined by flow cytometry; mitochondrial membrane permeability and reactive oxygen species were evaluated by rhodamine 123 and DCFH-DA. Transwell assay was used to evaluate the invasiveness of propolis-treated cells. Samples were grouped: Cluster 1 contained diterpenes and benzophenones and showed the highest antiradical activity; Cluster 2 was characterized by triterpenes, fatty acid, and diterpenes. Usm contained diterpenes and triterpenes different of the other samples and Sil contained triterpenes and flavonoids. Apoptosis, mitochondrial membrane alteration, and suppression of cell invasion were the main mechanisms involved in the inhibition of OSA cells in vitro, suggesting the potential of Colombian propolis to discover new antitumor drugs.

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.

Immunomodulatory action of Copaifera spp oleoresins on cytokine production by human monocytes.

Copaifera spp oleoresins have been used in folk medicine for centuries; nevertheless, its immunomodulatory action has not been investigated. Thus, the goal of this study was to characterize different oleoresins and to verify their action on human monocytes regarding pro- and anti-inflammatory cytokine production (TNF-α and IL-10, respectively). The chemical composition of Brazilian Copaifera reticulata, Copaifera duckey and Copaifera multijuga oleoresins was analyzed by HPLC-MS. Cell viability was assessed by MTT method after incubation of cells with Copaifera spp. Noncytotoxic concentrations of oleoresins were incubated with human monocytes from healthy donors, and cytokine production was determined by ELISA. HPLC-MS analysis for terpenes allowed the identification of six diterpene acids and one sesquiterpene acid. Oleoresins exerted no cytotoxic effects on human monocytes. All oleoresins had a similar profile: LPS-induced TNF-α production was maintained by oleoresins, while a significant inhibitory action on IL-10 production was seen. Copaifera oleoresins seemed to exert an activator profile on human monocytes without affecting cell viability. Such effect may be due to the presence of either diterpene or sesquiterpene acids; however, further studies are necessary to determine the involvement of such compounds in Copaifera immunomodulatory effects.

Cymbopogon martinii essential oil and geraniol at noncytotoxic concentrations exerted immunomodulatory/anti-inflammatory effects in human monocytes.

OBJECTIVES: In traditional medicine, plants have formed the basis of sophisticated systems that have been in existence for thousands of years and still provide mankind with new remedies. Cymbopogon martinii, known as palmarosa, has been used in aromatherapy as a skin tonic due to its antimicrobial properties. It has also used in Ayurvedic medicine for skin problems and to relieve nerve pain. The immunomodulatory action of C. martinii essential oil (EO) and geraniol was evaluated regarding the production of pro- and anti-inflammatory cytokines (tumour necrosis factor (TNF)-α and IL-10, respectively) by human monocytes in vitro. METHODS: Monocyte cultures were incubated with EO or geraniol. After 18 h, cytotoxicity assays were performed using 3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyltetrazolium bromide method, and cytokine production was determined by ELISA. KEY FINDINGS: The variables showed no cytotoxic effects on monocytes. TNF-α production was not affected by C. martinii and geraniol, and only the concentration of 5 µg/ml of C. martinii stimulated its production. On the other hand, all concentrations of C. martinii and geraniol increased IL-10 production by human monocytes. CONCLUSIONS: Data showed that noncytotoxic concentrations of EO and geraniol exerted an anti-inflammatory action by increasing IL-10 production; moreover, geraniol seemed to be probably responsible for EO immunomodulatory activity in our assay condition.