Use of Stingless Bee Propolis and Geopropolis against Cancer-A Literature Review of Preclinical Studies.

Cancer is one of the major maladies affecting humankind and remains one of the leading causes of death worldwide. The investigation of the biological activities of stingless bee products, especially propolis and geopropolis, has revealed promising therapeutic properties, especially in the research on new antineoplastic agents. This literature review of preclinical trials, involving biological assays of antitumor activity and identification of the chemical composition of propolis and geopropolis of stingless bee species, describes the cytotoxicity in tumor lineages (breast, lung, ovarian, liver, mouth, pharynx, larynx, colon, stomach, colorectal, cervix, kidney, prostate, melanoma, human glioblastoma, canine osteosarcoma, erythroleukemia, human chronic myelocytic leukemia, and human promyelocytic leukemia) of propolis and geopropolis of 33 species of stingless bees. The chemical composition of propolis and geopropolis was identified, indicating that these belong to the chemical classes of phenolic acids, flavonoids, coumarins, benzophenones, anthraquinones, alkaloids, terpenes, steroids, saponins, fatty acids, and carbohydrates and are possibly responsible for the cytotoxicity in tumor cells. Apoptosis was one of the main mechanisms of cytotoxicity of extracts and substances isolated from stingless bee products. Although the results found are encouraging, other preclinical studies and clinical trials are essential for the discovery of new anticancer agents.

Cytotoxicity and Pro-Apoptotic, Antioxidant and Anti-Inflammatory Activities of Geopropolis Produced by the Stingless Bee Melipona fasciculata Smith.

Geopropolis is produced by some stingless bee species, such as Melipona fasciculata Smith, a native species from Brazil. This study aims to investigate the antioxidant and anti-inflammatory activities and cytotoxicity effects of geopropolis hydroethanolic extracts against lung (H460 and A549) and ovarian (A2780 and ES2) cancer cell lines and non-tumor (HUVEC) cell lines using chemical identification by LC/MS/MS analysis and in silico assays to determine which compounds are associated with bioactivity. The antioxidant activity of extracts and inhibitory activity against COX enzymes were assessed by in vitro assays; cytotoxicity effect was evaluated by the MTT assay; cell cycle was assessed by flow cytometry and apoptosis by Western blotting. The geopropolis extracts showed great radical scavenging potential, preferential inhibition of COX-2, decreased cancer cell viability, non-cytotoxic effects against the non-tumoral cell line, besides modulating the cell cycle and inducing cancer cell apoptosis through the activation of caspase-3 and PARP protein cleavage. The in silico study suggests that corilagin, typhaneoside, taraxerone and marsformosanone, identified by LC/MS/MS, can be associated with anti-inflammatory activity and cytotoxic effects. Thus, the current study suggests the potential of geopropolis concerning the research field of new pharmacological alternatives regarding cancer therapy.

Anti-Inflammatory and Antinociceptive Activity of Pollen Extract Collected by Stingless Bee Melipona fasciculata.

The stingless bee, Melipona fasciculata Smith (Apidae, Meliponini), is a native species from Brazil. Their products have high biotechnological potential, however there are no studies about the biological activities of pollen collected by M. fasciculata. In this context, the present study investigated the chemical composition, anti-oxidant, anti-inflammatory, and analgesic activities of hydroethanolic pollen extracts collected by M. fasciculata in three cities in Maranhão State, Brazil. We verified the antioxidant activity of the extracts and inhibitory activity against the cyclooxygenase enzyme using in vitro assays and in allowed to select the extract with higher efficiency to be used on in vivo assays. In these trials, the selected extract showed high anti-inflammatory activity as well as nociceptive effects at central and peripheral level, suggesting that this extract acts on inhibition of histamine release and decreased synthesis of prostaglandins and the in-silico study suggested that polyphenols and acids fatty acids in the extract may be associated with these activities. The results of the present study report the high biological potential of pollen extract and we conclude that the pollen collected by M. fasciculata can be considered as the object of research for new pharmacological alternatives.

Chemical composition and antioxidant activity of geopropolis produced by Melipona fasciculata (Meliponinae) in flooded fields and cerrado areas of Maranhão State, northeastern Brazil / Composição química e atividade antioxidante da geoprópolis de Melipona fasciculata (Meliponinae) produzida em áreas de campos alagados e de cerrado no Estado do Maranhão, Nordeste do Brasil

Geopropolis, a mixture of plant resin, wax, soil and salivary secretion, is produced by the stingless bee Melipona fasciculata. This aim of this study was to investigate the chemical composition and antioxidant activity of geopropolis collected from beehives in two phytogeographical regions, flooded fields and cerrado, in the municipalities of Palmeirândia and Fernando Falcão, Maranhão State, northeastern Brazil. The geopropolis compounds were identified by gas chromatography-mass spectrometry (GC/MS). Additionally, total phenolic content was determined with the FolinCiocalteu reagent and antioxidant activity was evaluated in vitro by 2,2-diphenyl-1-picrylhydrazyl (DPPH) and ferric reducing antioxidant power (FRAP) assays. The four geopropolis samples varied in terms of total phenolic content and antioxidant activity and the highest values were observed for geopropolis from Fernando Falcão. Triterpenes such as cycloartane, ursane and oleanane and phenolic acids (protocatechuic acid and gallic acid) were identified in the geopropolis from Palmeirândia, while the phenolic acids, gallic and ellagic acid were the main compounds in geopropolis from Fernando Falcão. The antioxidant property of geopropolis is due to its high total phenolic content and predominance of gallic acid and ellagic acid. The results showed that the plant resources in two phytogeographical regions of Maranhão used by bees for the production of geopropolis contribute to the chemical composition and bioactivity of this product.

Geoprópolis, uma mistura de resinas vegetais, cera, terra e secreção salivar, produzida pela abelha sem ferrão Melipona fasciculata. Este estudo investigou a composição química e a atividade antioxidante da geoprópolis coletada em colmeias em duas regiões fitogeográficas de campos alagados e de cerrado, nos municípios de Palmeirândia e Fernando Falcão, no Estado do Maranhão, Nordeste do Brasil. Os compostos da geoprópolis foram identificados por cromatografia gasosa acoplada a espectrometria de massas (CG/EM). Foram determinados os teores de fenólicos totais pelo reagente de FolinCiocalteu, e atividade antioxidante utilizando o ensaio in vitro com 2,2-difenil-1-picrilhidrazil (DPPH) e capacidade redutora do ferro (FRAP). As quatro amostras de geoprópolis apresentaram variações no teor de fenólicos totais e atividade antioxidante, as geoprópolis de Fernando Falcão, apresentaram maiores teores. Nas geoprópolis do município de Palmeirândia foram identificados, triterpenos do tipo cicloartano, ursano e oleanano e ácidos fenólicos (ácido protocatecuico e ácido gálico), enquanto que na geoprópolis de Fernando Falcão, ácidos fenólicos, ácido gálico e elágico foram os principais constituintes. A propriedade antioxidante da geoprópolis pode ser atribuída aos altos teores de fenólicos totais e de ácido gálico e elágico. Os resultados demonstram que as fontes vegetais das duas regiões fitogeográficas do Maranhão, Brasil, utilizadas pelas abelhas para a produção da geoprópolis contribuem para a composição química e bioatividade deste produto.