Brazilian propolis: Chemical composition, regional variability, and bioactive potential.

Prostate cancer represents an ideal disease for chemopreventive intervention. Propolis possesses immuno-modulatory, anti-tumour and chemopreventive properties. The tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) is an important endogenous anti-cancer agent that induces apoptosis selectively in tumour cells. However, some cancer cells are resistant to TRAIL-mediated apoptosis. Naturally occurring phenolic and polyphenolic compounds sensitize TRAIL-resistant cancer cells and augment the apoptotic activity of TRAIL. The ethanolic extract of Brazilian green propolis (EEP) is rich in phenolic components. Our in vitro results indicate the potential targets in the TRAIL-induced apoptotic pathway for the cancer chemopreventive activity of Brazilian propolis. We examined the cytotoxic and apoptotic effects of Brazilian EEP and its bioactive components in combination with TRAIL on LNCaP prostate cancer cells. The chemical composition of Brazilian green propolis was determined by high performance liquid chromatography-diode array detection. The cytotoxicity was measured by 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl-tetrazolium and lactate dehydrogenase assays. Apoptosis was detected using annexin V-FITC by flow cytometry and fluorescence microscopy. The mitochondrial membrane potential (∆Ψm) was evaluated using DePsipher staining by fluorescence microscopy. Flow cytometry was used to analyse death receptor (TRAIL-R1 and TRAIL-R2) expression in LNCaP cells. The inhibition of nuclear factor-κB (NF-κB) (p65) activation in cancer cells was confirmed by the ELISA-based TransAM NF-κB kit. The LNCaP cells were shown to be resistant to TRAIL-induced apoptosis. Our study demonstrates that EEP sensitizes TRAIL-resistant prostate cancer cells. The main phenolic components detected in Brazilian green propolis are artepillin C, quercetin, kaempferol and p-coumaric acid. Brazilian propolis and its bioactive components markedly augmented TRAIL-mediated apoptosis and cytotoxicity in prostate cancer cells. Brazilian EEP enhanced the expression of TRAIL-R2 and the activity of NF-κB in LNCaP cells. The co-treatment of prostate cancer cells with 100 ng/ml TRAIL and 50 µg/ml EEP increased the percentage of apoptotic cells to 65.8 ± 1.2% and caused a significant disruption of ∆Ψm in LNCaP cells. We show that Brazilian EEP helped cells overcome TRAIL resistance by engaging both intrinsic and extrinsic apoptotic pathways and regulating NF-κB activity. The data demonstrate the important role of Brazilian green propolis and its bioactive compounds in prostate cancer chemoprevention through the enhancement of TRAIL-mediated apoptosis.

Propolis is produced by honeybees from materials collected from plants they visit. It is a resinous material having mixtures of wax and bee enzymes. Propolis is also known as bee glue and used by bees as a building material in their hives, for blocking holes and cracks, repairing the combs and strengthening their thin borders. It has been extensively used since ancient times for different purposes in traditional human healthcare practices. The quality and composition of propolis depend on its geographic location, climatic zone and local flora. The New Zealand and Brazilian green propolis are the two main kinds that have been extensively studied in recent years. Their bioactive components have been found to possess a variety of therapeutic potentials. It was found that Brazilian green propolis improves the cognitive functions of mild cognitive impairments in patients living at high altitude and protects them from neurodegenerative damage through its antioxidant properties. It possesses artepillin C (ARC) as the key component, also known to possess anticancer potential. The New Zealand propolis contains caffeic acid phenethyl ester (CAPE) as the main bioactive with multiple therapeutic potentials. Our lab performed in vitro and in vivo assays on the extracts prepared from New Zealand and Brazilian propolis and their active ingredients. We provided experimental evidence that these extracts possess anticancer, antistress and hypoxia-modulating activities. Furthermore, their conjugation with γCD proved to be more effective. In the present review, we portray the experimental evidence showing that propolis has the potential to be a candidate drug for different ailments and improve the quality of life.

Among the natural products, Brazilian propolis stands out because it is considered a source for the discovery of new bioactive compounds. In the last decade, a new Brazilian propolis has been described, known as red propolis due to its reddish pigment. Since then, numerous studies revealing its major components and their pharmacological activity have been described. Thes, this research had the objective of performing an integrative review of the literature on the biological activity of Brazilian red propolis. Scientific studies in the PubMed, SciElo and LILACS database were reviewed and analyzed using an inductive approach and indirect documentation technique. A total 418 publications were found, and onclusion and exclusion criteria were subsequently applied, selecting a total of 18 articles. The Brazilian propolis presents numerous pharmacological properties, especially the antibacterial, antfugal, antoxidant and anti-inflammatory effects. In addition, the chemical composition of this substance is different from other types of propolis already reported in the literature, presenting flavonoids never before reported. In this way, its chemical characteristics suggest probable therapeutic use for the human organism.

ABSTRACTBackgroundIn Amsterdam, in 2024, patch testing with Brazilian propolis yielded high rates of positive reactions (> 20%), whereas reactivity to Chinese propolis was significantly lower (3.5%). Differences in the composition were suggested as a possible explanation.Objectives1. To study the composition of 3 propolis samples (2 Chinese and 1 Brazilian) used for preparing commercial test allergens; 2. To study the influence of different enrichment times on the qualitative and quantitative composition of Brazilian propolis.Materials and MethodsAnalyses were performed using gas chromatography–mass spectrometry/flame ionisation detection (GC–MS/FID) of the volatile components obtained by headspace SPME (solid phase microextraction).ResultsA strong difference between the composition of the Brazilian propolis sample and both samples of Chinese propolis was found. Major ingredients in Brazilian propolis were hydrocinnamic acid (16.9%), (E)‐nerolidol (7.41%), spathulenol (5.45%) and junenol (4.01%). Major ingredients in Chinese propolis were (E)‐cinnamyl alcohol (8.08% and 24.96%), 2‐phenethyl alcohol (8.93% and 11.25%), α‐curcumene (8.77% and 8.81%) and guaiol (5.96% and 5.72%).ConclusionsThe volatile fractions of Brazilian propolis and Chinese propolis used for patch testing have very different compositions. Whether this causes or contributes to the differences in patch test reactivity has to be investigated further.

Abutilon hirtum (Lam.) Sweet (Malvaceae) commonly known as Vadathuthi . It is used as one of the most important drugs in traditional system of medicine to treat various ailments. The plant is used for to its various properties as demulcent, diuretics, anti-diabetics, anthelmintic, laxative, wound healing properties, antibacterial and antifungal properties. The present study revealed the presence of phytochemicals like Diethyl Phthalate (19.171%),Benzaldehyde 4-propyl (5.219%),Methoxyacetic acid 3-tridecyl ester (5.196%),Sulfurous acid dodecyl 2-propyl ester (0.455%),Sulfurous acid, butyl dodecyl ester (0.442%) etc ., from the chloroform extracts of leaves in A. hirtum . In the present study an attempt was made to investigate the phytochemical present in the extracts in the preliminary level by using Gas Chromatography coupled with Mass Spectrometry (GC-MS). The study will provide information for the correct identification of the crude drug. This will be further considered for pharmacological activities and isolation of individual components would however, help to find new drugs.The results are reported for the first time in A. hirtum.

Propolis, also known as bee-glue, is a resinous substance produced by honeybees from materials collected from plants they visit. It contains mixtures of wax and bee enzymes and is used by bees as a building material in their hives and by humans for different purposes in traditional healthcare practices. Although the composition of propolis has been shown to depend on its geographic location, climatic zone, and local flora; two largely studied types of propolis: (i) New Zealand and (ii) Brazilian green propolis have been shown to possess Caffeic Acid Phenethyl Ester (CAPE) and Artepillin C (ARC) as the main bioactive constituents, respectively. We have earlier reported that CAPE and ARC possess anticancer activities, mediated by abrogation of mortalin-p53 complex and reactivation of p53 tumor suppressor function. Like CAPE, Artepillin C (ARC) and the supercritical extract of green propolis (GPSE) showed potent anticancer activity. In this study, we recruited low doses of GPSE and ARC (that did not affect either cancer cell proliferation or migration) to investigate their antistress potential using in vitro cell based assays. We report that both GPSE and ARC have the capability to disaggregate metal- and heat-induced aggregated proteins. Metal-induced aggregation of GFP was reduced by fourfold in GPSE- as well as ARC-treated cells. Similarly, whereas heat-induced misfolding of luciferase protein showed 80% loss of activity, the cells treated with either GPSE or ARC showed 60–80% recovery. Furthermore, we demonstrate their pro-hypoxia (marked by the upregulation of HIF-1α) and neuro-differentiation (marked by differentiation morphology and upregulation of expression of GFAP, β-tubulin III, and MAP2). Both GPSE and ARC also offered significant protection against oxidative stress and, hence, may be useful in the treatment of old age-related brain pathologies.

Propolis: Properties, Application, and Its Potential

The use of Brazilian propolis for discovery and development of novel anti-inflammatory drugs

The tumor microenvironment, characterized by regions of hypoxia, low nutrition, and acidosis due to incomplete blood vessel networks, has been recognized as a major factor that influences not only the response to conventional anti-cancer therapies but also malignant progression and metastasis. However, exploiting such a cumbersome tumor microenvironment for cancer treatment could provide tumor-specific therapeutic approaches. In particular, hypoxia is now considered a fundamentally important characteristic of the tumor microenvironment in which HIF-1 mediated gene regulation being essential for angiogenesis and tumor development. This has led to the current extensive interest in the drug discovery for tumor microenvironment including tumor specific potential molecular targets for cancer therapeutics. Propolis has pleiotropic effects and contains a variety of bioactive polyphenolic compounds. Some flavonoids of them have been reported to inhibit HIF-1α. We therefore evaluated the effects of composition of Brazilian propolis on cellular responses to hypoxia or nutrition deprivation stress for the development of novel anti-cancer drug targeting the tumor microenvironment. Materials and Method: The ethanol extract of Brazilian propolis was subjected to a series of chromatographic separations to examine HIF-1 inhibition and cytotoxicity under hypoxic and/or glucose deprived condition. The HIF-1α trans-activation effect was evaluated by HIF-1 reporter assay using stable cell lines expressing p2.1. The effect on unfolded protein response (UPR) activation in tumor cell induced by glucose deprivation or 2-deoxyglucose was also examined by GRP78 promoter reporter assay. We performed Immunoblot analysis of the HIF-1α and UPR target genes. The effects on HIF-1α dependent gene expression were investigated by RT-PCR using HCT116 cells. Result: The propolis whole extract increased HRE-dependent luciferase activity in a dose-dependent manner. From a series of chromatographic separations, we obtained fractions 3, 5 and 8 that inhibited HIF-1-dependent induction of luciferase, while fractions 6 and 10-13 increased the luciferase activity. Cinnamic acid derivative, GPU-215 was isolated from Fr.6 reduced HIF1 transactivation activity, expression of HIF-1α protein and GLUT1 mRNA under hypoxia, while flavonoid, GPU-216 from Fr.8 increased HIF-1α transactivation activity and UPR activation. Conclusion: We discovered promising compounds from Brazilian propolis for novel anti-cancer drug targeting tumor microenvironment. GPU-215 has inhibitory effect on HIF-1α expression and function, while GPU-216 increased HIF-1α transactivation and UPR activation. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 765.

Propolis has been considered a resinous substance with a complex chemical composition that is collected from several plant species by Apis mellifera bees, and used by man as an alternative to the healing of diseases and to keep a good health. The chemical composition of propolis is related to the biodiversity of the region visited by the bees and also to the season of collection. This research purpose was to optimize the production methodology of propolis’ ethanol extract production and to evaluate the effect of seasonality in the chemical composition and biological activities of this product. Propolis’ samples were collected from the apiary at the Instituto Federal de Educação, Ciência e Tecnologia do Sul de Minas Gerais - Campus Muzambinho and were used to make ethanol extracts. In the optimization stage, different ethanolic solution concentration, extraction method and drying temperatures were used. For the analysis of the seasonal effect, propolis was collected from the same place in different seasons. The results showed that the 80% ethanolic solution, the extraction temperature of 70oC and drying at 45oC were the ones that stood out the most. Regarding the effect of seasonality on the chemical composition and biological activities of propolis, it is clear that there are differences between the propolis collected in different seasons.

Indonesia has a potency to produce its own propolis, however the propolis market in Indonesia is dominated by imported product, such as from Brazil. Currently, still there is no reasearch which evaluate bioactive compound and nutrient content of Indonesian Propolis (IP) compare with Brazilian Propolis (BP). The objectives of this study were to analyze bioactive compounds and nutrient contents of IP compared to BP. Bioactive compounds and nutrients content were analyzed by gas chromatography–mass spectrophotometry. The results<br />showed both IP and BP contain fenol, α-amyrin, cylolanost, and pyrimidines. Bioactive compounds which specifically found in IP were eudesmane compound, ethyl acridine, lupeol, friedooleanan; while β amyrin and cinnamic acid compound only found in BP. The nutrient contents of IP were higher than BP except for vitamin A. In conclusion, IP might have potential health benefit, similar to BP.<br /><br />

Chemical composition and larvicidal activity of edible plant-derived essential oils against the pyrethroid-susceptible and -resistant strains of Aedes aegypti (Diptera: Culicidae)

Propolis is an organotherapeutic product collected by honey bees that contains a large number of phytoconstituents, possessing excellent pharmacological properties. In this study, phenolic composition and antioxidant capacity were evaluated in different types of Brown, Green and mixture of Red, Green I and Brown II (RGB) Brazilian propolis. Ultrasonic-assisted extraction was performed by direct solvent extraction (DSE) and successive solvent extraction (SSE) methods. The ethanolic extract of Green I propolis by SSE was higher in total phenolics (403.88 mg GAE/g extract), flavonoids (311.57 mg QE/g extract), and DPPH· scavenging activity (82.33 µMol TE/g extract) compared to other Brazilian propolis samples. Moreover, different solvent phases were used in the HPLC-DAD analysis and the results were validated by linearity and sensitivity. The optimized method was proven to be precise revealing good separation of standard phenolic compounds. Thermal stability of the compounds was accessed by using different column oven temperatures (40, 50 and 60 °C), and the results showed that lower temperature (40° C) retains the maximum contents of total phenolics in the 80% ethanolic extract of Green I propolis (253.71 mg/g extract) by DSE compared to other propolis samples. This extract (109.35 mg/g extract) also obtained a higher amount of total phenolic compounds in the SSE compared to ethyl acetate and acetone extracts. Among the phenolic compounds, artepillin C (60.10 mg/g extract) was higher in the SSE of Green I propolis 80% ethanolic extract. Thus, this study optimized the extraction and HPLC analytical conditions for the determination of phenolic composition and antioxidant capacity in different samples of Brazilian propolis.

The effect of Brazilian Green Propolis extract on inflammation in patients with chronic kidney disease on peritoneal dialysis: A randomised double-blind controlled clinical trial

Aims: There is a high risk associated with using artificial materials like polyethylene or foil for wrapping foods before cooking. The present study investigated the phytochemical and nutrient composition of Thaumatococus daniellii leaf, a local food wrapper.
 Place and Duration of Study: Biochemistry Unit, Department of Science Laboratory Technology, Imo State Polytechnic Umuagwo, between April and May 2018.
 Methodology: The phytochemical compounds were analyzed using gas chromatography coupled with mass spectrometry (GC-MS) while proximate and vitamin composition was determined using standard analytical methods. 
 Results: The GC-MS phytochemical analysis revealed the presence of eight (8) bioactive compounds 1,2,3,4-Butanetetrol, d-Glycero-d-idoheptose, Cyclopentane,1-ethyl-1-methyl-, 6-Octyl-1-ol,3,7-dimethyl-, 2-Octenal, E- Octane,1-chloro-,2-Acetoxy-1,1,10-trimethyl-6,9-epidioxydecalin and Bicyclo[3.1.1]heptan-3-ol,2,6,6-trimethyl-,(1α,2β,3α,5α)- while vitamin assay results showed that Thaumatococcus daniellii leaf contained 3.1mg/100g of vitamin A, 1.07 mg/100 g vitamin B1, 1.32 mg/100 g vitamin B3, 1.11 mg/100 g of vitamin B5, 16.34 mg/100 g of vitamin B6, 11.86 mg/100 g of vitamin B12 and 25.19 mg/100 g of vitamin C. Result of proximate analysis indicates that Thaumatococcus daniellii leaf contains 10.15% ash, 9.67% moisture, 20.41% protein, 11.42% lipids, 13.78% fibre and 34.57% carbohydrate.
 Conclusion: In summary, our findings indicate that Thaumatococcus daniellii leaves contain bioactive compounds, an appreciable number of vitamins and high nutritional constituents. Hence Thaumatococcus daniellii leaves can be incorporated into animal feed, taking into cognizance the high protein, fat and vitamin contents. These suggest that it may play critical medicinal and nutritional roles and probably be a safer alternative to polyethylene paper and aluminum foil wraps; hence justifying its local usage as food wrapper. The leaves may also serve as a lead for the production of a healthier material for wrapping local foods.