Component Of Propolis Research Articles

Artepillin C, a Key Component of Brazilian Propolis, Induces Thermogenesis in Inguinal White Adipose Tissue of Mice through a Creatine-Metabolism-Related Thermogenic Pathway.

Induction of beige adipocytes in white adipose tissue (WAT) is a potential therapeutic target for the treatment of obesity because beige adipocytes release excess energy via uncoupling-protein-1-associated thermogenesis. In this study, we investigated how artepillin C (ArtC) promotes thermogenesis in vivo. We demonstrated that 28 day administration of ArtC (10 mg/kg of body weight) to mice significantly induced thermogenesis in beige adipocytes in inguinal WAT (iWAT) and suppressed reductions in core body temperature induced by cold exposure at 4 °C. Moreover, ArtC-induced thermogenesis in iWAT was significantly inhibited by treatment with a creatine metabolism inhibitor, and ArtC significantly upregulated the expression of creatine-metabolism-related enzymes in the thermogenic pathway. These results indicate that ArtC induces thermogenesis in beige adipocytes in iWAT, and the observed ArtC-induced thermogenesis is associated with the creatine-metabolism-related thermogenic pathway, which is characteristically observed in beige adipocytes.

Propolis Components and Biological Activities from Stingless Bees Collected on South Sulawesi, Indonesia

Three new compounds, namely sulabiroins A (1) and B (2), and 2',3'-dihydro-3'-hydroxypapuanic acid (3), were isolated from the propolis of stingless bees (Tetragonula aff. biroi) collected on South Sulawesi, Indonesia. In addition, ten known compounds, (–)-papuanic acid (4), (–)-isocalolongic acid (5), isopapuanic acid (6), isocalopolyanic acid (7), glyasperin A (8), broussoflavonol F (9), (2S)-5,7-dihydroxy-4'-methoxy-8-prenylflavanone (10), isorhamnetin (11), (1'S)-2-trans,4-trans-abscisic acid (12), and (1'S)-2-cis,4-trans-abscisic acid (13) were identified. The structures of the new and known compounds were determined by spectroscopic analysis. The absolute configurations of sulabiroins A (1) and B (2) were determined by X-ray crystallography analysis and ECD calculation, respectively. The propolis from stingless bee (Tetragonula aff. biroi) collected on South Sulawesi contained compounds not present in propolis from other regions. Sulabiroin A (1) and isorhamnetin (11) were examined for xanthine oxidase (XO) inhibitory activity as one of biological activities; isorhamnetin (11) exhibited potent XO inhibitory activity, with an IC50 value of 3.9 µm.

Applying GC-MS analysis to identify chemical composition of Iranian propolis prepared with different solvent and evaluation of its biological activity.

Background:Propolis as a natural product has shown beneficial effects on human health. This study was aimed to investigate the chemical compositions and biological activity of three different extracts of propolis from two distinct geographic areas in Iran.Methods:The chemical composition of Iranian propolis extracts that were collected in the Spring of 2016 from two provinces in northern Iran: Ardabil and Polur in Mazandaran Province were measured through gas chromatography-mass spectrometry (GC-MS) methods. In addition, antimicrobial activity and cytotoxicity effect on HN5 and LNCaP cell lines were evaluated. The data were analyzed using one-way ANOVA and p<0.05 was considered as significant.Results:The GC-MS analysis identified the presence of compounds that belonged to the different groups such as aromatics acids and their related esters, flavonoid and flavonoid derivatives and terpenes. Flavanone was the most dominant compound of flavonoids. The maximum growth inhibition was observed against S. aureus of ethanolic extract of propolis (p<0.05). Moreover, cytotoxicity showed that ethanolic and dichloromethane extracts had more inhibitory effects on cell lines than the water extract.Conclusion:The results determined that extracts had the highest percentage of flavonoids. Therefore, it is expected that the synergistic effect of the main components of propolis is related to the increase of biological activity of propolis.

In vitro and in vivo anti-inflammatory properties of Mayan propolis

Introduction Propolis has been used traditionally for different human diseases and even recently as dental biomaterials because of its antibacterial, antimycotic, and anti-inflammatory properties. However, a proper correlation between in vitro and in vivo anti-inflammatory properties has not been clearly established. Methods The composition of propolis was determined by high-performance liquid chromatography–ultraviolet mass spectrometry (HPLC-UV-MS). Viability of ethanolic propolis solution was evaluated by thiazolyl blue tetrazolium bromide (MTT) assay on murine macrophages. The anti-inflammatory properties were assessed both in vitro through the enzyme-linked immunosorbent assay (ELISA) quantification of various cytokines and in vivo by induced edemas. Results Chemical analysis showed pinocembrin, pinobanksin-3-O-acetate, and pinobanksin-3-O-propionate as the main components of propolis. Macrophage viability was high (106%) when propolis was used up to 50 µg/mL. ELISA studies showed a reduction in the expression of pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α) up to 145 pg/mL, 350 pg/mL, and 210 pg/mL, respectively, while the anti-inflammatory cytokines (IL-10 and IL-4) were increased up to 833 pg/mL and 446 pg/mL. Finally, edema was reduced on paw and ear mice by 9% and 22%, respectively. Conclusion Mayan propolis has strong in vitro anti-inflammatory properties without compromising macrophage viability, resulting in a low-to-mild in vivo anti-inflammatory response.

Caffeic acid phenethyl ester (CAPE): cornerstone pharmacological studies and drug delivery systems

Propolis is a natural product with a plethora of biological effects, utilized by traditional medicine since antiquity. However, its application as a pharmaceutical is hindered by its variable composition and difficult standardization. CAPE has been shown to be a major component of propolis, with a large contribution to its pharmacological effects, among which the anti-inflammatory, antioxidant and antineoplastic have been attracting most attention. The current review article aims to present the cornerstone pharmacological studies of CAPE throughout the years, following its discovery, which confirmed its primary importance among propolis constituents and opened the path to its intensive research as a potential pharmaceutical. We present the diversity of drug delivery systems of CAPE, which have been developed to improve its efficacy in in vitro and in vivo disease models and discuss their primary promises and weaknesses. The increased interest in recent years over more practical approaches of CAPE research such as its pharmaceutical formulation comes to show that it has a potential to become commercialized as a pharmaceutical.

Caffeic Acid Phenethyl Ester (CAPE) Induces VEGF Expression and Production in Rat Odontoblastic Cells.

Caffeic acid phenethyl ester (CAPE), the main component of propolis, has various biological activities including anti-inflammatory effect and wound healing promotion. Odontoblasts located in the outermost layer of dental pulp play crucial roles such as production of growth factors and formation of hard tissue termed reparative dentin in host defense against dental caries. In this study, we investigated the effects of CAPE on the upregulation of vascular endothelial growth factor (VEGF) and calcification activities of odontoblasts, leading to development of novel therapy for dental pulp inflammation caused by dental caries. CAPE significantly induced mRNA expression and production of VEGF in rat clonal odontoblast-like KN-3 cells cultured in normal medium or osteogenic induction medium. CAPE treatment enhanced nuclear factor-kappa B (NF-κB) transcription factor activation, and furthermore, the specific inhibitor of NF-κB significantly reduced VEGF production. The expression of VEGF receptor- (VEGFR-) 2, not VEGFR-1, was up regulated in KN-3 cells treated with CAPE. In addition, VEGF significantly increased mineralization activity in KN-3 cells. These findings suggest that CAPE might be useful as a novel biological material for the dental pulp conservative therapy.

Perbedaan ketebalan odontoblast-like cells setelah aplikasi CAPE dan Kalsium Hidroksida

Background : CAPE is the main component of propolis, it has several biology and fpharmocological advantages as antioxidant, antiinflammation, anticancer and as an immunomodulator. There were the research before of CAPE is capable to stimulate the production of the TGF-β 1 and collagen sintesis by the pulp tissue with many superiority compare to Ca(OH)2, recently Ca(OH)2 is the gold standard for pulp capping treatment procedure. Objective : To determine and compare the effectiveness of CAPE and Ca(OH)2 to the thickness of odontoblast-like cells in rat pulp tissue. Methods : Maxillary first molar tooth of wistar mice was class 1 preparated until the pulp opened, then Ca(OH)2 was aplicated for 14 and 28 days, CAPE for 14 and 28 days. After application of Ca(OH)2 and propolis extract, the tooth was filled with RMGIC. Teeth were extracted on defined day and processed for histological evaluation. Result : There is a significant difference in the thickness of odontoblast-like cells after application of CAPE for 14 days with Ca(OH)2 for 14 days and CAPE for 28 days with Ca(OH)2 for 28 days. Conclusion : odontoblast-like cells after aplication of CAPE extract material is thicker than Ca(OH)2.

Caffeic Acid Phenethyl Ester Reduces Hypoxia-Induced Reactive Oxygen Species and Mitigatates Inflammation in Corneal Endothelial BCE C/D-1b Cells

Oxygen supply is crucial to the health of avascular human cornea where low-oxygen-transmissible soft contact lenses often cause keratitis upon excessive wear time. Caffeic acid phenethyl ester, an active component of propolis, has anti-oxidative and anti-inflammatory properties. This study investigated the in vitro effects of caffeic acid phenethyl ester on corneal inflammation and its underlying action. We measured NF-κB activity and Dichloro-dihydro-fluorescein diacetate staining to demonstrate that caffeic acid phenethyl ester ameliorates hypoxia-induced inflammation of corneal endothelial cells and reactive oxygen species formation. The results may provide a new strategy to mitigate keratitis by caffeic acid phenethyl ester treatment.

Effect of propolis phenolic compounds on free fatty acid receptor 4 activation.

Propolis is known to have multiple biological and pharmacological properties including the regulation of energy homeostasis. Although phenolic compounds are considered to be the major active components in propolis, there is little information available about their mechanisms underlying the regulation of energy homeostasis. In this study, the effects of five phenolic compounds in propolis, chrysin, pinocembrin, galangin, pinobanksin, and caffeic acid phenethyl ester (CAPE) were evaluated on the activation of free fatty acid receptor 4 (FFA4), which are involved in the control of energy homeostasis by enhancing insulin signaling, increasing glucose uptake, and regulating adipogenesis. The results showed that three phenolic compounds exhibited the activation of FFA4, which were ranked in the order of pinocembrin, CAPE and pinobanksin in FFA4-expressing cells. These results suggest that some phenolic compounds in propolis, particularly pinocembrin, may affect the control of energy homeostasis via the activation of FFA4.

Antiproliferative Acylated Glycerols from New Zealand Propolis.

Previous work has shown that a number of phenolic components of NZ propolis possess antiproliferative activity against certain human gastrointestinal cancer cell lines. Here we report on a series of acylglycerols isolated from the nonpolar fraction of propolis resin, which represent further bioactive constituents unrelated to the more usual phenolic compounds generally found in propolis. NZ propolis is sourced from poplar trees, and the acylglycerols have been shown to be present in the leaves and buds of some common poplars. The compounds are a series of monoglycerides containing 3,8-dihydroxy fatty acids, many of which are further acylated with acetic acid residues. The dihydroxy fatty acids are C18 to C24, with the most abundant being C20 and C22. These acylglycerols were found to have strong antiproliferative activity against three human gastrointestinal cell lines, particularly gastric cancer cell line NCI-N87, where one example shows an IC50 of less than 50 μM.

Caffeic acid phenethyl ester suppresses androgen receptor signaling and stability via inhibition of phosphorylation on Ser81 and Ser213

BackgroundAndrogen receptor (AR) plays important role in the development, progression, and metastasis of prostate cancer (PCa). Caffeic acid phenethyl ester (CAPE) is the main component of honey bee propolis. We determined if CAPE affects the signaling and stability of AR in PCa cells.MethodsEffects of CAPE on AR transcriptional activity and localization were determined by reporter gene assay and immunofluorescent microscopy. Western blotting, fluorescent polarization, computer simulation, and animal experiment were performed to investigate the molecular mechanism how CAPE reduces the stability of AR.ResultsCAPE treatment dose-dependently suppressed the transcriptional activity of AR as well as the protein levels of AR and its target gene PSA. Cyclohexamide treatment revealed that androgen stabilized AR protein, but AR stability was diminished by CAPE. Fluorescence microscopy demonstrated that androgen promoted the nucleus translocation of AR in PCa cells, while treatment with CAPE reduced protein level of AR in both nucleus and cytoplasm. CAPE treatment suppressed the phosphorylation of Ser81 and Ser213 on AR, which regulates the stability of AR. CDK1 and AKT are the kinases phosphorylating Ser81 and Ser213 on AR, respectively. CAPE treatment significantly reduced the protein level and activity of CDK1 and AKT in PCa cells. Overexpression of CDK1 or AKT rescued the AR protein level under CAPE treatment.ConclusionsOur results suggested that CAPE treatment reduced AR stability and AR transcriptional activity in PCa cells, implying the possibility of using CAPE as a treatment for advanced PCa.Graphical abstract

Does propolis can relief toothache???

Objective: The aim of this literature review is to highlights the role and mechanisms of propolis at the molecular level in relief toothache caused by dental pulp inflammation.Methods: This review complied data from our study as well as from other researchers, focusing on molecular mechanism of inflammation, dental pain mechanism caused by inflammation and the role of propolis on inflammatory process.Results: Both in vitro and in vivo or even clinical research revealed thatpropolis has anti-inflammatory. Propolis could suppresses cyclooxygenase(COX) and lipoxygenase (LOX) enzymes during inflammation. COX-2 is mainly inhibited by flavonoid which suppresses prostaglandin endoperoxide synthase at high concentration depending on the hydrophilicity and structure whereas LOX is mainly inhibited by quercetin component of propolis. The major component of propolis is the caffeic acid (3.4-dihydroxycinnamic acid) phenethyl ester (CAPE). It has anti-inflammatory by inhibits LOX and COX enzymes that are involved in the AA metabolism pathways.Conclusion: It could be that propolis effective to relief toothache (odontalgia).

Caffeic Acid Phenethyl Ester Inhibits the Proliferation of HEp2 Cells by Regulating Stat3/Plk1 Pathway and Inducing S Phase Arrest.

Caffeic acid phenethyl ester (CAPE), an active polyphenolic component of honeybee propolis, has been demonstrated to have many medicinal properties. However, the antitumor effect and mechanism of CAPE on laryngeal carcinoma cells have not been examined. In this study, we treated HEp2 cells with various concentration of CAPE, and the results showed that CAPE can reduce the viability of HEp2 cells with IC50 values of 23.8 ± 0.7 µM for 72 h. Meanwhile, CAPE significantly inhibited activation of signal transducer and activator of transcription (Stat)3 in a concentration dependent manner in HEp2 cells and regulated the expression and transcription of Plk1. AG490, a specific Stat3 inhibitor, not only inhibited the activation and expression of Stat3, but also inhibited the expression of Plk1 in HEp2 cells, so Stat3 was probably involved in the regulation of Plk1 in HEp2 cells. In addition, treatment of CAPE leaded to a blockage of cell cycle in S phase in HEp2 cells. Therefore, CAPE inhibited the proliferation of HEp2 Cells probably by regulating Stat3/Plk1 pathway and inducing S phase arrest.

PH and Charge Effects Behind the Interaction of Artepillin C, the Major Component of Green Propolis, With Amphiphilic Aggregates: Optical Absorption and Fluorescence Spectroscopy Studies.

Brazilian green propolis is one of the bee products most consumed in the world to prevent diseases, owing antioxidant, antimicrobial, anti-inflammatory and antitumor activities. The major component of Brazilian green propolis is Artepillin C (ArtC), a cinnamic acid derivative with two prenylated groups that improve the affinity of the compound for lipophilic environment. Here, we have employed optical absorption and fluorescence techniques to draw conclusions on how ArtC interacts with amphiphilic aggregates commonly used as model membranes having different charges in the polar head group. Optical absorption spectra were representative of the protonation state of ArtC, dictated by the local pH at the surface of micelles and lipid vesicles. Fluorescence results showed that, in the presence of micelles and vesicles, the polarizability around ArtC was modified, compared to the value in aqueous medium, and the molecule should be located preferentially on the surface region of the model membranes, with an enhanced interaction with the less ordered state of the lipid vesicles.

Immunostymulujące działanie propolisu

Research on experimental animals conducted for nearly 30 years clearly prove that the ethanol and water extracts of propolis provided parenterally have an immunostimulatory effect. In addition, it was revealed that in case of experimental animals immunized with specific antigens, the influence of propolis extracts and their components increased the agglutination titre, phagocytosis and antibody production compared to the antigens themselves. Contemporary research on immunostimulatory properties of propolis extracts clearly indicate the activation of macrophages and the increase of antimicroorganisms immunity, as well as stimulation of the antibody production under the influence of ethanol and water extracts from propolis and their components (immunoadjuvants).The most important immunostimulatory components of propolis include caffeic acid, dicaffeoylquinic acids and caffeic phenylethyl ester (CAPE). The research presented in this study creates the possibility of applying propolis extracts and their components in practice for the production of immune serum on an industrial scale.

Caffeic Acid Phenethyl Ester and Its Fluorinated Derivative as Natural Anti-obesity Agents (P06-089-19)

ObjectivesCaffeic acid phenethyl ester (CAPE), an active component of propolis from honeybee hives, is well studied for its beneficial effects on cancer, inflammation and diabetes. There are however limited studies investigating the effects of CAPE on obesity. Currently, several natural products are under investigation for their effects on adipocyte life cycle. A multi-targeted approach for prevention and treatment of obesity includes targeting adipocytes at all the stages of life cycle by decreasing adipocyte differentiation, inducing lipolysis and/or by inducing adipocyte apoptosis. In this study, we examined the effects of CAPE on preadipocyte viability, adipogenesis and lipolysis. Earlier reports on CAPE indicate that CAPE is liable to enzymatic hydrolysis in vivo making this compound unstable for therapeutic applications. In the current study, we compared the anti-adipogenic effects of CAPE with its novel fluorinated derivative (FCAPE), a more stable compound. Methods3T3-L1 pre-adipocytes were differentiated using a cocktail consisting of insulin, dexamethasone, and isobutyl methyl xanthine in DMEM supplemented with 10% FBS following adipogeneic differentiation. Pre- and mature adipocytes were incubated with CAPE or FCAPE for 24–48 hours and their effects on viability, lipolysis, and adipogenesis was tested using Prestoblue, Lipolysis assay (Zen-Bio) and AdipoRed assay respectively. ResultsOur results indicate that neither CAPE nor FCAPE significantly altered preadipocyte viability within the tested dose range. Although both CAPE and FCAPE significantly decreased adipogenesis compared to control, FCAPE decreased lipid content by 73.6 ± 1.6% while CAPE reduced lipid content by only 36.8 ± 9.1% at 25 μM concentration. In contrast to adipogenesis data, our preliminary results with lipolysis assay indicate that only CAPE, but not FCAPE induces lipolysis in mature adipocytes. ConclusionsThese findings suggest that both CAPE and FCAPE possess anti-adipogenic properties. Further studies are needed to elucidate their differential effects on adipogenesis and lipolysis. Funding SourcesThis study was funded by the Department of Research, PCOM.

Caffeic Acid Phenethyl Ester (CAPE) Protects PC12 Cells Against Cisplatin-Induced Neurotoxicity by Activating the AMPK/SIRT1, MAPK/Erk, and PI3k/Akt Signaling Pathways.

Peripheral sensory neuropathy (PSN) is a well-known side effect of cisplatin characterized by axonal damage. In the early stage of neurotoxicity, cisplatin affects proteins that modulate neurite outgrowth and neuroplasticity, without inducing mitochondrial damage or apoptosis. There are no preventive therapies for cisplatin-induced peripheral neuropathy; therefore, measures to improve axonal growth and connectivity would be beneficial. Caffeic acid phenethyl ester (CAPE) is a bioactive component of propolis with neurotrophic and neuroprotective activities. We have recently showed that CAPE protects against cisplatin-induced neurotoxicity by activating NGF high-affinity receptors (trkA) and inducing neuroplasticity. We have now assessed other potential early targets of cisplatin and additional mechanisms involved in the neuroprotection of CAPE. Cisplatin reduced axonal cytoskeletal proteins (F-actin and β-III-tubulin) without inducing oxidative damage in PC12 cells. It also reduced energy-related proteins (AMPK α, p-AMPK α, and SIRT1) and glucose uptake. At this stage of neurotoxicity, glutamate excitotoxicity is not involved in the toxicity of cisplatin. CAPE attenuated the downregulation of the cytoskeleton and energy-related markers as well as SIRT1 and phosphorylated AMPK α. Moreover, the neuroprotective mechanism of CAPE also involves the activation of the neurotrophic signaling pathways MAPK/Erk and PI3k/Akt. The PI3K/Akt pathway is involved in the upregulation of SIRT1 induced by CAPE, but not in the upregulation of cytoskeletal proteins. Altogether, these findings suggest that the neuroprotective effect of CAPE against cisplatin-induced neurotoxicity involves both (a) a neurotrophic mechanism that mimics the mechanism triggered by the NGF itself and (b) a non-neurotrophic mechanism that upregulates the cytoskeletal proteins.

Effects of caffeic acid phenethyl ester (CAPE) on angiogenesis, apoptosis and oxidatıve stress ın various cancer cell lines

ABSTRACTCancer is a common cause of death worldwide. Approximately 80% of cancer patients use complementary or alternative medicines for treatment. Caffeic acid phenethyl ester (CAPE), the main active component of propolis, exhibits cytotoxic, antiproliferative and anti-cancer effects. Despite its anticancer effects CAPE exhibits no known harmful effects toward normal cells. We investigated the effects of CAPE on angiogenesis, apoptosis and oxidative stress using MDA MB-231, N2a and COLO 320 cell lines and CAPE treatments at 24 and 48 h. A two dimensional cell culture system was used and the findings were evaluated by an indirect immunohistochemical method and H-scores were calculated. CAPE was effective for all three cancer cell lines. After 24 and 48 h, we found a significant decrease in live cells and increased stress in the cells based on e-NOS and i-NOS levels.

Cycloartane-Type Triterpenes and Botanical Origin of Propolis of Stingless Indonesian Bee Tetragonula sapiens.

This study clarifies the chemical constituents and botanical origin of Tetragonula sapiens Cockerell bee propolis collected from Southeast Sulawesi, Indonesia. Propolis samples and resin of Mangifera indica were extracted with 99% ethanol to obtain an ethanol extract of propolis (EEP) and an ethanol extract of M. indica resin (EEM). Column chromatography, thin-layer chromatography (TLC), and high-performance liquid chromatography (HPLC) were developed and used for the separation and isolation of compounds from the ether-soluble fraction. The structure of the compounds was determined by nuclear magnetic resonance (NMR) spectroscopic analysis, and their molecular weight analyzed by gas chromatography–mass spectrometry (GC–MS). The HPLC chromatogram of the EEP was then compared with the HPLC chromatogram of EEM to investigate the botanical origin of propolis. Five compounds were isolated from the EEP, and their structures were determined as mangiferolic acid, cycloartenol, ambonic acid, mangiferonic acid, and ambolic acid, which are cycloartane-type triterpenes. The characteristic peak of the HPLC chromatograms of EEP and EEM showed a similar pattern, which is that the main components of propolis were also found in M. indica resin. These results suggested that the propolis from Southeast Sulawesi was rich in cycloartane-type triterpenes, and the plant source of the propolis could be Mangifera indica (mango).

Caffeic acid phenethyl ester protects against oxidative stress and dampens inflammation via heme oxygenase 1

Periodontal disease is associated with chronic oxidative stress and inflammation. Caffeic acid phenethyl ester (CAPE), which is a potent inducer of heme oxygenase 1 (HO1), is a central active component of propolis, and the application of propolis improves periodontal status in diabetic patients. Here, primary murine macrophages were exposed to CAPE. Target gene expression was assessed by whole-genome microarray, RT-PCR and Western blotting. The antioxidative and anti-inflammatory activities of CAPE were examined by exposure of the cells to hydrogen peroxide, saliva and periodontal pathogens. The involvement of HO1 was investigated with the HO1 inhibitor tin protoporphyrin (SnPP) and knockout mice for Nrf2, which is a transcription factor for detoxifying enzymes. CAPE increased HO1 and other heat shock proteins in murine macrophages. A p38 MAPK inhibitor and Nrf2 knockout attenuated CAPE-induced HO1 expression in macrophages. CAPE exerted strong antioxidative activity. Additionally, CAPE reduced the inflammatory response to saliva and periodontal pathogens. Blocking HO1 decreased the antioxidative activity and attenuated the anti-inflammatory activity of CAPE. In conclusion, CAPE exerted its antioxidative effects through the Nrf2-mediated HO1 pathway and its anti-inflammatory effects through NF-κB inhibition. However, preclinical models evaluating the use of CAPE in periodontal inflammation are necessary in future studies.