artepillin-c and baccharin

Breast cancer has the highest incidence and mortality in females, while prostate cancer has the second-highest incidence in males. Studies have shown that compounds from Brazilian green propolis have antitumor activities and can selectively inhibit the AKR1C3 enzyme, overexpressed in hormone-dependent prostate and breast tumors. Thus, in an attempt to develop new cytotoxic inhibitors against these cancers, three prenylated compounds, artepillin C, drupanin and baccharin, were isolated from green propolis to synthesize new derivatives via coupling reactions with different amino acids. All obtained derivatives were submitted to antiproliferative assays against four cancer cells (MCF-7, MDA MB-231, PC-3, and DU145) and two normal cell lines (MCF-10A and PNT-2) to evaluate their cytotoxicity. In general, the best activity was observed for compound6e, derived from drupanin, which exhibited half-maximal inhibitory concentration (IC

Topics: Amino Acids; Antineoplastic Agents, Phytogenic; Cell Line, Tumor; Cell Proliferation; Cinnamates; Dose-Response Relationship, Drug; Drug Screening Assays, Antitumor; Humans; Molecular Structure; Phenylpropionates; Propolis; Structure-Activity Relationship; Trichothecenes

Propolis, a compound produced by honeybees, has long been used in food and beverages to improve health and prevent diseases. We previously reported that the ethanol extracts of Brazilian green propolis and its constituents artepillin C, kaempferide, and kaempferol mitigate oxidative stress-induced cell death via oxytosis/ferroptosis. Here, we investigated the potential of Brazilian green propolis and its constituents to protect against endoplasmic reticulum stress in the mouse hippocampal cell line HT22. Ethanol extracts of Brazilian green propolis, artepillin C, and kaempferol attenuated tunicamycin-induced unfolded protein response and cell death. Interestingly, artepillin C inhibited both tunicamycin-induced protein aggregation in HT22 cells and the spontaneous protein aggregation of mutant canine superoxide dismutase 1 (E40K-SOD1-EGFP) in Neuro2a cells. These findings indicate that in addition to oxidative stress, the ethanol extracts of Brazilian green propolis help prevent endoplasmic reticulum stress-related neuronal cell death, which is proposedly involved in several neurodegenerative diseases. Moreover, artepillin C, a major constituent of Brazilian green propolis, may exhibit chemical chaperone-like properties.

Topics: Animals; Brazil; Cell Death; Cell Line; Cell Survival; Cinnamates; Coumaric Acids; eIF-2 Kinase; Endoplasmic Reticulum Stress; Ethanol; Eukaryotic Initiation Factor-2; Flavonoids; Hippocampus; Kaempferols; Membrane Proteins; Mice; Oxidative Stress; Phenylpropionates; Propolis; Protective Agents; Protein Aggregates; Protein Serine-Threonine Kinases; Trichothecenes; Tunicamycin

Topics: Animals; Anti-Bacterial Agents; Antioxidants; Bees; Biofilms; Brazil; Chromatography, High Pressure Liquid; Cinnamates; Dietary Supplements; Flavonoids; Metabolomics; Microbial Sensitivity Tests; Phenylpropionates; Propolis; Pseudomonas aeruginosa; Staphylococcus aureus; Trichomonas vaginalis; Trichothecenes

This study evaluated the antiproliferative activity of the Brazilian green propolis and Baccharis dracunculifolia extracts and their major compounds artepillin C and baccharin in different tumor cell lines. The lowest IC50 values observed for Brazilian green propolis and B. dracunculifolia extracts were 41.0 ± 4.5 µg/mL for U343 and 44.9 ± 7.1 µg/mL for HepG2, respectively. Regarding artepillin C and baccharin, the lowest IC50 values were 20.1 ± 2.9 for U343 and 13.0 ± 1.5 µg/mL for B16F10, respectively. For the association of artepillin C plus baccharin, the lowest IC50 result was 35.2 ± 0.5 µg/mL for B16F10. Artepillin C and baccharin were more cytotoxic than both Brazilian green propolis and B. dracunculifolia extracts. No additive or synergistic effect was observed for the association of artepillin C plus baccharin.

Topics: Antineoplastic Agents; Antineoplastic Agents, Phytogenic; Apitherapy; Baccharis; Brazil; HeLa Cells; Hep G2 Cells; HT29 Cells; Humans; Inhibitory Concentration 50; MCF-7 Cells; Neoplasms; Phenylpropionates; Phytotherapy; Plant Extracts; Propolis; Trichothecenes

The human aldo-keto reductase (AKR) 1C3, also known as type-5 17β-hydroxysteroid dehydrogenase and prostaglandin F synthase, has been suggested as a therapeutic target in the treatment of prostate and breast cancers. In this study, AKR1C3 inhibition was examined by Brazilian propolis-derived cinnamic acid derivatives that show potential antitumor activity, and it was found that baccharin (1) is a potent competitive inhibitor (K(i) 56 nM) with high selectivity, showing no significant inhibition toward other AKR1C isoforms (AKR1C1, AKR1C2, and AKR1C4). Molecular docking and site-directed mutagenesis studies suggested that the nonconserved residues Ser118, Met120, and Phe311 in AKR1C3 are important for determining the inhibitory potency and selectivity of 1. The AKR1C3-mediated metabolism of 17-ketosteroid and farnesal in cancer cells was inhibited by 1, which was effective from 0.2 μM with an IC(50) value of about 30 μM. Additionally, 1 suppressed the proliferation of PC3 prostatic cancer cells stimulated by AKR1C3 overexpression. This study is the first demonstration that 1 is a highly selective inhibitor of AKR1C3.

Topics: 3-Hydroxysteroid Dehydrogenases; Aldo-Keto Reductase Family 1 Member C3; Brazil; Crystallography, X-Ray; Humans; Hydroxyprostaglandin Dehydrogenases; Male; Molecular Conformation; Nuclear Magnetic Resonance, Biomolecular; Propolis; Stereoisomerism; Trichothecenes

Brazilian green propolis is a popular health supplement because of its various biological properties. The ethanol extract of Brazilian green propolis (EEBP) is characteristic for its herb-like smell and unique pungent taste. However, the ingredients responsible for its pungency have not yet been identified. This study provides the first evidence that artepillin C is the main pungent ingredient in EEBP and that it potently activates human transient receptor potential ankyrin 1 (TRPA1) channels. EEBP was fractionated using column chromatography with a step gradient elution of an ethanol-water solution, and the fractions having the pungent taste were determined by sensory tests. HPLC analysis revealed that the pungent fraction was composed primarily of artepillin C, a prenylated derivative of cinnamic acid. Artepillin C was also identified as the pungent compound of EEBP by organoleptic examiners. Furthermore, the effects of artepillin C and other cinnamic acids found in EEBP on TRPA1 channels were examined by calcium imaging and plate reader-based assays in human TRPA1-expressing cells to investigate the molecular mechanisms underlying their pungent tastes. Artepillin C and baccharin activated the TRPA1 channel strongly, whereas drupanin caused a slight activation and p-coumaric acid showed no activation. Because the EC(50) values of artepillin C, baccharin, and allyl isothiocyanate were 1.8 µM, 15.5 µM, and 6.2 µM, respectively, artepillin C was more potent than the typical TRPA1 agonist allyl isothiocyanate. These findings strongly indicate that artepillin C is the main pungent ingredient in EEBP and stimulates a pungent taste by activating TRPA1 channels.

Topics: Calcium; Calcium Channels; Cell Line; Chemistry, Pharmaceutical; Chromatography, High Pressure Liquid; Cinnamates; Coumaric Acids; Dietary Supplements; Dose-Response Relationship, Drug; Drug Design; Humans; Isothiocyanates; Models, Chemical; Nerve Tissue Proteins; Phenylpropionates; Plant Extracts; Propionates; Propolis; Taste; Transfection; Transient Receptor Potential Channels; Trichothecenes; TRPA1 Cation Channel

Bee products (including propolis, royal jelly, and bee pollen) are popular, traditional health foods. We compared antioxidant effects among water and ethanol extracts of Brazilian green propolis (WEP or EEP), its main constituents, water-soluble royal jelly (RJ), and an ethanol extract of bee pollen.. The hydrogen peroxide (H2O2)-, superoxide anion (O2.-)-, and hydroxyl radical (HO.)- scavenging capacities of bee products were measured using antioxidant capacity assays that employed the reactive oxygen species (ROS)-sensitive probe 5-(and-6)-chloromethyl-2',7'-dichlorodihydrofluorescein diacetate, acetyl ester (CM-H2DCFDA) or aminophenyl fluorescein (APF).. The rank order of antioxidant potencies was as follows: WEP > EEP > pollen, but neither RJ nor 10-hydroxy-2-decenoic acid (10-HDA) had any effects. Concerning the main constituents of WEP, the rank order of antioxidant effects was: caffeic acid > artepillin C > drupanin, but neither baccharin nor coumaric acid had any effects. The scavenging effects of caffeic acid were as powerful as those of trolox, but stronger than those of N-acetyl cysteine (NAC) or vitamin C.. On the basis of the present assays, propolis is the most powerful antioxidant of all the bee product examined, and its effect may be partly due to the various caffeic acids it contains. Pollen, too, exhibited strong antioxidant effects.

Topics: Acetylcysteine; Animals; Ascorbic Acid; Bees; Caffeic Acids; Chromans; Cinnamates; Coumaric Acids; Fatty Acids; Fatty Acids, Monounsaturated; Free Radical Scavengers; Phenylpropionates; Plant Extracts; Pollen; Propolis; Quinic Acid; Trichothecenes