PMID: 

Pharm Dev Technol. 2020 Mar 20:1-10. Epub 2020 Mar 20. PMID: 32192406

Abstract Title: 

Quercetin-loaded nanoparticles enhance cytotoxicity and antioxidant activity on C6 glioma cells.

Abstract: 

Quercetin (Qu) is a natural flavonoid present in many commonly consumed food items. The dietary phytochemical quercetin prevents tumor proliferation and is a potent therapeutic cancer agent. The purpose of this study was to synthesize and characterize quercetin-loaded poly(lactic-co-glycolic acid) nanoparticles (QuNP, QuNP, and QuNP) with different size and encapsulation properties and to evaluate theiractivity on C6 glioma cells. Nanoparticles were synthesized by single emulsion solvent evaporation method. Then, particle size, zeta potential, polydispersity index and encapsulation efficiency of nanoparticles were determined. Particle size of QuNP, QuNP, and QuNPs were determined as 215.2 ± 6.2, 282.3 ± 7.9, and 584.5 ± 15.2 nm respectively. Treating C6 glioma cells with all nanoparticle formulations effectively inhibited the cell proliferation. QuNPs were showed the lowest ICvalue in 48 h with 29.9 μg/ml and achieved higher cellular uptake among other nanoparticles and Qu. Additionally, 48-h treatment with QuNPs significantly decreased MDA level (14.90 nmol/µg protein) on C6 glioma cells which is related to reduced oxidative stress in cells. Findings of this study revealed that quercetin's cellular uptake and anti-oxidant activity is improved by small-sized QuNPs in C6 glioma cells.

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PMID: 

Eur J Pharm Sci. 2020 Mar 18:105314. Epub 2020 Mar 18. PMID: 32200044

Abstract Title: 

Quercetin lipid nanoparticles functionalized with transferrin for Alzheimer's disease.

Abstract: 

Quercetin was encapsulated in lipid nanoparticles (SLN and NLC) to take advantage of its neuroprotective properties in Alzheimer's disease. The nanoparticles were functionalized with transferrin to facilitate the passage across the blood-brain barrier through the transferrin receptors overexpressed in brain endothelial cells. NMR and FTIR confirmed the functionalization of the nanoparticles with transferrin. TEM results showed all nanoparticles presented spherical morphology. Nanoparticles exhibited size around 200 nm and zeta potential values higher than -30 mV. Quercetin entrapment efficiency was around 80-90%. LDH cytotoxicity assays in hCMEC/D3 cell line demonstrated that even for the highest concentration (30μM) nanoparticles did not reveal cytotoxicity after 4 hours of incubation. Permeability studies across hCMEC/D3 cell monolayers showed NLC permeate more the blood-brain barrier, while amyloid-beta studies demonstrated NLC-transferrin have the capacity to inhibit fibril formation. Nanoparticles seemto be suitable for brain applications, mainly for Alzheimer's disease due to inhibition of amyloid-beta aggregation.

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PMID: 

Microorganisms. 2020 Feb 12 ;8(2). Epub 2020 Feb 12. PMID: 32059431

Abstract Title: 

Propolis AffectsGrowth, Biofilm Formation, eDNA Release and Phenazine Production: Potential Involvement of Polyphenols.

Abstract: 

() is an opportunistic pathogen responsible for a wide range of clinical conditions, from mild infections to life-threatening nosocomial biofilm-associated diseases, which are particularly severe in susceptible individuals. The aim of thisstudy was to assess the effects of an Albanian propolis on several virulence-related factors of, such as growth ability, biofilm formation, extracellular DNA (eDNA) release and phenazine production. To this end, propolis was processed using three different solvents and the extracted polyphenolic compounds were identified by means of high performance liquid chromatography coupled to electrospray ionization mass spectrometry (HPLC-ESI-MS) analysis. As assessed by a bioluminescence-based assay, among the three propolis extracts, the ethanol (EtOH) extract was the most effective in inhibiting both microbial growth and biofilm formation, followed by propylene glycol (PG) and polyethylene glycol 400 (PEG 400) propolis extracts. Furthermore,exposure to propolis EtOH extract caused a decrease in eDNA release and phenazine production. Finally, caffeic acid phenethyl ester (CAPE) and quercetin decreased upon propolis EtOH extract exposure to bacteria. Overall, our data add new insights on the anti-microbial properties of a natural compound, such as propolis against. The potential implications of these findings will be discussed.

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PMID: 

World Neurosurg. 2020 Mar 18. Epub 2020 Mar 18. PMID: 32200016

Abstract Title: 

The Impact of Propolis Factor Caffeic Acid Phenethyl-Ester on the Cerebral Vasospasm and Early Brain Damage in the Exparimentally Induced Subarachnoid Hemorrhage on Rats.

Abstract: 

AIM: CAPE, a phenolic compound, besides being one of the biologically active components of propolis, is a compound with antioxidant, antiinflammatory, antiviral, reperfusion damage prevention, immune stimulant and carcinostatic, anticancer properties. The aim of this study was to investigate the possible effects of CAPE on cerebral vasospasm and early brain injury, which were experimentally administered intraperitoneally in rats with subarachnoid hemorrhage.MATERIAL AND METHODS: 32 Wistar Albino rats weighing 200-300 grams were used in our study. The rats divided into three groups namely as Control group (n = 10), subarachnoid hemorrhage group (n = 11) and subarachnoid hemorrhage + CAPE group (n = 11) were evaluated according to the Ischemia index in hippocampal CA3 regions and the morphometric analysis of basilar artery diameter after being sacrified at the end of 72th hour.RESULTS: A significant difference was found between group-1 and group-2 for the CA-3 region, it was concluded that early brain damage occurred after subarachnoid hemorrhage. When the neuronal damage in CA-3 region was evaluated between group-2 and group-3, a statistically significant difference was found between the groups. There was a statistically significant difference between group-1 and group-3 in terms of ischemia detection.CONCLUSION: It was shown that CAPE has a preventive effect on early brain injury after SAH and has a positive effect on reducing cerebral vasospasm. Our study is the first study in the literature showing that CAPE inhibits ischemic brain injury following SAH.

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PMID: 

Molecules. 2020 Mar 12 ;25(6). Epub 2020 Mar 12. PMID: 32178333

Abstract Title: 

Effects of Propolis and Phenolic Acids on Triple-Negative Breast Cancer Cell Lines: Potential Involvement of Epigenetic Mechanisms.

Abstract: 

Triple-negative breast cancer is an aggressive disease frequently associated with resistance to chemotherapy. Evidence supports that small molecules showing DNA methyltransferase inhibitory activity (DNMTi) are important to sensitize cancer cells to cytotoxic agents, in part, by reverting the acquired epigenetic changes associated with the resistance to therapy. The present study aimed to evaluate if chemical compounds derived from propolis could act as epigenetic drugs (epi-drugs). We selected three phenolic acids (caffeic, dihydrocinnamic, and-coumaric) commonly detected in propolis and the (-)-epigallocatechin-3-gallate (EGCG) from green tea, which is a well-known DNA demethylating agent, for further analysis. The treatment with-coumaric acid and EGCG significantly reduced the cell viability of four triple-negative breast cancer cell lines (BT-20, BT-549, MDA-MB-231, and MDA-MB-436). Computational predictions by molecular docking indicated that both chemicals could interact with the MTAse domain of the human DNMT1 and directly compete with its intrinsic inhibitor-Adenosyl-l-homocysteine (SAH). Although the ethanolic extract of propolis (EEP) did not change the global DNA methylation content, by using MS-PCR (Methylation-Specific Polymerase Chain Reaction) we demonstrated that EEP and EGCG were able to partly demethylate the promoter region ofin BT-549 cells. Also, in vitro treatment with EEP altered the RASSF1 protein expression levels. Our data indicated that some chemical compound present in the EEP has DNMTi activity and can revert the epigenetic silencing of the tumor suppressorThese findings suggest that propolis are a promising source for epi-drugs discovery.

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PMID: 

Oxid Med Cell Longev. 2020 ;2020:4014838. Epub 2020 Feb 26. PMID: 32184916

Abstract Title: 

Chemopreventive Effects of Propolis in the MNU-Induced Rat Mammary Tumor Model.

Abstract: 

Currently, one of the central problems in cancer management is the relapse of disease following conventional treatments, yet few therapeutic agents targeting resistance and tolerance exist. Propolis is known as a healing agent since ancient times. Therefore, over time, its curative properties have kept the interest of scientists, thus leading permanently to investigations of its other possible undiscovered effects. In this context, current experiments were performed to establish the chemopreventive potential of propolis extract (PE) (1.05 mg/kg BW/day) in N-methyl-N-nitrosourea- (MNU-) induced rat mammary tumors. MNU-inoculated/PE-treated rats had tumors of different physical attributes compared with control rats MNU-inoculated. The number of developed tumors (mean 49% versus 100%), incidence (mean 49% versus 100%), multiplicity (1.8 versus 3.7 (

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PMID: 

Enferm Clin. 2020 Mar ;30 Suppl 2:96-99. PMID: 32204266

Abstract Title: 

Propolis and honey trigona decrease leptin levels of central obesity patients.

Abstract: 

OBJECTIVE: This study aimed to examine whether honey and propolis Trigona can reduce the level of leptin in central obesity human.METHODS: It was a quasi-experimental study, population and sample were central obesity and normal weight as control. Sample size was 30 participants taken using purposive sampling.RESULTS: Intervention as long as 14 days make an increased level of leptin as many as 97.076pg/ml in control group and decreasing respectively 171.803pg/ml and 245.293pg/ml in honey and propolis intervention group, both significant statistically. The dose of honey given was 105mg/days divided into 3 packs, and each pack contains 35mg. The dose of propolis was 60mg/days and divided into 3 capsules, each of it contains 20mg. Intervention as long as 14 days and leptin levels examined using human ELISA Kit three times, that is before intervention, 7 days after the intervention and 14 days after intervention.CONCLUSION: Honey and propolis Trigona has the ability to decrease leptin level of central obesity participants. These honey bee products are potential to be a dietary supplement for central obesity patients.

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PMID: 

Am J Chin Med. 2020 Mar 5:1-18. Epub 2020 Mar 5. PMID: 32138531

Abstract Title: 

Wigg. Attenuates Inflammatory Responses in Murine Microglia through the Nrf2/HO-1 and NF-B Signaling Pathways.

Abstract: 

As a long-established medicinal and edible homologous plant,Wigg. is widely distributed in Asia, Europe, and other parts of the world.is reported to exert a variety of biological and pharmacological activities, including anticancer, hepatoprotective, and anti-obesity effects. In this study, we evaluated the anti-inflammatory effects of ethanol extracts of(A-TOW) by examining the suppression of proinflammatory mediators in LPS-stimulated BV2 and mouse hippocampus. Furthermore, A-TOW also inhibited the nuclear translocation of nuclear factorB p65 caused by stimulation with LPS. In addition, A-TOW regulates heme oxygenase (HO)-1 expression through the nuclear translocation of nuclear factor E2-related factor 2 (Nrf2) in BV2 cells. The effects of A-TOW on the over-expression of proinflammatory mediators were partially reversed by transfection of the cells with HO-1 siRNA. These findings suggest that the potent anti-inflammatory activity of, possibly through the regulation of Nrf2/HO-1 and NF-B signaling pathway.

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PMID: 

Phytother Res. 2020 Mar 6. Epub 2020 Mar 6. PMID: 32144852

Abstract Title: 

Janus kinase 2 inhibition by Licochalcone B suppresses esophageal squamous cell carcinoma growth.

Abstract: 

Esophageal cancer (EC) is one of the leading causes to cancer death in the worldwide and major population of EC is esophageal squamous cell carcinoma (ESCC). Still, ESCC-targeted therapy has not been covered yet. In the present study we have identified that Licochalcone B (Lico B) inhibited the ESCC growth by directly blocking the Janus kinase (JAK) 2 activity and its downstream signaling pathway. Lico B suppressed KYSE450 and KYSE510 ESCC cell growth, arrested cell cycle at G2/M phase and induced apoptosis. Direct target of Lico B was identified by kinase assay and verified with in vitro and ex vivo binding. Computational docking model predicted for Lico B interaction to ATP-binding pocket of JAK2. Furthermore, treatment of JAK2 clinical medicine AZD1480 to ESCC cells showed similar tendency with Lico B. Thus, JAK2 downstream signaling proteins phosphorylation of STAT3 at Y705 and S727 as well as STAT3 target protein Mcl-1 expression was decreased with treatment of Lico B. Our results suggest that Lico B inhibits ESCC cell growth, arrests cell cycle and induces apoptosis, revealing the underlying mechanism involved in JAK2/STAT3 signaling pathways after Lico B treatment. It might provide potential role of Lico B in the treatment of ESCC.

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PMID: 

Biomolecules. 2020 Feb 13 ;10(2). Epub 2020 Feb 13. PMID: 32070026

Abstract Title: 

Licochalcone D Induces ROS-Dependent Apoptosis in Gefitinib-Sensitive or Resistant Lung Cancer Cells by Targeting EGFR and MET.

Abstract: 

Licochalcone D (LCD), a flavonoid isolated from a Chinese medicinal plant, has a variety of pharmacological activities. However, the anti-cancer effects of LCD on non-small cell lung cancer (NSCLC) have not been investigated yet. The amplification of(hepatocyte growth factor receptor) compensates for the inhibition of epidermal growth factor receptor (EGFR) activity due to tyrosine kinase inhibitor (TKI), leading to TKI resistance. Therefore, EGFR and MET can be attractive targets for lung cancer. We investigated the anti-proliferative and apoptotic effects of LCD in lung cancer cells HCC827 (gefitinib-sensitive) and HCC827GR (gefitinib-resistant) through 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, pull-down/kinase assay, cell cycle analysis, Annexin-V/7-ADD staining, reactive oxygen species (ROS) assay, mitochondrial membrane potential (MMP) assay, multi-caspase assay, and Western blot analysis. The results showed that LCD inhibited phosphorylation and the kinase activity of EGFR and MET. In addition, the predicted pose of LCD was competitively located at the ATP binding site. LCD suppressed lung cancer cells growth by blocking cell cycle progression at the G2/M transition and inducing apoptosis. LCD also induced caspases activation and poly (ADP-ribose) polymerase (PARP) cleavage, thus displaying features of apoptotic signals. These results provide evidence that LCD has anti-tumor effects by inhibiting EGFR and MET activities and inducing ROS-dependent apoptosis in NSCLC, suggesting that LCD has the potential to treat lung cancer.

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