Flavonoids In Propolis Research Articles

A Validated RP-HPLC–DAD Method for Analyzing Flavonoids in Caatinga Brazilian Green Propolis from Mimosa tenuiflora Produced by Apis mellifera

A Validated RP-HPLC–DAD Method for Analyzing Flavonoids in Caatinga Brazilian Green Propolis from Mimosa tenuiflora Produced by Apis mellifera

Caffeic acid phenethyl ester ameliorates colistin-induced nephrotoxicity in rats via modulation of FOXO1/Nrf2/Sirt1 axis.

Colistin (Cst) is one of the antimicrobial peptides and is reserved for use against multi-drug-resistant Gram-negative bacteria. However, the clinical value of Cst is limited by its nephrotoxic adverse effects. Caffeic acid phenethyl ester (CAPE) is a honeybee propolis flavonoid recognised for its diverse pharmacological potential. It has demonstrated d antioxidant and anti-inflammatory properties, as well as protective effects against chemically induced toxicity in variuos biological systems. This study aimed to investigate the impact of CAPE on nephrotoxicity induced in rats by Cst. Animals were randomly divided into five groups. Group 1 served as control, group 2 received CAPE (10 mg/kg) orally, group 3 received Cst IP, group 4 received Cst + CAPE (5 mg/kg) and group 5 received Cst + CAPE (10 mg/kg). All treatments were given daily for 10 consecutive days. CAPE notably attenuated Cst-inducednephrotoxicity as shown by reducing urea serum levels, creatinine, cystatin C, urinary protein contents and urinary N-acetyl-β-D-glucosaminidase (NAG). This was confirmed by histological investigations that indicated amelioration of histopathological changes in the kidney architecture as well as the deposition of collagen in renal tissues. CAPE exhibited antioxidant effects supported by the prevention of rise in Cst-induced lipid peroxidation and depletion of superoxide dismutase and catalase enzymatic activities. In addition, CAPE inhibited the expression of the inflammatory markers including tumour necrosis factor-α, nuclear factor kappa B and interleukin-6. These actions were associated with modulation of messenger ribonucleic acid (mRNA) expression of Bax and Bcl-2 in favour of anti-apoptosis. CAPE inhibited Cst-induced rise in forkhead box O1 (FOXO1) expression and downregulation of nuclear factor erythroid 2-related factor 2 (Nrf2) and Sirtuin 1 (Sirt1) immune-expression. CAPE protects against nephrotoxicity induced by Cst in ratsprimarily through its antioxidant, antiinflammatory and antiapoptotic activities. These pritective effects are mediatedvia modulation of FOXO1/Nrf2/Sirt1 axis.

Inhibitory Effects of Propolis Flavonoids on Migration and Invasion of Laryngeal Cancer Cell and Analysis of Related Signal Pathways

Laryngeal cancer (LGC) is a malignant tumor that occurs in the larynx, and it is mainly treated through chemotherapy, radiotherapy, and surgery. Nevertheless, the five-year survival rate for patients is poor. Bee propolis contains various bioactive compounds and abundant anti-tumor active ingredients. Nevertheless, research on the use of propolis extracts for the treatment of LGC is relatively limited. This research aimed to demonstrate the inhibitory effects of ethanol extracts of propolis on migration (Mig) and invasion (Inv ) of LGC cells, as well as the related signaling pathways. The effects of graded ethanol extraction of propolis on the proliferation (Pro), Inv, Mig, apoptosis (Apo), and related signaling pathways of Hep-2 cells were analyzed. Propolis was extracted using ethanol (0%, 25%, 50%, 75%, and 100%) for the graded extraction of crude propolis. The flavonoid content and yield of the extracts were determined. The effects of various concentrations of propolis flavonoids on the clearance of 2,2-diphenyl-1-picrylhydrazyl (DPPH) radicals, O2- radicals, and 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonate) (ABTS) radicals were evaluated, as well as their effects on the Pro inhibition of normal human pancreatic ductal epithelial (hTERT-HPNE) cells. Hep-2 cells of LGC were cultured using media containing 0, 25, 50, and 100 μmol/L propolis flavonoids. The cell Pro activity, Inv, Mig, Apo, and expression of PI3K/Akt pathway-related proteins were evaluated using CCK-8 assay, Transwell chamber assay, acridine orange/ethidium bromide (AO/EB) double staining method, and Western blotting, respectively. It was revealed that extraction with 50% ethanol solution yielded a higher content and yield of flavonoids, which were 51.20% and 7.42%, respectively. As the concentration of propolis flavonoids increased, the clearance rates of DPPH, O2-, and ABTS radicals, as well as the inhibition of hTERT-HPNE Pro, gradually increased. The maximum clearance rates were 84.1%, 26.6%, and 92.3%, respectively, while the maximum cell Pro inhibition rate was only 8.6%. Relative to the 0 μmol/L propolis flavonoid treatment group, the Hep-2 cells treated with 25, 50, and 100 μmol/L propolis flavonoids exhibited decreased cell Pro activity, reduced number of invasive and migratory cells, increased Apo rate, decreased PI3K and p-Akt proteins, and demonstrated a concentration-dependent effect (P < 0.05). In summary, the extraction with 50% ethanol solution resulted in a higher yield of flavonoids. Propolis flavonoids demonstrated marked antioxidant activity and did not cause damage to normal hTERT-HPNE cells. They exhibited inhibitory effects on the Pro, Inv, and Mig of Hep-2 cells in LGC, and promoted cell Apo. These effects may be associated with PI3K/Akt signaling inhibition.

The effect of nano propolis on surface color changes of nanohybrid composite resins

Background: Nanohybrid composite resins have many advantages, but one disadvantage is their absorbent nature which can lead to discoloration. Phenols and flavonoids in nano propolis cause diffusion and affect the matrix and pigments of nanohybrid composite resins. The accumulation of reduction-oxidation reactions causes new compounds of nanohybrid composite resins to occur so that they have different colors. Objective: The study was conducted to determine the changes in surface color of nanohybrid composite resin after immersion in nano propolis at 5% concentration. Methods: Research experimental laboratory method with pre and post test design was applied to 25 nanohybrid composite resin fruit samples of size (5x5x1.5) mm embedded in bovine incisive, then immersed in 5% nano propolis and 25 ml of distilled water at 37oC for five days. The color change (ΔE) was measured with a DSLR camera and processed with Adobe Lightroom Classic software in CIE L*a*b* format. Results: The anova test on ΔE in the data showed the p-value of sphericity assumed was smaller than 0.05. There is a difference in the average measurement results on the first day to the fifth day in the treatment group. Independent t-test of control and treatment data showed a significant difference in measurement results. The results of the post hoc test with the Tukey method showed that the treatment groups at 4x24 hours and 5x24 hours did not have significant differences. P-value at 4x24 hours and 5x24 hours was 0.957. Conclusion: There was a change in the surface color of the nanohybrid composite resin after being immersed in a nano-solution of propolis with a concentration of 5%.

Pinocembrin's protective effect against acute pancreatitis in a rat model: The correlation between TLR4/NF-κB/NLRP3 and miR-34a-5p/SIRT1/Nrf2/HO-1 pathways

BackgroundAcute pancreatitis (APS) is a prevalent acute pancreatic inflammation, where oxidative stress, inflammatory signaling pathways, and apoptosis activation contribute to pancreatic injury. MethodsPinocembrin, the predominant flavonoid in propolis, was explored for its likely shielding effect against APS provoked by two intraperitoneal doses of L-arginine (250 mg / 100 g) in a rat model. ResultsPinocembrin ameliorated the histological and immunohistochemical changes in pancreatic tissues and lowered the activities of pancreatic amylase and lipase that were markedly elevated with L-arginine administration. Moreover, pinocembrin reinstated the oxidant/antioxidant equilibrium, which was perturbed by L-arginine, and boosted the pancreatic levels of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1). Pinocembrin markedly reduced the elevation in serum C-reactive protein (CRP) level induced by L-arginine. Additionally, it decreased the expression of high motility group box protein 1 (HMGB1), toll-like receptor 4 (TLR4), nuclear factor kappa B (NF-κB), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and NOD-like receptor (NLR) Family Pyrin Domain Containing 3 (NLRP3) inflammasome in the pancreas. Furthermore, it also reduced myeloperoxidase (MPO) activity. Pinocembrin markedly downregulated miR-34a-5p expression and upregulated the protein levels of peroxisome proliferator-activated receptor alpha (PPAR-α) and Sirtuin 1 (SIRT1) and the gene expression level of the inhibitor protein of NF-κB (IκB-α), along with normalizing the Bax/Bcl-2 ratio. ConclusionsPinocembrin notably improved L-arginine-induced APS by its antioxidant, anti-inflammatory, and anti-apoptotic activities. Pinocembrin exhibited a protective role in APS by suppressing inflammatory signaling via the TLR4/NF-κB/NLRP3 pathway and enhancing cytoprotective signaling via the miR-34a-5p/SIRT1/Nrf2/HO-1 pathway.

Cubic liquid crystals containing propolis flavonoids as in situ thermo-sensitive hydrogel depots for periodontitis treatment: Preparation, pharmacodynamics and therapeutic mechanisms

Propolis has a long ethnopharmacological history for oral periodontal diseases treatment. Propolis flavonoids are main active components for anti-inflammation and tissue protection. However, the intractable dissolution properties of propolis flavonoids and complex oral environment pose great challenges for periodontal delivery. In addition, the therapeutic mechanism as well as the therapeutic correlation of inflammation resolution and tissue regeneration remain unclear for propolis flavonoids. In this study, we constructed an in situ thermosensitive depot systems using total flavonoids from propolis-loaded cubic liquid crystals (TFP-CLC) hydrogel for periodontal delivery. TFP-CLC inhibited inflammatory cell infiltration, reactive oxygen species and the expression of inflammatory cytokines of NF-κB and IL-1β. In addition, alveolar bone and collagen were significantly regenerated after TFP-CLC administration according to micro-CT and immunohistochemistry. Mechanism studies suggested that TFP-CLC alleviated inflammation and promoted alveolar bone repair via regulating TLR4/MyD88/NF-κB p65 and RANK/NF-κB signaling pathways, respectively. Correlation analysis further confirmed that the inflammatory resolution produced by TFP-CLC could accelerate periodontal tissue regeneration. In summary, TFP-CLC is a promising multifunctional in situ thermo-sensitive hydrogel depots for periodontitis treatment.

Antioxidant And Anti-Mycotoxin Activities, And Cytotoxicity Properties In Vitro Of Propolis Extracts

Abstract: The present study aims to determine the antioxidant activity and cytotoxic activity of propolis and evaluate the anti-mycotoxin activity of different propolis extracts. The three extracts of propolis (ethyl acetate, ethanol (75%), and water) were subjected to testing of the antioxidant potential, and total phenolic and flavonoid contents. determination of the cytotoxicity activity by standard cell culture method against colon and liver and the ability of propolis extracts to control aflatoxin (AF) production. The results revealed that the highest value of antioxidant activities was found for propolis ethyl acetate extract with an average % inhibition of 63.42%. the highest amount of propolis's total phenolic and flavonoid contents using ethyl acetate extract were 149.5 µg gallic acid equivalent/mg extract and 218.1 µg quercetin equivalent/mg extract, respectively. The three propolis extracts affect liver and colon human cell cancer. Ethyl acetate extract of propolis showed the lowest IC50 with the highest anti-cancer activity on the liver cancer cell line. In comparison, water extract showed the lowest IC50 with the greatest anticancer activity on the colon cancer cell line (50 and 54 µg/ml, respectively). Using different concentrations of propolis to reduce AF levels led to the complete disappearance of AF production at 100, 200, and 400 mg/ml concentrations of Ethyl acetate extract against AF production. In conclusion, these obtained findings indicated that propolis extracts exhibited substantial antioxidant and anti-cancer activities.

Construction of propolis flavonoids-phospholipid complex loaded O/W submicron emulsion for enhancing in-vivo dilution stability and gastrointestinal absorption efficiency

Although numerous propolis flavonoids (EEP) formulations have been developed as dietary supplements for assisting blood glucose regulation, their bioavailability and bioactivity are limited due to the lower solubilities in aqueous media. To address this challenge, a novel O/W submicron emulsion was constructed to efficiently deliver propolis flavonoids and improve the absorption efficiency. Results showed that this delivery vehicle exerted inspiring features of nano-scaled droplet size, narrow particle distribution and higher cargo loading efficiency. Compared to conventional preparations, EEP submicron emulsion exhibited excellent stability against dilution with different pH buffers and maintained physicochemical characteristics within six months. Most importantly, EEP submicron emulsion could be efficiently absorbed through gastrointestinal (GI) tract via multiple-uptake routes and dramatically enhanced the bioavailability of propolis flavonoids. In conclusion, O/W submicron emulsion is a promising carrier for improving the in vivo utilization efficiency of water-insoluble flavonoids in functional foods.

Correlation between total phenolic and flavonoid contents and biological activities of 12 ethanolic extracts of Iranian propolis.

Propolis is a resinous substance produced by honey bees that is very popular as a natural remedy in traditional medicine. The current research is the first study on the biological properties of ethanolic extracts of propolis (EEP) from several different regions (12) of Iran. Total phenolic and flavonoid contents (TPC and TFC) of Iranian EEPs were variable between 26.59-221.38 mg GAE/g EEP and 4.8-100.03 mg QE/g EEP. The DPPH scavenging assay showed all the studied EEP samples, except for the sample with the lowest TPC and TFC (P6), have suitable antioxidant activity. All the EEPs inhibited both cholinesterase enzymes (acetylcholinesterase: AChE, butyrylcholinesterase: BuChE) but most of them exhibited a distinct selectivity over BuChE. Evaluation of the antibacterial activity of the EEP samples using four pathogenic bacteria (B. cereus, S. aureus, A. baumannii, and P. aeruginosa) demonstrated that the antibacterial properties of propolis are more effective on the gram-positive bacterium. Spearman correlation analysis showed a strong positive correlation between TPC and TFC of the Iranian EEPs and their antioxidant, anticholinesterase, and antibacterial activities. Considering that there is ample evidence of anticholinesterase activity of flavonoids and a significant correlation between the anticholinesterase activity of the studied Iranian EEPs and their total flavonoid content was observed, the interaction of 17 well-known propolis flavonoids with AChE and BuChE was explored using molecular docking. The results indicated that all the flavonoids interact with the active site gorge of both enzymes with high affinity. Summing up, the obtained results suggest that Iranian propolis possesses great potential for further studies.

Propolis flavonoids liposome ameliorate doxorubicin-induced cardiotoxicity in rats

Propolis flavonoids liposome ameliorate doxorubicin-induced cardiotoxicity in rats

Gastroprotective and ulcer healing potentials of Nigerian Bee Propolis flavonoid extract on acetic acid-induced gastric ulcers in albino rats (Wistar Strains)

Gastroprotective and ulcer healing potentials of Nigerian Bee Propolis flavonoid extract on acetic acid-induced gastric ulcers in albino rats (Wistar Strains)

The Antioxidant and Anti-Inflammatory Effects of Flavonoids from Propolis via Nrf2 and NF-κB Pathways.

Accumulating evidence shows that oxidative stress and inflammation contribute to the development of cardiovascular disease. It has been suggested that propolis possesses antioxidant and anti-inflammatory activities. In this study, the antioxidant and anti-inflammatory effects of the main flavonoids of propolis (chrysin, pinocembrin, galangin, and pinobanksin) and propolis extract were researched. The results showed that the cellular ROS (Reactive oxygen species) levels, antioxidant enzymes, Nrf2 (Nuclear factor erythroid 2-related factor 2) nuclear translocation, and the expression of NQO1 (NAD(P)H:quinone oxidoreductase 1) and HO-1 (heme oxygenase 1) were regulated by different concentrations of individual flavonoids and propolis extract, which showed good antioxidant and pro-oxidant effects. For example, ROS levels were decreased; SOD and CAT activities were increased; and the expression of HO-1 protein was increased by chrysin. The results demonstrated that NO (Nitric Oxide), NOS (Nitric Oxide Synthase), and the activation of the NF-κB signaling pathway were inhibited in a dose-dependent manner by different concentrations of individual flavonoids and propolis extract. Moreover, the results revealed that the phytochemicals presented antioxidant effects at lower concentrations but pro-oxidant effects and stronger anti-inflammatory effects at higher concentrations. To maintain the balance of antioxidant and anti-inflammatory effects, it is possible that phytochemicals activate the Nrf2 pathway and inhibited the NF-κB (Nuclear factor kappa B) pathway.

Determination of the effect of green extraction solvents on the phenolic acids and flavonoids of propolis

The present study investigated the extraction of phenolic compounds from propolis according to solvent factor. The propolis samples were extracted in four different solvents, which water, ethanol-water (70%), dimethyl sulfoxide (DMSO), and L-lysine (8%), and were analyzed 36 phenolic compounds by HPLC-DAD. Statistically significant differences in solubility of the phenolic compound at various levels were detected among the solvents (P

Propolis efficacy on SARS-COV viruses: a review on antimicrobial activities and molecular simulations.

This current study review provides a brief review of a natural bee product known as propolis and its relevance toward combating SARS-CoV viruses. Propolis has been utilized in medicinal products for centuries due to its excellent biological properties. These include anti-oxidant, immunomodulatory, anti-inflammatory, anti-viral, anti-fungal, and bactericidal activities. Furthermore, studies on molecular simulations show that flavonoids in propolis may reduce viral replication. While further research is needed to validate this theory, it has been observed that COVID-19 patients receiving propolis show earlier viral clearance, enhanced symptom recovery, quicker discharge from hospitals, and a reduced mortality rate relative to other patients. As a result, it appears that propolis could probably be useful in the treatment of SARS-CoV-2-infected patients. Therefore, this review sought to explore the natural properties of propolis and further evaluated past studies that investigated propolis as an alternative product for the treatment of COVID-19 symptoms. In addition, the review also highlights the possible mode of propolis action as well as molecular simulations of propolis compounds that may interact with the SARS-CoV-2 virus. The activity of propolis compounds in decreasing the impact of COVID-19-related comorbidities, the possible roles of such compounds as COVID-19 vaccine adjuvants, and the use of nutraceuticals in COVID-19 treatment, instead of pharmaceuticals, has also been discussed.

Phytochemical Constituents of Propolis Flavonoid, Immunological Enhancement, and Anti-porcine Parvovirus Activities Isolated From Propolis

Propolis is widely used in health preservation and disease healing; it contains many ingredients. The previous study had revealed that the ethanolic or water extracts of propolis have a wide range of efficacy, such as antiviral, immune enhancement, anti-inflammatory, and so on, but its antiviral components and underlying mechanism of action remain unknown. In this study, we investigated the chemical composition, anti-porcine parvovirus (PPV) effectiveness, and immunological enhancement of propolis flavone ethanolic extracts. The chemical composition of propolis flavone was distinguished by ultra-performance liquid chromatography-quadrupole/time-of-flight tandem mass spectrometry analysis. In this study, the presence and characterization of 26 major components were distinguished in negative ionization modes to evaluate the effects of propolis flavonoid used as an adjuvant on the immune response of Landrace–Yorkshire hybrid sows immunized with an inactivated vaccine of PPV. Thirty Landrace-Yorkshire hybrid sows were randomly assigned to one of three groups, and the sows in the adjuvant groups were intramuscularly injected with PPV vaccine with a 2.0-ml propolis flavonoid adjuvant (PA) and oil emulsion adjuvant. After that, serum hemagglutination inhibition antibody titers and specific immunoglobulin (Ig)M and IgG subclasses were measured to evaluate the adjuvant effects of propolis flavonoid on the humoral immune responses, as well as peripheral lymphocyte proliferation activity and serum concentrations of Th1 and Th2 cytokines for cellular immunity. Results indicated an enhancing effect of PA on IgM, interleukins 2 and 4, interferon-γ, and IgG subclass responses. Especially in the effect of improving cellular immune response, the PA was the best. These findings suggested that PA can significantly enhance the immune responses against the PPV vaccine and could be an alternative way to improve PPV vaccination in sows. Furthermore, we screened the PF chemical components to the effectiveness of anti-PPV. Ferulic acid has an excellent anti-PPV effect.

Comparative study of royal jelly, propolis, and photobiomodulation therapies in 5-fluorouracil-related oral mucositis in rats.

This study aimed to evaluate the effects and mechanisms of action of royal jelly (RJ) and propolis compared to photobiomodulation therapy (PBMT) in an animal model of 5-fluorouracil-related oral mucositis (OM). Seventy-two male Wistar rats were randomly allocated to four groups (n = 18 each): control (no treatment), PBMT (intraoral laser, 6J/cm2), RJ, and propolis. On days 0 and 2, the animals received an injection of 5-fluorouracil (5-FU). The buccal mucosa was scratched (days 3 and 4) and the treatments were initiated on day 5. Six animals of each group were euthanized on days 8, 10, and 14. Phytochemical analysis (thin-layer chromatography, TLC) and clinical, histopathological, and immunohistochemical analysis of pS6, pAKT, and NF-κB were performed, and oxidative stress markers were also investigated. TLC revealed the presence of large amounts of sucrose (Rf 0.34) in RJ and of flavonoids in propolis. Lower clinical OM scores were observed on day 8, and improved morphological data were observed on day 10 in the PBMT, RJ, and propolis groups (p < 0.05). On day 8, immunoexpression of pS6, pAKT, and NF-κB was increased compared to control. On day 14, reduced glutathione (GSH) antioxidant levels were increased in the propolis group compared to control (p < 0.05). Our results showed that RJ and propolis, as well as PBMT, are effective in the treatment of OM. Considering that some patients who develop OM do not have access to PBMT, the present study demonstrated that topical application of RJ and propolis may be an important alternative for the treatment of OM.

Targeting CoV-2 spike RBD and ACE-2 interaction with flavonoids of Anatolian propolis by in silico and in vitro studies in terms of possible COVID-19 therapeutics.

Propolis is a multi-functional bee product rich in polyphenols. In this study, the inhibitory effect of Anatolian propolis against SARS-coronavirus-2 (SARS-CoV-2) was investigated in vitro and in silico. Raw and commercial propolis samples were used, and both samples were found to be rich in caffeic acid, p-coumaric acid, ferulic acid, t-cinnamic acid, hesperetin, chrysin, pinocembrin, and caffeic acid phenethyl ester (CAPE) at HPLC-UV analysis. Ethanolic propolis extracts (EPE) were used in the ELISA screening test against the spike S1 protein (SARS-CoV-2): ACE-2 interaction for in vitro study. The binding energy values of these polyphenols to the SARS-CoV-2 spike and ACE-2 protein were calculated separately with a molecular docking study using the AutoDock 4.2.6 program. In addition, the pharmacokinetics and drug-likeness properties of these eight polyphenols were calculated according to the SwissADME tool. The binding energy value of pinocembrin was highest in both receptors, followed by chrysin, CAPE, and hesperetin. Based on the in silico modeling and ADME (absorption, distribution, metabolism, and excretion) behaviors of the eight polyphenols, the compounds exhibited the potential ability to act effectively as novel drugs. The findings of both studies showed that propolis has a high inhibitory potential against the Covid-19 virus. However, further studies are now needed.

Potential hepatoprotective effects of flavonoids contained in propolis from South Sulawesi against chemotherapy agents.

The use of doxorubicin and epirubicin as chemotherapy agent causes side effects such as liver damage due to oxidative stress by reactive oxygen species (ROS) that cause increased of ALT and AST level as liver parameter. One source of natural antioxidants as ROS neutralizer comes from flavonoid that contain in propolis. Most researchers claim that flavonoid can be used to protect the liver. The aim of this study was to test the hepatoprotective effect of flavonoid in propolis from South Sulawesi against doxorubicin and epirubicin. The experiment included male Sprague dawley rats divided into nine groups. The rats received the microcapsule propolis or the quercetin orally for 15 days. The hepatotoxicity was promoted by injection epirubicin and doxorubicin (i.v.) with a cumulative dose of 9 mg/kg. In this study, total polyphenol and flavonoid tests of propolis have been carried out, there were 1.1% polyphenols and 2.7% flavonoids, the antioxidant activity tests showed IC50 value of 9849 ppm and LCMS/MS tests supported the presence of phenolic compounds in propolis from South Sulawesi. Liver parameter was measured and the results showed that the propolis 200 mg/kg group produced the lowest ALT and had potential protective effect against doxorubicin and epirubicin-induced hepatotoxicity.

Metabolic products of European-type propolis. Synthesis and analysis of glucuronides and sulfates

Ethnopharmacological relevancePropolis is a bee-derived product used since antiquity for its general health-giving properties and is especially noted for its anti-bacterial activity. In more recent times, propolis has been employed against more specific targets such as antiproliferative effects vs cancer cells, wound healing and type-2 diabetes. Aim of the studyEuropean (poplar)-type propolis from New Zealand contains a number of hydroxy cinnamic acid esters and a set of aglycone flavonoid compounds, mainly chrysin, galangin, pinocembrin and pinobanksin. Propolis is usually taken orally and propolis metabolites quickly appear in the plasma of the ingested. In this work we aimed to identify the major flavonoid plasma metabolites by direct analysis of the plasma. Materials and methodsAfter consumption of a large dose of propolis in a single sitting, blood samples were taken and analysed using LCMS/MS. The major flavonoid metabolites identified were also synthesised using chemical (sulfates) or enzymatic methods (glucuronides). ResultsBoth the sulfate and glucuronide conjugates of the four major propolis flavonoids are readily detected in human plasma after propolis ingestion. Preparation of the sulfates and glucuronides of the four major flavonoids allowed the relative proportions of the various metabolites to be determined. Although the sulfates are seen as large peaks in the LCMS/MS, the glucuronides are the dominant conjugate species. ConclusionsThis study shows most of the flavonoids in the plasma are present as 7-O-glucuronides with only galangin showing some di-glucuronidation (3,7-O-diglucuronide). No evidence was found for hydroxy cinnamic acid type metabolites in the plasma samples.

Propolis, Bee Honey, and Their Components Protect against Coronavirus Disease 2019 (COVID-19): A Review of In Silico, In Vitro, and Clinical Studies.

Despite the virulence and high fatality of coronavirus disease 2019 (COVID-19), no specific antiviral treatment exists until the current moment. Natural agents with immune-promoting potentials such as bee products are being explored as possible treatments. Bee honey and propolis are rich in bioactive compounds that express strong antimicrobial, bactericidal, antiviral, anti-inflammatory, immunomodulatory, and antioxidant activities. This review examined the literature for the anti-COVID-19 effects of bee honey and propolis, with the aim of optimizing the use of these handy products as prophylactic or adjuvant treatments for people infected with severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). Molecular simulations show that flavonoids in propolis and honey (e.g., rutin, naringin, caffeic acid phenyl ester, luteolin, and artepillin C) may inhibit viral spike fusion in host cells, viral-host interactions that trigger the cytokine storm, and viral replication. Similar to the potent antiviral drug remdesivir, rutin, propolis ethanolic extract, and propolis liposomes inhibited non-structural proteins of SARS-CoV-2 in vitro, and these compounds along with naringin inhibited SARS-CoV-2 infection in Vero E6 cells. Propolis extracts delivered by nanocarriers exhibit better antiviral effects against SARS-CoV-2 than ethanolic extracts. In line, hospitalized COVID-19 patients receiving green Brazilian propolis or a combination of honey and Nigella sativa exhibited earlier viral clearance, symptom recovery, discharge from the hospital as well as less mortality than counterparts receiving standard care alone. Thus, the use of bee products as an adjuvant treatment for COVID-19 may produce beneficial effects. Implications for treatment outcomes and issues to be considered in future studies are discussed.