Phytochemical investigation,physicochemical characterization,and antimicrobial activities of Ethiopian propolis

Propolis is a natural resin substance produced by honeybees by collecting from parts of plants, buds, and exudates that are used for several biological activities such as antimicrobial, and fungicide functions. This study aimed to analyze the phytochemical, physicochemical, and antimicrobial activity of propolis collected from Boji Dirmaji and Fincha’a districts of western Ethiopia. The physicochemical characteristics, phytochemical screening, and antimicrobial activity of Ethiopian propolis against Aspergillus niger, Escherichia coli, and Staphylococcus aureus were evaluated using the disk diffusion method from its essential oils and crude ethanol extract were evaluated based on standard procedures. The results indicated that propolis was rich in saponins, tannins, flavonoids, steroids, triterpenes, and glycosides. Physicochemically, n-hexane extractable substances ranged between 8.6 and 33.9%, resins soluble 14.8–16.8%, insoluble residues 70.8–85.5%, moisture 1.7–4.6%, and ash content 2.8–9.7%, and 4.8 pH. The antimicrobial activities of essential oils propolis were active against Escherichia coli with an average inhibition zone of 18.3 ± 0.52 mm and 18.9 ± 0.06 mm at concentrations of 10 and 20 μl in Dirmaji districts. Moreover, the crude ethanol extracted propolis had nearly the same effect of inhibition to Escherichia coli. However, both crude extract and its essential oils didn’t show any activity on Staphylococcus aureus and Aspergillus niger. The analyzed propolis is promising antimicrobial activity from Gram-negative which is very notorious for people of the world.     

A reinforced nanofibrous patch with biomimetic mechanical properties and chondroinductive effect for rotator cuff tissue engineering

Patch augmented surgery has been a feasible technique for rotator cuff repair. An ideal rotator cuff tissue engineering patch should have proper mechanical properties to match the native tendons and sufficient biological effect to promote tendon-bone healing. In this study, kartogenin (KGN)-grafted poly (ether-ester-urethane)urea/gelatin composite nanofibrous patches (PEEUU-GEL-KGN) were fabricated via electrospinning process followed by crosslinking of GEL and covalent grafting of KGN. The optimized PEEUU-GEL-KGN nanofibrous patches exhibited biomimetic mechanical properties, including sufficient tensile strength, non-linear stress-strain profiles, and remarkable elasticity and cyclical properties. In vitro investigations revealed that the patches possessed outstanding biocompatibility and performed a sustained release of KGN for a long time. Modification with GEL and KGN significantly improved hydrophilicity of the patches, promoted the adhesion, spreading, and proliferation of mesenchymal stem cells and upregulated the expression of cartilage-related genes. In vivo studies demonstrated that the implanted PEEUU-GEL-KGN patches effectively improved the tissue cellularity and collagen alignment, accelerated the fibrocartilage regeneration, augmented the biomechanical strength of the repaired enthesis, and reinforced the fixing of the tendon to the bone. Overall, the PEEUU-GEL-KGN patches enhanced tendon-bone healing and resisted rotator cuff re-tear. Therefore, the PEEUU-GEL-KGN patch is a highly promising candidate for rotator cuff tissue engineering.     

Designing New Antibacterial Wound Dressings: Development of a Dual Layer Cotton Material Coated with Poly(Vinyl Alcohol)_Chitosan Nanofibers Incorporating Agrimonia eupatoria L. Extract

Wounds display particular vulnerability to microbial invasion and infections by pathogenic bacteria. Therefore, to reduce the risk of wound infections, researchers have expended considerable energy on developing advanced therapeutic dressings, such as electrospun membranes containing antimicrobial agents. Among the most used antimicrobial agents, medicinal plant extracts demonstrate considerable potential for clinical use, due primarily to their efficacy allied to relatively low incidence of adverse side-effects. In this context, the present work aimed to develop a unique dual-layer composite material with enhanced antibacterial activity derived from a coating layer of Poly(vinyl alcohol) (PVA) and Chitosan (CS) containing Agrimonia eupatoria L. (AG). This novel material has properties that facilitate it being electrospun above a conventional cotton gauze bandage pre-treated with 2,2,6,6-tetramethylpiperidinyl-1-oxy free radical (TEMPO). The produced dual-layer composite material demonstrated features attractive in production of wound dressings, specifically, wettability, porosity, and swelling capacity. Moreover, antibacterial assays showed that AG-incorporated into PVA_CS’s coating layer could effectively inhibit Staphylococcus aureus (S. aureus) and Pseudomonas aeruginosa (P. aeruginosa) growth. Equally important, the cytotoxic profile of the dual-layer material in normal human dermal fibroblast (NHDF) cells demonstrated biocompatibility. In summary, these data provide initial confidence that the TEMPO-oxidized cotton/PVA_CS dressing material containing AG extract demonstrates adequate mechanical attributes for use as a wound dressing and represents a promising approach to prevention of bacterial wound contamination.     

Evaluation of Total Phenolic and Flavonoid Contents,Antibacterial and Antibiofilm Activities of Hungarian Propolis Ethanolic Extract against Staphylococcus aureus

Propolis is a natural bee product that is widely used in folk medicine. This study aimed to evaluate the antimicrobial and antibiofilm activities of ethanolic extract of propolis (EEP) on methicillin-resistant and sensitive Staphylococcus aureus (MRSA and MSSA). Propolis samples were collected from six regions in Hungary. The minimum inhibitory concentrations (MIC) values and the interaction of EEP-antibiotics were evaluated by the broth microdilution and the chequerboard broth microdilution methods, respectively. The effect of EEP on biofilm formation and eradication was estimated by crystal violet assay. Resazurin/propidium iodide dyes were applied for simultaneous quantification of cellular metabolic activities and dead cells in mature biofilms. The EEP1 sample showed the highest phenolic and flavonoid contents. The EEP1 successfully prevented the growth of planktonic cells of S. aureus (MIC value = 50 µg/mL). Synergistic interactions were shown after the co-exposition to EEP1 and vancomycin at 10⁸ CFU/mL. The EEP1 effectively inhibited the biofilm formation and caused significant degradation of mature biofilms (50–200 µg/mL), as a consequence of the considerable decrement of metabolic activity. The EEP acts effectively as an antimicrobial and antibiofilm agent on S. aureus. Moreover, the simultaneous application of EEP and vancomycin could enhance their effect against MRSA infection.     

Sintered and 3D-Printed Bulks of MgB2-Based Materials with Antimicrobial Properties

Pristine high-density bulk disks of MgB₂ with added hexagonal BN (10 wt.%) were prepared using spark plasma sintering. The BN-added samples are machinable by chipping them into desired geometries. Complex shapes of different sizes can also be obtained by the 3D printing of polylactic acid filaments embedded with MgB₂ powder particles (10 wt.%). Our present work aims to assess antimicrobial activity quantified as viable cells (CFU/mL) vs. time of sintered and 3D-printed materials. In vitro antimicrobial tests were performed against the bacterial strains Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 27853, Staphylococcus aureus ATCC 25923, Enterococcus faecium DSM 13590, and Enterococcus faecalis ATCC 29212; and the yeast strain Candida parapsilosis ATCC 22019. The antimicrobial effects were found to depend on the tested samples and microbes, with E. faecium being the most resistant and E. coli the most susceptible.     

Preparation and Investigation of Thermally Annealed Zein–Propolis Electrospun Nanofibers for Biomedical Applications

Zein, a corn-derived protein, has a variety of applications ranging from drug delivery to tissue engineering and wound healing. This work aims to develop a biocompatible scaffold for dermal applications based on thermally annealed electrospun propolis-loaded zein nanofibers. Pristine fibers' biocompatibility is determined in vitro. Next, propolis from Melipona quadrifasciata is added to the fibers at different concentrations (5% to 25%), and the scaffolds are studied. The physicochemical properties of zein/propolis precursor dispersions are evaluated and the results are correlated to the fibers' properties. Due to zein's and propolis' very favorable interactions, which are responsible for the increase in the dispersions surface tension, nanometric size ribbon-like fibers ranging from 420 to 575 nm are obtained. The fiber's hydrophobicity is not dependent on propolis concentration and increases with the annealing procedure. Propolis inhibitory concentration (IC₅₀) is determined as 61.78 µg mL⁻¹. When loaded into fibers, propolis is gradually delivered to cells as Balb/3T3 fibroblasts and are able to adhere, grow, and interact with pristine and propolis-loaded fibers, and cytotoxicity is not observed. Therefore, the zein–propolis nanofibers are considered biocompatible and safe. The results are promising and provide prospects for the development of wound-healing nanofiber patches—one of propolis' main applications.     

Antimicrobial Activity of MgB2 Powders Produced via Reactive Liquid Infiltration Method

We report for the first time on the antimicrobial activity of MgB₂ powders produced via the Reactive Liquid Infiltration (RLI) process. Samples with MgB₂ wt.% ranging from 2% to 99% were obtained and characterized, observing different levels of grain aggregation and of impurity phases. Their antimicrobial activity was tested against Staphylococcus aureus ATCC BAA 1026, Enterococcus faecalis ATCC 29212, Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 27853, and Candida albicans ATCC 10231. A general correlation is observed between the antibacterial activity and the MgB₂ wt.%, but the sample microstructure also appears to be very important. RLI-MgB₂ powders show better performances compared to commercial powders against microbial strains in the planktonic form, and their activity against biofilms is also very similar.     

Bionanocomposite of Au decorated MnO2 via in situ green synthesis route and antimicrobial activity evaluation

Green synthesis gaining a significant importance for the preparation of nanoparticles (NPs) and NPs-based biocomposites gained much attention in biological applications. In the current study, gold (Au) nanoparticles were prepared via green approach using cinnamon extract. The Au nanocomposite (NC) was prepared with MnO₂ nanofiber mesh structure. The NC was characterized by XRD, SEM, FT-IR, EDX, UV–visible and DLS techniques. The MnO₂ nanofibers diameter was in 10–25 nm range, which was arranged in a mesh form and Au NPs was combined with nanofibers randomly. The MnO₂-Au NC antimicrobial activity was measured against Escherichia coli, Pseudomonas aeruginosa and Staphylococcus aureus strains. The antimicrobial activity of MnO₂-Au NC was highly promising against tested microorganisms in comparison to control (ciprofloxacin, a standard drug). The antimicrobial activity of MnO₂-Au NC was found in following order; > S. aureus > E. coli > P. aeruginosa with the zones inhibition of 22, 18 and 15 (mn), respectively. The MIC (minimum inhibitory concentration) values were 316, 342 and 231 (µg/mL) for E. coli, P. aeruginosa and S. aureus, respectively. In view of promising antimicrobial activity, the MnO₂-Au NC prepared via green approach could have potential applications in medical field and future study can be engrossed on the biocompatibility evaluation of MnO₂-Au NC using bioassays.     

Transition behaviors and hybrid nanofibers of poly(vinyl alcohol) and polyethylene glycol–POSS telechelic blends

We report solution properties of the blend solutions of poly(vinyl alcohol) (PVA) and poly(ethylene glycol) (PEG)–POSS telechelic and its corresponding hybrid nanofibers prepared by electrospinning. The morphologies, microstructures, and wettability of the resulting PVA/PEG3.4k–POSS hybrid nanofibers are studied. The morphologies of the resultant PVA/PEG3.4k–POSS nanofibers are regular with the fiber diameter ranging from 610 ± 110 to 810 ± 280 nm. When the content of PEG3.4k–POSS telechelic increases above 20 wt.%, the beaded fiber morphologies are observed due to severe aggregations of the PEG3.4k–POSS telechelics as well as increased viscosity at higher concentration. In addition, the solution properties of pure PEG3.4k–POSS telechelic solution (ca. 3–5 wt.%) and PVA/PEG3.4k–POSS solutions blended with PVA are explored, and found to show the reversible turbid-to-transparent transition behavior with respect to the solution temperature. Water contact angle measurement of the PVA/PEG3.4k–POSS nanofiber membranes demonstrates an enhanced hydrophobic nature due to the incorporated POSS moieties.     

Potential of Carvacrol and Thymol in Reducing Biofilm Formation on Technical Surfaces

Polyvinyl chloride (PVC), polypropylene (PP), polyethylene (PE), and stainless steel (SS) are commonly used in medicine and food production technologies. During contact with microorganisms on the surface of these materials, a microbial biofilm is formed. The biofilm structure is difficult to remove and promotes the development of pathogenic bacteria. For this reason, the inhibition of biofilm formation in medical and food production environments is very important. For this purpose, five naturally occurring compounds were used for antimicrobial screening tests. The two with the best antimicrobial properties were chosen to inhibit the biofilm formation of Staphylococcus aureus and Pseudomonas aeruginosa. After 3 days of exposure, thymol reduced the amount of biofilm of Pseudomonas aeruginosa within the range of 70–77% and 52–75% for Staphylococcus aureus. Carvacrol inhibited the formation of biofilms by up to 74–88% for Pseudomonas aeruginosa and up to 86–100% for Staphylococcus aureus. Those phenols decreased the enzyme activity of the biofilm by up to 40–100%. After 10 days of exposure to thymol, biofilm formation was reduced by 80–100% for Pseudomonas aeruginosa and by about 79–100% for Staphylococcus aureus. Carvacrol reduced the amount of biofilm by up to 91–100% for Pseudomonas aeruginosa and up to 95–100% for Staphylococcus aureus.     

The effect of preparation temperature on the mechanical and antibacterial properties of poly(vinyl alcohol)/silver nitrate films

There has been a growing interest in developing antibacterial polymeric materials. The logical consequence following development of a new material is optimisation of its processing conditions and investigation of the influence of processing parameters on functionality of a given material. The present work deals with investigation of the effect of preparation temperature on the mechanical and antibacterial properties of polymer films based on poly(vinyl alcohol) (PVA) and silver nitrate (0, 1, 3, 5, 7, 9 wt.% silver content). The mechanical properties of the films prepared at various temperatures (25, 35, 50, 60, 75 °C) were characterized by using stress-strain analysis. Antibacterial properties were determined by using an agar diffusion test and a dilution and spread plate technique against both Gram positive (Staphylococcus aureus) and Gram negative (Escherichia coli, Pseudomonas aeruginosa and Klebsiella pneumoniae). The results show significant effect of the elevated temperature on the samples properties.     

Characterization,mechanical, and antibacterial properties of nanofibers derived from olive leaf,fumitory, and terebinth extracts

In this study, nanofiber structures were obtained with convenient polymers (PVA [polyvinyl alcohol] and PCL [poly ^o-caprolactone]) derived from the herbal extracts of olive leaves, fumitory, and terebinth plants. Optimum nanofiber structures were identified by measuring viscosity and conductivity values and performing morphological analysis, characterization, and mechanical tests of the prepared solutions. The potential use for wound healing at the most efficient level was determined as a result of antibacterial analysis of the structures obtained. APT (PVA/terebinth) and BFO (PCL/fumitory) nanofibers had the thinnest diameter range and the highest strength values. In terms of the determination of antibacterial effects, nanofiber structures of all 3 plant species proved to be effective against bacteria. The greatest effect was observed against Escherichia coli in the nanofiber structure containing olive leaves, with a zone diameter of 32 mm. In addition, APT and BFO nanofibers had the highest values of thinness and strength. In these 2 samples, using BFO against Staphylococcus aureus and APT against Candida albicans increased their areas of activity. In the literature review, no study was available about obtaining nanofibers, especially from fumitory and terebinth plants. This study aimed to increase knowledge on obtaining nanofiber structures, including various polymers derived from olive leaves, fumitory, and terebinth plants.     

Chemotactic ion-releasing hydrogel for synergistic antibacterial and bone regeneration

The repair of critical-sized bone defects remains a major concern in clinical care. Herein, a multifunctional hydrogel is rationally designed to synergistically photothermal antibacterial and potentiate bone regeneration via adding magnesium oxide nanoparticle and black phosphorus nanosheet (BPNS) into poly(vinyl alcohol)/chitosan hydrogel (PVA/CS-MgO-BPNS). Under the dual effect of near-infrared irradiation and CS intrinsic antibacterial properties, PVA/CS-MgO-BPNS hydrogel can kill more than 99.9% of Staphylococcus aureus and Escherichia coli. The released Mg ions stimulate the migration of mesenchymal stem cells (MSCs) to hydrogels and synergize with released phosphate to promote osteogenic differentiation. The PVA/CS-MgO-BPNS hydrogel also promotes calcium phosphate particle formation and therefore improves the biomineralization ability. Furthermore, the potential molecular mechanism of PVA/CS-MgO-BPNS to regulate MSCs migration and differentiation is through activating phosphoinositide 3-kinase (PI3K)-Akt signaling pathways through RNA-seq analysis. Finally, the PVA/CS-MgO-BPNS hydrogel could significantly promote endogenous bone tissue regeneration in the rat skull defect model. Taken together, this easy fabricated multifunctional hydrogel has good clinical applicability for the repair of large-scale bone defects.     

Analytical methods applied to diverse types of Brazilian propolis

Propolis is a bee product, composed mainly of plant resins and beeswax, therefore its chemical composition varies due to the geographic and plant origins of these resins, as well as the species of bee. Brazil is an important supplier of propolis on the world market and, although green colored propolis from the southeast is the most known and studied, several other types of propolis from Apis mellifera and native stingless bees (also called cerumen) can be found. Propolis is usually consumed as an extract, so the type of solvent and extractive procedures employed further affect its composition. Methods used for the extraction; analysis the percentage of resins, wax and insoluble material in crude propolis; determination of phenolic, flavonoid, amino acid and heavy metal contents are reviewed herein. Different chromatographic methods applied to the separation, identification and quantification of Brazilian propolis components and their relative strengths are discussed; as well as direct insertion mass spectrometry fingerprinting.Propolis has been used as a popular remedy for several centuries for a wide array of ailments. Its antimicrobial properties, present in propolis from different origins, have been extensively studied. But, more recently, anti-parasitic, anti-viral/immune stimulating, healing, anti-tumor, anti-inflammatory, antioxidant and analgesic activities of diverse types of Brazilian propolis have been evaluated. The most common methods employed and overviews of their relative results are presented.     

Production and characterization of elastomeric cardiac tissue-like patches for Myocardial Tissue Engineering

Cardiovascular disease remains the leading cause of death. Damaged heart muscle is the etiology of heart failure. Heart failure is the most frequent cause of hospital and emergency room admissions. As a differentiated organ, current therapeutics and techniques can not repair or replace the damaged myocardial tissue. Myocardial tissue engineering is one of the promising treatment modalities for repairing damaged heart tissue in patients with heart failure. In this work, random Polylactic acid (PLA), Polylactic acid/Polyethylene glycol (PLA/PEG) and random and aligned Polylactic acid/Polyethylene glycol/Collagen (PLA/PEG/COL) nanofiber patches were successfully produced by the electrospinning technique. In vitro cytotoxic test (MTT), morphological (SEM), molecular interactions between the components (FT-IR), thermal analysis (DSC), tensile strength and physical analysis were carried out after production. The resulting nanofiber patches exhibited beadless and smooth structures. When the fiber diameters were examined, it was observed that the collagen doped random nanofiber patches had the lowest fiber diameter value (755 nm). Mechanical characterization results showed that aligned nanofiber patches had maximum tensile strength (5.90 MPa) values compared to PLA, PLA/PEG, and PLA/PEG/COL (random). In vitro degradation test reported that aligned patch had the highest degradation ratio. The produced patches displayed good alignment with tissue on cardiomyocyte cell morphology studies. In conclusion, newly produced patches have noticeable potential as a tissue-like cardiac patch for regeneration efforts after myocardial infarction.     

Propolis Extract and Its Bioactive Compounds—From Traditional to Modern Extraction Technologies

Propolis is a honeybee product known for its antioxidant, anti-inflammatory, anticancer, and antimicrobial effects. It is rich in bioactive molecules whose content varies depending on the botanical and geographical origin of propolis. These bioactive molecules have been studied individually and as a part of propolis extracts, as they can be used as representative markers for propolis standardization. Here, we compare the pharmacological effects of representative polyphenols and whole propolis extracts. Based on the literature data, polyphenols and extracts act by suppressing similar targets, from pro-inflammatory TNF/NF-κB to the pro-proliferative MAPK/ERK pathway. In addition, they activate similar antioxidant mechanisms of action, like Nrf2-ARE intracellular antioxidant pathway, and they all have antimicrobial activity. These similarities do not imply that we should attribute the action of propolis solely to the most representative compounds. Moreover, its pharmacological effects will depend on the efficacy of these compounds’ extraction. Thus, we also give an overview of different propolis extraction technologies, from traditional to modern ones, which are environmentally friendlier. These technologies belong to an open research area that needs further effective solutions in terms of well-standardized liquid and solid extracts, which would be reliable in their pharmacological effects, environmentally friendly, and sustainable for production.     

Bioprospecting the Antibiofilm and Antimicrobial Activity of Soil and Insect Gut Bacteria

Antimicrobial resistance is a growing concern in public health and current research shows an important role for bacterial biofilms in recurrent or chronic infections. New strategies, therefore, are necessary to overcome antimicrobial resistance, through the development of new therapies that could alter or inhibit biofilm formation. In this sense, antibiofilm natural products are very promising. In this work, a bioprospection of antimicrobial and antibiofilm extracts from Uruguayan soil bacteria and insect gut bacteria was carried out. Extracts from extracellular broths were tested for their ability to inhibit planktonic cell growth and biofilm formation. Genomic analysis of Bacillus cereus ILBB55 was carried out. All extracts were able to inhibit the growth of, at least, one microorganism and several extracts showed MICs lower than 500 µg mL⁻¹ against microorganisms of clinical relevance (Staphylococcus aureus, Pseudomonas aeruginosa, and Enterobacter cloacae). Among the extracts evaluated for biofilm inhibition only ILBB55, from B. cereus, was able to inhibit, S. aureus (99%) and P. aeruginosa (62%) biofilms. Genomic analysis of this strain showed gene clusters similar to other clusters that code for known antimicrobial compounds. Our study revealed that extracts from soil bacteria and insect gut bacteria, especially from B. cereus ILBB55, could be potential candidates for drug discovery to treat infectious diseases and inhibit S. aureus and P. aeruginosa biofilms.     

Development of Antimicrobial Laser-Induced Photodynamic Therapy Based on Ethylcellulose/Chitosan Nanocomposite with 5,10,15,20-Tetrakis(m-Hydroxyphenyl)porphyrin

The development of new antimicrobial strategies that act more efficiently than traditional antibiotics is becoming a necessity to combat multidrug-resistant pathogens. Here we report the efficacy of laser-light-irradiated 5,10,15,20-tetrakis(m-hydroxyphenyl)porphyrin (mTHPP) loaded onto an ethylcellulose (EC)/chitosan (Chs) nanocomposite in eradicating multi-drug resistant Pseudomonas aeruginosa, Staphylococcus aureus, and Candida albicans. Surface loading of the ethylcelllose/chitosan composite with mTHPP was carried out and the resulting nanocomposite was fully characterized. The results indicate that the prepared nanocomposite incorporates mTHPP inside, and that the composite acquired an overall positive charge. The incorporation of mTHPP into the nanocomposite enhanced the photo- and thermal stability. Different laser wavelengths (458; 476; 488; 515; 635 nm), powers (5–70 mW), and exposure times (15–45 min) were investigated in the antimicrobial photodynamic therapy (aPDT) experiments, with the best inhibition observed using 635 nm with the mTHPP EC/Chs nanocomposite for C. albicans (59 ± 0.21%), P. aeruginosa (71.7 ± 1.72%), and S. aureus (74.2 ± 1.26%) with illumination of only 15 min. Utilization of higher doses (70 mW) for longer periods achieved more eradication of microbial growth.     

Functional Modification of Cellulose Acetate Microfiltration Membranes by Supercritical Solvent Impregnation

This study investigates the modification of commercial cellulose acetate microfiltration membranes by supercritical solvent impregnation with thymol to provide them with antibacterial properties. The impregnation process was conducted in a batch mode, and the effect of pressure and processing time on thymol loading was followed. The impact of the modification on the membrane’s microstructure was analyzed using scanning electron and ion-beam microscopy, and membranes’ functionality was tested in a cross-flow filtration system. The antibiofilm properties of the obtained materials were studied against Staphyloccocus aureus and Pseudomonas aeruginosa, while membranes’ blocking in contact with bacteria was examined for S. aureus and Escherichia coli. The results revealed a fast impregnation process with high thymol loadings achievable after just 0.5 h at 15 MPa and 20 MPa. The presence of 20% of thymol provided strong antibiofilm properties against the tested strains without affecting the membrane’s functionality. The study showed that these strong antibacterial properties could be implemented to the commercial membranes’ defined polymeric structure in a short and environmentally friendly process.     

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.