Our propolis extract is processed from the highest quality propolis in a non-GMO, organic whole grain alcohol so that every nutrient of propolis is fully preserved and extracted into the alcohol. It is highly concentrated (75%) and highly potent. Packaging is in dark bottles with pipette for easier handling.
Suggested Use: Shake well before using. For adults, mix 2 mL of extract in 2 oz (60 mL) of water one time daily, preferably with a meal. It can be consumed straight or mixed with liquids. Also, it may be used externally as a liquid band-aid.
Propolis is the third most important component of bee products. It is composed mainly of resin (50%), wax (30%), essential oils (10%), pollen (5%), and other organic compounds (5%) . Phenolic compounds, esters, flavonoids, terpenes, beta-steroids, aromatic aldehydes, and alcohols are the important organic compounds present in propolis . Twelve different flavonoids, namely, pinocembrin, acacetin, chrysin, rutin, luteolin, kaempferol, apigenin, myricetin, catechin, naringenin, galangin, and quercetin; two phenolic acids, caffeic acid and cinnamic acid; and one stilbene derivative called resveratrol have been detected in propolis extracts by capillary zone electrophoresis . Propolis also contains important vitamins, such as vitamins B1, B2, B6, C, and E and useful minerals such as magnesium (Mg), calcium (Ca), potassium (K), sodium (Na), copper (Cu), zinc (Zn), manganese (Mn), and iron (Fe). A few enzymes, such as succinic dehydrogenase, glucose-6-phosphatase, adenosine triphosphatase, and acid phosphatase, are also present in propolis .
The molecular mechanisms responsible for the wound-healing activity of propolis is shown in Figure 4. Fibronectin (FN) is a multifunctional glycoprotein of high molecular weight, which influences the structural stability and functional properties of various organs and tissues (Stoffels, 2013). The fibronectin matrix and its accumulation are essential for cell migration, cell proliferation, cell differentiation, cell adhesion, apoptosis, cellular signaling, angiogenesis, collagen biosynthesis, re-epithelialization, clot formation, and platelet activity. Fibronectins are also important in the repair mechanisms for conditions such as glycoprotein intensified degradation, which leads to a defective cellular microenvironment and affliction in the structure of granulation tissues. This condition may prevent the wound from healing or inhibit the repair process. The accumulation of fibronectin in the extracellular space also modulates the secretion of other repairing components such as collagen type I and type III, tenascin, laminin, and fibrillin.
Honeybees use propolis primarily as a thermo isolation material by sealing the cracks in wooden walls and other parts of the hive and strengthening the construction of wax combs. Additionally, it is a crucial part of collective social immunity at the colony level.
Geopropolis is a slightly different type of bee glue, a mixture of resins, wax, clay, or soil. It is produced by a stingless bee from genus Melipona. Dos Santos et al. (2017) determined polyphenols, flavanones, terpenoids, but also di- and trigalloyl and phenylpropanoid heteroside derivatives in hydroethanolic extracts of geopropolis , while the main phenolic compounds of geopropolis from Brazil were gallic (6) and ellagic acid (7) (Figure 3) .
The most abundant flavonoids found in propolis samples from Italy were chrysin (8), galangin (9), pinocembrin (10) and pinobanksin-3O-acetate (11). The most representative phenolic acids were caffeic acid (12), p-coumaric acid (13), and ferulic acid (14), as well as their derivatives, 3,4-dimethoxycaffeic acid (15; DMCA) and caffeic acid prenyl (16), benzyl (17), phenylethyl (18; CAPE), and cinnamyl (19) esters (Figure 4) . This kind of polyphenol content is typical for poplar propolis.
One of the most studied active compounds of a poplar-type propolis is caffeic acid phenethyl ester (CAPE) (18). It is a potent antioxidant extracted from propolis, with excellent anti-inflammatory, wound-healing, antidiabetic, organ protective, anticancer, and antimicrobial properties [74,75]. CAPE inhibits NF-κB and PI3/Akt and modulates MAPK pathways [74,75]. However, the effect on these pathways will depend on the cell type and probably on the concentrations of CAPE . For example, in primary human CD4+ T cells, CAPE induced caspase-3 expression, inhibited NF-κB activation, protein kinase B (Aκt) phosphorylation, IFN-γ, and IL-5 secretion, with no effect on p38 MAPK phosphorylation . On the other hand, in the neuropathic pain model, CAPE suppressed the phosphorylation of p38 MAPK, inhibited NF-κB, and decreased the expression of pro-inflammatory TNF-α, IL-1β, and IL-6 . Thus, in both of these studies, CAPE had an anti-inflammatory effect.
For instance, caffeic acid and ethanolic extract of Brazilian propolis suppressed LPS-induced signaling pathways, like p38 MAPK, JNK1/2, and NF-κB in macrophages . ERK1/2 was not affected by propolis extract . An aqueous propolis extract inhibited macrophage apoptosis via glutathione (GSH) and the TNF/NF-κB pathway . The ethanolic extract of Chinese poplar propolis protected vascular endothelial cells (VECs) from LPS-induced oxidative stress and inflammation, a result of inhibiting autophagy and MAPK/NF-κB signaling pathway, and reducing the phosphorylation of JNK, ERK1/2, and p38 MAPK .
It seems that no matter the origin and composition, propolis extracts will exert antioxidant action, but possibly through slightly different mechanisms of action. The EtOH extract of Brazilian red propolis (EERP) suppressed ROS generation and cytotoxicity by activating the Nrf2-ARE intracellular antioxidant pathway . Zhang et al. (2016) reported that EtOH extracts of Chinese propolis (EECP) and EtOH extracts of Eucalyptus propolis (EEEP) improve antioxidant gene expression only via ERK/-Nrf2 signaling pathway, while EtOH extracts of Baccharis propolis (EEBGP) strengthen the antioxidant system by activating p38 MAPK and accelerating nucleus translocation of Nrf2 .
Propolis extracts are active against yeasts, fungi, viruses, bacteria, and even parasites, being the most effective against Gram-positive bacteria, such as Streptococcus and S. aureus, Bacillus subtilis, E. faecalis, and against yeasts of Candida species [119,120]. The antimicrobial activity is often prescribed to its polyphenols that increase bacterial membrane permeability, disturb the membrane potential, reduce ATP production, and decrease bacterial mobility . Some of them damage the biofilm and have anti-quorum sensing activity .
Due to these deficiencies of such traditional liquid propolis extracts, various improved solutions are developed and described in numerous scientific and patent literatures. Some selected, typical improved solutions are presented in this article.
Except by a simple maceration process in a single extraction vessel, optionally equipped with a suitable stirrer for adequate agitation of the propolis mass during the maceration process, the extraction can be performed by percolation or with a Soxhlet apparatus . These techniques significantly speed up the extraction process and somewhat increase the extraction efficiency expressed through the quantitative content of certain marker propolis components.
Sosonowski described the preparation of the liquid propolis extracts obtained by maceration of the crude propolis with various alternative organic solvents (OS) such as: methanol (MeOH), 1-propanol (n-PrOH), 2-propanol (2-PrOH), 1-butanol (n-BuOH), 2-butanol (s-BuOH), tert-butanol (t-BuOH), diethylether (Et2O), 1,2-propylene glycol (1,2-PG), dimethylsulfoxide (DMSO), ethylene glycol (ETG), benzyl benzoate (BnBz), polyethylene glycol (PEG), acetone, and glacial acetic acid (HOAc) at a low (1:2) ES-to-propolis weight ratio (w/w) . Such liquid extracts were optionally converted to dry extracts by evaporation of the respective solvents at elevated temperatures (70 C) under vacuum.
Among more polar extraction solvents, especially convenient are 1,2-PG, PEG (200, 400, or 600), or glycerol (GL), which are relatively non-toxic, safe, and widely used as pharmaceutical excipients or as diluents and humectants in numerous pharmaceutical products [8,135,136].
The least polar ES that could be employed for the propolis extraction are various fixed and essential oils. The former are various triglycerides, plant oils such as sunflower, rapeseed, sesame, olive, and soybean oils. They are able to extract predominantly non-polar propolis compounds from the starting crude propolis. In this manner, Galeotti and coworkers (2018) described the extraction with plant oil and obtained the corresponding liquid extract of similar TPC like with GL as the ES . This type of extract is suitable for manufacturing various pharmaceutical and cosmetic products containing fatty phase, wherein such lipophilic ingredients could be readily homogenized.
Similarly, Savickas and coworkers (2001) described a unique waterless ES based on a mixture of EtOH (96%) and sunflower oil . Such a liquid propolis extract is also suitable for non-aqueous pharmaceutical and cosmetic formulations.
Keskin (2020) described the use of orange peel essential oil (OPEO) predominantly based on d-limonene as a green and renewable ES for propolis . The extraction was performed at 1:10 w/v ratio of the crude propolis to the ES during 48 h at r.t. with constant stirring. After subsequent filtration, the resulting liquid extract was of a high total phenolic content (mg of gallic acid equivalents per mL) and high total flavonoid content (mg). The former parameter was about 50% lower, while the latter was around 28% lower than at 70% EtOH-based extract . 59ce067264