this sticky , greenish - brown product has different compositions depending on the location of the bees and what trees and flowers they have access to .
propolis from turkey or egypt will not have the same chemical properties as propolis from europe or brazil .
this is because it is very difficult for researchers to come to general conclusions about its health benefits .
caffeic acid phenethyl ester ( cape ) [ figure 1 ] is one of important compounds found in propolis that has antiviral , antioxidant , anti - inflammatory , antiproliferative , antitumor , and immunomodulatory effects .
this marvelous compound has been used to prevent oxidative stress - based deterioration in cells / tissues / organs in both cell culture and experimental animals . lately ,
the protection of cape on central and peripheral nervous system as well as a reproductive system have been extensively reviewed [ 3 - 5 ] .
it has extensively been used to treat a broad of malignancies including hodgkin s and non - hodgkin s lymphoma , burkitt s lymphoma , chronic lymphocytic leukemia , ewing s sarcoma , breast cancer , testicular cancer , etc .
it has toxic effects in almost every system in the human body including the heart , liver , and kidney of which mostly due to its structural properties prone to induce oxidative stress in vitro and in vivo .
the chemical illustration of caffeic acid phenethyl ester this study aimed to collect data and compare the protective effects of propolis and cape against cp - induced injury in animals .
, ameliorative effect of propolis against cp - induced toxicity in mice was studied by el - naggar et al . .
it throws light on the side effects of a common anticancer agent , cp , used in the treatment of various malignancies and possible remedies to prevent that type of side effects in vital organs such as liver and kidney .
uysal et al .   conducted an experimental animal study to determine protective role of cape on cp - induced hemorrhagic cystitis ( hc ) . while cp - induced hc
lead to increase in superoxide dismutase , catalase , and malondialdehyde activities / levels , cape significantly reduced these parameters showing the protective effects .
in addition to this biochemical effects , cape also ameliorates edema , hemorrhage , inflammation , and mucosal ulceration of cp - induced hc .
we published a review article about toxicities of some therapeutic compounds and the protective effect of cape on chemotherapy- and radiotherapy - induced toxicity .
we have shown that cape has protective effects on oxidative stress - induced toxicities by doxorubicin ( nephrotoxicity ) , cisplatin ( nephrotoxicity , ototoxicity , and hepatotoxicity ) [ 10 - 13 ] , and bleomycin ( lung fibrosis ) . currently , there is no medically recommended dose for propolis , since the mixture of propolis is subjected to change depending on its source .
the most successful medical application field of propolis is beauty and skin care , especially in acne vulgaris because of its antibacterial , antiviral , antifungal , and anti - inflammatory properties . despite the fact that both water and ethanolic extractions of propolis have been used in the in vivo and in vitro experiments , water - soluble extracts of propolis exhibit higher antioxidant and inhibitory activities
as compared ethanolic extract in vitro . in this perspective , even though the extraction method selection is dependent on the authors desire , it would be expected for authors to study propolis for their experiments comparatively by selecting propolis extracted by both extraction methods .
cape is the most potent antioxidant agent of propolis mixture having free radical scavenging activity and potent inhibition of nf-b .
so , the protective antioxidant effect of ethanol extract of propolis on organs depends mostly on cape rather than other polyphenolic compounds such as flavonoids , phenolic acids , and their esters [ figure 2 ] .
cape was shown to completely block the production of reactive oxygen species in human neutrophils and in the xanthine / xanthine oxidase systems at 10 m concentration by its competent antioxidant capacity .
indeed , cape has a regulatory effect on antioxidant enzyme activities such as catalase , superoxide dismutase , and glutathione peroxidase   [ figure 2 ] . proposed mechanism of how cyclophosphamide - induced oxidative stress is blocked by antioxidant enzymes in several parts of hepatocytes and renal cells and how cape shows its protective effects against oxidative stress .
aas : amino acids , cape : caffeic acid phenethyl ester , cat : catalase , fe : ferrous iron , gpx : glutathione peroxidase , gsh : reduced glutathione , gr : glutathione reductase , gssg : oxidized glutathione , h2o : water , nadp : oxidized nicotinamide adenine dinucleotide phosphate , nadph : reduced nicotinamide adenine dinucleotide phosphate , o2 : molecular oxygen , o2 : superoxide anion radical , oh : hydroxyl ion , oh : hydroxyl radical , onoo : peroxynitrite , no : nitric oxide , nos : nitric oxide synthase , pufa : polyunsaturated fatty acid , sod : superoxide dismutase it has been shown that cape application to the rats modifies the enzyme activity of cytochrome p450 ( cyp ) isoforms involved in the activation of diethylnitrosamine such as cyp1a1/2 and cyp2b12 .
furthermore , treatment with cape of carbon tetrachloride - induced hepatotoxicity in mice blocks cyp2e1-mediated ccl4 bioactivation and protects against fas / fasl - mediated apoptosis .
it will be very interesting to see the effect of cape on cyp2b6 , which constitutes 3 - 6% of total hepatic cyp content and metabolizes several pharmaceuticals including cp . to achieve this , further studies on the every single bioactive constituent of propolis such as cape and some other polyphenols are necessary to identify interactions mediating their biological effects on cyp2b6 , since there are roughly 150 different polyphenolic compounds within propolis .
as a conclusion , studying propolis to prevent cp - induced oxidative stress in animals has several limitations since the proposed effect can not be specified to one or several molecules within the mixture . in that case
, every single bioactive constituent of propolis needs to be studied to show the source of real effects and the molecular mechanisms of this effects .
 propolis is a mixture having hundreds of polyphenols including caffeic acid phenethyl ester ( cape ) . 
 they have been using in several medical conditions / diseases in both in vitro and in vivo experimental setup . 
 cyclophosphamide ( cp ) has been used to treat a broad of malignancies including hodgkin s and non - hodgkin s lymphoma , burkitt s lymphoma , chronic lymphocytic leukemia , ewing s sarcoma , breast cancer , testicular cancer , etc . 
 it may cause several side effects after treatment . in this mini review , 
 the protective effects of propolis and cape were compared each other in terms of effectiveness against cp - induced injuries . 