Propolis: chemical diversity and challenges in quality control

Propolis is a resinous natural product produced by honeybees using beeswax and plant exudates. The chemical composition of propolis is highly complex, and varies with region and season. This inherent chemical variability presents several challenges to its standardisation and quality control. The present review was aimed at highlighting marker compounds for different types of propolis, produced by the species Apis mellifera, from different geographical origins and that display different biological activities, and to discuss strategies for quality control. Over 800 compounds have been reported in the different propolises such as temperate, tropical, birch, Mediterranean, and Pacific propolis; these mainly include alcohols, acids and their esters, benzofuranes, benzopyranes, chalcones, flavonoids and their esters, glycosides (flavonoid and diterpene), glycerol and its esters, lignans, phenylpropanoids, steroids, terpenes and terpenoids. Among these, flavonoids (> 140), terpenes and terpenoids (> 160) were major components. A broad range of biological activities, such as anti-oxidant, antimicrobial, anti-inflammatory, immunomodulatory, and anticancer activities, have been ascribed to propolis constituents, as well as the potential of these compounds to be biomarkers. Several analytical techniques, including non-separation and separation methods have been described in the literature for the quality control assessment of propolis. Mass spectrometry coupled with separation methods, followed by chemometric analysis of the data, was found to be a valuable tool for the profiling and classification of propolis samples, including (bio)marker identification. Due to the rampant chemotypic variability, a multiple-marker assessment strategy considering geographical and biological activity marker(s) with chemometric analysis may be a promising approach for propolis quality assessment.