The first results, published by Lavie and his group, pointed to two flavonoid aglycones as antibacterial agents in propolis: galangin and pinocembrin (Villanueva et al., 1964; Villanueva et al., 1970).

 Further research on European samples supported these results and added a few other phenolics to the list: pinobanksin, pinobanksin-3-O-acetate, benzyl-p-coumarate and caffeic acid esters (Metzner et al., 1979).

 Pinocembrin and the caffeate mixture were found to be the main anti-fungal substances in propolis, as well (Metzner et al., 1979). Phenolic acids, such as caffeic and ferulic, were also indicated as antibacterial constituents. In recent studies, propolis and some of its cinnamic and flavonoid components were found to uncouple the energy traducing cytoplasmic membrane and to inhibit bacterial motility, which may contribute to the anti-microbial action (Mirzoeva et al., 1997).

Recent studies on tropical, especially Brazilian, samples lead to the discovery of new antibacterial compounds. A number of them are phenolics and their derivatives, although completely different from those found in European propolis. The most important ones are carbon-prenylated derivatives of p-coumaric acid, the 3,5-diprenyl-p-coumaric acid being one of the major antibacterial compounds in Brazilian propolis (Aga et al., 1994).

 In propolis from the Canary Islands, antibacterial furofuran lignans were found (Christov et al., 1999). Antibacterial substances of non-phenolic nature were isolated from Brazilian propolis, as well; these are diterpenic acids with a labdane skeleton (Bankova et al., 1996). Obviously, flavonoids are not by far the only antibacterial constituents of propolis.

Anti-viral action is another important biological property of propolis. Once again, it is attributed to the phenolic compounds, mainly esters of caffeic and ferulic acids (3- methylbut-2-enyl caffeate, 3-methylbutyl ferulate), caffeic acid itself, and some flavonoid aglycones (luteolin, quercetin) (Amoros et al., 1992, Serkedjieva et al., 1992).

According to the latest investigations, the anti-inflammatory activity of propolis is connected to its radical scavenging activity to a great extent. Natural phenolics are among the substances known as potential radical scavengers. In detailed studies on radical scavenging action of individual components, caffeic acid phenethyl ester, together with the flavonoids galangin, kaempferol, and kaempferid, were identified as active components in exerting propolis' renowned anti-inflammatory activity (Krol et al., 1996). Phenolics were reported to affect the activity of several systems known to be involved in the inflammatory process.

During the last five years, a number of publications appeared detailing the hepatoprotective effect of propolis in different experimental systems. Remirez et al. (1997) suggested that this effect could be because of the anti-oxidative action of propolis extracts. Caffeic and ferulic acids and their esters were found to be the main anti-oxidative components of European propolis; the activity of the flavonoid aglycones was significantly lower (Marinova et al., 1989). From Brazilian propolis, two dicaffeoylquinic acid derivatives were isolated as hepatoprotective agents: 3,4--dicaffeoylquinic acid and its methyl ester (Basnet et al., 1996).

Alcohol extracts of propolis possess local anaesthetic action, according to German authors. The substances responsible are again pinocembrin and a mixture of caffeate esters (Paintz & Metzner, 1979).

Special attention has been directed toward the anti-tumor effects of propolis. Caffeic acid phenethyl ester (CAPE) is the anti-tumor substances from propolis that has received the most attention. Its anti-tumor properties were discovered in a bioassay-guided chemical study of propolis by the research group of Koji Nakanishi (Grundberger et al., 1988) and examined thoroughly. CAPE was found to inhibit human breast carcinoma and melanoma cell lines in culture. Human tumor cells displayed a significantly greater sensitivity to the action of CAPE than the analogous normal lines of non-tumorous cells in that the CAPE was more toxic to the tumor cells than to the normal ones.

Similar results were obtained using other propolis constituents with similar structures: methyl caffeate and phenethyl ester of dimethylcaffeic acid (Rao et al., 1992). Brazilian propolis delivered structurally different anti-tumor agents: carbon-prenylated derivatives of p-coumaric acids, e.g. 3,5-diprenyl-p-coumaric acid and similar molecules showed cytotoxic activity in vitro against human tumor cell lines, as well as in vivo in mice transplanted with human tumor cells (Kimoto et al., 1998). Another group of anti-tumor propolis constituents was isolated from Brazilian samples, too: clerodane diterpenic acids, active against human hepatocelular carcinoma (Matsuno et al., 1997). At present this field is being studied extensively by several research group in Japan.