Documente Academic
Documente Profesional
Documente Cultură
MC Marcucci
Summary — The plant sources and chemical composition of propolis are reviewed. The chemical
constituents that may be relevant to its biological and therapeutic activity are discussed. The cyto-
toxic activity and antimicrobial and pharmacological properties of propolis are presented. Propolis
components, which cause allergy and are responsible for anticancer activity, eg, caffeic acid derivatives,
are reported. The therapeutic efficacy of propolis in treating diseases caused by microorganisms is
described. Some recent concepts about propolis and its use in medicine are presented.
of them, isopentyl ferulate, significantly inhib- observed in some plant fungi in vitro (La
ited the infectious activity of influenza virus Torre et al, 1990).
A (Hong Kong strain) at 50 mg/ml (Serked-
jieva et al, 1992). Similar results were found
by Amoros et al (1994) when the in vitro Cytotoxic activity
activity of 3-methylbut-2-enyl caffeate iden-
tified in propolis samples was tested against Extracts of propolis have been examined
herpes simplex virus type 1 (HSV-1).The for in vitro cytotoxic activity by different meth-
same synthetic compound showed strong
ods of tissue culture in some cell lines.
inhibition of HSV-1 growth at a concentration Hladón et al (1980) investigated the cyto-
of 25 mg/ml. Some authors suggested that static activity of propolis extracts on human
the antiviral activity of propolis is due to both KB (nasopharinx carcinoma) and HeLa
the main constituents and the minor com-
(human cervical carcinoma) cell lines. The
ponents like 3-methylbut-2-enyl caffeate ethereal propolis fraction (DEEP) exhibited
and 3-methylbutyl ferulate (Bankova et al,
the strongest cytostatic activity. The sec-
1987; Amoros et al, 1994).
ondary fractions of ethyl acetate and butanol
of DEEP presented a good activity. Inter-
mediate activity was verified in the
Antifungal activity /DEEP fraction. The killing action of
3
CHCl
propolis on HeLa cells was tested by Ban
Millet-Clerc et al (1987) reported that propo- et al (1983). A concentration of 10 mg/ml
lis exhibited an important antifungal activ- caused 50% inhibition of colony-forming
ity against Trichophyton and Mycrosporum ability. In assessing the killing action of
in the presence of propylene glycol, which propolis, flavonoids were also tested. HeLa
interacts synergistically at a 5% concentra- cells were found to be more sensitive to
tion. Combinations of some antimycotic quercetin and rhamnetin, but less sensitive
drugs with propolis (10%) increased their to galangin. Grunberger et al (1988)
activity on Candida albicans yeasts. The described caffeic acid phenethyl ester
greatest synergistic effect against most (CAPE) as the compound partially respon-
strains was obtained when propolis was sible for the cytostatic properties of propo-
added to antifungal drugs (Holderna and lis. The effect of CAPE on human cancer
Kedzia, 1987). Valdés et al (1987) tested cell lines was tested in breast carcinoma
30 propolis samples produced in Cuba (MCF-7) and melanoma (SK-MEL-28 and
SK-MEL-170) cell lines in culture. A dose drugs (Hollands et al, 1988a). Propolis
of 10 μg/ml of CAPE completely inhibited preparations were classified as a good coc-
the incorporation of [H]thymidine into the
3 cidiostat against Chilomonas paramecium
DNA of breast carcinoma. More dramatic (Hollands etal, 1988b). Torres et al (1990)
effects were observed in the melanoma, evaluated the effect of EEP on the growth of
colon (HT 29) and renal carcinoma cell lines, the protozoan parasite Giardia lamblia in
but the CAPE effect on normal fibroblasts vitro. At an EEP concentration of 11.6 mg/ml
and melanocytes was significantly less. there was a 98% inhibition effect.
Because the cytostatic action of CAPE is
more effective in transformed cells, it is rea-
sonable to assume that it is responsible for Other properties
the claimed carcinostatic properties of
propolis. Many other biological and pharmacological
The antitumoral activity of caffeic acid properties of propolis have been described
derivatives, eg, methyl ferulate, methyl acetyl by various authors, including regeneration of
ferulate, methyl acetyl isoferulate and methyl cartilaginous tissue (Scheller et al, 1977a),
diacetyl caffeate, was reported by Inayama bone tissue (Stojko et al, 1978) and dental
et al, 1984. The effect of other caffeic acid pulp (Scheller et al, 1978; Magro Filho and
derivatives has been investigated by König Perri de Carvalho, 1990), anaesthetic activ-
(1988). Ross (1990) reported that the cyto- ity (Paintz and Metzner, 1979), hepato-
toxic effect of propolis in vitro against Chi- protective activity (Giurgea et al, 1985, 1987;
nese hamster ovary cancer cell lines was Hollands et al, 1991; Tushevskii et al, 1991),
due to naphthalene derivatives in propolis. increasing the number of plaque-forming
In vitro tests of extracts of Brazilian propolis cells in the spleen of populations of immu-
from A mellifera on human hepatocellular nized males (Scheller et al, 1988),
carcinoma, KB and HeLa cell lines showed immunomodulatory action (Benková et al,
that the cytotoxic effects were caused by 1989; Dimov et al, 1991, 1992), immuno-
quercetin, caffeic acid and phenyl ester con- genic properties (Scheller et al, 1989d), liver
stituents of propolis (Matsuno, 1992). detoxifying action, choleretic and antiulcer
Scheller et al (1989c) reported a cytotoxic action in vitro (Kedzia et al, 1990), antioxi-
activity of propolis in mice bearing Ehrlich dant activity (Yanishlieva and Marinova,
carcinoma in vivo. 1986; Krol et al, 1990; Scheller et al, 1990;
Dobrowolski et al, 1991; Misic et al, 1991;
Olinescu, 1991; Volpert and Elstner, 1993a,
Antiprotozoan activity 1993b), anticaries in rats (Ikeno et al, 1991),
protection agent against gamma irradiation
Scheller in mice (Scheller et al, 1989b), antileish-
et al (1977b) reported antiproto-
maniosis in hamster (Sartori et al, 1994),
zoan activity of propolis (EEP) in vitro on 3
strains of Trichomonas vaginalis. EEP solu- antitrypanosomal agent (Higashi et al, 1991)
tions in vitro presented a lethal activity on and inhibition of dihydrofolate reductase
strains at a concentration of 150 mg/ml. activity (Strehl et al, 1994).
The antiprotozoan activity of propolis
was verified in experimental animals infected
with Eimeria magna, E media and E per- Toxicity
forans treated with 3% EEP and other
antiprotozoan drugs. The coccidiostatic As propolis use increases, its side-effects
effect of propolis was higher than other are observed more frequently (Wanscher,
1976; Petersen, 1977; Monti et al, 1983; as anti-acne lotion, face creams, ointments,
Ayala et al, 1985; Machácková, 1985; lotions and solutions (Debuyser, 1983; Leje-
Rudzki et al, 1985; Tosti et al, 1985; Cirasino une et al, 1988; Pons and Cueto, 1988,
et al, 1987; Hausen et al, 1987b; Sartoris 1989; Goetz, 1990).
et al, 1987; Young, 1987; Hay and Greig,
1990). Propolis contains some compounds
which cause toxicity. Beekeeper’s dermati- Propolis in dermatology
tis due to propolis is well known and an
apparent association between sensitivity to Bolshakova (1975) treated 110 patients
propolis and to poplar resins has been infected with Trichophyton on the hairy zone
observed (Hausen et al, 1987a, b).
of the head with 50% propolis (as an
Hausen et al (1987b) described the inci-
unguent). In 97 patients, it was found to pro-
dence of nearly 200 cases of allergic con- duce excellent results. Other examples of
tact dermatitis due to propolis. They identified the treatment of dermatological diseases
a substance 1,1-dimethylallyl caffeic acid were described when propolis was used as
(LB-1) responsible for the allergy. They also an antiseptic (Bolshakova, 1975; Gafar et
described the sensitizing properties of LB- al, 1986), antimycotic (Holderna and Kedzia,
1 in guinea pigs provoked by several propo- 1987; Millet-Clerc et al, 1987), bacteriostatic
lis samples, demonstrating that this com-
(Soboleva et al, 1990; Dobrowolski et al,
pound is the main sensitizer in propolis. The 1991; Stark and Glinski, 1993; Ventura Coll
flavonoid tectochrysin was considered a sec- et al, 1993), antiviral (Giurcaneanu et al,
ond allergen, although Schmalle et al (1986) 1988; Vachy et al, 1990) and fungistatic
stated that tectochrysin was a very weak
(Millet-Clerc et al, 1987) agent. Many other
sensitizer. Hashimoto et al (1988) verified
propolis applications in dermatology have
the allergenic properties of phenylethyl and been described. It has been used for wound
prenyl esters of caffeic acids from propolis. healing, tissue regeneration, treatment of
Observations of propolis used orally sug- burns, neurodermatitis, microbial eczema,
gest that intestinal absorption could play an contact dermatitis, leg ulcers, psoriasis, mor-
important role in propolis sensitization. Lim- phea, herpes simplex and genitalis, pruri-
itingthe extent of oral administration may tus ani, dermatophytes, trophic ulcers, pulp
be useful in preventing propolis allergy gangrene and as an astringent (Bolshakova,
(Angelini et al, 1987; Hausen et al, 1987a, 1975; Molnar-Toth, 1975; Scheller et al,
1988; Kleinhans, 1987; Trevisan and Kokelj, 1977a, 1978; Ghisalberti, 1979; Korsun,
1987; Machácková, 1988). 1983; Gafar et al, 1986; Hausen et al,
1987a; Giurcaneanu et al, 1988; Ponce de
Leon and Benitez, 1988; Goetz, 1990; Fierro
Therapeutic activity Morales, 1994).
parts of the world. Many European coun- Matel et al (1973) described the treatment of
tries are interested in natural products to 126 subjects suffering of external otitis,
heal diseases and propolis is an important chronic mesotympanic otitis and tympan
product used for this purpose. It is found in perforation with propolis solutions (5-10%)
pharmaceutical and cosmetic products, such which had a positive therapeutic result in
most cases. Propolis effects in other ORL patients were studied, 48 children and 90
diseases were reported: acute inflamma- adults, and treated with propolis (in children,
tions of the (Kachnii, 1975; Palos et al,
ear concentration of 10% and adults 20%). At
1989), treatment of mesotympanitis (Pop- these concentrations, 52% of the children
nikolov et al, 1973), pharyngitis showed a cure. In adults, the propolis effect
(Doroshenko, 1975), tuberculosis (Karimova was the same as tinidazole, an antiproto-
and Rodionova, 1975), chronic bronchitis zoan drug. When the propolis concentra-
(Chuhrienko et al, 1989; Scheller et al, tion was elevated to 30%, there was a
1989a), rhinopharyngolaryngitis (Isakbaev, higher efficacy (60% cure versus 40% with
1986), pharyngolaryngitis (Lin et al, 1993a) tinidazole). Some authors described the use
vasomotor catarrh treatment (Zommer- of propolis in the following therapies: acute
Urbanska et al, 1987) and rhinitis (Nuñez colitis, chronic colitis, acute gastric ulcers,
et al, 1988/1989). and acute duodenal ulcers (Gorbatenko,
1971; Makarov 1972; Nikolov et al, 1973;
Kabanov et al, 1989).
Propolis in gynecological diseases
peutic) very good results were obtained in 53 sidiary treatment in oral hygiene.
cases, good results in 24, and satisfactory in
28 cases. The results obtained by Roman et
al (1989) confirm that propolis potentiates Other propolis uses in therapy
the antiseptic, antifungal and antit-
rychomonas actions of specific chemical The use of propolis has been reported for
medicines. Stojko and Stojko (1993) also
other diseases (human and veterinary)
reported the use of propolis preparations including osteoarthritis (Lin et al, 1993b),
for treatment of gynecological disorders.
eyes diseases (Popescu et al, 1993), as
an antiinflammatory agent (Mihail et al,
1984; Christova, 1985; Busciglio, 1988;
Propolis in stomatology Soboleva et al, 1990; Olinescu, 1991; Fierro
Morales, 1994), angiology (Gonzalez et al,
Mirayes et al (1988) described a clinical 1988/1989) and orthopedic treatment (Que-
assay with an extract of propolis that showed sada and Cueto, 1988/1989). The diverse
its efficacy against giardiasis. Some 138 use of propolis in clinical trials shows that its
therapeutic efficacy lies mainly in diseases (tableau I). Les principaux constituants chi-
caused by microbial contaminations. miques sont discutés par rapport à leurs
activités biologiques et thérapeutiques : acti-
vité antibactérienne, antivirale, antifongique
DISCUSSION et cytotoxique. Certains composés, par
exemple les dérivés de l’acide caféique, ont
une action allergène et carcinogène. On
Based on the very complex chemical com-
rapporte les nombreuses études cliniques
position of propolis and its pharmacologi- concernant l’utilisation thérapeutique de la
cal and therapeutic properties, we conclude
that propolis is a very powerful natural prod- propolis, principalement contre les mala-
dies microbiennes, dans divers domaines
uct produced by bees. It can be used to
treat human and veterinary diseases with (dermatologie, ORL, gynécologie, odonto-
great success. Nevertheless, it is evident logie). En conclusion, on souligne la néces-
sité de développer des tests chimiques pré-
that propolis cannot be a remedy for all dis-
cis pour standardiser le produit.
eases and any who make such claims are
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