Journal of Ethnopharmacology 68 (1999) 307 – 314

www.elsevier.com/locate/jethpharm

Short communication

Improving effects of the extracts from Eugenia uniflora on

hyperglycemia and hypertriglyceridemia in mice
Ichiro Arai a,*, Sakae Amagaya a, Yasuhiro Komatsu a, Minoru Okada a,
Toshimitsu Hayashi b, Mie Kasai c, Munehisa Arisawa c, Yasunori Momose d
a
Central Research Laboratories, Tsumura & Company, Ibaraki 300 -11, Japan
b
Department of Medical Resources, Faculty of Pharmaceutical Sciences, Toyama Medical and Pharmaceutical Uni6ersity,
Toyama, Japan
c
Laboratory of Herbal Garden, Faculty of Pharmaceutical Sciences, Toyama Medical and Pharmaceutical Uni6ersity,
Toyama, Japan
d
Department of Clinical Pharmacy, School of Pharmaceutical Science, Toho Uni6ersity, Chiba, Japan
Received 5 January 1999; received in revised form 7 January 1999; accepted 22 April 1999

Abstract

EtOH (70%) extracts from the leaves of Eugenia uniflora were separated into six fractions with different polarity
and molecular size, i.e. NP-1–NP-6. In an oral glucose tolerance test, NP-1 and 4 inhibited the increase in plasma
glucose level. However, in an intraperitoneal glucose tolerance test, such an inhibitory effect was not seen. Thus, the
effects of NP-1 and 4 were apparently due to the inhibition of glucose absorption from the intestine. In a sucrose
tolerance test, all fractions inhibited the increase in plasma glucose level. In an oral corn oil tolerance test, NP-3 and
4 showed an inhibitory effect on the increase in plasma triglycerides level. On the other hand, NP-3, 4, 5 and 6
inhibited maltase and sucrase activities and all fractions except for NP-1 showed an inhibitory effect on lipase activity
dose-dependently. The inhibition of the increase in plasma glucose level by NP-3, 4, 5 and 6 in the oral sucrose
tolerance test and the inhibition of the increase in plasma triglycerides by NP-3 and 4 in the oral corn oil tolerance
test were apparently due to the inhibition of the decomposition of carbohydrates and fats in the intestine, respectively.
© 1999 Elsevier Science Ireland Ltd. All rights reserved.

Keywords: Eugenia uniflora; Glucose tolerance test; Sucrose tolerance test; Corn oil tolerance test; a-Glucosidase; Pancreatic lipase

1. Introduction

Eugenia uniflora L. is a Myrtaceae plant widely

* Corresponding author. Fax: +81-298-89-3858. distributed in South America, Southern Asia and
E-mail address: arai – ichirou@mail.tsumura.co.jp (I. Arai) Africa. In South America the leaves of this plant

0378-8741/99/$ - see front matter © 1999 Elsevier Science Ireland Ltd. All rights reserved.
PII: S 0 3 7 8 - 8 7 4 1 ( 9 9 ) 0 0 0 6 6 - 5
308 I. Arai et al. / Journal of Ethnopharmacology 68 (1999) 307–314
have been used to treat hypercholesterolemia,
gout, hypertension, digestive disease, rheumatism,
cough, fever, hepatic disease, amygdalitis, sore
throat and hemorrhoids (Schmada-H., 1988). In
Paraguay, it is called ‘‘N0 angapiry’’ and has been
used for obesity and diabetes (Ferro et al., 1988;
Japan International Cooperation Agency, 1991).
Recently, extracts from E. uniflora have been
reported to show reduction of blood pressure in
hypertensive patients (González et al., 1984) and
rabbits (Takesaki et al., 1990), have inhibitory
activities against xanthine oxidase (Schmada-H. et
al., 1987; Theoduloz et al., 1988), carragenin-in-
duced paw edema in rats (Schapoval et al., 1994)
and intestinal transit in mice (Schapoval et al.,
1994) and rats (Almeida et al., 1995), antimicro-
bial activities (Adebajo et al., 1989; Lima et al.,
1993), prolongation of pentobarbital sleeping time
in mice (Schapoval et al., 1994) and relaxation of
thoracic aorta of rats (Wazlawik et al., 1997). In
addition, decrease in plasma cholesterol and
triglycerides levels in hypertensive patients was
also reported (González et al., 1984).
In this paper, the results of studies on the
effects of the separated fractions of 70% EtOH
extracts from the leaves of E. uniflora on hyper-
glycemia and hypertriglyceridemia after carbohy-
drate and fat load in mice are described and some
possible mechanisms are discussed.
2. Materials and methods
2.1. Plant materials
Dried leaves of E. uniflora were purchased from
a herbalist at Asuncion, Paraguay and identified
by Professor Isabel Basualdo (Faculty of Chem-
istry and Pharmacy, Asuncion University,
Asuncion, Paraguay). Voucher specimens 005264-
005267 were deposited at the herbarium of
Toyama Medical and Pharmaceutical University
(Toyama, Japan).
2.2. Preparation of extract
Dry powdered leaves of E. uniflora were ex-
tracted three times with 70% EtOH under reflux
for 3 h (Fig. 1). The combined extracts were
concentrated under reduced pressure, followed by
partition between n-BuOH and H2O. The n-
BuOH-soluble fraction was further partitioned be-
tween n-hexane and H2O to give n-hexane-
(NP-1) and H2O-soluble fractions. The H2O-solu-
ble fraction was further extracted by EtOAc to
give an EtOAc-soluble fraction (NP-2), an H2O-
soluble fraction (NP-3) and a precipitate (NP-4).
On the other hand, the H2O-soluble fraction par-
titioned between n-BuOH and H2O was further
separated by centrifugal ultrafiltration (Centricut
10, Kurabo, Osaka, Japan) to give two fractions,
i.e. NP-5 with a higher molecular weight (\
10 000) and NP-6 with a lower molecular weight
(B10 000).
2.3. Reagents
Carboxymethyl cellulose, glucose, maltose, su-
crose, corn oil, triolein and porcine pancreatic
lipase were purchased from Wako Pure Chemical
Industries (Osaka, Japan). Tolbutamide, met-
formin and tris(hydroxymethyl)aminomethane
(Tris) were purchased from Sigma (St. Louis,
MO, USA). Tween 80 was purchased from Tokyo
Kasei Kogyo (Tokyo, Japan). Dimethyl sulfoxide
was purchased from Nakarai Tesque (Kyoto,
Japan). Voglibose was obtained from Takeda
Chemical (Osaka, Japan).
Fig. 1. Fractionation of 70% EtOH extract from the leaves of
E. uniflora. Percentage in parenthesis indicates the yield.
 I. Arai et al. / Journal of Ethnopharmacology 68 (1999) 307–314
2.4. Animals
Six-week-old male ICR strain mice were ob-
tained from Charles River Japan (Tokyo, Japan),
fed with normal chow, MF (Oriental Yeast,
Tokyo, Japan) and used for each experiment after
fasting for 18 h.
2.5. Carbohydrate tolerance test
NP-1, 4, 5 or 6 (300 mg/kg) in 1% Tween 80, or
NP-2 or 3 in 0.5% carboxymethyl cellulose was
administered orally to the mice. In the positive
control group of the glucose and sucrose tolerance
test, 200 mg/kg of tolbutamide or metformin and
0.05 mg/kg of voglibose in 1% Tween 80 were
administered, respectively. In the negative control
group, only 0.5% carboxymethyl cellulose or 1%
Tween 80 was administered. In the glucose toler-
ance test, 2 g/kg of glucose was administered
orally or intraperitoneally to the mice 30 min after
drug administration. In the sucrose tolerance test,
2 g/kg of sucrose was administered orally to the
mice simultaneously with drug administration.
Immediately before and 0.5, 1, 2 and 3 h after the
loading of glucose or sucrose, 20 ml of blood was
collected via the retro-orbital sinus. The blood
was diluted 1:3 with 20 U/ml heparinized saline
and centrifuged at 3000 rpm for 10 min at 4°C.
The concentration of glucose in the supernatant
was measured by a clinical glucose analyzer CGA-
101 (Shimadzu, Kyoto, Japan) and the increases
after carbohydrate load were calculated.
2.6. Corn oil tolerance test
NP-2 or 3 (1 g/kg) in 0.5% carboxymethyl
cellulose, or NP-4 and 5 in 1% Tween 80 was
administered orally to the mice. In the control
group, only 0.5% carboxymethyl cellulose or 1%
Tween 80 was administered. Simultaneously with
drug administration, 5 ml/kg of corn oil was
administered orally to the mice. Immediately be-
fore and 1.5, 3 and 4.5 h after the loading of corn
oil, 20 ml of blood was collected via the retro-or-
bital sinus. The blood was diluted to 1:1.5 with 20
U/ml heparinized saline and centrifuged at 3000
rpm for 10 min at 4°C. The concentration of
309
triglycerides in supernatant was measured by a
clinical biochemical analyzer COBAS MIRAS
(Hoffmann-La Roche, Basel, Germany) and the
increases after corn oil load were calculated.
2.7. Effects on a-glucosidases
An enzyme solution was prepared from rat
small intestinal brush boarder membranes
(Kessler et al., 1978). The test samples (final con-
centration: 0.1 and 1 mg/ml) or voglibose (final
concentration: 0.13 mg/ml) were dissolved in
dimethyl sulfoxide (final concentration: 0.2%) and
incubated with 10 mg/ml maltose or sucrose and
enzyme solution in 20 mM phosphate buffer (pH
6.8) at 37°C for 30 min. The productive glucose
was measured by a clinical glucose analyzer
(CGA-101, Shimadzu, Kyoto, Japan). The in-
hibitory activities against glucose production from
maltose and sucrose were calculated in compari-
son with the value of a blank, and expressed as
inhibition percentages of maltase and sucrase,
respectively.
2.8. Effects on pancreatic lipase
Test samples (final concentration: 0.1, 0.3 and 1
mg/ml) were dissolved in dimethyl sulfoxide (final
concentration: 0.2%) and incubated with 0.4 mg/
ml triolein and 0.5 mg/ml pancreatic lipase in 200
mM Tris–HCl buffer (pH 8.0) at 37°C for 10
min. The productive nonesterified fatty acids were
measured by a clinical biochemical analyzer
COBAS MIRAS (Hoffmann-La Roche, Basel,
Germany). The inhibitory activities against nones-
terified fatty acids production were calculated in
comparison with the value of a blank, and ex-
pressed as inhibition percentages of pancreatic
lipase.
2.9. Statistical analysis
The values in Figs. 2–4 were expressed as a
mean9 S.E. Statistical analysis was conducted us-
ing Student’s t-test. The values in Table 1 were
expressed as a mean of duplicate.
310 I. Arai et al. / Journal of Ethnopharmacology 68 (1999) 307–314

Fig. 2. Effect of each fraction from the leaves of E. uniflora on increase in plasma glucose level after oral and intraperitoneal glucose
load in mice. NP-1 and 4 (300 mg/kg), tolbutamide (200 mg/kg) or metformin (200 mg/kg) was orally administered to mice ( ,
n=6). In the control groups (, n= 6), vehicles were administered. Thirty minutes after the administrations of the drugs, glucose
(2 g/kg) was administered orally or intraperitoneally to all mice. Blood was collected periodically and the plasma glucose
concentrations were measured and expressed as an increase from the reference value obtained before glucose load. Each of the values
is expressed in terms of mean 9 S.E. Statistical analyses were conducted using Student’s t-test. * And ** indicate significant
difference at P B0.05 and 0.01 vs. each control group.

3. Results 3.2. Effects on the sucrose tolerance test

3.1. Effects on the glucose tolerance test
In the oral glucose tolerance test, NP-1 and
4 (300 mg/kg) significantly inhibited the in-
crease in plasma glucose level after glucose load
(Fig. 2). NP-2 (300 mg/kg) also slightly inhibited
the increase in glucose, while NP-3, 5 and 6
showed no inhibitory effect (data not shown). In
comparative groups, both tolbutamide and met-
formin (200 mg/kg) significantly inhibited the in-
crease in glucose level. In the intraperitoneal
glucose tolerance test, however, no inhibitory ef-
fects of NP-1 and 4 on the increase in plasma
glucose concentration were seen (Fig. 2). The
inhibitory effects of tolbutamide and metformin
were also observed after intraperitoneal glucose
load.
In the oral sucrose tolerance test, all fractions
at 300 mg/kg significantly inhibited the increase in
plasma glucose concentration after sucrose load
(Fig. 3). In a comparative group, voglibose (0.05
mg/kg) significantly inhibited the increase in
glucose.
3.3. Effects on the corn oil tolerance test
In the oral corn oil tolerance test, NP-3 and 4
(1 g/kg) significantly inhibited the increase in
plasma triglycerides concentration after corn oil
load (Fig. 4), while NP-2 and 5 did not.
3.4. Effects on a-glucosidases acti6ities
NP-3, 4, 5 and 6 (0.1 and 1 mg/ml) inhibited
maltase and sucrase activity dose-dependently
 I. Arai et al. / Journal of Ethnopharmacology 68 (1999) 307–314 311

(Table 1). On the other hand, such inhibitory
effects were not observed in NP-1 and 2. In the
reference group, voglibose (0.13 mg/ml) inhibited
maltase and sucrase activities up to about 90%.
3.5. Effects on pancreatic lipase acti6ities
All fractions except for NP-1 (0.3 and 1 mg/ml)
inhibited pancreatic lipase activity dose-depen-
dently (Table 1).
4. Discussion
Upper-body obesity, glucose intolerance, hyper-
triglyceridemia and hypertension are considered
to be risk factors for cardiovascular disease and
called the ‘‘deadly quartet’’ (Kaplan, 1989). Thus,
improvements of postprandial hyperglycemia and
hypertriglyceridemia are regarded to be important
for diabetic and obese patients. In Paraguayan
folk medicine, the leaves of E. uniflora have been
used for diabetes and obesity, but their pharmaco-
logical effects and mechanisms have not been
elucidated fully. Therefore, we investigated the
effects of six fractions from the leaves of E.
uniflora on carbohydrate and fat tolerance in
mice.
Starch in meals is first decomposed to oligosac-
charides (maltose, maltotriose and a-dextrin) by
a-amylase of saliva and pancreatic juice, and sec-
ondarily to glucose by a-glucosidase (maltase and
a-dextrinase) in the brush border of the intestine
(Balfour and McTavish, 1993). Sucrose in meals is
also decomposed to glucose and fructose by su-
crase, another a-glucosidase. Subsequently, these
monosaccharides are absorbed. Therefore drugs
that inhibit a-glucosidase activities and glucose
absorption had been developed for diabetes
(Lebovitz, 1992). Thus, we examined the effects of
the fractions from the leaves of E. uniflora on
hyperglycemia after oral and intraperitoneal glu-
cose, and oral sucrose load in mice, and also on
maltase and sucrase activities in vitro.
In the carbohydrate tolerance test, NP-1 (300
mg/kg, p.o.) significantly improved hyperglycemia
after oral glucose load, but not after intraperi-
toneal (i.e. not through the intestine) load (Fig. 2).
On the other hand, tolbutamide, one of the sul-

Fig. 3. Effect of each fraction from the leaves of E. uniflora on increase in plasma glucose level after oral sucrose load in mice. NP-1,
2, 3, 4, 5 and 6 (300 mg/kg) or voglibose (0.05 mg/kg) was orally administered to mice ( , n =6). In the control groups (, n = 6),
vehicle was administered. Sucrose (2 g/kg) was orally administered together with the drugs to all mice. Blood was collected
periodically and the plasma glucose concentrations were measured and expressed as an increase from the reference value obtained
before sucrose load. Each of the values is expressed in terms of mean 9S.E. Statistical analyses were conducted using Student’s
t-test. * And ** indicate significant difference at PB 0.05 and 0.01 vs. each control group.
312 I. Arai et al. / Journal of Ethnopharmacology 68 (1999) 307–314
Fig. 4. Effect of each fraction from the leaves of E. uniflora on
increase in plasma triglycerides level after oral corn oil load in
mice. NP-2, 3, 4 and 5 (1 g/kg) was orally administered to
mice ( , n = 5). In the control groups (, n = 5), vehicle was
administered. Corn oil (5 ml/kg) was orally administered
together with drugs to all mice. Blood was collected periodi-
cally and the plasma triglycerides concentrations were mea-
sured and expressed as an increase from the reference value
obtained before corn oil load. Each value is expressed in terms
of mean9 S.E. Statistical analyses were conducted using Stu-
dent’s t-test. * And ** indicate significant difference at PB
0.05 and 0.01 vs. each control group.
fonylureas that stimulate insulin secretion
(Skillman and Feldman, 1981), and metformin,
one of the biguanides that inhibit hepatic glucose
output (Dunn and Peters, 1995), improved hyper-
glycemia after both oral and intraperitoneal glu-
cose load (Fig. 2). Consequently, the improved
mechanism of NP-1 on hyperglycemia after oral
glucose load can be assumed not to be the same
as that of tolbutamide or metformin, but to in-
hibit glucose absorption from the intestine.
NP-1 also improved hyperglycemia after oral su-
crose load (Fig. 3), but it had no inhibitory effect
on a-glucosidases up to 1 mg/ml (Table 1).
Thus, the improving effect of NP-1 on hyper-
glycemia after sucrose load can also be assumed
to be derived from the inhibition of glucose ab-
sorption.
NP-2 (300 mg/kg, p.o.) slightly but significantly
improved hyperglycemia after oral glucose (data
not shown) and sucrose load (Fig. 3). The in-
hibitory effects of NP-2 at 1 mg/ml on maltase
were also weak, and none were found on sucrase
at this dose (Table 1). These results thus indicate
that there was little improving effect of NP-2 on
postprandial hyperglycemia.
NP-3, 5 and 6 (300 mg/kg, p.o.) significantly
improved hyperglycemia after oral sucrose load
(Fig. 3), but not after oral glucose load (data not
shown), and inhibited a-glucosidases at 0.1 and 1
mg/ml dose-dependently (Table 1). Thus, these
improving effects on hyperglycemia after sucrose
load can be assumed to be derived from the
inhibition of a-glucosidase (sucrase) activity like
voglibose (Horii et al., 1986), one of the a-glucosi-
dase inhibitors.
NP-4 (300 mg/kg, p.o.) significantly im-
proved hyperglycemia after oral glucose load, but
not after intraperitoneal glucose load (Fig. 2). On
the other hand, NP-4 inhibited a-glucosidase
activities at 0.1 and 1 mg/ml dose-dependently
(Table 1) and improved hyperglycemia after
oral sucrose load (Fig. 3). Consequently,
NP-4 can be assumed to be effective for postpran-
dial hyperglycemia by its inhibition of carbohy-
drate decomposition as well as glucose
absorption.
Fats in meals are decomposed to fatty
acids and glycerol by pancreatic lipase and
absorbed (Thompson, 1978). Recently, the in-
hibitor of pancreatic lipase has been developed as
a drug for hypertriglyceridemia (Ogawa et al.,
1986; Mutoh et al., 1994). Thus, we examined
the effects of fractions from the leaves of E.
uniflora on hypertriglyceridemia after oral corn oil
load in mice and pancreatic lipase activities in
vitro.
NP-3 and 4 (1 g/kg, p.o.) significantly improved
hypertriglyceridemia after corn oil load, but NP-1
and 5 did not (Fig. 4). On pancreatic lipase activ-
ities, NP-2, 3, 4, 5 and 6 inhibited the activity at
0.3–1 mg/ml dose-dependently (Table 1). From
these results, NP-3 and 4 can be assumed to be
effective on postprandial hypertriglyceridemia via
inhibition of pancreatic lipase. The reason why
NP-2 and 5 inhibited pancreatic lipase, but did
not improve hypertriglyceridemia, is still unclear.
However, it was speculated that these fractions
 I. Arai et al. / Journal of Ethnopharmacology 68 (1999) 307–314 313

Table 1
Inhibition percentage of each fraction from the leaves of E. uniflora on a-glucosidases and pancreatic lipase activities. In
alpha-glucosidases assays, NP-1, 2, 3, 4, 5 and 6 (final concentration: 0.1 and 1 mg/ml) or voglibose (final concentration: 0.13 mg/ml)
was dissolved in dimethyl sulfoxide (final concentration: 0.2%) and incubated with 10 mg/ml of maltose or sucrose and enzyme
solution in 20 mM phosphate buffer (pH 6.8) at 37°.

Fraction Dose (mg/ml) a-Glucosidase Pancreatic lipase

Maltase Sucrase

NP-1 0.1 0.0 0.0 0.0

0.3 ND ND 0.0
1.0 0.0 0.0 0.0
NP-2 0.1 0.0 0.0 18.6
0.3 ND ND 73.3
1.0 28.2 0.0 100.0
NP-3 0.1 66.8 32.0 0.0
0.3 ND ND 23.3
1.0 95.0 98.0 100.0
NP-4 0.1 41.4 7.6 9.3
0.3 ND ND 51.2
1.0 84.6 91.2 97.0
NP-5 0.1 51.4 52.3 1.2
0.3 ND ND 14.0
1.0 87.4 93.8 78.0
NP-6 0.1 47.9 56.3 7.0
0.3 ND ND 39.5
1.0 90.9 97.0 84.9
Voglibose 0.00013 88.7 90.2 ND

also inhibited lipoprotein lipase and inhibited the References

decomposition of triglycerides in the blood.
In conclusion, the separated fractions from the
leaves of E. uniflora have improving effects on
postprandial hyperglycemia and hypertriglyce-
ridemia, and these mechanisms can be assumed to
be the inhibition of sugar and fat decomposition,
and glucose absorption. Consequently, the leaves
of E. uniflora may be useful for diabetes and
obesity.
Phytochemical analysis of the leaves of E.
uniflora have shown the presence of volatile oils,
i.e. monoterpenes and sesquiterpenes (Rücker et
al., 1977; Weyerstahl et al., 1988; Alice et al., 1991;
Henriques et al., 1993), flavonoids (Schmada-H. et
al., 1987; Alice et al., 1991) and tannins (Alice et
al., 1991; Lee et al., 1997). Further studies into the
isolation and identification of the active principles
in each fraction are currently under investigation.
Adebajo, A.C., Oloke, K.J., Aladesanmi, A.J., 1989. Antimi-
crobial activities and microbial transformation of volatile
oils of Eugenia uniflora. Fitoterapia 60, 451 – 455.
Alice, C.B., Vargas, V.M.F., Silva, G.A.A.B., et al., 1991.
Screening of plants used in south Brazilian folk medicine.
J. Ethnopharmacol. 35, 165 – 171.
Almeida, C.E., Karnikowski, M.G., Foleto, R., Baldisserotto,
B., 1995. Analysis of antidiarrhoeic effect of plants used in
popular medicine. Rev. Saude Publica 29, 428 – 433.
Balfour, J.A., McTavish, D., 1993. Acarbose. An updata of its
pharmacology and therapeutic use in diabetes mellitus.
Drugs 46, 1025 – 1054.
Dunn, C.J., Peters, D.H., 1995. Metformin. A review of its
pharmacological properties and therapeutic use in non-in-
sulin-dependent diabetes mellitus. Drugs 49, 721 – 749.
Ferro, E., Schinini, A., Maldonado, M., Rosner, J., Schmada-
H, G., 1988. Eugenia uniflora leaf extract and lipid
metabolism in Cebus apella monkeys. J. Ethnopharmacol.
24, 321 – 325.
González, J.J., Sanabria, C., Frutos, C., Chiola, M., de Garay,
J.M.R.J.C., 1984. Evaluación del efecto de la Eugenia
314 I. Arai et al. / Journal of Ethnopharmacology 68 (1999) 307–314
uniflora (Ńangapiry) sobre la hipertensión arterial en una
población urbano-rural del Paraguay. Rev. Inst. Investig.
Cienc. Salud 1, 11 – 17.
Henriques, A.T., Sobral, M.E., Caudura, A.D., Schapoval,
E.E.S., Bassani, V.L., 1993. Aromatic plants from Brazil.
II. The chemical composition of some Eugenia essential
oils. J. Essent. Oil Res. 5, 501–505.
Horii, S., Fukase, H., Matsuo, T., Kameda, Y., Asano, N.,
Matsui, K., 1986. Synthesis and a-D-glucosidase inhibitory
activity of N-substituted valiolamine derivatives as poten-
tial oral antidiabetic agents. J. Med. Chem. 29, 1038–1046.
Japan International Cooperation Agency, 1991. Photographs
of Paraguayan medicinal plants. Japan International Co-
operation Agency, Tokyo, p. 57.
Kaplan, N.M., 1989. The deadly quartet. Upper-body obesity,
glucose intolerance, hypertriglyceridemia, and hyperten-
sion. Arch. Intern. Med. 149, 1514–1520.
Kessler, M., Acuto, O., Storelli, C., Murer, H., Müller, M.,
Semenza, G., 1978. A modified procedure for the rapid
preparation of efficiently transporting vesicles from small
intestinal brush border membranes. Their use in investigat-
ing some properties of D-glucose and choline transport
systems. Biochim. Biophys. Acta 506, 136–154.
Lebovitz, H.E., 1992. Oral antidiabetic agents. The emergence
of alpha-glucosidase inhibitors. Drugs 44 (Suppl. 3), 21–
28.
Lee, M., Nishimoto, S., Yang, L., et al., 1997. Two macro-
cyclic hydrolysable tannin dimers from Eugenia uniflora.
Phytochemistry 44, 1343–1349.
Lima, E.O., Gompertz, O.F., Giesbrecht, A.M., Paulo, M.Q.,
1993. In vitro antifungal activity of essential oils obtained
from officinal plants against dermatophytes. Mycoses 36,
333 – 336.
Mutoh, M., Nakada, N., Matsukuma, S., et al., 1994.
Panclicins, novel pancreatic lipase inhibitors. I. Taxonomy,
fermentation, isolation and biological activity. J. Antibiot.
47, 1369 – 1375.
Ogawa, K., Terada, T., Muranaka, Y., Hamakawa, T., Hashi-
moto, S., Fujii, S., 1986. Studies of hypolipidemic agents.
I. Syntheses and hypolipidemic activities of 1-substituted
2-alkanone derivatives. Chem. Pharm. Bull. 34, 1118 –
1127.
Rücker, V.G., Silva, G.A.A.B., Bauer, L., Schikarski, M.,
1977. New constituents of Stenocalyx michelii. Planta Med.
31, 322 – 327.
Schapoval, E.E.S., Silveira, S.M., Miranda, M.L., Alice, C.B.,
Henriques, A.T., 1994. Evaluation of some pharmacologi-
cal activities of Eugenia uniflora L. J. Ethnopharmacol. 44,
137 – 142.
Schmada-H, G., 1988. Ethnobotanical observations on
Paraguayan Myrtaceae. I. J. Ethnopharmacol. 22, 73 – 79.
Schmada-H, G., Theoduloz, C., Franco, L., Ferro, B.E., de
Arias, A.R., 1987. Preliminary pharmacological studies on
Eugenia uniflora: xanthine oxidase inhibitory activity. J.
Ethnopharmacol. 21, 183 – 186.
Skillman, T.G., Feldman, J.M., 1981. The pharmacology of
sulfonylureas. Am. J. Med. 70, 361 – 372.
Takesaki, R., Momose, Y., Nakanishi, S., Arisawa, M., Mor-
ita, N., Watanabe, H., 1990. Abstract Papers of the 37th
Annual Meeting of the Japanese Society Of Pharmacog-
nosy. The Japanese Society of pharmacognosy, Tokyo, p.
53.
Theoduloz, C., Franco, L., Ferro, E., Schmada-H, G., 1988.
Xanthine oxidase inhibitory activity of Paraguayan Myr-
taceae. J. Ethnopharmacol. 24, 179 – 183.
Thompson, A.B.R., 1978. Disturbance in Lipid and Lipo-
protein Metabolism. American Physiological Society, New
York, p. 31.
Wazlawik, E., Da Silva, M.A., Peters, R.R., et al., 1997.
Analysis of the role of nitric oxide in the relaxant effect of
the crude extract and fractions from Eugenia uniflora in the
rat thoracic aorta. J. Pharm. Pharmacol. 49, 433 – 437.
Weyerstahl, P., Marschall-Weyerstahl, H., Christiansen, C.,
Oguntimein, B.O., Adeoye, A.O., 1988. Volatile con-
stituents of Eugenia uniflora leaf oil. Planta Med. 54,
546 – 549.