Journal of Ethnopharmacology 81 (2002) 191 /197

www.elsevier.com/locate/jethpharm

Anti-diabetic activity of Bauhinia forficata decoction in

streptozotocin-diabetic rats
M.T. Pepato a,*, E.H. Keller a, A.M. Baviera a, I.C. Kettelhut b, R.C. Vendramini a,
I.L. Brunetti a
a
Departamento de Análises Clı́nicas, Faculdade de Ciências Farmacêuticas de Araraquara, UNESP, R. Expedicionários do Brasil 1621 Araraquara, SP,
Brazil
b
Departamento de Bioquı́mica, Faculdade de Medicina de Ribeirão Preto, USP, Av. Bandeirantes 3900 Ribeirao Preto, SP, Brazil

Received 11 November 2000; received in revised form 5 February 2002; accepted 10 March 2002

Abstract

The effects of using Bauhinia forficata leaf decoction (150 g leaf/l water; 35.29/7.8 ml/100 g body weight mean daily dose) as a
drinking-water substitute for about 1 month on streptozotocin-diabetes (STZ-diabetes) in male Wistar rats were investigated. The
physico-metabolic parameters measured were: body weight, food and liquid intake, urinary volume, hepatic glycogen, serum
triglycerides and cholesterol, plasma glucose, urinary glucose and urea, and the weight of epididymal and retroperitoneal adipose
tissue and soleus and extensor digitorum longus muscles. The STZ-diabetic rats treated with decoction showed a significant
reduction in serum and urinary glucose and urinary urea as compared to the STZ-diabetic control, no difference being seen between
decoction-treated and -untreated non-diabetic rats. The other physico-metabolic factors showed no changes in treated STZ-diabetic
rats. The improvement in carbohydrate metabolism seen in the rats treated with Bauhinia forficata decoction does not appear to be
linked to the inhibition of glycogenolysis or the stimulation of glycogenesis nor does it appear to act in a way similar to insulin or the
sulfonylureas, although it may act by the inhibition of neoglycogenesis in a manner similar to that of the biguanides. # 2002
Elsevier Science Ireland Ltd. All rights reserved.

Keywords: Anti-diabetic activity; Bauhinia forficata ; Anti-hyperglycemic effect; Streptozotocin-diabetic rats

1. Introduction known as Pata de Vaca (cows hoof). This species is an

The genus Bauhinia belongs to the family Caesalpi-
niaceae (formally Leguminosae) (Viana et al., 1999;
Panda and Kar, 1999) and has some species that are
used as traditional folk medicines in the treatment of
diabetes. Studies carried out with Bauhinia manca ,
Bauhinia divaricata, Bauhinia purpurea and Bauhinia
variegata have demonstrated hypoglycemic activity in
laboratory animals (Vasconcelos, 2000; Ivorra et al.,
1989).
Bauhinia forficata is the Bauhinia species most used
as an anti-diabetic herbal remedy in Brazil, where it is
* Corresponding author. Tel.:
/55-16-201-6546; fax:
/55-16-232-
0880.
E-mail address: pepatomt@fcfar.unesp.br (M.T. Pepato).
0378-8741/02/$ - see front matter # 2002 Elsevier Science Ireland Ltd. All rights reserved.
PII: S 0 3 7 8 - 8 7 4 1 ( 0 2 ) 0 0 0 7 5 - 2
arboreal plant of Asiatic origin which adapts well to the
Brazilian climate, reaching 12 m in height (Miyake et al.,
1986; Donato, 1995).
The first reports of Bauhinia forficata hypoglycemic
activity in diabetic patients were made by Juliani (1929)
and Juliani (1931). The fact that few reports of the
effects of this plant occur in the literature, and that those
which do give contradictory results (Caricati-Neto et al.,
1985; Russo et al., 1990) or unsuccessful results (Costa,
1945), makes it important that more detailed investiga-
tions using good experimental models are carried out on
the effects of oral treatment with this plant. In this paper
we investigate the effects of oral treatment with a
decoction of Bauhinia forficata on characteristic meta-
bolic parameters of streptozotocin-diabetic and non-
diabetic rats.
192 M.T. Pepato et al. / Journal of Ethnopharmacology 81 (2002) 191 /197
2. Materials and methods
2.1. Decoction preparation
Material from a Bauhinia forficata tree in the
Medicinal Plants Garden of the School of Pharmacy,
Araraquara, São Paulo State, Brazil was identified,
authenticated and deposited in the Herbarium of the
Department of Industrial Pharmacy, Federal University
of Santa Maria, Rio Grande do Sul, Brazil as accession
No. 119, by Dr Gilberto Dolejal Zanetti. Leaves were
collected from this tree between April and May (the end
of Autumn in the Southern Hemisphere) and a decoc-
tion prepared by the method normally used in the
Araraquara region, i.e. boiling 150 g of fresh leaves in 1
l of water for 5 min, allowing the decoction to stand for
30 min and filtering it through a simple paper filter. The
final yield was 87% by volume, the decoction being
prepared every 2 or 3 days and kept in brown-glass
bottles at 4 8C.
2.2. Animals and their treatment
All rats were fed a normal laboratory chow diet
containing (wt./wt.) 16% protein, 66% carbohydrate and
8% fat and were housed under a 12:12 h light:dark cycle
at 22 /25 8C. The experimental protocols and the
treatment and care of the rats had the prior approval
of the ethics committee.
A group of male Wistar rats were adapted to
metabolic cages for 2 or 3 days. The animals were
then anesthetized with ethyl ether and 40 mg/kg body
weight streptozotocin (STZ) dissolved in 0.01 M citrate
buffer, pH 4.5, was injected into the jugular vein. The
rats were fasted for 14/16 h and their mean weight was
1609/2 g. Another group of rats weighing 1449/2 g were
treated in the same way except that they received STZ at
a the dose 50 mg/kg body weight because young rats
proved to be more resistant than older ones to the
diabetogenic action of STZ (Pepato et al., 1996). All rats
were returned to their metabolic cages where they had
free access to food and water.
2.2.1. Decoction administration
2.2.1.1. Diabetic group. Body weight, serum glucose
levels, urinary glucose excretion and food intake were
measured 3 days after STZ injection (40 mg/kg) and
used as parameters to obtain matching pairs of rats with
diabetes of a similar level of severity. One rat of each
pair was randomly assigned to the experimental group
which was to receive Bauhinia forficata decoction in
place of drinking-water (the STZ Bauhinia forficata -
treated (STZBFT) group), while the other rat of each
pair was assigned to the control group which received
drinking-water (the STZ control (STZCONT) group).
Both groups received water for the first five days after
STZ injection, after which the water in the cages of the
STZBFT group was replaced by Bauhinia forficata
decoction while the rats in the STZCONT group
continued to have access to plain water. Body weight,
food and liquid intake, urine excretion, plasma glucose
(blood collected from the tip of the tail) and urinary
glucose and urea were measured about every 7 days up
to 36 days after STZ injection (31 days of treatment).
We chose chronic treatment because previous experi-
ments in our laboratory had shown that acute treatment
with Bauhinia forficata decoction produced no altera-
tion in the level of glycemia. After 31 days of chronic
treatment with Bauhinia forficata decoction (mean daily
dose 35.29/7.8 ml/100 g body weight), the rats were
sacrificed by decapitation and samples of the free
running blood collected for the determination of the
plasma level of glucose, serum cholesterol and triglycer-
ides. The epididymal fat-pad and the retroperitoneal
adipose tissue lying over the psoas, the soleus and
extensor digitorum longus (EDL) muscles were removed
and weighed and the liver removed for glycogen
determination.
2.2.1.2. Non-diabetic group. After an adaptation period
in metabolic cages the rats were paired according to
body weight (1249/1.5 g) and randomly assigned to
either the non-diabetic Bauhinia forficata -treated
(NDBFT) group which received Bauhinia forficata
decoction in place of drinking-water (mean daily dose
18.69/0.66 ml/100 g body weight) or the non-diabetic
control (NDCONT) group which had access to plain
water. The experiment continued for 34 days during
which time similar physico-metabolic determinations
were made as for the STZ-diabetic rats.
2.2.2. Insulin administration
Eight days after of STZ (50 mg/kg) injection rats in
the diabetic insulin group (DI) were treated twice a day
(9 a.m. and 6 p.m.) by subcutaneous injection of 3 units
of NPH insulin (Biohulin NU-100, Biobrás, Montes
Claros, MG, Brazil) for 38 days, after which the same
metabolic parameters were evaluated. The diabetic
control group (DCONT) received the same volume of
0.9% NaCl solution, administered identically. These
insulin-treated rats served as a further control for the
experimental model.
2.3. Chemical and statistical analyses
Urinary glucose was measured by the o -toluidine
method of Duboswski (1962) and urea by the urease
method (Bolleter et al., 1961; Bergemeyer, 1985).
Hepatic glycogen was extracted with 30% KOH and
precipitated with alcohol (Carrol et al., 1956) and the
quantity recovered determined (in triplicate) by the
 M.T. Pepato et al. / Journal of Ethnopharmacology 81 (2002) 191 /197
colorimetric anthrone method of Collowick and Kaplan
(1957), using an Hitachi U 3000 or Micronal B 382
spectrophotometer. Serum glucose, cholesterol and
triglycerides were determined in a Bayer Technicon
RA-100 autoanalyzer. All reagents were purchased
from Merk or Sigma and were of at least analytical
grade purity.
The animal data was assessed by Analysis of Variance
and the Student’s t -test at a significance level of P B/
0.05.
3. Results
Before administration of Bauhinia forficata decoction
both groups of STZ-treated rats presented practically
the same degree of physico-metabolic symptoms as seen
in the diabetic state.
Figs. 1 /3 show data for plasma glucose, urinary
glucose and urinary urea levels respectively for the non-
diabetic (NDBFT and NDCONT) and diabetic
(STZBFT and STZCONT) groups of rats. It can be
seen that after 31 days of treatment the diabetic group
treated with decoction showed a significant reduction in
plasma glucose (P B/0.05) (Fig. 1) and urinary glucose
(P B/0.01) (Fig. 2) and urinary urea (P B/0.05) levels
Fig. 1. The effect of Bauhinia forficata decoction on the levels of plasma glucose of the STZ-diabetic rats. Arrow indicates the beginning of Bauhinia
forficata treatment. All values represent means9/standard error of the mean (n/10). The Analysis of Variance was performed on the whole set of
results from day 4 to day 31 of treatment.
193
(Fig. 3) in relation to the STZCONT. The beneficial
effect of Bauhinia forficata decoction on plasma glucose
level appeared on about the 18th day of treatment (23
days after STZ injection). Although Fig. 3 shows that, as
compared to the non-diabetic group untreated
(NDCONT), the non-diabetic group treated with decoc-
tion (NDBFT) showed an increase in the level of urinary
urea on day 13 of Bauhinia forficata treatment and an
increase in plasma glucose on day 16 of treatment (Fig.
1). Comparison of both non-diabetic groups (NDBFT
and NDCONT) during the whole 34 days of treatment
showed no overall significant differences between these
two groups regarding glycemia and urinary urea.
The mean level of plasma glucose and urinary urea
recorded during of the experiment (31 days for the STZ-
diabetic groups and 34 days for the non-diabetic
groups), which was significantly higher in the STZ-
diabetic groups than in the non-diabetic groups, irre-
spective of whether or not the rats were treated with
Bauhinia forficata decoction. The difference in plasma
glucose and urinary urea between the non-diabetic
group not treated (NDCONT) and the diabetic group
not treated (STZCONT), was 321 mg/dl for glucose and
223 mg/24 h 100 g body weight for urinary urea.
Similarly, the difference in these values between the
non-diabetic group treated with decoction (NDBFT)
194 M.T. Pepato et al. / Journal of Ethnopharmacology 81 (2002) 191 /197
Fig. 2. The effect of Bauhinia forficata decoction on the levels of
urinary glucose of non-diabetic and STZ-diabetic rats. Arrow indicates
the beginning of Bauhinia forficata treatment. All values represent
means9/standard error of the mean (n/10). The Analysis of Variance
was performed on the whole set of results from day 3 to day 31 of
treatment.
and the STZ-diabetic group treated with decoction
(STZBFT) was 234 mg/dl for glucose and 98 mg/24 h
100 g body weight for urinary urea. It should be noted
that the differences are higher in the groups which did
not receive decoction, supporting the beneficial effects
Bauhinia forficata decoction presented above.
Table 1 shows that treatment with Bauhinia forficata
decoction did not produce any alterations in body
weight, water or food intake, urinary volume, serum
lipids or hepatic glycogen either in non-diabetic or STZ-
diabetic rats. Comparing the data for the STZBFT and
STZCONT groups with that of their matched controls,
NDBFT and NDCONT groups, it can be seen that there
are significant differences in body weight gain (Dw ),
food and liquid intake and urinary volume. Although
there was no significant difference regarding hepatic
glycogen between the two Bauhinia forficata untreated
groups (NDCONT and STZCONT) there was a sig-
nificant difference between the two Bauhinia forficata
treated groups (NDBFT and STZBFT).
Table 2 shows the metabolic parameters of STZ-
diabetic rats before and after treatment with insulin (DI)
or NaCl solution (DCONT). It can be seen that, as
expected, there was a significant improvement in the
metabolic status of the rats after treatment with insulin,
indicating that the experimental model adopted was
adequate.
The lipid-related data in Table 1 shows that there was
no significant alteration in the level of serum lipids over
a diabetic period of about 1 month, although the
significant differences in epididymal fat-pad tissue and
retroperitoneal adipose tissue between the two groups of
STZ-diabetic rats (STZBFT and STZCONT) as com-
pared with the two groups of non-diabetic rats (NDBFT
and NDCONT) shown in Table 3 indicates fat mobili-
zation. Treatment with Bauhinia forficata decoction did
not significantly affect the weight of either adipose or
muscle tissue.
4. Discussion
By reducing plasma and urinary glucose and urinary
urea (Figs. 1/3), oral treatment of STZ-diabetic rats
with Bauhinia forficata , carried out by replacing their
drinking-water with Bauhinia forficata decoction, pro-
duced a beneficial effect on the STZ-induced diabetes of
the rats.
As early as 1941 Juliani working with pancreatecto-
mized or with adrenaline administration in dogs and
rabbits, had noticed that the administering of tablets
containing the active components of Bauhinia forficata
produced prophylactic anti-hyperglycemic effect in rela-
tion to diabetogenic states and had beneficial effects on
hyperglycemia in transitory diabetes (Juliani, 1941).
Vasconcelos et al. (2000) observed a hypoglycemic effect
when a leaf extract of Bauhinia forficata was adminis-
tered to hyperglycemic rats previously injected with
scorpion venom.
Previously published work (Almeida and Agra, 1986;
Vasconcelos et al., 2000) corroborates our results which
show that Bauhinia forficata has no effect on glycemia in
non-diabetic rats. Furthermore, the data given in Table
1 show that there was no significant difference in liquid
intake between the two groups (NDCONT and
NDBFT) of non-diabetic rats (indicating that the
decoction was palatable for the rats).
It is well known that sulfonylureas produce hypogly-
cemia in non-diabetic animals because of the ability of
these compounds to stimulate b pancreatic cells to
liberate more insulin, although sulfonylureas do not
reduce glycemia in alloxan-diabetic animals (Goth,
1978). However, exogenous insulin administration re-
duces glycemia in non-diabetic, STZ-diabetic and al-
loxan-diabetic animals (Gilman et al., 1981). In our
study, treatment of STZ-diabetic rats either with insulin
or with Bauhinia forficata induced a fall in the level of
 M.T. Pepato et al. / Journal of Ethnopharmacology 81 (2002) 191 /197 195

Fig. 3. The effect of Bauhinia forficata decoction on the levels of urinary urea of non-diabetic and STZ-diabetic rats. Arrow indicates the beginning
of Bauhinia forficata treatment. All values represent means9/standard error of the mean (n/10). The Analysis of Variance was performed on the
whole set of results from day 3 to day 31 of treatment.

glycemia and urinary glucose and urea (Table 2, Figs.
1 /3).
Since Bauhinia forficata did not reduce glycemia in
non-diabetic animals it is possible that its mechanism of
action is different to that both of the sulfonylureas and
insulin. These data support the work of Russo et al.
(1990), who found no significant differences in the level
of serum insulin between subjects of control groups and
type II diabetic and non-diabetic groups who were
administered Bauhinia forficata chronically or acutely.
It has also been reported (Mirsky, 1956) that diabetic
animals present higher insulinase activities than non-

Table 1
Metabolic parameters of non-diabetic and STZ-diabetic rats treated or untreated with Bauhinia forficata decoction

Metabolic parameters Non-diabetic groups STZ-diabetic groups

Untreateda Treated for 34b days (NDBFT) Untreateda Treated for 31b days (STZBFT)
(NDCONT) (STZCONT)

Body weight (g)c 233.69/3.7 232.19/3.5 225.19/6.1 221.69/6.1

Change in body weight (Dw )c 109.09/3.4 108.09/3.3 63.79/5.8*** 57.79/6.6***
Food intake (g/24 h)c,d 11.99/0.3 11.69/0.2 14.29/0.6** 13.19/0.6*
Liquid intake (ml/24 h)c,d 18.49/0.3 18.69/0.3 40.39/3.9*** 35.49/3.3***
Urinary volume (ml/24 h)c,d 4.19/0.3 4.39/0.3 25.19/3.2*** 19.09/3.2***
Triglycerides (mg/dl) 78.29/10.0 61.39/7.2 85.59/13.5 60.69/7.5
Cholesterol (mg/dl) 65.29/3.4 60.09/2.3 56.19/2.6 54.39/2.8
Hepatic glycogen (mg%) 3.99/0.1 4.19/0.4 3.39/0.7 2.89/0.4*

Dw/Difference in body weight (measured about every 7 days post STZ administration) as compared to body weight on the day of STZ injection;
Significant at *P B/0.05, **P B/0.01, ***P B/0.001 for comparisons between non-diabetic and STZ-diabetic groups. All values represent means9/
standard error of the mean (n/10).
a
Drinking-water in place of Bauhinia forficata decoction.
b
Bauhinia forficata decoction in place of drinking-water.
c
Mean9/standard error of the mean of 5 determinations made during the treatment period.
d
Per 100 g of body weight.
196 M.T. Pepato et al. / Journal of Ethnopharmacology 81 (2002) 191 /197

Table 2
Metabolic parameters of STZ-diabetic rats before and after treatment with insulin

Metabolic parameters Before insulin treatment After 22 days insulin treatment After 38 days insulin treatment

DCONT DI DCONT DI DCONT DI

Body weight (g) 1589/4 1619/4 1929/12$$ 2539/9* 1999/12$$ 3049/14*

Fluid intake (ml/24 h) 679/5 669/3 589/6 329/3* 749/4 289/3*
Food intake (g/24 h) 20.49/1.23 18.59/0.7 26.89/3.0$ 13.19/1.0* 20.39/2.2 9.69/0.3*
Urinary volume (ml/24 h) 399/4 429/3 449/5 179/2* 549/4$$$ 159/2*
Urinary glucose (g/24 h) 1.899/0.18 1.779/0.23 1.89/0.20 0.369/0.06* 3.869/0.24$$$ 0.739/0.09*
Urinary urea (mg/24 h) 4219/35 4129/22 3789/36 1629/16* 3599/33$ 1199/8*
Plasma glucose (mg/dl) 5049/22 5129/38 5779/22$$$ 689/4* 6629/26$$$ 749/6*

Treatment was started 8 days after STZ injection. Except for body weight and plasma glucose, all values are reported per 100 g body weight. DI,
diabetic insulin group, DCONT, diabetic control group. All values represent means9/standard error of the mean (n/10). *P B/0.001, diabetic
treated group compared to the same group before insulin treatment; $P B/0.05, $$P B/0.01, $$$P B/0.001, DCONT compared to the same group
before insulin treatment (paired Student t -test).

diabetic animals, while Achrekar et al. (1991) found
reduced insulin degradation after the administration of
the pulp and seeds of Eugenia jambolana (‘Jambolan’)
because of insulinase inhibition, an effect similar to the
chemical tolbutamide which is also an insulinase in-
hibitor (Mirsky and Diengoff, 1957). Taken together
these reports may explain why Bauhinia forficata
decoction showed hypoglycemic action only in diabetic
rats, and the investigation of the effect of Bauhinia
forficata decoction on insulinase activity may well
confirm the hypothesis that this plant contains chemi-
cals with anti-insulinase activity that may well be useful
in maintaining the levels of any residual insulin which
may be present in diabetics.
The fact that in our study there was no effect on
hepatic glycogen levels in both the diabetic and non-
diabetic groups (Table 1) suggests that the drop in
glycemia in diabetic animals does not involve a reduc-
tion in glycogenolysis and/or increase in glycogenesis,
similar results having been seen in rabbits treated with
Jambolan seeds (Kedar and Chakrabarti, 1983). This,
along with the reduction in glycemia seen in the STZ-
diabetic rats treated with Bauhinia forficata decoction
(Fig. 1), suggests that the decoction increased the
sensitivity of cells to any residual insulin present in the
rats, in other words, in moderate diabetes decoction
increased insulin efficiency.
The results obtained for hepatic glycogen and glyce-
mia along with the reduction in urinary urea seen in the
STZ-diabetic rats treated with decoction suggests that
the mechanism of action of Bauhinia forficata is related
to a reduction in counterregulatory hormones and/or
the inhibition of gluconeogenesis in a manner similar to
that caused by the biguanides (Akhrar and Iqbal, 1991).
The fact that there was no alteration in urinary urea in
the non-diabetic group (Fig. 3) may have been related to
their lower intake of decoction (Table 1).
The decreased rates of glucose (Fig. 2) and urea
excretion (Fig. 3) could not be accounted for by reduced
carbohydrate and protein intake because there was no
alteration in food intake in animals treated with
decoction (Table 1).
The maintenance of muscle weight seen in the non-
diabetic group is consistent with the results for urinary
urea. In the STZ-diabetic group there was a drop in
urinary urea but, again, no alteration in muscle weight
(Table 3), although it is possible that this parameter is
insufficiently sensitive in this case. The hypothesis that

Table 3
Weight of epididymal and retroperitoneal adipose tissue, and soleus and EDL muscles in non-diabetic and diabetic rats treated and untreated with
Bauhinia forficata decoction

Weight of tissue/100 g body Non-diabetic groups STZ-diabetic groups

weight

Untreateda Treated for 34b days Untreateda Treated for 31b days
(NDCONT) (NDBFT) (STZCONT) (STZBFT)

Epididymal 0.7289/0.015 0.7399/0.048 0.3829/0.076*** 0.3909/0.085**

Retroperitoneal 0.5279/0.045 0.5159/0.036 0.2749/0.081* 0.2109/0.086**
Soleus 0.0869/0.002 0.0839/0.003 0.0929/0.004 0.0909/0.003
EDL 0.0949/0.003 0.0949/0.003 0.0869/0.004 0.0889/0.004

Significant at *P B/0.05, **P B/0.01 or ***P B/0.001 for comparisons between non-diabetic and STZ-diabetic groups. All values represent
means9/standard error of the mean (n/10).
a
Drinking-water in place of Bauhinia forficata decoction.
b
Bauhinia forficata decoction in place of drinking-water.
 M.T. Pepato et al. / Journal of Ethnopharmacology 81 (2002) 191 /197
the decoction could inhibit enzymes involved in the urea
cycle should be considered.
The improvement in urinary urea excretion in STZ-
diabetic rats treated with decoction, was not sufficient to
reach the levels observed in the non-diabetic rats, and
there being no alteration in urea levels in the non-
diabetic rats. Similar results were obtained with diabetic
rabbits treated with Eugenia jambolana (Kedar and
Chakrabarti, 1983) and non-diabetic rats treated with
Allium cepa (onion) (Babu and Srinivasan, 1997).
As expected, we observed a sharp reduction in
epididymal and retroperitoneal adipose tissue in the
STZ-diabetic rats as compared to the non-diabetic rats
(Table 3). The maintenance of serum triglyceride levels
(Table 1) in STZ-diabetic rats treated with Bauhinia
forficata decoction is in accord with the results for
epididymal and retroperitoneal adipose tissue (Table 3).
Pharmacological, biochemical, histological and che-
mical studies are needed to elucidate the exact mechan-
ism of action of Bauhinia forficata leaf decoction and to
isolate any active compounds. Such investigations
should also be carried out regarding type 2 diabetes.
Acknowledgements
We thank FAPESP, FUNDUNESP and PADC-
FCF- Araraquara-UNESP for financial support. We
are also grateful to the technicians A.O. Lourenzoni,
T.N. Nunes and F.A. Iagame for their help and to Dr
G.D. Zanetti, Industrial Pharmacy Department Herbar-
ium, Federal University of Santa Maria, Rio Grande do
Sul, Brazil for identification and authentication of
Bauhinia forficata . Eduardo Henrique Keller and
Amanda Martins Baviera received a fellowship from
FAPESP.
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