Journal of Ethnopharmacology 105 (2006) 196–200

Anti-diabetic potentials of Momordica charantia and Andrographis

paniculata and their effects on estrous cyclicity
of alloxan-induced diabetic rats
B.A.S. Reyes a,b,∗ , N.D. Bautista c , N.C. Tanquilut b , R.V. Anunciado d , A.B. Leung c ,
G.C. Sanchez b , R.L. Magtoto a,c , P. Castronuevo e , H. Tsukamura f , K.-I. Maeda f
a Thomas Jefferson University, Department of Neurosurgery, Farber Institute for Neurosciences, Philadelphia, Pennsylvania 19107, USA
b Institute of Veterinary Medicine and Zootechnics, Pampanga Agricultural College, Magalang 2011, Pampanga, Philippines
c Institute of Animal Science, Pampanga Agricultural College, Magalang 2011, Pampanga, Philippines
d College of Veterinary Medicine, University of Philippines, Los Banos, Laguna, Philippines
e Department of Biology, Kutztown University, Kutztown, PA 19530, USA
f Graduate School of Bioagricultural Science, Nagoya University, Nagoya 464-8601, Japan

Received 10 March 2005; received in revised form 14 October 2005; accepted 18 October 2005
Available online 18 November 2005

Abstract
Momordica charantia and Andrographis paniculata are the commonly used herbs by the diabetic patients in Pampanga, Philippines. While
the anti-diabetic potential of Momordica charantia is well established in streptozocin- or alloxan-induced diabetic animals, the anti-diabetic
potential of Andrographis paniculata in alloxan-induced diabetic rat is not known. Neither the effects of these herbs on estrous cyclicity of alloxan-
induced diabetic rats are elucidated. Thus, in these experiments, Momordica charantia fruit juice or Andrographis paniculata decoction was orally
administered to alloxan-induced diabetic rats. Rats that were treated with Momordica charantia and Andrographis paniculata had higher body
weight (BW) compared with diabetic positive control (P < 0.01) from day 22 to day 27 (D27) but exhibited lower BW than the non-diabetic control
(P < 0.05). These rats had lower feed (P < 0.05) and liquid intakes (P < 0.01) compared with diabetic positive control from day 17 to D27, but similar
with the non-diabetic control. The blood glucose levels in these groups were significantly reduced from day 12 to D27 compared with diabetic
positive control (P < 0.01), however, comparable with non-diabetic control. The diabetic positive control had extended mean estrous cycles (8 days)
compared to Momordica charantia and Andrographis paniculata-treated diabetic rats (5 days; P < 0.05). Our results suggest that the anti-diabetic
potentials of Momordica charantia and Andrographis paniculata could restore impaired estrous cycle in alloxan-induced diabetic rats.
© 2005 Elsevier Ireland Ltd. All rights reserved.

Keywords: Momordica charantia; Andrographis paniculata; Diabetes; Alloxan; Estrous cycle

1. Introduction defects in insulin secretion, insulin action or both (Atkinson

Diabetes mellitus is the most common endocrine disease
(Sexton and Jarow, 1997) and a predominant health concern
affecting 16 million Americans (Yeh et al., 2003). It affected
2–3% of the total world population in 1995 (Felig et al., 1995)
and had an increasing prevalence worldwide in 1998 (Alberti
and Zimmet, 1998). Diabetes mellitus leads to metabolic abnor-
malities and is characterized by hyperglycemia resulting from
∗ Corresponding author. Tel.: +1 215 503 5862; fax: +1 215 955 7921.
E-mail address: bsr103@jefferson.edu (B.A.S. Reyes).
and Maclaren, 1994; Yki-Jarvinen, 1994; Teixeira et al., 2000).
Insulin-dependent diabetes mellitus or Type 1 is conventionally
treated with exogenous insulin while the non-insulin-dependent
diabetes mellitus or Type 2 is treated with oral hypoglycemic
agents such as sulphonylureas and biguanides among others
(Felig et al., 1995; Rosak, 2002). Complementary and alterna-
tive medicine is widely used (Eisenberg et al., 1998; Maclennan
et al., 1996; Payne, 2001) and, in the Philippines diabetes mel-
litus is commonly treated using medicinal plants (De Padua et
al., 1997).
Momordica charantia and Andrographis paniculata are com-
monly used herbs in the province of Pampanga, Philippines.

0378-8741/$ – see front matter © 2005 Elsevier Ireland Ltd. All rights reserved.
doi:10.1016/j.jep.2005.10.018
 B.A.S. Reyes et al. / Journal of Ethnopharmacology 105 (2006) 196–200
Momordica charantia is a member of Cucurbitaceae, com-
monly known as ku gua, karela, bittergourd or bitter melon.
It is the most popular herbal resource (Marles and Farnsworth,
1995) and is often used to treat diabetes (Arvigo and Balick,
1993). The anti-diabetic potential of Momordica charantia is
well established in streptozocin- or alloxan-induced diabetic
rats, mice and rabbit (Akhtar et al., 1981; Sarkar et al., 1996;
Kar et al., 2003), genetically diabetic mice (Miura et al., 2001)
and in humans with Type 2 diabetes (Srivastava et al., 1993).
Andrographis paniculata (Burm F) Nees belongs to family
Acanthaceae, commonly known as “King of Bitters” and has
been used to treat various diseases (Vedavathy and Rao, 1991;
Caceres et al., 1997; Kumar et al., 2004). Unlike Momordica
charantia, the hypoglycemic effects of Andrographis panicu-
lata have only been studied in streptozotocin-induced diabetic
rats (Zhang and Tan, 2000) and in normal rabbits (Borhanuddin
et al., 1994). Thus, using alloxan-induced diabetic rats, the
anti-diabetic potential of Andrographis paniculata was investi-
gated.
Diabetes mellitus has been shown to suppress reproductive
functions in humans (Griffin et al., 1994; Sexton and Jarow,
1997) and animals (Angell et al., 1996; Cagampang et al., 1997;
Steger and Rabe, 1997). Specifically, diabetes mellitus sup-
presses luteinizing hormone secretion in streptozocin-induced
diabetic rats (Cagampang et al., 1997) and disrupts estrous cycle
(Cox et al., 1994). Estrous cycle is the period of reproductive
cyclicity in animals that usually lasts for 4–5 days in rodents
(Pineda, 2003). Though the hypoglycemic effect of Momordica
charantia is well documented in diabetic animal models (Akhtar
et al., 1981; Sarkar et al., 1996; Miura et al., 2001; Kar et
al., 2003), it is not known whether this effect is accompanied
by the restoration of reproductive functions such as estrous
cyclicity. Hence, this study also aimed to elucidate the poten-
tial of Momordica charantia and Andrographis paniculata in
the restoration of impaired estrous cyclicity in alloxan-induced
diabetic rats.
2. Materials and methods
2.1. Plant material
The elongated fruits of Momordica charantia were purchased
from the local market and leaves of Andrographis paniculata
were gathered from the campus of Pampanga Agricultural Col-
lege, Magalang, Pampanga, Philippines. Plant materials were
authenticated at the Botanical Herbarium, Museum of Natu-
ral History, University of the Philippines, Los Banos, College,
Laguna, Philippines with accession numbers 67268 and 67267
for Momordica charantia and Andrographis paniculata, respec-
tively.
2.2. Preparation of fruit juice and decoction
Fruits of Momordica charantia were washed, sliced and
placed in a juicer (Sanyo S6-J6, Osaka, Japan) to obtain the fruit
juice. About 20 g Andrographis paniculata leaves were boiled
in 100 ml of water for 5 min and decoction was filtered.
197
2.3. Animals and treatment
2.3.1. Animals
Female Sprague–Dawley rats weighing 140–150 g were
obtained from the Research and Biotechnology Division, St.
Lukes Medical Center, Quezon City, Philippines and were indi-
vidually caged. Estrous cycles were recorded daily. Food and
water were given ad libitum. Rats were maintained on normal
laboratory chow diet containing 16% protein.
2.3.2. Induction of diabetes
Only rats showing at least three consecutive estrous cycles
were selected. Estrous cycle was monitored daily via vaginal
cytology. Alloxan, dissolved in saline was injected intraperi-
toneally, at a dose of 125 mg/kg body weight (BW). The induc-
tion of alloxan-induced diabetes was confirmed by determining
the urinary and glucose levels.
2.3.3. Treatments
Twenty rats were used in this study at five rats per group.
However, 15 were alloxan-induced diabetics and they were
randomly assigned to three groups 4 days after alloxan injec-
tion. Only rats positive for urinary glucose and with a blood
glucose level above 300 mg/dl including polydipsia, polyuria
and polyphagia were used. The first was given Momordica
charantia juice, the second with Andrographis paniculata
decoction, and the third served as diabetic positive con-
trol. The fourth group served as the non-diabetic control. At
20 ml/kg BW per day, groups one and two were orally given
Momordica charantia juice and Andrographis paniculata decoc-
tion, respectively. Half of the dose given at 800 h and the
other half at 1600 h. Groups three and four were not given
Momordica charantia juice or with Andrographis paniculata
decoction.
2.3.4. Data collection
The BW, daily feed and liquid intake, and blood glucose lev-
els were measured at day 1 (D1), day 7 (D7), day 12 (D12), day
17 (D17), day 22 (D22) and day 27 (D27). For blood glucose
levels, it was determined using Glucose Kit Reagent (Biosys-
tems S.A., Barcelona, Spain) from blood collected from the
tip of the tail. Samples were run in triplicate. Urinary glucose
was detected from D1–D12, D17, D22 and D27 using urine test
strips.
2.4. Statistical analysis
All data were expressed as mean ± S.E.M. The effects of
Momordica charantia juice or with Andrographis paniculata
decoction on BW, feed intake, liquid intake and blood glu-
cose levels were determined using one-way analysis of variance
(Graph Pad In Stat, Graph Pad Software Inc., San Diego, CA,
USA) followed by post-hoc Tukey–Kramer multiple compar-
isons test. The herbs’ effects on estrous cycles were analyzed
using Student’s t-test.
198 B.A.S. Reyes et al. / Journal of Ethnopharmacology 105 (2006) 196–200

Fig. 1. Mean body weight (A), feed intake (B), liquid intake (C) and blood glucose levels (D) of non-diabetic control and alloxan-induced diabetic rats treated and
non-treated with Momordica charantia juice and Andrographis paniculata decoction (n = 5). Values are means ± S.E.M. Values with different letters are significantly
different (* P < 0.05; ** P < 0.01) from each other in each time point studied (Tukey–Kramer multiple comparisons test after ANOVA).

3. Results

Fig. 1 presents BW (Fig. 1A), feed intake (Fig. 1B), and liq-
uid intake (Fig. 1C) of the alloxan-induced diabetic rats treated
with Momordica charantia juice and Andrographis paniculata
decoction, the diabetic positive control, and of the non-diabetic
control. Prior to alloxan treatment, all groups had compara-
ble BW, feed intake and liquid intake. Momordica charan-
tia juice and Andrographis paniculata decoction significantly
increased the BW (P < 0.01) and lowered the feed (P < 0.05)
and liquid (P < 0.01) intakes of the alloxan-induced diabetic
rats compared with diabetic positive control on D17–D27. Fig. 2. Mean estrous cycle of non-diabetic control and alloxan-induced diabetic
However, compared with the non-diabetic control, Momordica rats treated or non-treated with Momordica charantia juice or Andrographis
charantia- and Andrographis paniculata-treated rats had sig- paniculata decoction (n = 5). * P < 0.05 vs. before alloxan administration.
nificantly lower BW (P < 0.01) but similar feed and liquid
intakes.
from 4.6 ± 0.20 to 7.65 ± 0.55 days. For Momordica charan-
The diabetic positive control showed urinary glucose from
tia juice- and Andrographis paniculata decoction-treated rats,
D4 or D5 until D27. Conversely, the urinary glucose was not
mean estrous cycle lengthened from 4.3 ± 0.10 to 5.24 ± 0.13
found in non-diabetic control from D1 to D27. The blood glucose
days and from 4.8 ± 0.23 to 5.36 ± 0.10 days, respectively but
levels in Momordica charantia juice- and Andrographis panic-
their differences were not significant.
ulata decoction-treated rats decreased markedly from D12 to
D27 compared to diabetic positive control (Fig. 1D; P < 0.01).
Compared with non-diabetic control, the blood glucose levels 4. Discussion
remained higher from D12 to D27 but no significant difference
was observed. Alloxan is cytotoxic to the pancreatic ␤ cells thus it is an
As shown in Fig. 2, rats in all groups displayed an estrous effective diabetes-induction agent. It has been widely used
cycle of 4–5 days prior to alloxan administration (non-diabetic to induce diabetes mellitus in experimental animal models
control: 4.4 ± 0.20 days; diabetic positive control: 4.6 ± 0.20 allowing investigation of hypoglycemic agents in the treatment
days; Momordica charantia juice-treated rats: 4.3 ± 0.10 days; of diabetes (Kar et al., 2003; Jayakar et al., 2004). Alloxan
Andrographis paniculata decoction-treated rats: 4.8 ± 0.23 injection consistently produced symptoms characteristic of
days). The mean estrous cycle length of diabetic positive diabetes mellitus including hyperglycemia, decreased insulin
control was extended (P < 0.05) after alloxan administration levels, polyuria and weight loss.
 B.A.S. Reyes et al. / Journal of Ethnopharmacology 105 (2006) 196–200
Significant reduction of blood glucose levels in alloxan-
induced diabetic rats treated with Momordica charantia con-
firms previous reports demonstrating the anti-hypoglycemic
effect of Momordica charantia in diabetic rat, mouse and rabbit
models (Akhtar et al., 1981; Sarkar et al., 1996; Miura et al.,
2001; Kar et al., 2003). Specifically, our results agree with the
studies of Kar and colleagues (Kar et al., 2003) indicating that
the blood glucose lowering effect of Momordica charantia in
alloxan-induced diabetic rats occurs within 2 weeks from the
onset of Momordica charantia treatment.
The treatment with Andrographis paniculata led to a signifi-
cant reduction of blood glucose levels indicating a hypoglycemic
effect. These data support previous investigations (Zhang and
Tan, 2000) in streptozocin-induced diabetic rats where Andro-
graphis paniculata extract at 400 mg/kg BW given twice a day
significantly reduced fasting serum glucose at the end of 14-day
period. In our experiment, it took a shorter period to attain a
significant reduction in the blood glucose level. This discrep-
ancy could be due to the difference in the diabetes induction
agents, for they used streptozocin whereas we used alloxan.
Sexton and Jarow (1997) pointed that in studies using diabetic rat
models, results could be influenced by diabetic induction agents
such streptozocin or alloxan. There was also a difference in the
sex and weight of rats, and the kind of preparation and doses.
They used male 200–250 g rats while we used female 140–150 g
rats. They administered Andrographis paniculata extract at
400 mg/kg while we used a decoction at 20 ml/kg. Another fac-
tor is that plant metabolites vary considerably in response to soil
type, humidity and climate prevailing during growth (Evans,
2002). Nevertheless, this is the first report showing evidence
that Andrographis paniculata possesses an anti-hyperglycemic
effect in a rat model treated with alloxan as a diabetic induction
agent.
The hypoglycemic potential of Momordica charantia in the
present study could be explained by the mechanisms previ-
ously described by several authors in a diabetic animal model
(Welihinda and Karunanayake, 1986; Welihinda et al., 1986;
Ahmed et al., 1998). As such, Momordica charantia increases
the renewal of ␤-cells in the pancreas or may permit the
recovery of partially destroyed ␤-cells (Ahmed et al., 1998)
and stimulates pancreatic insulin secretion (Welihinda et al.,
1982). These could likely explain the significant increase in
the plasma insulin level when streptozocin-induced diabetic
rats were treated with Momordica charantia (Sharma et al.,
1995). Furthermore, Momordica charantia displays insulin-like
properties (Ng et al., 1986), remarkably stimulates glycogen
storage by the liver (Welihinda et al., 1986) and improves periph-
eral glucose uptake (Welihinda and Karunanayake, 1986). On
the other hand, when streptozocin-induced diabetic rats were
given Andrographis paniculata, the plasma insulin level did
not increase (Zhang and Tan, 2000) suggesting that Andro-
graphis paniculata does not act as an insulin secretagogue.
Andrographolide, a principle with the highest content in Andro-
graphis paniculata (Shen et al., 2002) is suggested to increase
glucose utilization in peripheral tissue via an insulin-dependent
mechanism (Yu et al., 2003). Taken together, the hypoglycemic
effects of Andrographis paniculata may be attributed in part
199
to its ability to increase glucose metabolism in a diabetic
rat model.
Glucose transporters mediate glucose uptake into the tis-
sues, and, of all the glucose transporters, only glucose trans-
porter 4 is insulin-responsive (Gorovits and Charron, 2003). A
decreasing expression of glucose transporter 4 mRNA and pro-
tein caused a reduction in insulin-mediated glucose uptake in
diabetes (Berger et al., 1989). Andrographolide administration
in streptozocin-induced diabetic mice increased glucose trans-
porter 4 (Yu et al., 2003). It is conceivable that Andrographis
paniculata can enhance the glucose uptake through its effects
on glucose transporter 4 gene expression. In the light of these
data using streptozocin as a diabetic induction agent, the mecha-
nism by which Andrographis paniculata reduces hyperglycemia
in alloxan-induced diabetic model needs further studies.
Impaired estrous cyclicity was evident in alloxan-induced
diabetic rats. This impairment supports several reports that
diabetes mellitus impairs reproductive functions (Griffin et
al., 1994; Angell et al., 1996; Cagampang et al., 1997;
Sexton and Jarow, 1997; Steger and Rabe, 1997). In fact,
diabetes mellitus suppressed luteinizing hormone secretion in
streptozocin-induced diabetic rats (Cagampang et al., 1997).
In the same manner, alloxan suppressed luteinizing hormone
secretion in female rats (Kinoshita et al., 2004). Addition-
ally, diabetic gilts did not exhibit estrous or ovulation (Cox
et al., 1994). Luteinizing hormone surge was also absent in
immature alloxan-induced diabetic rats that led to anovulation
(Kirchick et al., 1978). In the present study, the remarkable
loss of body weight in diabetic rats could likely explain the
impaired estrous cyclicity since it is generally accepted that the
loss of BW causes a reduction in luteinizing hormone release
in rats (Campbell et al., 1977). Treating alloxan-induced dia-
betic rats with Momordica charantia and Andrographis pan-
iculata significantly increased BW and reduced blood glucose
levels. Both of these results could be major contributing fac-
tors to the subsequent normalization of the prolonged estrous
cycles. However, further investigations are required to address
this issue.
In summary, the results of the present study show that Andro-
graphis paniculata possesses anti-diabetic potential in alloxan-
induced diabetic rats. Moreover, this is the first physiological
evidence that the anti-diabetic potentials of Momordica charan-
tia and Andrographis paniculata restore the impaired estrous
cyclicity in alloxan-induced diabetic rat model.
Acknowledgements
The authors are thankful to Dr. Zosimo Battad, President,
Pampanga Agricultural College, Magalang, Pampanga, Philip-
pines for providing necessary facilities and support.
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