J Nat Med
DOI 10.1007/s11418-012-0674-7
ORIGINAL PAPER
Protein tyrosine phosphatase 1B inhibitory activity of Indonesian
herbal medicines and constituents of Cinnamomum burmannii
and Zingiber aromaticum
Azis Saifudin • Shigetoshi Kadota • Yasuhiro Tezuka
Received: 4 April 2012 / Accepted: 9 May 2012
Ó The Japanese Society of Pharmacognosy and Springer 2012
Abstract We screened water and methanol extracts of 28
Indonesian medicinal plants for their protein tyrosine
phosphatase 1B (PTP1B) inhibitory activities. Nine water
extracts, i.e., Alstonia scholaris leaf, Blumea balsamifera,
Cinnamomum burmannii, Cymbopogon nardus, Melaleuca
leucadendra, Phyllanthus niruri, Piper nigrum, Syzygium
aromaticum, and Sy. polyanthum, exhibited C70 % inhi-
bition at 25 lg/mL, whereas 11 methanol extracts, i.e.,
Als. scholaris, Andrographis paniculata, B. balsamifera,
Ci. burmannii, Curcuma heyneana, Glycyrrhiza glabra,
M. leucadendra, Punica granatum, Rheum palmatum, Sy.
polyanthum, and Z. aromaticum, exhibited C70 % inhibi-
tion at 25 lg/mL. Water extracts of B. balsamifera (IC50,
2.26 lg/mL) and M. leucadendra (IC50, 2.05 lg/mL), and
methanol extracts of Ci. burmannii (IC50, 2.47 lg/mL), Pu.
granatum (IC50, 2.40 lg/mL), and Sy. polyanthum (IC50,
1.03 lg/mL) exhibited strong inhibitory activity, which
was comparable with that of the positive control, RK-682
(IC50, 2.05 lg/mL). The PTP1B inhibitory activity of the
constituents of Ci. burmannii and Z. aromaticum was
then evaluated. 50 -Hydroxy-5-hydroxymethyl-400 ,500 -meth-
ylenedioxy-1,2,3,4-dibenzo-1,3,5-cycloheptatriene (2; IC50,
29.7 lM) and trans-cinnamaldehyde (5; IC50, 57.6 lM)
were the active constituents of Ci. burmannii, while
humulatrien-5-ol-8-one (21; IC50, 27.7 lM), kaempferol-
3,40 -di-O-methyl ether (32; IC50, 17.5 lM), and (S)-6-ging-
erol (33; IC50, 28.1 lM) were those of Z. aromaticum. These
results suggest that these medicinal plants may contribute to
the treatment and/or prevention of type II diabetes and/or
obesity through PTP1B inhibition.
A. Saifudin  S. Kadota  Y. Tezuka (&)
Institute of Natural Medicine, University of Toyama,
Toyama, Japan
e-mail: tezuka@inm.u-toyama.ac.jp
Keywords Protein tyrosine phosphatase 1B  Inhibitor 
Indonesian medicinal plant  Cinnamomum burmannii 
Zingiber aromaticum
Introduction
Protein tyrosine phosphatase 1B (PTP1B) is an enzyme
found in important insulin-targeted tissues such as liver,
muscle, and fat. PTP1B plays a key role as a negative
regulator in insulin signal transduction [1] by dephospho-
rylating activated insulin receptors (IR) or insulin receptor
substrates (IRS) [2, 3]. In excess, PTP1B will impair
insulin down-regulation [4–6] leading to type II diabetes
mellitus. PTP1B is also found in the brain, where it plays
an important role in energy regulation by interfering
with the leptin receptor; this has implications for body
weight status. Mice lacking neuronal PTP1B fail to
gain weight [7, 8]. These studies suggest that PTP1B
inhibitors can be employed as an agent for the treatment of
type II diabetes mellitus or to reduce fat content in
obese patients. Thus, PTP1B inhibition using small mole-
cules is attracting interest in the research area of drug
discovery for the treatment of type II diabetes and obesity
[9–13].
The plant kingdom is a potential resource for discov-
ering small molecules that can be applied as agents for the
treatment of metabolic disorders such as diabetes and
obesity. In many developing countries, herbal medicines
have greater importance in the primary health care of
individuals and communities, and there has been an
increase in the international trade of herbal medicine
products. In certain areas, medicinal plants such as Glyc-
yrrhiza glabra, Andrographis paniculata, and Phyllanthus
niruri [14] have been used to treat type II diabetes. In vitro,
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 J Nat Med

animal model and clinical studies have also shown that
numerous plants including Piper nigrum [15], Punica
granatum [16], Cinnamomum spp. [17, 18], and Syzygium
aromaticum [19] possess antidiabetes-related activities.
Moreover, pterocarpans, isoprenylated flavonoids, catechin
derivatives, sesquiterpenes, and ursane-type triterpenes
have been reported to inhibit PTP1B activities [20–23].
In Indonesia, herbal medicines known as ‘‘Jamu’’ [24]
have been used since ancient times and remain popular in
the Indonesian healthcare system. In this study, we evalu-
ated the PTP1B inhibitory activity of 28 medicinal plants
that are generally found in Indonesian traditional medicines
[24, 25] (Table 1). In this paper, we report on the results of
screening crude drug extracts for PTP1B inhibitory activity

Table 1 Indonesian medicinal plants, part used, local name, voucher specimen numbers, and protein tyrosine phosphatase 1B (PTP1B)
inhibitory activities at 25 lg/mL
No. Plant name Part used Local name Voucher Water extract Methanol extract
specimen
number Inhibition IC50 Inhibition IC50
(%)a,b (lg/mL)b (%)a,b (lg/mL)b

1 Alpinia galanga (L.) Swartz. Rhizome Laos TMPW 22261 0.0 ± 5.5 64.1 ± 5.5
2 Alstonia scholaris (L.) R. Br. Bark Pulai TMPW 22262 0.0 ± 1.6 0.0 ± 3.3
3 Als. scholaris (L.) R. Br. Leaf Pulai TMPW 22263 87.4 ± 1.3 10.3 72.3 ± 11.2 9.45
4 Alyxia reinwardtii Bl. Bark Pulosari TMPW 22264 0.0 ± 1.5 0.0 ± 0.1
5 Amomum compactum Soland. Fruit Kapulaga TMPW 22265 0.0 ± 3.2 12.6 ± 2.7
ex Maton
6 Am. compactum Soland. ex Rhizome Kapulaga TMPW 22266 38.2 ± 4.3 0.0 ± 3.2
Maton
7 Andrographis paniculata Aerial part Sambiloto TMPW 22267 40.0 ± 11.5 74.8 ± 1.9 13.4
(Burm. F.) Nees
8 Blumea balsamifera DC Leaf Sembung manis TMPW 24921 96.8 ± 2.5 2.26 78.0 ± 3.8 5.64
9 Cinnamomum burmannii Bark Kayu manis TMPW 22269 86.6 ± 3.7 6.26 95.7 ± 2.8 2.47
Nees ex Bl.
10 Curcuma aeruginosa Roxb. Rhizome Temuireng TMPW 22270 0.0 ± 1.8 59.1 ± 3.6
11 Cu. heyneana Val. & V. Zijp Rhizome Temu giring TMPW 22271 0.0 ± 2.6 81.9 ± 4.6 7.14
12 Cu. xanthorrhiza Roxb. Rhizome Temu lawak TMPW 22272 12.7 ± 1.8 5.0 ± 3.6
13 Cymbopogon nardus Aerial part Daun sereh TMPW 24905 85.2 ± 1.7 10.6 0.0 ± 2.9
(L.) Ness
14 Glycyrrhiza glabra L. Stem Kayu legi TMPW 22275 9.7 ± 1.2 89.8 ± 6.9 5.38
15 Melaleuca leucadendra L. Fruit Kayu putih TMPW 22276 95.6 ± 3.6 2.05 96.4 ± 3.3 3.37
16 Phyllanthus niruri L. Aerial part Meniran TMPW 24930 81.3 ± 12.1 11.0 69.8 ± 2.3
17 Piper cubeba L Fruit Kemukus TMPW22277 0.0 ± 5.7 1.3 ± 3.0
18 Pi. nigrum L. Leaf Merica putih TMPW 22279 75.0 ± 4.0 13.1 0.0 ± 4.1
19 Punica granatum L. Fruit Delima putih TMPW 22280 0.0 ± 5.9 88.9 ± 3.5 2.40
20 Rheum palmatum L. Root Klembak TMPW 22281 40.8 ± 5.3 91.8 ± 0.3 4.68
21 Santalum album L. Wood Kayu cendana TMPW 22282 31.8 ± 2.5 19.2 ± 2.3
22 Strychnos ligustrina Bl. Leaf Bidara laut TMPW 22284 1.9 ± 0.8 0.0 ± 3.2
23 Syzygium aromaticum (L.) Flower Cengkeh TMPW 22286 83.8 ± 5.5 4.07 29.0 ± 6.6
Merr. & L.M. Perry
24 Sy. polyanthum (Wight) Leaf Daun salam TMPW 24909 88.0 ± 1.0 3.57 97.2 ± 0.4 1.03
Waplers
25 Tamarindus indica L. Fruit Asem TMPW 22287 2.0 ± 0.5 0.0 ± 5.3
26 Tinospora crispa (L.) Diels Stem Brotowali TMPW 22288 7.5 ± 5.5 0.0 ± 1.0
27 Zingiber aromaticum Val. Rhizome Lempuyang wangi TMPW 22289 11.2 ± 5.6 84.4 ± 3.1 14.4
28 Z. cassumunar Roxb. Rhizome Bengle TMPW 22290 5.7 ± 0.7 67.4 ± 0.7
a
Data are expressed as mean ± SD (n = 3)
b
Positive control RK-682: inhibition at 25 lg/mL, 84.0 ± 1.5 %; IC50, 2.05 lg/mL

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J Nat Med
and the inhibitory activities of Cinnamomum burmannii
and Zingiber aromaticum.
Materials and methods
Plant materials
Unless otherwise stated, the plant materials used in this
study (Table 1) were purchased from GORO traditional
market, Jakarta during May 2002, and were authenticated
by Dr. Sucipto (PJ. Bintang Terang Lestari, Traditional
Medicine Supplier, Jakarta). Alpinia galanga, Ci. bur-
mannii, Ph. niruri, and Syzygium polyanthum were pur-
chased from Pasar Genteng Surabaya Indonesia during
August 2006 and authenticated by Dr. Aty Widyawaruyanti
(Faculty of Pharmacy, Airlangga University). Voucher
specimens are preserved in the Museum of Materia Med-
ica, Analytical Research Center for Ethnomedicines,
Institute of Natural Medicine, University of Toyama,
Toyama, Japan.
Preparation of test solutions
Each medicinal plant (25–150 g) was cut into small pieces
and extracted with water (150–400 mL, reflux 2 h, 92).
After filtration, the water solution was concentrated under
reduced pressure, followed by lyophilization, to produce a
water extract. The residue was extracted with methanol–
water (1:1) (150–300 mL, 2 h, 92) and then macerated
with methanol (200–400 mL, reflux, 1 h, 92). For the
PTP1B inhibitory assay, extracts were dissolved in distilled
water or dimethylsulfoxide (DMSO) at a concentration of
1 mg/mL and aliquots of the solution were added to each
well. The final concentration of DMSO was 2.5 %, which
did not influence to the activity of PTP1B. The inhibitory
ratio (%) of DMSO at 5 % was 1.7 %.
Constituents of Cinnamomum burmannii and Zingibera
aromaticum
Constituents of Ci. burmannii [cinnamic aldehyde
cyclic syringylglycerol 1,3-acetal (1), 50 -hydroxy-5-
hydroxymethyl-400 ,500 -methylenedioxy-1,2,3,4-dibenzo-1,3,
5-cycloheptatriene (2), coumarin (3), cinnamyl acetate (4),
trans-cinnamaldehyde (5), cinnamyl alcohol (6), cinnamic
acid (7), sinapaldehyde (8), trans-ferulaldehyde (9),
syringaldehyde (10), 2,6-dimethoxy-1,4-benzoquinone
(11), trans-cinnamyl-3-phenylpropionate (12), (S)-abscisic
acid (13), (?)-piniresinol (14), (?)-syringaresinol (15),
(?)-medioresinol (16), and (2)-(2R,3R)-40 -hydroxy-5,7,30 -
trimethoxyflavan-3-ol (17), Fig. 1] were previously iso-
lated from a methanol extract by a combination of column
chromatography and preparative thin layer chromatography
(TLC) [26]. Whereas constituents of Z. aromaticum [(2R,
3S,5R)-2,3-epoxy-6,9-humuladien-5-ol-8-one (18), (2R,3R,
5R)-2,3-epoxy-6,9-humuladien-5-ol-8-one (19), zerum-
bone epoxide (20), (5R)-2,6,9-humulatrien-5-ol-8-one
(21), zerumbone (22), kaempferol-3-O-(2,3-di-O-acetyl-
a-L-rhamnopyranoside) (23), kaempferol-3-O-(2,3,4-tri-
O-acetyl-a-L-rhamnopyranoside) (24), kaempferol-3-O-(2,
4-di-O-acetyl-a-L-rhamnopyranoside) (25), kaempferol-3-
O-(3,4-di-O-acetyl-a-L-rhamnopyranoside) (26), kaempf-
erol-3-O-(2-O-acetyl-a-L-rhamnopyranoside) (27), ka-
empferol-3-O-(3-O-acetyl-a-L-rhamnopyranoside) (28),
kaempferol-3-O-(4-O-acetyl-a-L-rhamnopyranoside) (29),
kaempferol-3-O-a-L-rhamnopyranoside (30), kaempferol-
3-O-methyl ether (31), kaempferol-3,40 -di-O-methyl ether
(32), (S)-6-gingerol (33), and trans-6-shogaol (34), Fig. 2]
were previously isolated from the methanol fraction of a
water extract by a combination of column chromatography
and preparative TLC [27]. The purity of each compound
was confirmed by TLC and 1H-NMR spectroscopy, which
did not show the presence of any impurity. For the
PTP1B inhibitory assay, all compounds were dissolved in
DMSO at a concentration of 1 mg/mL and aliquots of the
solution were added to each well. The final concentration
of DMSO was 1 %, which did not influence to the activity
of PTP1B.
PTP1B inhibitory assay
The assay was performed in 96-well clear polystyrene
microplate (Corning, USA, Corning, NY) according to a
published procedure [28] with slight modifications. Each
well contained 0.05 lg PTP1B (Enzo Life Sciences,
Farmingdale, NY), 2 mM p-nitrophenyl phosphate (pNPP;
Wako Pure Chemical Industries, Osaka, Japan), and
50 mM citrate buffer containing 0.1 mM NaCl, 1 mM
dithiothreitol (DTT), and 1 mM N,N,N’,N’-ethylenedia-
mine tetraacetate (EDTA). The final volume of the mixture
was 200 lL. The reaction was initiated by addition of
pNPP, incubated at 37 °C for 30 min, and terminated with
the addition of a stop solution (10 M NaOH). The amount
of p-nitrophenol produced was estimated by measuring the
absorbance at 405 nm using a Perkin-Elmer HTS 7000
bioassay reader. To identify the level of nonenzymatic
substrate hydrolysis, the absorbance of wells containing
only buffer and pNPP were measured for correction. The
difference between full enzymatic activity and the correc-
tion was set arbitrarily to 100 % activity. The percent
residual activity was calculated using the following for-
mula: residual activity (%) = [Abs(full enzymatic)-Abs(test
sample)-Abs(correction)/(Abs(full enzymatic)-Abs(correction))] 9
100, where Abs(full enzymatic) was the absorbance of
p-nitrophenol liberated by the enzyme in the system
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 J Nat Med

Fig. 1 Structures of OCH3 O

compounds isolated from
HO
Cinnamomum burmannii O O O
OH
O
H3CO
O
HO
3
OH
1 2
O
R2 R1 4 R1 = CH2OAc, R 2 = R3 = R4 = H H3CO
5 R1 = CHO, R 2 = R3 = R4 = H H

R3 6 R1 = CH2OH, R2 = R3 = CH3, R4 = H
HO
R4 7 R1 = COOH, R2 = R3 = R4 = H
OCH3
8 R1 = CHO, R 2 = OCH3, R3 = OH, R4 = OCH3
10
9 R1 = CHO, R 2 = H, R3 = OH, R4 = OCH3

OCH3 OH
O
O
O O
O
O OCH3 OH
12
11 13
OCH3

OH OH
O
H3CO O
R2 OCH3
R1 H H

14 R1 = R2 = H OH
O
HO OCH3 17
15 R1 = OCH3, R2 =H
H3CO 16 R1 = R2 = OCH3

Fig. 2 Structures of H OH H R H R OH
compounds isolated from O O O
Zingiber aromaticum HO O

O O O
H H
OH O
18 19 R = OH 21 R = OH R3O O
20 R = H 22 R = H R2O
OR1
OR O OH 23 R1 = R2 = Ac, R3 = H
H3CO 24 R1 = R2 = R3 = Ac
HO O
25 R1 = R3 = Ac, R2 = H
OCH3
HO 33 26 R1 = H, R2 = R3 = Ac
OH O 27 R1 = Ac, R2 = R3 = H
O
28 R1 = R3 = H, R2 = Ac
31 R = H H3CO
29 R1 = R2 = H, R3 = Ac
32 R = CH3
30 R1 = R2 = R3 = H
HO 34

without a test sample whereas Abs(test sample) was that with C98 %; Enzo Life Sciences) [29] and ursolic acid (purity
a test sample. The assays were performed in triplicate for C90 %; Tokyo Chemical Industry, Tokyo, Japan) [23],
all samples. Known phosphatase inhibitors, RK-682 (purity were used as the positive controls.

123
J Nat Med

Results and discussion PTP1B inhibitory activities of the constituents of Ci. bur-
mannii and Z. aromaticum that were isolated in our laboratory.
The water and methanol extracts of all 28 samples of Indo- Of the 17 compounds isolated from Ci. Burmannii (Fig. 1),
nesian medicinal plants were screened for their ability to 50 -hydroxy-5-hydroxymethyl-400 ,500 -methylenedioxy-1,2,3,4-
inhibit PTP1B-mediated dephosphorylation of pNPP. Of the dibenzo-1,3,5-cycloheptatriene (2) and trans-cinnamaldehyde
28 water extracts, water extracts of Alstonia scholaris leaf (5) produced the 88.7 and 98.0 % inhibition at 10 lg/mL,
(87.4 %), Blumea balsamifera (96.8 %), Ci. burmannii respectively (Table 2). This inhibition was concentration-
(86.6 %), Cymbopogon nardus (85.2 %), Melaleuca leuca- dependent and the IC50 values were determined as 29.7 and
dendra (95.6 %), Ph. niruri (81.3 %), Pi. nigrum (75.0 %), 57.6 lM, respectively. However, compounds 4, 6, and 7,
Sy. aromaticum (83.8 %), and Sy. polyanthum (88.0 %) which shared the same skeleton as 5, exhibited only 1.1, 9.0,
exhibited more than 70 % inhibition at a concentration and 0.0 % inhibition at 10 lg/mL, respectively. Thus, the
of 25 lg/mL (Table 1). Amomum compactum rhizome aldehyde group in 5 may correlate with its PTP1B inhibitory
(38.2 %), An. paniculata (40.0 %), Rheum palmatum activity. Indeed, the catalytic loop in PTP1B is known to
(40.8 %), and Santalum album (31.8 %) exhibited moderate interact with an aldehyde group [31]. Moreover, compounds 8
inhibition of 30–70 %, whereas the remainder showed only and 9, which possessed a cinnamaldehyde structure exhibited
weak inhibition, i.e., B30 % inhibition. Of the metha- no inhibition, indicating the importance of the substitutions in
nol extracts, Als. scholaris leaf (72.3 %), An. paniculata the phenyl ring. Trans-cinnamaldehyde was reported as the
(74.8 %), B. balsamifera (78.0 %), Ci. burmannii (95.7 %), main constituent (86.3 %) of a methanol extract of Ci. bur-
Curcuma heyneana (81.9 %), G. glabra (89.8 %), M. leu- mannii [32], whereas compound 2 was present at only minor
cadendra (96.4 %), Pu. granatum (88.9 %), R. palmatum levels [26]. Thus, trans-cinnamaldehyde (5) could contribute
(91.8 %), Sy. polyanthum (97.2 %), and Z. aromaticum to the PTP1B inhibitory effect of the extract. The potential
(84.4 %) exhibited 70 % or more inhibition at 25 lg/mL efficacy of trans-cinnamaldehyde against type II diabetes and
(Table 1). Alp. galanga (64.1 %), Cu. aeruginosa (59.1 %), obesity was reported recently [31–35], whereas trans-cinna-
Ph. niruri (69.8 %), and Z. cassumunar (67.4 %) exhibited maldehyde has also been explored as a template for developing
moderate inhibition of 30–70 %, whereas the remainder PTP1B inhibitors [31].
exhibited less than 30 % inhibition.
The concentration-dependency of inhibition and the
IC50 values were determined for the 20 extracts exhibit-
ing more than 70 % inhibition (Table 1). Of these, the Table 2 PTP1B inhibitory activity (%) of constituents of Cinnamo-
water extracts of B. balsamifera (IC50, 2.26 lg/mL) and mum burmannii and Zingiber aromaticum at 10 lg/mL. Data are
expressed as means ± SD (n = 3)
M. leucadendra (IC50, 2.05 lg/mL), and the methanol
extracts of Ci. burmannii (IC50, 2.47 lg/mL), Pu. granatum Compound Inhibition IC50 Compound Inhibition IC50
(IC50, 2.40 lg/mL), and Sy. polyanthum (IC50, 1.03 lg/mL) no. (%) (lM) no. (%) (lM)
exhibited strong inhibitory activity that was comparable with 1 6.1 ± 2.7 18 52.0 ± 9.5
the positive control, RK-682 (IC50, 2.05 lg/mL). 2 88.7 ± 5.5 29.7 19 48.9 ± 3.0
To the best of our knowledge, there are no previous 3 7.0 ± 3.9 20 62.6 ± 5.2
reports related to the possible treatment of diabetes and/or 4 1.1 ± 6.3 21 86.0 ± 5.0 27.7
obesity with Als. scholaris, B. balsamifera, Cu. heyneana, 5 98.3 ± 1.6 57.6 22 15.9 ± 4.1
Cy. nardus, M. leucadendra, Rh. palmatum, Sy. polyant- 6 9.0 ± 1.2 23 25.9 ± 6.7
hum, and Z. aromaticum. However, M. leucadendra fruit is
7 0.0 ± 3.8 24 32.8 ± 0.4
known to have significant PTP1B inhibitory activity (IC50,
8 0.0 ± 2.4 25 20.0 ± 2.8
2.05 lg/mL) and it contains ursane-type triterpenes such us
9 0.0 ± 4.5 26 16.9 ± 3.2
betulinic acid and ursolic acid [30]. Previously, ursane-type
10 0.0 ± 17.1 27 10.5 ± 1.9
triterpenes including ursolic acid were found to exhibit
11 0.7 ± 7.5 28 0.0 ± 2.3
PTP1B inhibition (IC50: 3.8–46 lM) and to contribute to
12 8.0 ± 1.7 29 0.0 ± 2.7
the PTP1B inhibition of Symplocos paniculata [22]. Thus,
13 0.0 ± 2.9 30 0.0 ± 1.3
the inhibitory activity of M. leucadendra fruit may be
14 0.0 ± 1.8 31 0.7 ± 3.1
partly due to ursane-type triterpenes such us betulinic acid
15 0.0 ± 2.1 32 95.3 ± 0.6 17.5
and ursolic acid.
16 0.0 ± 3.3 33 75.3 ± 1.5 28.1
In a course of studies of Indonesian Jamu medicines, we
17 0.0 ± 4.2 34 12.3 ± 5.9
previously examined the constituents of methanol extracts
of Ci. burmannii and Z. aromaticum [26, 27] and isolated RK-682 5.57 Ursolic 19.7
acid
17 compounds from each (Figs. 1, 2). Thus, we tested the

123

Of the 17 compounds isolated from Z. aromaticum
(Fig. 2), (5R)-2,6,9-humulatrien-5-ol-8-one (21), kaempf-
erol-3,40 -di-O-methyl ether (32), and (S)-6-gingerol (33)
exhibited 86.0, 95.3, and 75.3 % inhibition at 10 lg/mL,
respectively (Table 2). Their inhibition was concentration-
dependent and their IC50 values were determined as 27.7,
17.5, and 28.1 lM, respectively. Among the humulane-
type diterpenes (18–22), (5R)-2,6,9-Humulatrien-5-ol-8-
one (21) exhibited the most potent activity and followed by
20 (62.6 % at 10 lg/mL), 18 (52.0 % at 10 lg/mL), 19
(48.9 % at 10 lg/mL), and 22 (15.9 % at 10 lg/mL). On
kaempferol derivatives (23–32), kaempferol-3,40 -di-O-
methyl ether (32) exhibited the potent inhibition, whereas
other kaempferol derivatives exhibited only weak inhibi-
tion. The inhibitory activity of 32 was slightly greater than
those of 21 and 33, while 21 and 33 were the first and
second major constituents of Z. aromaticum [27]. Thus,
these constituents could make a major contribution to the
PTP1B inhibitory effect of the methanol extract.
Conclusion
In conclusion, these results demonstrated that the Indone-
sian medicinal plants, Alstonia scholaris, Andrographis
paniculata, Blumea balsamifera, Cinnamomum burmannii,
Curcuma heyneana, Cymbopogon nardus, Glycyrrhiza
glabra, Melaleuca leucadendra, Phyllanthus niruri, Piper
nigrum, Punica granatum, Rheum palmatum, Syzygium
aromaticum, Sy. polyanthum, and Z. aromaticum may be
employed for the treatment and/or prevention of type II
diabetes and/or obesity.
Acknowledgments We are thankful to Dr. Sucipto (PJ. Bintang
Terang Lestari, Traditional Medicine Supplier, Jakarta) and Dr. Aty
Widyawaruyanti (Faculty of Pharmacy, Airlangga University) for
their authentication of the plant materials. One of the authors (A.S.)
would like to thank the Indonesian Ministry of Education for a Ph.D.
grant.
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