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Study on the antiinflammatory activity of Artocarpus altilis leaves extract in mice

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In addition to the body's response to injury, inflammation is a physiological process underlying the progression various diseases. Investigation for the discovery and development of antiinflammatory agents from natural sources is a promising strategy for curing inflammatory diseases. Breadfruit or Artocarpus altilis, is an Indonesian native plant traditionally used for the treatment of various disease including inflammatory-related diseases such as arthritis, tumors, pain, gastritis and atherosclerosis. Scientific evidence regarding the antiinflammatory effect of A.altilis leaf is limited. This study aimed to investigate the antiinflammatory activities of A.altilis leaf extract (AAE). The expression and the activity of COX, the enzyme responsible for prostaglandins formation, were also evaluated. The A.altilis leaf was extracted in ethyl acetate and the dried extract was used for the experiments in mice models. We employed a carrageenan-induced paw edema in mice to evaluate the antiinflammatory activities. The level of COX-2 expression in the paw tissues were determined using immunohistochemistry, whereas COX-2 inhibitory activity was tested on in vitro enzymatic assays. We found that AAE at the doses of 250, 500 and 1000 mg/kgBW significantly reduced the volume of paw edema until 6 hours of observation. In vitro enzymatic assays revealed that AAE has a lower IC50 against COX-2 compared to COX-1, suggesting the higher selectivity for COX-2. In addition, the level of COX-2 expression in the hind paws was also significantly reduced upon AAE treatment in dose-dependent manner. These indicated that AAE has a potency to be further developed as antiinflammatory agent or as a source of lead compounds acting as antiinflammation. © 2015, International Journal of Pharmacognosy and Phytochemical Research. All rights reserved.
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International Journal of Pharmacognosy and Phytochemical Research 2015; 7(6); 1080-1085
ISSN: 0975-4873
Research Article
*Author for Correspondence
Study on the Antiinflammatory Activity of Artocarpus altilis Leaves
Extract in Mice
Fakhrudin, N*1,2, Hastuti, S1, Andriani, A1, Widyarini, S3, Nurrochmad, A1
1Faculty of Pharmacy, Universitas Gadjah Mada, Sekip Utara, Yogyakarta, 55281, Indonesia; 2Center for Natural
Antiinfective Research, Faculty of Pharmacy, Universitas Gadjah Mada, Sekip Utara, Yogyakarta, 55281, Indonesia;
3Department of Veterinary Pathology, Faculty of Veterinary Medicine, Universitas Gadjah Mada, Sekip Utara,
Yogyakarta, 55281, Indonesia.
Available Online:11th October, 2015
ABSTRACT
In addition to the body's response to injury, inflammation is a physiological process underlying the progression various
diseases. Investigation for the discovery and development of antiinflammatory agents from natural sources is a promising
strategy for curing inflammatory diseases. Breadfruit or Artocarpus altilis, is an Indonesian native plant traditionally
used for the treatment of various disease including inflammatory-related diseases such as arthritis, tumors, pain, gastritis
and atherosclerosis. Scientific evidence regarding the antiinflammatory effect of A.altilis leaf is limited. This study aimed
to investigate the antiinflammatory activities of A.altilis leaf extract (AAE). The expression and the activity of COX, the
enzyme responsible for prostaglandins formation, were also evaluated. The A.altilis leaf was extracted in ethyl acetate
and the dried extract was used for the experiments in mice models. We employed a carrageenan-induced paw edema in
mice to evaluate the antiinflammatory activities. The level of COX-2 expression in the paw tissues were determined
using immunohistochemistry, whereas COX-2 inhibitory activity was tested on in vitro enzymatic assays. We found that
AAE at the doses of 250, 500 and 1000 mg/kgBW significantly reduced the volume of paw edema until 6 hours of
observation. In vitro enzymatic assays revealed that AAE has a lower IC50 against COX-2 compared to COX-1,
suggesting the higher selectivity for COX-2. In addition, the level of COX-2 expression in the hind paws was also
significantly reduced upon AAE treatment in dose-dependent manner. These indicated that AAE has a potency to be
further developed as antiinflammatory agent or as a source of lead compounds acting as antiinflammation.
Keyword: Artocarpis altilis, antiinflammation, cyclooxygenase
INTRODUCTION
Inflammation is a body response to injuries induced by a
variousstimuli, such as infectious agents from
microorganisms, noxious substances, physical damages,
and changes induced by malignant cells. Various
pathological conditions, including atherosclerosis, sepsis,
cancer, arthritis and metabolic syndromes are related with
inflammatory condition1. Currently, no satisfying drug is
available for the treatment of these inflammatory-related
diseases. There are two antiinflammatory drugs available
in the clinic: corticosteroids and non-steroidal
antiinflammatory drugs (NSAID). Despite the fact that
corticosteroids and NSAID (non-steroidal
antiinflammatory drugs) remain the common choice for
the treatment of inflammatory diseases, the usage of these
drugs are restricted by their undesirable side effects and
the limited potency to reduce the symptoms of
inflammation. Moreover, chronic use of corticosteroids
antiinflammatory drugs has been limited as they exhibited
a weight gain, osteoporosis and immunosuppressive
effects. Whereas high dose NSAID medication leads to
gastrointestinal tract-related toxicities2. Consequently, the
development of novel potential antiinflammatory agents
with a desirable side effect is a great of interest.
Many therapeutic targets have been identified to interfere
the inflammatory processes. One of the most important
therapeutic target is cyclooxygenase (COX)3. COX-1 is
constitutively expressed, whereas COX-2 is an inducible
enzyme expressed during the inflammatory processes4.
COX-2 is responsible for the formation of prostaglandins
and has a key role for therapeutic intervention in pain and
inflammatory-related diseases5,6. Inhibition of COX-2
activity has become an important target for combating
inflammatory disorders3,7,8. COX-2 was the established
therapeutic target in inflammation and aspirin is the fist
NSAID inhibitor of COX-2. Inhibition of COX-2 activity
interferes the production of prostaglandins, the
inflammatory mediators that play a crucial role in the
development of inflammatory responses and varios
pathophysiological conditions5,9. Unfortunately, the use
of aspirin is associated with the undisired side effects
including renal toxicity and gastrointestinal bleeding10. In
addition, the newer selective COX-2 inhibitor, the
“coxib“ derivatives, still exhibits severe cardiovascular
side effects11-13. Consequently, the exploration for finding
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IJPPR, Volume 7, Issue 6 : December 2015 Page 1081
the alternative therapeutic agent targeting COX-2 is a
promising research.
Medicinal plants have significant contribution to the
drugs development and discovery and still provide
abundant and promising source for lead structures as drug
candidates. Many plants have been used by folk for
decades to treat various human diseases including
inflammatory diseases. Artocarpus altilis (Moraceae),
commonly known in Indonesia as Sukun, is a flowering
tree native to Indonesia and New Guinea, and spreading
throughout Southeast Asia and Africa. Indonesian people
consume the starchy fruit part after boiling and frying it at
all stage of growth as it provides high amount of fibers
and carbohydrates as well as contains protein, vitamins,
calcium, magnesium, potassium, copper, iron, niacin,
thiamin, riboflavin, lutein, and phenolics14,15. Although
the fruit of A. altilis has been acknowledges as a potential
food source for food security for the growing global
population15, the leaf part is underutilized and known to
be a non-toxic suggesting the safety in therapeutic uses16.
The leaves of A. altilis have been traditionally used by
folk for treating various disorders such as hypertension,
liver cirrhosis, diabetes, hypercholesterolemia, and also
used in inflammatory conditions such as arthritis, pain,
gastritis and stroke17,18. Previous studies showed that A.
altilis contains various non-polar a non-glycoside
prenylated flavonoids19-22 responsible for several
pharmacological activities including anticancer23,24,
antiausteric19, antioxidant25, antiinflammation26,
antiplatelet22 and antiatherosclerotic27. The leaves were
also known to contain lutein, sitosterol, squalene,
unsaturated triglycerides, polyprenol, unsaturated fatty
acids28. Previous study demonstrated that AAE showed a
promising antihypertension activity via inhibition of
angiotensin converting enzyme activity29 and exhibited
antiatherosclerosis activity30. However, only little
scientific data is available regarding the antiinflammatory
activity of AAE both in vitro and in vivo studies. In this
study, we investigated the antiinflammatory activity of
AAE in mice and the effects on the expression and the
activity of cyclooxygenase-2 (COX-2).
MATERIALS AND METHODS
Plant material
The main material used in this study is Artocarpus altilis
leaves. The leaves were harvested from Melati district,
Sleman, Yogyakarta, Indonesia. Plant identification was
done by the botanist at the Department of Pharmaceutical
Biology, Faculty of Pharmacy, Universitas Gadjah Mada,
Indonesia. Freshly harvested leaves were dried at 50°C in
the oven for 48 h and further grinded before the
extraction.
Reagents and Chemicals
Indomethacin and carrageenan were purchased from
Sigma Aldrich (Saint Louis, MO, USA), ethyl acetate and
aquadest were obtained from local supplier (Brataco
Chemika, Yogyakarta, Indonesia), whereas dimethyl
sulfoxide and the PBS components were obtained from
EMerck (Darmstadt, Germany). Colorimetric-based COX
Inhibitor Screening Assay was purchased from Caymann
Chemical (Michigan, USA, catalog number 760111) and
COX-2 antibody was obtained from Santa Cruz
Biotechnology (Texas, USA, catalog number sc-1747-R).
Extraction
The extraction of plant material was done using
maceration method. The dried A. altilis leaves (500 gram)
were macerated three times in ethyl acetate (2.5 L). After
filtration, the solvent was evaporated using a vacuum
rotary evaporator instrument under a reduced pressure to
dryness.
Animals
Male BALB/c mice (20-30 g) were used in this study.
They were housed in a controlled environment and fed
with standard pellet diet and water ad libitum. After
acclimatization for at least one week before the
experimental session, the mice were randomized and
divided into 6 groups. All the experimental protocols
were performed according to the guidelines approved by
Institutional Animal Ethic Committee (number 192/KEC-
LPPT/IX/2014), Universitas Gadjah Mada, Indonesia.
Carrageenan-induced paw edema
The acute inflammatory activity was evaluated using
Carrageenan-induced paw edema assay as previously
described31. Paw edema was induced by subplantar
injection of freshly prepared 200 μL carrageenan 1%
(solution in distilled water) in to the right hind paws. The
animals were randomly divided into 5 groups of 5
animals each. All groups, except the untreated group,
were given single dose of extracts (250, 500 or 1000
mg/kgBW), solvent or indomethacin (5 mg/kgBW), 30
minutes prior to paw edema induction using carrageenan.
The volume of the paw edema was measured using
plethysmometer every 30 minutes for 6 hours after
carrageenan administration. The antiinflammatory
activity (percentage activity) was determined based on
the paw edema volume differences between the extracts-
treated and the solvent-treated groups after 6 hours.
Immunohistochemistry of COX-2
After the measurement of paws edema, the mice were
sacrified and the soft plantar region sections of the hind
paw were cut and fixed in 10% buffered formalin for 24
hours and further embedded with parafin32. The parafin-
embedded blocks were cut with a thickness of 4 mm,
flattened and then attached to the glass slides coated with
poly-lysine. Antigen recovery was done by addition of
xylol and ethanol to deparafinize and dehydrate the
sections, respectively, and further washed in a phosphate
buffered saline (PBS) solution. The sections were
incubated for 10 minutes in a peroxidase blocking
solution containing 3% H2O2 to abolish endogenous
peroxidase activity and further incubated 10 minutes in a
bloking buffer containing 5% bovine serum albumin
(BSA). The sections were incubated overnight at 4°C
with diluted mice primary antibody (anti COX-2, 1:250
dilution in PBS-BSA) and then washed in PBS for 5
minutes. The secondary biotinylated universal antibody
(antiIgG) at 1:200 dilution was added and the sections
were incubated for 5 minutes at room temperature.
Following washingwith PBS for 5 minutes, the sections
were incubated for 10 minutes in the conjugated-
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IJPPR, Volume 7, Issue 6 : December 2015 Page 1082
streptavidin peroxidase complex. After another 5 minutes
washing with PBS, the sections were stained by
incubation (10 minutes) in peroxidase substrate solution
containing 3,3'diaminobenzidine-peroxide (DAB) at 1:9
dilution, and counter-stained with Mayer hematoxylin
(100 µl for 2 minutes). The stained sections were then
dehydrated using ethanol and xylol, added mounting
media and embedded in microscope slides for
immunohistochemistry analisis. When the cytoplasm was
stained brown, COX-2 immunostaiting was considered
positive. COX-2 expression was evaluated based on the
percentage of positive cells according to the previous
method32,33. The percentage of COX-2 expression was
determined by calculating the COX-2 expressing cells
(positive cells) in the extracts-treated groups compared to
the solvent-treated group. The cell counting was done in a
light microscope observed under 1000X magnification at
5 different fields.
COX-1 and COX-2 enzymatic assays
The COX-1 and COX-2 inhibitory activities of the
extracts were evaluated using a colorimetric-based COX
Inhibitor Screening Assay (Caymann, catalog number
760111) that employs peroxidase component of
cyclooxygenase. The activity of peroxidase is measured
colorimetrically at 590 nm based on the generation of
oxidized N,N,N',N'-tetramethyl-p-phenylenediamine
Figure 1. The AUC for time-response curves of paw edema on carrageenan-induced paw edema in mice (5 animals
per group). The A. altilis extract (AAE) were tested at 250, 500 and 1000 mg/kgBW and indomethacin (5 mg/kgBW)
was used as a positive control.
Figure 2. Antiinflammatory activity of A. altilis extract
on carrageenan-induced paw edema in mice (5 animals
per group). The extracts were tested at 250, 500 and
1000 mg/kgBW and indomethacin (5 mg/kgBW) was
used as a positive control. The values are mean ±
standard errors. * p< 0.05; ** p< 0.01
(ANOVA/Dunnett, compared to solvent-treated group).
Figure 3. Effect of A. altilis extract on the inhibition of
COX-2 expression on carrageenan-induced paw edema in
mice (5 animals per group). Mice paws were cut and fixed
in buffered formalin and COX-2 expression was quantified.
The extracts were tested at 250, 500 and 1000 mg/kgBW
and indomethacin (5 mg/kgBW) was used as a positive
control. The values are mean ± standard errors. * p< 0.05;
** p< 0.01 (ANOVA/Dunnett, compared to solvent-treated
group).
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IJPPR, Volume 7, Issue 6 : December 2015 Page 1083
(TMPD)34. The assay was performed according to the
manufacturer's spesified protocol.
Statistical Analysis
Data from all experiments were presented as mean values
with ± standard error mean (SEM). Statistical analysis
was performed by one-way analysis of variance
(ANOVA) with Dunnet post hoc test, p < 0.05 was
considered statistically significant.
RESULTS AND DISCUSSION
The leaf of A. altilis is used in Indonesia as an herbal
medicine preparation to treat various diseases including
inflammatory diseases. Although the leaves were
traditionally prepared for the medication as a decoct
dosage form, our preliminary study revealed that the A.
altilis leaves ethyl acetate extract (AAE) demonstrated a
higher antiinflammatory activity compared to the aquoeus
extract35. In this present study, we examined the
antiinflammatory effects of AAE in mice using acute
experimental model of inflammation. We employed
carrageenan-induced paw edema which represents a
common simple method for antiinflammatory evaluation
and then we studied the more specific antiinflammatory
effect on the COX-2 expression and activity. We found
that AAE exhibited antiinflammatory activity by reducing
carrageenan-induced paw edema in dose-dependent
manner (Figure 1 and 2). Paw edema is a common feature
for an acute inflammatory process36. Thus, the reduction
of carrageenan-induced edema volume upon AAE
treatment indicated that the extract has an acute anti-
inflammatory activity. However, the activity is lower
compared to the positive control, indomethacin.
One of the key factor responsible for the progression of
inflammatory process is cyclooxygenase (COX) enzymes,
especially COX-2. This inducible enzyme is over
expressed in inflammation and is known to be responsible
for the formation of prostaglandins from arachidonic acid.
Thus, we investigated the effect of AAE on the COX-2
expression and activity. COX-2 expression in the soft
plantar region sections of the hind paw was investigated
using immunohistochemistry, whereas the COX-2
enzymatic activity was evaluated using a colorimetric-
based COX inhibitor assay. Our study indicated that
COX-2 expression was reduced (Figure 3 and 4) and the
COX-2 activity was also inhibited (Figure 5) upon AAE
treatment in dose-dependent manner. Although
indomethacin (5 mg/kgBW) demonstrated stronger
activity, the higher concentration of indomethacin or the
extract might be required to completely inhibit COX-2
expression to the lower level. These results indicated that
Figure 4. Representative pictures showing COX-2 expression in the soft plantar region sections of the hind paw. The
pictures were taken in a light microscope observed under 1000X magnification at 5 different fields. The cox-2
expressing cells were colored in dark brown. A: solvent-treated goup, B: indomethacin-treated group, C: AAE 250
mg/kgBW, D: AAE 250 mg/kgBW.
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IJPPR, Volume 7, Issue 6 : December 2015 Page 1084
Figure 5. Artocarpus altillis extract inhibited COX-1
and COX-2 activity in vitro. The extract was was
dissolved in DMSO and prepared in 5 different
concentrations, each in a triplicate (n=3). The values are
means ± standard errors.
AAE, at least in part, exerts antiinflammatory activity via
targeting both the expression and activity of COX-2.
To determine the selectivity of AAE on COXs inhibition,
we also investigated the inhibitory effect of the extract on
COX-1 (Figure 5). Interestingly, AAE demonstrated a
potent COX-2 inhibition activity (IC50: 3,17µg/ml) in
comparison to that of COX-1 (IC50: 23,45), indicating
that this extract contains a promising compound with a
high potency to be developed as a selective COX-2
inhibitor. These indicate that AAE exerted
antiinflammatory activity, at least partly by inhibiting the
activity and the expression of COX-2. As COX-2 has a
crucial role in inflammation and it still represents a
potential therapeutic target for inflammation37,38, the
inhibition of COX-2 activity and expression upon AAE
treatment makes A. altilis as a potential source of natural
compounds with a promising antiinflammatory activity.
To determine the selectivity of AAE against COX-1 and
COX-2, we tested the potency of AAE in inhibiting
COX-1 and COX-2 in in vitro enzymatic assays. Figure 5
demonstrates that AAE inhibited both COX-1 (IC50:
23.45 μg/ml) and COX-2 (IC50: 3.17 μg/ml).
Interestingly, AAE shows more potent inhibition against
COX-2 compared to COX-1, indicating that this extract
contains a promising compound with a high potency to be
developed as a selective COX-2 inhibitor.
Our study clearly demonstrates that the AAE exhibited a
promising antiinflammatory activity in an experimental
model of acute inflammation in mice. These results are in
accordance with the previous study showing that A. altilis
contains several antiinflammatory flavonoids with a
distinct mechanism of action39. Artocarpin, a prenylated
flavonoid isolated from A. altilis was also claimed to be a
compound responsible for the antiinflammatory activities
as it decreased the level of TNFα and IL-, a major pro-
inflammatory transcription factor and a pro-inflammatory
cytokine, respectively26. These findings provide the
scientific evidence for the traditional use of A. altilis
leaves for the treatment of inflammatory diseases17.
In summary, we demonstrate that AAE exhibited
antiinflammatory activity in mice experimental models. It
inhibited carrageenan-induced paw edema and reduced
the expression and activity of COX-2. Additionally, it
showed a higher selectivity against COX-2 in comparison
to COX-1. These findings suggested that A. altilis leaves
could be a potential source for the discovery of novel
antiinflammatory compounds for drugs or dietary
supplements.
ACKNOWLEDMENT
This research was supported by Hibah Penelitian
Unggulan Perguruan Tinggi (PUPT), the Directorate
General of Higher Education, Ministry of Education and
Culture, Republic of Indonesia, (Grant number: LPPM-
UGM/344/LIT/2014). We also thank Setiono for an
excellent technical support.
REFERENCES
1. Weiss U. Inflammation. Nature. 2008;454(7203):427.
2. Dequeker J. NSAIDs/corticosteroids--primum non
nocere. Advances in experimental medicine and
biology. 1999;455:319-25.
3. FitzGerald GA. COX-2 and beyond: approaches to
prostaglandin inhibition in human disease. Nat Rev
Drug Discov. 2003;2(11):879-90.
4. Dubois RN, Abramson SB, Crofford L, Gupta RA,
Simon LS, A. Van De Putte LB, et al.
Cyclooxygenase in biology and disease. The FASEB
Journal. 1998;12(12):1063-73.
5. Ricciotti E, FitzGerald GA. Prostaglandins and
Inflammation. Arteriosclerosis, Thrombosis, and
Vascular Biology. 2011;31(5):986-1000.
6. Medzhitov R. Origin and physiological roles of
inflammation. Nature. 2008;454(7203):428-35.
7. Flower RJ. The development of COX2 inhibitors. Nat
Rev Drug Discov. 2003;2(3):179-91.
8. Maroon JC, Bost JW, Maroon A. Natural anti-
inflammatory agents for pain relief. Surg Neurol Int.
2010;1:80.
9. Simmons DL, Botting RM, Hla T. Cyclooxygenase
Isozymes: The Biology of Prostaglandin Synthesis
and Inhibition. Pharmacological reviews.
2004;56(3):387-437.
10. Thiagarajan P, Jankowski JA. Aspirin and NSAIDs;
benefits and harms for the gut. Best practice &
research Clinical gastroenterology. 2012;26(2):197-
206.
11. Bresalier RS, Sandler RS, Quan H, Bolognese JA,
Oxenius B, Horgan K, et al. Cardiovascular Events
Associated with Rofecoxib in a Colorectal Adenoma
Chemoprevention Trial. New England Journal of
Medicine. 2005;352(11):1092-102.
12. Silverstein FE, Faich G, Goldstein JL, et al.
Gastrointestinal toxicity with celecoxib vs
nonsteroidal anti-inflammatory drugs for osteoarthritis
and rheumatoid arthritis: The class study: a
randomized controlled trial. JAMA.
2000;284(10):1247-55.
13. Rainsford KD. Anti-inflammatory drugs in the 21st
century. Sub-cellular biochemistry. 2007;42:3-27.
Fakhrudin et.al. / Study on Antiinflammatory…
IJPPR, Volume 7, Issue 6 : December 2015 Page 1085
14. Appiah F, Oduro I, Ellis WO. Proximate and Mineral
Composition of Artocarpus altilis Pulp Flour as
Affected by Fermentation. Pakistan Journal of
Nutrition. 2011;10(7):653-7.
15. Jones AMP, Ragone D, Tavana NG, Bernotas DW,
Murch SJ. Beyond the Bounty: Breadfruit (Artocarpus
altilis) for food security and novel foods in the 21st
Century. Ethnobotany Research and Applications.
2011;9.
16. Sairam S, Urooj A. Safety Evaluation of Artocarpus
altilis as Pharmaceutical Agent in Wistar Rats. Journal
of Toxicology. 2014;2014:980404.
17. Jagtap UB, Bapat VA. Artocarpus: a review of its
traditional uses, phytochemistry and pharmacology.
Journal of ethnopharmacology. 2010;129(2):142-66.
18. Lans CA. Ethnomedicines used in Trinidad and
Tobago for urinary problems and diabetes mellitus.
Journal of ethnobiology and ethnomedicine.
2006;2:45.
19. Nguyen MT, Nguyen NT, Nguyen KD, Dau HT,
Nguyen HX, Dang PH, et al. Geranyl
dihydrochalcones from Artocarpus altilis and their
antiausteric activity. Planta medica. 2014;80(2-3):193-
200.
20. Patil AD, Freyer AJ, Killmer L, Offen P, Taylor PB,
Votta BJ, et al. A new dimeric dihydrochalcone and a
new prenylated flavone from the bud covers of
Artocarpus altilis: potent inhibitors of cathepsin K. J
Nat Prod. 2002;65(4):624-7.
21. Shamaun SS, Rahmani M, Hashim NM, Ismail HB,
Sukari MA, Lian GE, et al. Prenylated flavones from
Artocarpus altilis. Journal of natural medicines.
2010;64(4):478-81.
22. Weng J-R, Chan S-C, Lu Y-H, Lin H-C, Ko H-H, Lin
C-N. Antiplatelet prenylflavonoids from Artocarpus
communis. Phytochemistry. 2006;67:824-9.
23. Jeon YJ, Jung SN, Chang H, Yun J, Lee CW, Lee J, et
al. Artocarpus altilis (Parkinson) Fosberg Extracts and
Geranyl Dihydrochalcone Inhibit STAT3 Activity in
Prostate Cancer DU145 Cells. Phytotherapy research :
PTR. 2015.
24. Kuete V, Nkuete AH, Mbaveng AT, Wiench B, Wabo
HK, Tane P, et al. Cytotoxicity and modes of action of
4'-hydroxy-2',6'-dimethoxychalcone and other
flavonoids toward drug-sensitive and multidrug-
resistant cancer cell lines. Phytomedicine :
international journal of phytotherapy and
phytopharmacology. 2014;21(12):1651-7.
25. Lan WC, Tzeng CW, Lin CC, Yen FL, Ko HH.
Prenylated flavonoids from Artocarpus altilis:
antioxidant activities and inhibitory effects on melanin
production. Phytochemistry. 2013;89:78-88.
26. Lee CW, Ko HH, Lin CC, Chai CY, Chen WT, Yen
FL. Artocarpin attenuates ultraviolet B-induced skin
damage in hairless mice by antioxidant and anti-
inflammatory effect. Food and chemical toxicology :
an international journal published for the British
Industrial Biological Research Association.
2013;60:123-9.
27. Wang Y, Deng T, Lin L, Pan Y, Zheng X. Bioassay-
guided isolation of antiatherosclerotic phytochemicals
from Artocarpus altilis. Phytotherapy research : PTR.
2006;20(12):1052-5.
28. Ragasa CY, Ng VA, Park JH, Kim DW, Cornelio K,
Shen CC. Chemical Constituents of Artocarpus altilis
and Artocarpus odoratissimus. Research Journal of
Pharmaceutical, Biological and Chemical Sciences.
2014;5(4):1081-7.
29. Siddesha JM, Angaswamy N, Vishwanath BS.
Phytochemical screening and evaluation of in vitro
angiotensin-converting enzyme inhibitory activity of
Artocarpus altilis leaf. Natural product research.
2011;25(20):1931-40.
30. Wang Y, Deng T, Lin L, Pan Y, Zheng X. Bioassay-
guided isolation of antiatherosclerotic phytochemicals
from Artocarpus altilis. Phytotherapy Research.
2006;20(12):1052-5.
31. Morris C. Carrageenan-Induced Paw Edema in the Rat
and Mouse. In: Winyard P, Willoughby D, editors.
Inflammation Protocols. Methods in Molecular
Biology. 225: Humana Press; 2003. p. 115-21.
32. Lucetti D, Lucetti E, Bandeira M, Veras H, Silva A,
Leal L, et al. Anti-inflammatory effects and possible
mechanism of action of lupeol acetate isolated from
Himatanthus drasticus (Mart.) Plumel. Journal of
Inflammation. 2010;7(1):60.
33. Hussein SZ, Mohd Yusoff K, Makpol S, Mohd Yusof
YA. Gelam honey attenuates carrageenan-induced rat
paw inflammation via NF-kappaB pathway. PloS one.
2013;8(8):e72365.
34. Badieyan ZS, Moallem SA, Mehri S, Shahsavand S,
Hadizadeh F. Virtual Screening for Finding Novel
COX-2 Inhibitors as Antitumor Agents. The open
medicinal chemistry journal. 2012;6:15-9.
35. Ajiningtyas RJ. Relationship study of total flavonoid
content with the antiinflammatory activity of ethyl
acetate, ethanol and aqueous extracts of Artocarpus
altilis (park.) Fosberg leaves [Undergraduated Thesis].
Yogyakarta: Undergraduate Thesis, Universitas
Gadjah Mada; 2015.
36. Wiig H. Pathophysiology of tissue fluid accumulation
in inflammation. The Journal of Physiology.
2011;589(12):2945-53.
37. Mendes RT, Stanczyk CP, Sordi R, Otuki MF, Santos
FAd, Fernandes D. Selective inhibition of
cyclooxygenase-2: risks and benefits. Revista
Brasileira de Reumatologia. 2012;52:774-82.
38. Melnikova I. Future of COX2 inhibitors. Nat Rev
Drug Discov. 2005;4(6):453-4.
39. Wei BL, Weng JR, Chiu PH, Hung CF, Wang JP, Lin
CN. Antiinflammatory flavonoids from Artocarpus
heterophyllus and Artocarpus communis. J Agric
Food Chem. 2005;53(10):3867-71.
... The most commonly used therapeutic agents for the treatment of inflammatory autoimmune disorders like CD and RA are glucocorticoids, disease-modifying anti-rheumatic drugs (DMARDs), and non-steroid anti-inflammatory drugs (NSAIDs) [22,23]. However, some patients may not respond to these treatments and long-term use of these medications can result in a number of side effects [22][23][24]. For example, continuous use of NSAIDs and glucocorticoids can lead to ulceration, osteoporosis, hypertension, and weight gain among others [22][23][24]. ...
... However, some patients may not respond to these treatments and long-term use of these medications can result in a number of side effects [22][23][24]. For example, continuous use of NSAIDs and glucocorticoids can lead to ulceration, osteoporosis, hypertension, and weight gain among others [22][23][24]. Side effects of DMARDs include gastrointestinal (GI) intolerance, hypersensitivity to the medication, production of antibodies against the medication, and an increased risk of developing opportunistic infections, particularly mycobacterial infections [23,25,26]. There is a need for safer and more effective therapies for patients with inflammatory autoimmune disorders. ...
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Crohn’s Disease (CD) and Rheumatoid Arthritis (RA) share some single nucleotide polymorphisms (SNPs) in protein tyrosine phosphatase non-receptor types 2 and 22 (PTPN2/22). Recently, we reported that clinical samples from CD and RA patients associated with PTPN2:rs478582 or PTPN22:rs2476601 genotypes were linked to overactive immune response and exacerbation of inflammation. Here, we investigated in vitro the effects of these SNPs in Jurkat T-cells using CRISPR-Cas9. All cells were evaluated for PTPN22/22 loss of function and effects on cell response. We measured gene expression via RT-qPCR and cytokines by ELISA. We also measured cell proliferation using a BrdU labeling proliferation ELISA, and T-cell activation using CD-25 fluorescent immunostaining. In PTPN2 SNP-edited cells, PTPN2 expression decreased by 3.2-fold, and proliferation increased by 10.2-fold compared to control. Likewise, expression of PTPN22 decreased by 2.4-fold and proliferation increased by 8.4-fold in PTPN22 SNP-edited cells. IFN-γ and TNF-α secretions increased in both edited cell lines. CD25 expression (cell activation) was 80.32% in PTPN2 SNP-edited cells and 85.82% in PTPN22 SNP-edited cells compared to 70.48% in unedited Jurkat T-cells. Treatment of PTPN2 and PTPN22-edited cells with a maximum 20 μM spermidine restored PTPN2/22 expression and cell response including cell proliferation, activation, and cytokines secretion. Most importantly, the effect of spermidine on edited cells restored normal expression and secretion of IFN-γ and TNF-α. The data clearly demonstrated that edited SNPs in PTPN2 or PTPN22 were associated with reduced gene expression, which resulted in an increase in cell proliferation and activation and overactive immune response. The data validated our earlier observations in CD and RA clinical samples. Surprisingly, spermidine restored PTPN2/22 expression in edited Jurkat T-cells and the consequent beneficial effect on cell response and inflammation. The study supports the use of polyamines dietary supplements for management of CD and in RA patients.
... The leaves were then oven-dried for 3 days at 45 º C and crushed into a fine powder. The dried powder of the plant materials was extracted using the maceration method according to a previous study with a few modifications (19). One kilogram of the dried plant powder was macerated with ten liters of ethanol (70%) for 24 hours, stirring every 3 hours. ...
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Introduction: As single extracts, Coccinia grandis and Blumea balsamifera have been known to have potent antioxidant activities. However, the synergistic antioxidant effect of the combination of these plant extracts was unknown. In this study, the combination of C. grandis and B. balsamifera extracts was investigated for its antioxidant and synergistic properties. Methods: Separately, C. grandis and B. balsamifera leaves were extracted with ethanol. After evaporation, the thick extracts were assayed for their total phenolic content (TPC) and total flavonoid content (TFC). The antioxidant properties of single and combined extracts were measured using the molybdenum(VI) reducing power, ferric reducing antioxidant power (FRAP), 2,2-diphenyl-1-picrylhydrazyl (DPPH), and 2,2-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS) methods. The possible synergism effect was evaluated using the checkerboard method and the combination index values were also calculated. Results: The TPC and TFC of the B. balsamifera extracts were much greater than that of C. grandis extract. In the molybdenum(VI) reducing power and FRAP assay, the reducing power of the extract combination increased as B. balsamifera extract concentration increased (P < 0.05). In the ABTS+ and DPPH radical scavenging assays, B. balsamifera extract demonstrated a higher antioxidant activity than C. grandis extract (P < 0.05). When combined, increasing the concentration of B. balsamifera caused an increase in the radical scavenging activity (P < 0.05). Synergism was observed in the combination of the extracts with low concentration ratios. Conclusion: In this study, we showed that the combination of C. grandis and B. balsamifera leaf extracts possessed synergistic antioxidant properties.
... However, the prolonged use of antibiotics has been known to cause bacterial resistance and organ damage (Fernández et al., 2019). Kalimantan mango (Mangifera casturi), which is popularly known as Kasturi plant, has been recognized to contain compounds with medicinal benefits (Fakhrudin et al., 2015) including terpenoids, saponins, and steroids in its stem (Chabib et al., 2018). In particular, the bark of Kasturi plant contains flavonoid compounds, alkaloids, phenols, and steroids (Sutomo et al., 2014). ...
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Endophytic bacteria are beneficial microorganisms living in the tis-sues system of various parts of a plant, including fruits, leaves, twigs, and roots. The bacteria are stated as forming colonies without caus-ing any damage to the plant. Thus, this study aimed at isolating endo-phytic bacterial from the leaves, barks, and fruits of Kasturi plant (Mangifera casturi), screening its endophytic bacteria, determining the potential of those endophytic bacteria, identifying 16S rRNA and analyzing potential growth of the bacteria. The isolated endophytic bacteria appeared to show potential activity against pathogenic bac-teria Propionibacterium acnes with disc-diffusion methods. Besides, the observations on bacterial activities showed isolate L2, S2 and F4 isolated from leaves, bark and fruits, respectively, as the most potent producers of antibacterial compounds. Technically, those activities were indicated by the formation of clear zones. Molecular identifica-tion was investigated by applying PCR amplification on 16S rRNA gene. Furthermore, the isolate L2 was identified as Enterobacter clo-acae with 99% sequence similarities; however, isolates S2 and F4 were identified as Escherichia coli. Therefore, these findings sug-gested that the identified strains would contribute to any further searches for new sources of anti-acne substances.
... Daun Kluwih juga diketahui mengandung GABA (Gamma Amino Butyric Acid) (Indrowati & Ariyanto 2012). Kandungan senyawa flavonoid pada Artocarpus altilis juga diketahui memiliki aktivitas sebagai antiinflamasi (Fakhrudin et al., 2015), antibakteri, antivirus (Sikarwar et al., 2014), antioksidan (Arif et al., 2018) dan memiliki aktivitas untuk menurunkan kadar glukosa darah penderita diabetes mellitus (Sogandi & Amelia) dengan dosis 50mg/kgBB (Eryuda & Soleha, 2016). ...
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Gastrointestinal infection is a common infection in Indonesia. Many bacteria could cause gastrointestinal disorder, including Shigella dysenteriae and Bacillus subtilis. Currently, they are treated using chemical and traditional drugs. One of the common pants in Indonesia is Kluwih (Artocarpus camansi). The objective our study to determine antibacterial activity and inhibitory mechanism of Kluwih leaf extract against pathogenic bacteria which cause gastrointestinal infection, i.e. Shigella dysenteriae and Bacillus subtilis. The extraction process used maceration technique using 96% ethanol solvent and the antibacterial activity was studied using agar diffusion method. The research result showed that Kluwih leaf extract had inhibitory power with KHM (minimum inhibitory concentration) value of 25% against S. dysenteriae and 6.25% against B. subtilis. The present study also revealed that Kluwih leaf was suspected to have inhibitory activity against bacteria by making holes in the membrane of bacterial cell, leading to the release of nucleic acid and protein and cell death. Keywords: antibacterial, Artocarpus camansi, kluwih, Shigella dysenteriae, Bacillus subtilis.
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Latar belakang: Artocarpus altilis adalah tumbuhan yang setiap bagiannya berkhasiat untuk kesehatan. Di Indonesia, penyebaran tanaman sukun hanya ditemukan di tempat tertentu dan belum dibudidayakan, namun tanaman ini kaya akan senyawa flavonoid, tanin dan saponin yang berpotensi sebagai antidiabetes dan antiinflamasi. Diabetes tipe 2 adalah sekelompok gangguan metabolik yang ditandai dengan kondisi hiperglikemia dan dapat disebabkan karena kurangnya produksi maupun gangguan pada kerja insulin. Penyakit ini merupakan penyakit degeneratif yang menjadi masalah kesehatan di dunia. Tata laksana diabetes dilakukan dengan modifikasi gaya hidup dan dibantu dengan penggunaan obat-obatan antidiabetes maupun terapi insulin. Inflamasi merupakan reaksi lokal tubuh yang ditandai dengan gejala tertentu. Pengobatan inflamasi dengan menggunakan obat sintetik banyak menimbulkan efek samping. Tujuan: Review ini dibuat untuk memberikan informasi tentang aktivitas antidiabetes dan antiinflamasi pada tanaman sukun. Hasil: Senyawa dengan aktivitas antidiabetik dari tanaman sukun dihasilkan oleh bagian batang, daun, dan buah yang diperoleh dari serangkaian hasil pengujian yang dimulai dengan uji fitokimia, dilanjutkan dengan pengujian aktivitas antidiabetes secara in vivo, in vitro, dan uji kalorimetri AlCl, aktivitas antiinflamasi dihasilan oleh bagian daun dan buah yang dibuktikan dari hasil pengujian aktivitas antiinflamasi secara in vitro dan in vivo. Kesimpulan: Tanaman sukun berpotensi dikembangkan sebagai pengobatan alternatif untuk penyakit diabetes dan mengatasi inflamasi.
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Background: Artocarpus altilis, A. Champeden, and Artocarpus heterophylus are popular species in Indonesia, and are commonly used as traditional medicine. Objective: This study aims to evaluate the diuretic effects of the ethyl acetate fraction of these three species on normotensive Wistar rats. Methods: The ethyl acetate fraction was prepared by a liquid-liquid extraction method. To evaluate diuretic effects, the sixty rats were divided into normal (distilled water), negative (4.5% NaCl), positive control (furosemide 5 mg/kg), and the testing groups. The testing groups were orally given the ethyl acetate fraction of A. altilis, Artocarpus champeden, and A. heterophylus at three dose levels of 25, 50, and 100 mg/kg. All animals were orally given 4.5% NaCl at a dose of 2 mL/200 g except the normal group; then the animals were given drugs according to group doses. Urine volume and electrolyte levels produced by the testing groups were compared to those of the control group. The concentration and ratio of ions were calculated to determine the natriuretic and carbonic anhydrase activities. Results: The ethyl acetate fractions of the three Artocarpus species at 100 mg/kg dose were more active than the standard furosemide (p < 0.05) to increase urinary excretion. Furthermore, at doses of 50 and 100 mg/kg, the fraction significantly increased the excretion of Na+, K+, and Cl- ions more than the standard (p < 0.05). The testing groups showed good natriuretic and carbonic anhydrase activities. Conclusions: The ethyl acetate fraction of A. altilis, A. champeden, and A. heterophylus leaves performed good diuretic and natriuretic activities. Therefore, the fractions can be considered as potential natural diuretic medicines.
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Breadfruit plant (Artocarpus altilis (Parkinson ex F.A Zorn) Fosberg) is a plant that is widely used and has economic value and has a high nutritional content. Breadfruit leaves contain many antioxidants such as flavonoids, xanthones, triterpenoids. Cytotoxic is a medicinal compound that can kill and inhibit the growth of developing cells. This researchaims to determine the value and cytotoxic activity of n-hexane extract of breadfruit leaves LC50 Artocarpus altilis (Parkinson ex F.A Zorn) Fosberg) by the Brine Shrimp Lethality Test (BSLT) method. The results of n-hexane extract of breadfruit leaves have cytotoxic activity with a value of 5.7557 μg / ml with a highly toxic category. Phytochemical screening showed n-hexane extracts of breadfruit leaves contained alkaloids, flavonoids, and steroids. This research can be concluded that breadfruit leavesLC50 (Artocarpus altilis (Parkinson ex F.A Zorn) Fosberg) have the potential to produce cytotoxic compounds.
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Based on the availability of many nutrients, Artocarpus altilis leaves have been widely employed as nutrients and nutraceuticals in recent years, or well known as Breadfruit or in Indonesia called Sukun. According to habits of community use A. altilis leaves in various way as a medicine, this article make respresentations as commonly known literature review about Artocarpus altilis leaves chemical constituent with health potential. This literature review utilizing academic databases such as PubMed, ScienceDirect and Google Scholar, included all journals recorded, classified, and analyzed in 12 years, from 2010 to 2022. The diversity of secondary metabolites present in this plant species especially flavonoids, terpenoids, steroids, phenols, saponins, alkaloids and tannins show that Artocarpus altilis leaf is a good candidate for source of health cause its compounds are used as a antioxidant, antiinflammatory, hypoglycemic properties, some cardiovascular problems, and many others. More research is needed for utilization as well as to study medicinal effects and bioaccesibility of these leaves for development of various drugs and functional foods.
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Objectives: Artocarpus is a tropical plant known for its high concentration of secondary metabolites, especially flavonoids and phenolics. This study aims to evaluate the potential use of ethanol extracts obtained from three species of Artocarpus (Artocarpus altilis, Artocarpus champeden, and Artocarpus heterophyllus) as gastroprotective agents. Methods: The gastroprotective potential of the extracts at concentrations of 100, 200, and 400 mg/kg BW was studied in an animal model induced by absolute ethanol. The animals were subjected to extract pre-treatment for 14 days. Subsequently, the gastroprotective potential was evaluated based on the area of the lesion, the volume of gastric fluid, gastric pH, total acidity, gastric wall mucus content, and microscopic lesions. Results: There was a significant decrease in the lesion area and gastric fluid volume in the animals that received pre-treated extracts of A. altilis, A. Champeden, and A. heterophyllus, as well as a significant increase in the pH and gastric wall mucus secretion when compared to the ethanol group (p<0.05), rather than the omeprazole or the normal group (p>0.05). Both macroscopic and microscopic examinations revealed a significant decrease in necrotic lesions. Conclusion: Extracts of A. altilis, A. Champeden, and A. heterophyllus are effective in lowering the risk of peptic ulcers since they have the potential to be used as natural gastroprotective agents.
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Indonesia is a country with large plant biodiversity with medicinal properties, such as “sukun” (Artocarpus altilis) or known as “breadfruit”. Breadfruit is a woody evergreen plant that has been used traditionally for various purposes, including medication. The fruit is rich in carbohydrates and fibers as a food source. The leaf and cortex are the most widely used for treating various diseases and other health benefits. This article aimed to present a comprehensive review on the potency of breadfruit from the perspective of ethnobotany, phytochemistry, pharmacology, and toxicology. The data in this narrative review was obtained from the scientific journals in the databases of Google Scholar, PubMed, Scopus, and ScienceDirect. Other credible sources, such as textbooks, student thesis, and patents were also used to support the main data. Based on the literature study, breadfruit has been used empirically in Indonesia as a medicinal herb. The scientific data of breadfruit showed antiinflammatory, antiplatelet, antioxidant, antiatherosclerosis, antihyperlipidemic, antimalaria, antidiabetic, cardioprotective, and anticancer activities. Breadfruit contains terpenoids, flavonoids, alkaloids, and phenolics as bioactive compounds. However, the unique compounds are geranylated and prenylated flavonoids such as cycloartenol, artonin V, and cyclomulberin. These compounds are distributed in the leaf, cortex, wood, and fruit. Limited data is available regarding the toxicology profile of breadfruit. Breadfruit leaves ethanol extract did not show any significant toxic effects in the animal experiments. However, the toxicity of the water extract is unclear, and thus, needs to be investigated to ensure its safety. Keywords: Artocarpus communis, bioactivity, chemical constituents, ethnopharmacology ABSTRAK Indonesia dikenal sebagai negara yang kaya akan keragaman tumbuhan berpotensi obat, diantaranya sukun (Artocarpus altilis). Sukun merupakan tanaman berkayu yang secara tradisional dimanfaatkan untuk berbagai keperluan termasuk pengobatan. Buah sukun mengandung karbohidrat dan serat sebagai sumber pangan. Daun dan batang sukun merupakan bagian yang paling banyak dimanfaatkan dalam pengobatan dan kesehatan. Reviu artikel ini bertujuan untuk mengkaji secara komprehensif potensi sukun dari sudut pandang etnobotani, fitokimia, farmakologi, dan toksikologi. Artikel narrative review ini ditulis berdasarkan data yang diperoleh dari kajian literatur hasil penelitian yang ada di basis data Google Scholar, PubMed, Scopus, dan ScienceDirect. Beberapa sumber pustaka lain seperti buku, naskah tugas akhir dan paten juga digunakan untuk memperkaya penulisan. Hasil kajian literatur sukun menunjukkan bahwa tanaman ini memiliki riwayat empiris digunakan sebagai obat tradisional di Indonesia. Hasil penelitian ilmiah menunjukkan sukun memiliki aktivitas antiinflamasi, antiplatelet, antioksidan, antiatherosklerosis, antihiperlipi-demia, antimalaria, antidiabetes, kardioprotektif, dan antikanker. Sukun mengandung senyawa terpenoid, flavonoid, alkaloid, dan senyawa fenolik. Senyawa khas dari tumbuhan genus Artocarpus ini adalah flavonoid dengan gugus geranil atau prenil, misalnya sikloartenol, artonin V, dan siklomulberin. Senyawa tersebut tersebar dalam daun, kulit kayu, batang, dan buah. Data terkait profil toksikologi sukun masih terbatas. Ekstrak etanol daun sukun tidak menunjukkan efek toksik pada hewan uji. Namun, ekstrak airnya belum memiliki profil toksikologi yang jelas sehingga perlu dilakukan pengujian untuk memastikan keamanannya. Kata kunci: Artocarpus communis, bioaktivitas, kandungan kimia, etnofarmakologi
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Chemical investigation of the dichloromethane extract of the leaves of Artocarpus altilis yielded β-sitosterol (1), unsaturated triglycerides (2), squalene (3), polyprenol (4), lutein (5) and unsaturated fatty acids. The structures of 1-5 were identified by comparison of their 1H and/or 13C NMR data with those reported in the literature. Chemical investigation of the dichloromethane extract of Artocarpus odoratissimus afforded 1, 2, and unsaturated fatty acids from the flesh of the fruit and seeds; and 1, unsaturated fatty acids and hydrocarbons from the fruit rind.
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This study was designed to elucidate the acute toxicity of Artocarpus altilis leaf and bark extracts. In acute toxicity study, no mortality or any toxic reaction was recorded in any group after 14 days of administering the extracts (2000 mg Kg(-1) BW). The extracts (ALA, ABA, ALM, and ABM) did not cause any behavioural or physical changes in experimental rats. There was no significant (P ≤ 0.05) difference in the biochemical parameters analysed between the groups. Slight elevation in activities of AST and ALT in extract treated groups was observed, but this did not exert any deleterious effect on the normal metabolism which was supported by the histopathology of liver. Histopathological studies showed no remarkable changes after 14 days of oral administration of ALA, ABA, ALM, and ABM extracts. The study contributes to establishing the nontoxic quality parameters of Artocarpus altilis leaf and bark parts and the results suggest the safety of the extracts in therapeutic uses.
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The Food and Agriculture Organization recently reported that the number undernourished people has reached a record high of 1.02 billion, most prevalent in the tropics. Breadfruit, Artocarpus altilis (Parkinson) Fosberg, is an underutilized Oceanic staple crop long recognized for its potential to alleviate hunger in tropical climates. Breadfruit can be grown sustainably with minimal agricultural inputs and can be multicropped with high value cash crops such as coffee, pepper, or vanilla. A great diversity of cultivars with varying nutritional and agronomic characteristics exists, yet few cultivars are widely cultivated. Recent developments in micropropagation have made possible large scale propagation and dissemination but to fully utilize this resource, a deeper understanding of the nutritional characteristics, and the development of new products and markets are needed. This review will highlight and describe the state of our current knowledge and the potential for breadfruit as a sustainable crop to provide new foods for Western markets and food security for the growing global population.
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Human pancreatic cancer cell lines have remarkable tolerance to nutrition starvation, which enables them to survive under a tumor microenvironment. The search for agents that preferentially inhibit the survival of cancer cells under low nutrient conditions is a novel antiausterity strategy in anticancer drug discovery. In this study, the methanolic extract of the leaves of Artocarpus altilis showed 100 % preferential cytotoxicity against PANC-1 human pancreatic cancer cells under nutrient-deprived conditions at a concentration of 50 µg/mL. Further investigation of this extract led to the isolation of eight new geranylated dihydrochalcones named sakenins A-H (1-8) together with four known compounds (9-12). Among them, sakenins F (6) and H (8) were identified as potent preferentially cytotoxic candidates with PC50 values of 8.0 µM and 11.1 µM, respectively.
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The activation of nuclear factor kappa B (NF-κB) plays a major role in the pathogenesis of a number of inflammatory diseases. In this study, we investigated the anti-inflammatory mechanism of Gelam honey in inflammation induced rats via NF-κB signalling pathway. Rats paw edema was induced by subplantar injection of 1% carrageenan into the right hind paw. Rats were pre-treated with Gelam honey at different doses (1 or 2 g/kg, p.o.) and NSAID Indomethacin (10 mg/kg, p.o.), in two time points (1 and 7 days). Our results showed that Gelam honey at both concentrations suppressed the gene expressions of NF-κB (p65 & p50) and IκBα in inflamed rats paw tissues. In addition, Gelam honey inhibited the nuclear translocation and activation of NF-κB and decreased the cytosolic degradation of IκBα dose dependently in inflamed rats paw tissues. The immunohistochemical expressions of pro-inflammatory mediators COX-2 and TNF-α were also decreased in inflamed rats paw tissues when treated with Gelam honey. The results of our findings suggest that Gelam honey exhibits its inhibitory effects by attenuating NF-κB translocation to the nucleus and inhibiting IκBα degradation, with subsequent decrease of inflammatory mediators COX-2 and TNF-α.
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A study was carried out on to assess the effect of fermentation on proximate composition of Artocarpus altilis pulp flour with the aim of expanding its use. Flours of unfermented and fermented A. altilis pulp were produced and standard procedures used to determine their proximate and mineral composition. Fermentation resulted in marginal increase in crude protein (from 3.80-4.43%) and ash (from 2.37-2.38%) content whereas, there was a marginal decrease in crude fibre (from 3.12-3.00%) and carbohydrate (from 79.24-76.71%) content. Fermentation resulted in significant decrease in calcium, iron, potassium, sodium and phosphorus contents of A. altilis flour. However, magnesium content was not affected by fermentation. This study shows that A. altilis pulp flour has good carbohydrate and mineral content and may therefore, be used as staples, to provide the energy and mineral needs of consumers. They would be useful in ensuring food security if promoted.
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Nature Rev. Drug Discovery 3, 879–890 (2003) Figure 3 of this review was inaccurately depicted. The sulphonamide groups in celecoxib and valdecoxib and the trifluromethyl group in celecoxib are now accurately depicted. An omitted chlorine group in etoricoxib is also now included.
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Artocarpus altilis (Parkinson) Fosberg has traditionally been used in Indonesia for the treatment of liver cirrhosis, hypertension, and diabetes. In many other countries, it is used for the treatment of malaria, yellow fever, and dengue fever. It has been reported that A. altilis extracts have antiatherosclerotic and cytoprotective effects, but its molecular targets in tumor cells are not yet fully understood. The A. altilis extracts and the partially purified fraction have been shown to inhibit STAT3 activity and the phosphorylation of STAT3 in a dose-dependent manner. To identify the active components, a bioassay-guided isolation of the partially purified fraction resulted in the identification of a geranyl dihydrochalcone, CG901. Its chemical structure was established on the basis of spectroscopic evidence and comparison with published data. The partially purified fraction and the isolated a geranyl dihydrochalcone, CG901, down-regulated the expression of STAT3 target genes, induced apoptosis in DU145 prostate cancer cells via caspase-3 and PARP degradation, and inhibited tumor growth in human prostate tumor (DU145) xenograft initiation model. These results suggest that A. altilis could be a good natural source and that the isolated compound will be a potential lead molecule for developing novel therapeutics against STAT3-related diseases, including cancer and inflammation. Copyright © 2015 John Wiley & Sons, Ltd.
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Carrageenin, from the Irish word “carraigin” meaning Irish moss, refers not only to a species of red alga Chondrus crispus found along rocky areas of the Atlantic coast of the British Isles, Europe, and North America, but also refers to its mucopolysaccharide extract, discovered by the British pharmacist Stanford in 1862. The name was later changed to carrageenan so as to comply with the “−an” suffix for polysaccharides. Structurally, the carrageenans are a complex group of polysaccharides made up of repeating galactose-related monomers and are of three main types; lambda, kappa, and iota ( see Chapter 33, Note 1). Each has their own gel characteristics which are all thermally reversible. The lambda form does not gel strongly at room temperature and is injectable to induce an inflammatory response. Inflammation induced by carrageenan, originally described by Winter ( 1), is acute, nonimmune, well-researched, and highly reproducible. Cardinal signs of inflammation—edema, hyperalgesia, and erythema—develop immediately following subcutaneous injection, resulting from action of proinflammatory agents—bradykinin, histamine, tachykinins, complement and reactive oxygen, and nitrogen species. Such agents can be generated in situ at the site of insult or by infiltrating cells. Neutrophils readily migrate to sites of inflammation and can generate proinflammatory reactive oxygen and other species. The inflammatory response is usually quantified by increase in paw size (edema) which is maximal around 5 h postcarrageenan injection ( see Fig. 1) and is modulated by inhibitors of specific molecules within the inflammatory cascade. Fig. 1. Inflammatory response post-carrageenan injection.