Pharmacology and Clinical Pharmacy Research ISSN:2527-7322 | e-ISSN: 2614-0020

Volume 4 No. 1 April 2019 doi: 10.15416/pcpr.v4i1.21397

Anti-Inflammatory Activity of Artocarpus altilis (Parkinson) Fosberg

in Wistar Male Rats

Hesti Riasari, Sani Nurlaela, Ginanjar C. Gumilang

Indonesia School of Pharmacy, Bandung, West Java, Indonesia

Abstract

Inflammation is a local reaction in vascular tissue characterized by several symptoms,

e.g., swelling, redness, and pain. Indonesia is one of the countries with high biodiversity,
including traditional medicinal plants. Artocarpus altilis is one the plants that is widely
used to treat inflammation. There is limited information on biological activity of A. altilis.
This study was performed to evaluate anti-inflammatory properties of A. altilis detached
and attached leaves in Wistar male rats. A. altilis was extracted using soxhlet method at
67.4 0C with methanol solvent. Inflammation was induced by the administration of car-
rageenan to the rats paw. Subsequently, the extract of A. altilis were orally administered.
The edema were measured using plethysmometer for 6 hours. We found that there were
differences in anti-inflammatory activity between detached and attached leaves. The in-
hibition of edema in attached leaves were 50% and 53.33% for the concentration of 50
mg and 100 mg, respectively. The greater inhibiton was observed in the detached leaves,
with 73.33% and 76.67% inhibition, for the concentration of 50 mg and 100 mg, respec-
tively. Nevertheless, the inhibition percentage was still below diclofenac sodium as a
positive control (83.33%). In conclusion, A. altilis leaves extracts showed good anti-in-
flammatory properties and has the potential for development of anti-inflammatory drug.

Keywords: Artocarpus altilis, carageenan, inflammation, edema

Introduction
Inflammation is a local response to celullar The increasing use of herbal medicine and
injury, characterized by capilary dilatation, phytonutrients has been observed during
swelling, redness, and pain. The treatment the last decade. The use of medicinal plant
includes the administration of anti- is preferred by many individuals since it
inflammatory drugs. Nevertheless, many may have fewer side effects compared to the
side effects were associated with the use of conventional treatment. It is estimated that
these drugs, such as gastrointestinal ulcer, up to four billion people worldwide rely on
bleeding, kidney failure, etc.1-3 herbal medicinal products.4,5

Corresponding author: Hesti Riasari. Indonesia School of Pharmacy, Bandung, West Java, Indonesia. Email: hmm_riasari@
yahoo.com
Received: 13 March 2019. Revised:6 April 2019. Published: 25 April 2019.

22
 Pharmacology and Clinical Pharmacy Research ISSN:2527-7322 | e-ISSN: 2614-0020
Volume 4 No. 1 April 2019

Table 1. Characteristics of A. Altilis Leaves

Leaves Ash (%) Water Soluble Compounds (%) Ethanol Soluble Compounds (%)
Attached 26.00 32.94 8.92
Detached 27.36 35.94 12.44

Indonesia is one of the country with highest Tools

biodiversity, including traditional medicinal The tools used in this study included
plants.6 A. altilis is one of the Indonesian rotary evaporator, waterbath, soxhlet,
traditional medicinal plants that is used to treat petri dish, volumetric pipette, erlenmeyer
inflammation. Previous study showed that flask, measuring cup, syringe, stirring
detached and attached leaves had significant rod, plethysmometer, analytical balance,
differences in defence response.7 Two types porcelain dishes, oven, desiccators, wood
of leaves might have different metabolites clamps, tube racks, drip plates, spatulas, and
which can influence its biological activities. spirits burners
Nevertheless, there is limited information on
biological activity of the variety of A. altilis Preparation and extraction
leaves. This study was performed to evaluate Plant determinantion was conducted at
anti-inflammatory properties of A. altilis in the herbarium of School of Life Sciences,
Wistar male rats. Bandung Institute of Technology. A. altilis
leaves were cleaned, chopped and dried.
Methods Phytochemical screening was performed
Materials to determine the content of secondary
The materials used in this study included the metabolites, such as alkaloids, flavonoids,
leaves of A. altilis (Park.) Fosberg which were tannins, phenolics, triterpenoids, steroids,
obtained from the Cipamokolan, Bandung, quinones, monoterpenes, sesquiterpenes,
West Java, Indonesia, methanol, distilled and saponins. Determination of ash content,
water, carrageenan, diclofenac sodium, and water and ethanol soluble compunds were
several phytochemical screening reagents, also performed. The leaves were extracted
e.g., ammonia, chloroform, hydrochloride, using soxhlet method with methanol solvent
gelatin solution, amyl alcohol, ether, vanilla, at 64.7 0C. Each filtrate was separated and
H2SO4p, KOH, Mayer, Dragendorff and evaporated using a rotary evaporator at 45 0C.
Lieberman-Burchard reagent.

Table 2. Phytochemical Screening of A. Altilis Leaves

Metabolites Attached Leaves Detached Leaves
Alkaloid - -
Flavonoid + +
Tannin + +
Phenolic + +
Monoterpene, sesquiterpene + +
Steroid + +
Triterpenoides - -
Quinone + +
Saponin - -

23
 Pharmacology and Clinical Pharmacy Research ISSN:2527-7322 | e-ISSN: 2614-0020
Volume 4 No. 1 April 2019

Table 3. Average of Edema Volume

Group V0 t1 t2 t3 t4 t5 t6
Negative control 0.035 0.051 0.061 0.061 0.063 0.065 0.065
Positive control 0.026 0.031 0.033 0.037 0.037 0.035 0.031
Attached 50 mg 0.028 0.035 0.04 0.043 0.043 0.043 0.043
Attached 100 mg 0.028 0.042 0.042 0.042 0.042 0.042 0.042
Detached 100 mg 0.025 0.032 0.033 0.033 0.035 0.035 0.032
Detached 50 mg 0.025 0.033 0.037 0.037 0.037 0.038 0.033

Anti-inflammatory activity assay (Parkinson) Fosberg. The yield of extracts

Experimental animals used in this study were were 11.12% and 13.05% for attached and
Wistar strain male rats (180-250 g). Male detached leaves, respectively. Methanol was
rats were selected to avoid the influence of selected as the solvent since it has better
hormonal change in inflammatory responses. polarity compared to other solvents. The
The animals were acclimatized for two temperature used in the extraction process
weeks before the experiment. The animals was based on the boiling point of the solvent.
were classified into 6 groups, each group The percentage of ash contents and water
consisting of 3 rats, i.e., negative control, soluble compounds of both types of leaves
positive control, and 4 treatment group with were relatively similar. However, the ethanol
different doses. The negative control group soluble compounds was higher in detached
was given 3 ml/200 g body weight 2% PGA leaves (12.44%) compared to attached
suspension orally, while the positive control leaves (8.92%). The results can be seen in
group was given 0.9 mg/ 200 g body weight the Table 1. Determination of ash content
diclofenac sodium orally. The experimental was conducted to determine the mineral
doses were 50mg/kg and and 100mg/kg and metal content from the initial process
body weight, for both detached and attached to the formation of extracts. Phytochemical
leaves. Inflammation was induced by screening showed that both types of leaves
administering carrageenan on rats paw. The contained flavonoids, tannins, phenolics,
volume of edema was measured, before and monoterpenes, sesquiterpenes, steroids, and
after the treatment. quinones (Table 2).

Results and Discussion The anti-inflammatory activity assay showed

The results of plant determination showed that there was a decrease in the volume of
that the plants used in this study was A. altilis edema in all groups, except negative control.

Table 4. Percentage of the Inhibition of Inflammation

Group V0 (%) T 1 (%) t 2 (%) t 3 (%) t 4 (%) t 5 (%) t 6 (%)
Negative control 0.00 0.00 0.00 0.00 0.00 0.00 0.00
Positive control 0.00 68.75 73.08 57.69 60.71 70.00 83.33
Attached 50 mg 0.00 56.25 53.85 42.31 46.43 50.00 50.00
Attached 100 mg 0.00 12.50 46.15 46.15 50.00 53.33 53.33
Detached 100 mg 0.00 12.50 69.23 69.23 64.29 66.67 76.67
Detached 50 mg 0.00 50.00 53.85 53.85 57.14 56.67 73.33

24
 Pharmacology and Clinical Pharmacy Research ISSN:2527-7322 | e-ISSN: 2614-0020
Volume 4 No. 1 April 2019

90.00%

80.00%

70.00%

60.00%
control
kontrol
50.00%
diclofenac
pembanding sodium
attached nempel
kuning 50 mg 50
40.00% attached nempel
kuning 100 mg 100
detachedjatuh
kuning 100 mg100
30.00% detachedjatuh
kuning 50 mg50

20.00%

10.00%

0.00%
V0 t1 t2 t3 t4 t5 t6

Figure 1. Percentage of Inflammation Over Observed Time

The smaller the average volume of edema, Conclusion

the better the anti-inflammatory effect of this A. altilis leaves extracts showed good anti-
particular compound. The largest inhibition inflammatory properties and has the potential
of inflammation was observed in positive for development of anti-inflammatory drug.
control group with 83.33% reduction of
edema. There were differences in anti- Acknowledgements
inflammatory activity between detached and None declared.
attached leaves. The inhibition of edema
in attached leaves were 50% and 53.33% Funding
for the concentration of 50 mg and 100 None.
mg, respectively. The greater inhibiton was
observed in the detached leaves, with 73.33% Conflict of Interest
and 76.67% inhibition, for the concentration None declared.
of 50 mg and 100 mg, respectively. Among
the treatment group, the extract of detached References
leaves 100 mg showed the best anti- 1. Chen L, Deng H, Cui H, et al. Inflammatory
inflammatory activity. Nevertheless, the responses and inflammation-associated
percentage of the reduction was still higher diseases in organs. Oncotarget.
than that of diclofenac sodium. 2017;9(6):7204–7218.
2. Martino JV, Van Limbergen J,
Differences in anti-inflammatory activity Cahill LE. The role of carrageenan
between detached and attached leaves might and carboxymethylcellulose in the
be due to differences in ethanol soluble development of intestinal inflammation.
compounds. Previous study showed that Frontiers in Pediatrics. 2017;5:96.
phenolic compounds might be responsible 3. Okin D, Medzhitov R. Evolution of
for anti-inflammatory activity of A. altilis inflammatory diseases. Current Biology.
plants. Further study is needed to confirm 2012;22(17):R733–R740.
and elucidate the structure of the active anti- 4. Welz AN, Emberger-Klein A, Menrad K.
inflammatory compound in A. altilis.8-13 Why people use herbal medicine: insights

25
 Pharmacology and Clinical Pharmacy Research ISSN:2527-7322 | e-ISSN: 2614-0020
Volume 4 No. 1 April 2019

from a focus-group study in Germany. Science. 2016;17(8):1199.

BMC Complementary and Alternative 12. Lan WC, Tzeng CW, Lin CC. Prenylated
Medicine. 2018;18(1):92. flavonoids from Artocarpus altilis:
5. Yin SY, Wei WC, Jian FY, et al. Antioxidant activities and inhibitory
Therapeutic applications of herbal effects on melanin production.
medicines for cancer patients. Evidence Phytochemistry. 2013;89:78–88.
Based in Complementary and Alternative 13. Tiraravesit N, Yakaew S, Rukchay R, et
Medicine. 2013;2013:302426. al. Artocarpus altilis heartwood extract
6. Sairam S, Urooj A. Safety evaluation of protects skin against UVB in vitro and
Artocarpus altilis as pharmaceutical agent in vivo. Journal of Ethnopharmacology.
in Wistar rats. Journal of Toxicology. 2015;175:153–162.
2014;2014:980404.
7. Liu G, Kennedy R, Greenshields DL, et
al. Detached and attached arabidopsis
leaf assays reveal distinctive defense
responses against hemibiotrophic
Colletotrichum spp. Molecular Plant
Interaction. 2007;20:1308–1319.
8. Nwokocha CR, Owu DU, McLaren M,
et al. Possible mechanisms of action
of the aqueous extract of Artocarpus
altilis (breadfruit) leaves in producing
hypotension in normotensive sprague-
dawley rats. Pharmaceutical Biology.
2012;50(9):1096-1102.
9. Riasari H, Sukrasno S, Ruslan H.
Metabolite profile of various development
bread fruit leaves (Artocarpus altilis.
Parkinson. Fosberg) and the identification
of their major componens. International
Journal of Pharmaceutical Sciences and
Research. 2015;6(5):2170-2177.
10. Turi CE, Liu Y, Ragone D. Breadfruit
(Artocarpus altilis and hybrids): A
traditional crop with the potential to
prevent hunger and mitigate diabetes in
Oceania. Trends in Food Science and
Technology. 2015;45:264–272.
11. Yao X, Wu D, Dong N, et al. Moracin
C, A Phenolic compound isolated
from Artocarpus heterophyllus,
suppresses lipopolysaccharide-activated
inflammatory responses in murine.
International Journal of Molecular

26