Anti-hyperuricemia Effect of Water Fraction Cinnamon

(Cinnamomum burmannii (Ness & T. Ness) Blume) on White Male

Rats

Dwitiyanti

, Ema Dewanti, and Rizky Arcinthya Rachmania

Faculty of Pharmacy and Science, Universitas Muhammadiyah Prof. DR. HAMKA,

Islamic Center, Jl. Delima II/IV Perumnas Klender, Jakarta Timur

Keywords: Hyperuricemia, Cinnamon, potassium oxonate

Abstract: Hyperuricemia is a condition of increased concentration of uric acid in the blood. Cinnamon bark

(Cinnamomum burmannii (Ness & T. Ness) Blume) has been used empirically to decrease uric acid levels.

This research is to determine the effect of water fraction from cinnamon bark as anti-hyperuricemia. For

being in hyperuricemia condition, the rats were provided with high-purine food and potassium oxonate

50mg/200gBW as an uricase inhibitor. As many as 4,108 mg dose/200gBW of Allopurinol was used as a

comparison for positive control. The dose of cinnamon bark used was 104 mg/200g BW for the first group,

208 mg/200g BB for the second group and 416 mg/200gBW for the third group. The result shows that the

second group can lower uric acid level (58,87%) and has a similar result with the positive group (P>0.05). It

concludes that the water fraction of cinnamon bark has antihyperuricemia effect.

1 INTRODUCTION

Uric acid is the final product formed from purine

compounds (adenine and guanine), produced in

tissues containing xanthine oxidase enzymes

especially in the liver and small intestine. Under

normal circumstances, uric acid may be excreted

through the kidneys. But if the synthesis of uric acid

is too much or its excretion through the kidneys is

too small, then the levels in the blood will increase.

The crystalline crystals that are difficult to dissolve

in all body fluids settle in the joints and tissues and

cause inflammation. Deposition of urate crystals

may also occur in the kidney and will eventually

damage the organ (Murray, et al. 2005).

Uric acid disease is commonly experienced by

people today, and mostly suffered by the productive

age group, of 30-50 years old, which can decrease

work productivity. Pathophysiological condition

occurs increased when levels of uric acid in blood

has increased beyond the normal limit, which is

called hyperuricemia. In hyperuricemia there will be

an accumulation of uric acid crystals in the joints

causing inflammation and pain or pain known as

gout (Priyanto 2008).

The main factor that affect hyperuricemia

incidence is unhealthy diet of high protein,

especially of animal protein that contains a lot of

high purine, which results in hyperuricemia. Gout

disease is a state of human metabolic disorder

suffered by more than 2 billion in the world and can

attack men, women, old or young, even young

children (Kramer 2002 in Astuti 2011). Pirai or gout

is characterized by recurrent episodes of acute

arthritis due to precipitation of monosodium urate

crystals in joints and surrounding tissues (Katzung et

al. 2012). This disease usually occurs due to an

increase in uric acid levels in the blood up to normal

> 7 mg/dl in men and > 6 mg/dl in women (Dipiro et

al. 2005). Hyperuricemia may occur due to

excessive production of uric acid, reduced uric acid

expenditure, or a combination of both (Christian

2013).

Today's society believes that treatment by using

natural ingredients is a natural way in the treatment

of gout (Kamalia 2010). In general, to overcome

hyperuricemia disease, synthetic drugs such as

allopurinol have been used, but allopurinol can

cause side effects such as skin, stomach, intestine

and blood disorders. To overcome this, alternative

102

Dwitiyanti, ., Dewanti, E. and Rachmania, R.

Anti-hyperuricemia Effect of Water Fraction Cinnamon (Cinnamomum burmannii (Ness T. Ness) Blume) on White Male Rats.

DOI: 10.5220/0008240101020106

In Proceedings of the 1st Muhammadiyah International Conference on Health and Pharmaceutical Development (MICH-PhD 2018), pages 102-106

ISBN: 978-989-758-349-0

medicine using medicinal plants are developed such

as cinnamon bark (Private and Ernawati 2010).

Cinnamon is one of the many spices found in

Indonesia and has been used since the past as

cooking herbs and traditional herbs (Gunawan

2011). The chemical content of cinnamon bark

includes essential oils, tannins, saponins and

polyphenols (Depkes 2008). According to Astawan

(2011) in Tuiyo et al. (2013), compounds with high

polyphenol content have high antioxidant activity as

well, to inhibit xanthine oxidase enzyme. Xanthine

oxidase enzyme serves to catalyze the changes of

purine into uric acid. By inhibiting the xanthine

oxidase enzyme, the formation of uric acid will be

hampered as well.

2 MATERIALS AND METHODS

The plant material used is cinnamon bark

(Cinnamomum burmannii (Ness & T. Ness) Blume)

obtained from BALITRO Bogor, West Java. The

chemicals used are 96% Ethanol, water, potassium

oxonate, chicken liver juice, allopurinol, and

TBHBA uric acid kit reagent. The test animals in

this study were Sprague Dawley male, white rats

weighing between 200-300 grams and about three

months old. The tool used is Spuit 1 cc, oral sonde

for rats, mouse scales, clinical spectrophotometers,

and glass tools commonly used in chemical

laboratories.

2.1 Determination of Plants

Cinnamon bark is detected in Herbarium

Bogoriense, Balitbang Botany-Puslitbang Biologi

LIPI-Cibinong.

2.2 Extraction

Rough powder of cinnamon bark extracted with 96%

ethanol (3 x 24 hours) is macerated at room

temperature. The solvent is then evaporated with a

rotary evaporator at a temperature of 50 ° C to

obtain a viscous extract.

2.3 Fractination

The extract was fractionated with aquadest and n-

hexane (1: 1). The fraction of the obtained aquadest

is then fractionated with ethyl acetate (1: 1).

2.4 Phytochemical Screening

Phytochemical screening was performed on thick

and viscous extracts to determine the presence of

secondary metabolite compounds such as alkaloid

compounds, polyphenols, flavonoids, saponins,

tannins, quinones, and terpenoids.

2.5 Determination of Drying

Determination of weight loss on drying was carried

out on extracts and cinnamon bark fractions dried at

105

C for 30 minutes in the oven. Drying is done

until the weight is fixed. The bottle is left closed and

cools in the desiccator to room temperature.

Table 1: Treatment group of anti-hyperuricemia fraction of cinnamon water

Groups Day I II III IV V VI

Treatment Normal

Control

Positive

Control

Negative

Control

Dose I Dose II Dose III

Day 0 Rat Fasting, then the blood was taken to know the beginning of uric acid levels

Day 1-14 The rats were orally fed with high purine

9 Intra

eritoneal Induction of

otassium oxonate

Day 9 The blood was taken two hours after administering potassium oxonate

(to check the increase of uric acid levels in blood )

Day 10 - Administered

Allopurinol

Administered

Na CMC

0,5%

The

fraction of

cinnamon

bark dose I

The

fraction of

cinnamon

bark dose II

The

fraction of

cinnamon

bark dose

III

Day 14 Induction of potassium oxonate after administering of the fraction, blood sample was taken 2

hours after the last fraction was administered (to check the lowering of uric acid levels or

effect of the fraction of cinnamon bark

)

Anti-hyperuricemia Effect of Water Fraction Cinnamon (Cinnamomum burmannii (Ness T. Ness) Blume) on White Male Rats

103

2.6 Anti-Hyperuricemia Activity

Testing

Rats were divided into control groups and test

groups, each group consisting of 4 rats (Table 1).

3 RESULTS AND DISCUSSION

3.1 Determination of Simplicia

The bark of cinnamon is determined in Herbarium

Bogoriense, Balitbang Botany-Puslitbang Biologi

LIPI-Cibinong. The results of determination show

that the plants used are Cinnamon (Cinnamomum

burmannii (Ness & T. Ness) Blume).

3.2 Ethanol Extract of Cinnamon Bark

Cinnamon bark (2 kg) extracted with 96% ethanol (3

x 24 hours) yielded a thickened extract of 521.6 g

(yield of 26.08%). The viscous extract obtained is

dark brown, smells distinctive and tastes bitter.

3.3 Weight Loss on Drying

Weight loss on drying are carried out to determine

residual substances that evaporate at 105

C. Based

on the test it is known that drying drift contained in

ethanol extract 96% cinnamon bark is 5.28%, and in

cinnamon, bark fraction is 4.48%.

3.4 Water Fraction of Cinnamon Bark

The cinnamon bark extract 451 g was fractionated

with aquadest, n-hexane and ethyl acetate yielding

81.52 g of water fraction (yield of 18.07%).

3.5 Secondary Metabolites in The

Extract

The phytochemical screening showed that in the

cinnamon extract and fraction there were various

secondary metabolites, shown in Table 2.

3.6 Anti-Hyperuricemia Activity

Increased uric acid level was performed by giving

15 g/15ml dose of chicken liver juice 2 times a day,

but the provision of chicken liver juice did not

provide significant results, due to mammals with

lower levels, there are uricase enzymes that play a

role in the process of uric acid conversion to become

allantoin. Allantoin is more soluble in water and

more easily excreted by the body of the mammal

(Katzung et al. 2012). Therefore, it takes the

induction of potassium oxonate to help increase uric

acid levels in mice to be more significant. Potassium

oxonate is used as a competitive inhibitor of uricase

enzyme work so that uric acid in rat blood can

accumulate cause hyperuricemia condition, the dose

used is 50mg/200gBW through intraperitonial.

To find out the anti-hyperuricemia activity,

cinnamon bark water was extracted to decrease uric

acid level in mouse blood, a variation of the dose

given was 104 mg/200g BW, 208 mg/200g BW, and

416 mg/200g BW 2 times a day.

The results of uric acid levels (table 3) obtained

showed that on Day 9 there was a significant

increase with chicken liver juice and oxonate

potassium induction, and decreased on Day 14 after

administration of ethyl acetate fraction of cinnamon

bark.

The normal group is a reference for the

occurrence of uric acid level on the Day 9, which is

decreased on the Day 14 without any treatment. In

the positive control, there was an increase of uric

acid on the Day 9 after the induction of potassium

oxonate which was decreased on the Day 14 after

the administration of allopurinol with the dose of

4,108 mg/200 gBW for 5 days. In the negative

Table 2: Phytochemical screening of cinnamon extract and fraction

No Ph

tochemical screenin

Observation

(

colours

)

Extract of ethanol 96% Fraction of Eth

l Acetate

1 Alkaloi

Old brown + +

2 Flavonoi

3 Saponin Foam + +

4 Tanin Blac

5 Steroid dan ter

enoi

-- -

Information :

(+) = Exist, (-) = no

MICH-PhD 2018 - 1st Muhammadiyah International Conference on Health and Pharmaceutical Development

104

group, there was also an increase of uric acid on the

Day 9 after the induction of potassium oxonate

which then decreased on the Day 14 after the

administration of Na CMC 0.5% for 5 days. In the

dose groups, there were increases of uric acid level

on the Day 9 after the induction of potassium

oxonate and then decreased on the day 14 after the

administration of all the dose fractions (I, II, III) for

5 days.

The highest percentage belonged to the positive

control that is Allopurinol with percentage of

62,77%. Second activity belonged to the group of

dose II with percentage equal to 58,87%. Third

activity belonged to dose I with the percentage equal

to 35,40%, followed by group Dose III with the

percentage of 17.70% (figure 1).

Table 3: Uric acid levels in rats

Time Grou

(

Normal Ne

ative Positive Dose I Dose II Dose III

0 3.30 3.46 3.36 3.25 3.29 3.17

3.03 3.21 3.23 3.12 3.16 3.21

3.12 3.50 3.49 3.07 3.12 3.47

3.21 3.11 3.09 3.32 3.21 3.24

Avera

e 3.16 3.32 3.29 3.19 3.19 3.27

Deviation

(SD)

0.10 0.16 0.15 0.10 0.06 0.12

9 3.28 8.16 8.24 8.42 8.26 8.21

3.19 8.27 8.31 8.17 8.16 8.06

3.42 8.38 8.42 8.09 8.31 8.31

3.36 8.24 8.26 7.96 8.14 7.94

Average 3.31 8.26 8.16 8.16 8.22 8.13

Deviation

(SD)

0.09 0.08 0.07 0.17 0.07 0.14

14 3.46 8.15 5.12 7.41 5.21 6.58

3.17 8.20 5.08 7.26 5.17 6.75

3.24 8.08 5.16 7.32 5.43 6.09

3.28 8.01 5.29 7.13 5.24 6.23

Avera

e 3.60 8.13 5.16 7.28 5.26 6.41

Deviation

(

)

0.11 0.07 0.08 0.10 0.10 0.26

Information :

Group I : normal control (no treatment)

Group II : positive control (allopurinol 4,108 mg/200 g BW)

Group III : negative control (Na CMC 0,5%)

Group IV : dose I (104 mg/200 gBW)

Group V : dose II (208 mg/200 gBW)

Group VI : dose III (416 mg/200 gBW)

Figure 2: The lowering of uric acid levels

Figure 1: Percentage of uric acid levels. Positive control

(allopurinol 4,108 mg/200 gBW). Dose I (Fraction of

cinnamon bark water 108 mg/200 gBW). Dose II (Fraction

of cinnamon bark water 204 mg/200 gBW). Dose III

(Fraction of cinnamon bark water 416 mg/200 gBW)

62.77%

35.40%

58.87%

17.70%

0.00%

10.00%

20.00%

30.00%

40.00%

50.00%

60.00%

70.00%

positive

control

dose III dose II dose I

Anti-hyperuricemia Effect of Water Fraction Cinnamon (Cinnamomum burmannii (Ness T. Ness) Blume) on White Male Rats

105

Data on the average decrease in uric acid levels

obtained from each group (Table 3) showed that

allopurinol could decrease uric acid levels by

62.77% (Figure 2). The activity approaching

allopurinol is owned by the dose group II which has

a percentage of 58.87%. In this case, it can be seen

that doses I, II and III have the ability to decrease

uric acid levels in the blood of white male rats, but

dose II can lower uric acid levels to near normal,

although not equivalent to allopurinol

and normal

controls. This is probably due to the concentration of

nutritious compounds contained in the bark of

cinnamon varies, and the timing of the fraction is too

short.

The data of uric acid levels (table 3) obtained

then tested with normality and homogeneity test.

Normality test using Kolmogorov Smirnov Test

showed that normal distributed data with

significance value 0,419 (p ≥ 0,05) data is said to be

normally distributed because having significance

value more than 0,05. While the homogeneity test

results showed a significance value of 0.114 (p≥

0.05) so that the data can be said to be

homogeneous. Further data were analyzed using

one-way variance analysis to know that the data

obtained had significant differences between groups

with days of each treatment.

The uric acid level data was continued with the

Tukey test to determine the significant differences in

each group. From the Tukey test it was found that

there was a significant difference between the dose I

test group and all groups, as well as on the dose III

test. However, in the dose II test group (204 mg/200

gBW) there was no significant difference with the

positive group (allopurinol 4.108 mg/200 gBW)

which means that the dose II had an anti-

hyperuricemia activity not much different from the

positive control group Phytochemical screening tests

show that cinnamon bark contains alkaloids,

flavonoids, saponins and tannins.

4 CONCLUSIONS

Based on the results of the study it can be concluded

that cinnamon bark fraction has activity with dose II

(204 mg/200gBW) as the most effective,

successfully decreasing uric acid level in rat blood

by a percentage equal to 58,87%. Normality test

using Kolmogorov Smirnov Test showed that the

data was normally distributed with significance

value of 0.419 (p ≥ 0,05), and the homogeneity test

showed significance value of 0,114 (p≥ 0,05) which

indicates that the data can be classifield as

homogeneous.

ACKNOWLEDGEMENTS

Authors would like to thank Lembaga Penelitian

dan Pengembangan University Of

Muhammadiyah Prof. Dr. Hamka (UHAMKA)

for supporting this research.

REFERENCES

Astuti, D. 2011. Efek Anti-hyperuricemia Kombinasi

Ekstrak Air Kelopak Rosella (Hibiscus sabdariffa L)

dan Akar Tanaman Akar Kucing (Acalypha indica L)

Pada Tikus Putih Jantan yang Diinduksi Kalium

Oksonat. Skripsi. Universitas Indonesia.

Departemen Kesehatan Republik Indonesia. 2008.

Farmakope Herbal Indonesia, Edisi 1. Jakarta. Hlm. 41

Gunawan, ES. 2011. Pengaruh Pemberian Ekstrak Kayu

Manis (Cinnamomum burmannii) Terhadap Gambaran

Mikroskopis Hepar, Kadar SGOT dan SGPT Darah

Mencit BALB/C yang Diinduksi Paracetamol.

Universitas Dipenogoro. Semarang.

Kamalia, L. 2010. Efektivitas fraksi etanol daun kembang

sungsang (Gloriosa superba L.). Skripsi. Universitas

Muhammadiyah Prof. Dr. Hamka. Jakarta.

Katzung, B.G., Masters, S.B. & Trevor, A.J. 2012. Basic

& Clinical Pharmacology, 12 Ed., New York:

McGraw-Hill.

Kristiani, Risa D. 2013. Pengujian Aktivitas Anti-

hyperuricemia Ekstrak Etanol Akar Pakis Tangkur

(Polypodium feei) Pada Mencit Jantan. Skripsi.

Fakultas Farmasi Universitas Padjajaran, Jatinangor.

Murray, RK, Granner DK, Mayes PA, Rodwell VW. 2005.

Biokimia Harper, Edisi 25. Terjemahan dari harper

biochemistry oleh andy hartanto. Buku Kedokteran

EGC, Jakarta.

Pribadi, FW dan Ernawati, DA. 2010. Efek Catechin

Terhadap Kadar Asam Urat, C–Reactive

Protein (CRP) dan Malondialdehid Darah Tikus Putih

(Rattus norvegicus) Hiperurisemia. Jurnal

Mandala of Health, Vol 4 No. 1. Universitas Jendral

Soedirman. Purwokerto.

Priyanto. 2008. Farmakologi Dasar. Lilian Batubara (eds).

Leskonfi. Jakarta.

Tuiyo KI, Hamsidar Hasan dan Moh Adam M. 2013. Uji

Efek Ekstrak Etanol Kayu Manis (Cinnamomum

burmannii) Terhadap Tikus Putih Jantan (Rattus

norvegicus). Jurnal Skripsi. UNG. Gorontalo.

MICH-PhD 2018 - 1st Muhammadiyah International Conference on Health and Pharmaceutical Development

106