The Effect of Ginger (Zingiber Officinale Roscoe) Fractionation in

Decreasing Uric Acid Level of Hyperuricemic White Mice

Tika Afriani

, Rizky Yulion

, Marlina Andriani

, Fahma Syufyani

, Darma Fadri

Department of Pharmacy, Mohammad Natsir University, Bukittinggi 26136, Indonesia

Medistra Health Institut, Lubuk Pakam, North Sumatera, Indonesia

Keywords: uric acid, ginger (Zingiber officinale Roscoe), fractionation, chicken liver, allopurinol

Abstract: This study aims to determine the effects of ginger fractionation on uric acid level of

hyperuricemic white mice. The study was conducted in 7 days using an in vivo experimental

method. Ginger was extracted with 70% ethanol and subsequently fractionated by using n-

hexane, ethyl acetate, and water residual solvents. The mice divided into six group treatments.

Doses used of the fraction n-hexane, ethyl acetate, and water residual were 100 mg/kg of body

weight and allopurinol as a standard was 10 mg/kg of body weight. The examination was carried

out on mice with hyperuricemic induced by fresh chicken liver juice 0.5 ml/20g of body weight

administered orally. The uric acid levels were measured by NESCO

Multi Check Digital tools.

The result of this study showed that ethyl acetate fraction doses 100 mg/kg of body weight are

the best fraction to lowering level of uric acid in blood serum.

1 INTRODUCTION

Gout is one of noncontagious disease that has high

prevalence in the world. Gout is considered to be

primarily a male disease, but there is a more equal

sex distribution among elderly patients (Pokhrel et

al., 2011). Based on World Health Organization

(WHO) survey, Indonesia is the largest state number

4 in the world whose population is suffering from

gout and uric acid disease is estimated to occur in

840 people of every 100,000 people. The prevalence

of uric acid disease in Indonesia occurs at age below

34 years old by 32% and above 34 years old by 68%

(WHO, 2015). In Indonesia, hyperuricemic attacking

people under 34 years old with prevalence 1.6-

13.6/100.000, and it is predicted keep increasing day

by day (Thayibah et al., 2018).

Gout is caused by increased levels of uric acid in

the blood (hyperuricemia) exceeding normal levels,

giving rise to needle-shaped uric acid crystals and

causing stiffness and inflammation in the joints.

Hyperuricemia is a condition where the kidneys fail

to excrete uric acid, resulting in high uric acid levels.

Hyperuricemia is a considered to be closely

associated with increased risk for developing gout,

cardiovascular diseases, hypertension, and metabolic

syndrome (Chen Yu-Chen et al., 2014)

High levels of uric acid are caused by the

deposition of monosodium crystals due to the

breakdown of purines or combination of both.

Normal uric acid levels in the blood range between

3.6 - 8.2 mg / dl in men and 2.3 - 6.1 mg / dl in

women. High level of uric acid serum caused by

disturbances metabolism of purine in the body,

heredity, lifestyle, and consume food containing

high purine, for example meat, shells and viscera

(Misnadiarly, 2017).

Everyone has uric acid in his body which in

normal metabolic condition used to produce uric

acid and the amount of uric acid must not exceed

normal. Uric acid provided by our body about 85

percent and it is mean that the body only needs

about 15 percent purine from food. If the body

consume high contain purine from food, it causing

gout disease and if can progress in to worse

condition into coronary heart disease because crystal

of uric acid in endhotelium can blocked blood

vessels. Therefore high uric acid levels should be

treated so that the impact does not fall in to worse

condition (Indriawan, 2010).

Afriani, T., Yulion, R., Andriani, M., Syufyani, F. and Fadri, D.

The Effect of Ginger (Zingiber Ofﬁcinale Roscoe) Fractionation in Decreasing Uric Acid Level of Hyperuricemic White Mice.

DOI: 10.5220/0009838404670474

In Proceedings of the International Conference on Health Informatics and Medical Application Technology (ICHIMAT 2019), pages 467-474

ISBN: 978-989-758-460-2

467

A variety of treatment techniques have been

used to treat gout, such as the use of Non-Steroidal

Anti-Inflammatory compounds (NSAIDs) and the

use of Xanthine Oxidase (XOD) inhibiting

compounds to reduce uric acid production.

Allopurinol is currently the most effective XOD

inhibitor, which is used for treating hyperuricemic

and gout by reducing circulating levels of uric acid

and vascular oxidative stress. However, serious side

effects include skin rashes and allergic reactions that

occur in some clinical patients (Chen Yu-Chen et al.,

2014). The emergence of side effects and various

deficiencies in modern medicine demands to find

drugs with the smallest possible side effects, one of

alternative to this situation is to use traditional

medicine.

Ginger is one of the herbs used for traditional

medicine in treating gout. Ginger (Zingiber

officinale Rosc) is a potential herbal plant according

to RISTOJA data in 2015 that is used by Indonesian

people for lowering of uric acid levels in the blood.

There are 178 plants used in the herb for

rheumatism/gout and ginger (Zingiber officinale

Rosc) is the most widely used herbal plant as a herb

to lower uric acid complaints in Indonesia. In

addition, ginger extract has also been done a

scientific search, get the result that ginger ethanol

extract (Zingiber officinale Rosc) can be potential as

anti hyperuricemia (Lallo, et al., 2018; Yulion, et al.,

2017) where the data supports this research.

Jolad et al. (2014) identified more than 60

compounds in fresh ginger grouped into two broader

categories; volatiles and non-volatiles. Volatile

compounds including sesquiterpene and mono

terpenoids hydrocarbons providing the distinct

aroma and taste of ginger and non-volatile

compounds include gingerols, shogaols, paradols

and zingerone.

Ginger contain secondary metabolite such as

phenolic compound, flavonoid which is can

lowering level of uric acid in the blood serum

(Andriani, 2018). The mechanism for lowering uric

acid levels is by inhibiting the conversion of

xanthine into uric acid. The level of uric acid can be

derived from excessive production or less excretion

through the kidney (Facchini, et al., 1991). This

study aims to determine the effect of ginger

fractionation (Zingiber officinale Rosc) for 7 days on

serum uric acid levels of mice induced by chicken

liver juice.

The absence of therapy that was found safe

and quick to patients with gout while patients with

gout is in reproductive age in productivity and

patients with gout is very big amount in Indonesia

that based on the above information then researchers

interested in doing research ginger (Z. officinale

Rosc) in lowering uric acid and in the form of

fractionate. From this research will be proven that

fractionation of ginger (Z. officinale Rosc) able to

lower the levels of uric acid in 7 day (

Lembaga Ilmu

Pengetahuan Indonesia, 2016).

The research was conducted to obtain activity

extract ethanol on antihiperurisemia in fractionate

with ethyl acetate, n-hexsan and fraction of water

from ginger (Zingiber officinale Rosc) using animal

testing male mice (Mus musculus) to be raised levels

uric acid first with induced chicken liver juice and to

compare positive impact with using allopurinol.

2 RESEARCH METHODOLOGY

Materials and Methods

The materials used in this study were chicken

liver juice, ethanol 70% (bratachem), ethyl acetate

(bratachem), n-hexsane (bratachem), aqua destilata

(bratachem), food standard Squeaky, allopurinol

(Kimia Farma), Na-CMC, Nesco

, and test strips

uric acid Nesco

Plant materials

Gingers (Z. officinale Rosc) were collected

from Sariak Laweh Sub-district of West Sumatra

province Agam Regency. This species was identified

by ANDA Herbarium Department of Biology

Faculty of Mathematics and Natural Sciences

University of Andalas.

Preparation of extracts

Ginger (Z. officinale Rosc) were washed well

to remove the dust and other foreign materials, dried

and grounded into tea size powder. The powder was

extracted by maceration with ethanol 70% for

overnight at room temperature. This process was

repeated two times with the same type and amount

of solvent. The extracts were combined and

evaporated by using rotary evaporator (Buchi

Rotavapor R-200) under reduce pressure to obtain

ethanol crude extract (Departemen Kesehatan,

2008).

Fractionation procedures

The ethanol crude extract from Z. officinale

Rosc was dissolved in distillated water. Then it was

extracted successively with different organic

ICHIMAT 2019 - International Conference on Health Informatics and Medical Application Technology

468

solvents which were hexane and ethyl acetate with

ratio 1:1 (v/v) in the separatory funnel. The funnel

was shaken for 2 minutes and left at room

temperature for 2 hours to settle down. The

procedure was repeated for several times to obtain

hexane, ethyl acetate, and residual water fractions.

All crude extracts were evaporated completely by

using rotary evaporator (Buchi Rotavapor R-200)

under reduce pressure to obtain dry crude extracts

(Arifin, Fahrefi, & Dharma, 2013; Ningdyah,

Alimuddin, & Jayuska, 2015; Parwata, Rita, &

Yoga, 2009; Tahir, Saleh, & Pasaribu, 2013).

Treatment of experimental animals and dosing

design

The mice were divided into six groups

containing seven animals in each with different

treatments on each group and given variation of

fraction with doses 100mg/kgBB in 7 days. A total

of 42 male mice with age 3-4 m and weighing 20-30

g were used for this study. The mice adapted for 7

days with the environment at constant temperature

before used as experimental objects. They were

given feed standard pellets and water during the

study. The mice were considered being healthy if the

difference of their weight before and after adaptation

less than 10% and indicates normal behavior

visually (Vogel, 2008).

Male mice were selected for this study based

on consideration that male mice are lack of estrogen.

This condition makes stress level of male mice

lesser than female mice, a factor that might

disruptive during the study period. And if they’ve

estrogen, the amount of this hormones exist only in

relatively few (Suhendi, Nurcahyanti, Muhtadi, &

Sutrisna, 2011).

Making inducers from chicken liver

Chicken liver juice used as inducers to make

hyperuricemic condition. The inducers given to mice

with oral using sonde with doses 25ml/kgBB

(Hayani dan Widyaningsih, 2011). Chicken liver is

one of food that have high contain of purine making

it suitable for hyperuricemic condition. Chicken

liver contain 150-1000 mg purine per 100g liver and

able to induce high uric acid levels.

Standard

Standard in this study using allopurinol, which is an

antigout drug. Allopurinol used as standard with

doses 10 mg/kgBB.

Antihyperuricemic activity

Preliminary study purpose to know the fraction that

has the best activity in lowering uric acid levels in

experimental animal blood. The mice were divided

into six groups containing seven animals in each

with different treatments on each group, as seen in

the following table:

Table 1. Group Treatments

No Group Treatment

Negative Control Administered orally solution

of Na-CMC 0.5%

Positive Control Induced by chicken liver

juice 0.5 ml/20g bw

Hyperuricemia +

ginger n-hexane

fraction

Induced by chicken liver

juice 0.5 ml/20g bw and n-

hexane fraction dose 100

mg/kg bw

Hyperuricemia +

ginger ethyl acetate

fraction

Induced by chicken liver

juice 0.5 ml/20g bw and

ethyl acetate fraction dose

100 mg/kg bw

Hyperuricemia +

remaining fraction of

ginger water

Induced by chicken liver

juice 0.5 ml/20g bw and

water residual fraction dose

100 mg/kg bw

Hyperuricemia +

allopurinol

Induced by chicken liver

juice 0.5 ml/20g bw and

allopurinol dose 10 mg/kg

At the early stage, all experimental animals are

conditioned to hyperuricemia except negative

control, using inducer chicken liver juice doses 0.5

mL/20g of body weight with oral administration of

Probe until the level of blood acidity increase. The

process of hyperuricemic condition carried out for

seven days. Fraction was given 1 hour after

induction process of hyperuricemic (Suhendi,

Nurcahyanti, Muhtadi, & Sutrisna, 2011) and then

uric acid levels measured everyday using NESCO

Multi Check Digital tools it done 2 hour after

fraction was given (Muhtadi, Suhendi, W., &

Sutrisna, 2013).

Statistical analysis

The statistically significant of difference was

calculated by the analysis of variance followed by

Duncan’s Multiple Range Test.

3 RESULTS AND DISCUSSION

A total of 600 grams of rhizomes have been dried,

refined and then extracted with ethanol 70%

producing a condensed extract of 160.5 grams. The

basic principle is to grind the plant material (dry or

wet) finer, which increases the surface area for

extraction thereby increasing the rate of extraction

The Effect of Ginger (Zingiber Ofﬁcinale Roscoe) Fractionation in Decreasing Uric Acid Level of Hyperuricemic White Mice

469

(Pandey and Tripathi, 2014). The pieces should not

be too big, otherwise the solvent will not be able to

penetrate the innermost cells. They also should not

be reduced to powder, that would result in losing the

volatile active ingredients contained inside the plant,

and also losing the difficult separation by filtration

of the plant material from the liquid used once

maceration is completed.

The solvent must be chosen based upon the

chemical nature of the compounds contained within

the plant. Since the end product will contain traces

of residual solvent, the solvent should be nontoxic

and should not interfere with the bioassay (Pandey

and Tripathi, 2014). Ethanol has been known as a

good solvent for polyphenol extraction and is safe

for human consumption (Quy Diem Do et al., 2014).

The reasons for the selection solvent consisting of

ethanol by 70% and water by 30% because ethanol

70% volatile, cheap, can afford and safe (Azis, et al.,

2014). The obtained yield was 26.75%. Results of

the result obtained, above the value stated in the

Indonesian Herbal Pharmacopeia is not less than

6.6% (Departemen Kesehatan, 2008).

Sample 600 grams dry extracted, with the

purpose to separate compounds based on their

relative solubilities in two different immiscible

liquids, usually water and an organic solvent

(Endarini, 2016). Extraction is the separation of

medicinally active portions of plant (and animal)

tissues from the inactive/inert components using

selective solvents through standard procedures.

During extraction, solvents diffuse into the solid

plant material and solubilize compounds with

similar polarity (Sruthi and Indira, 2016).

Technique extraction that used in research it is

technique maceration because this technique

relatively simple does not require an apparatus

complicated and can avoid all compound due to heat

components (Efendi, 2018). Maceration is an

extractive technique that is conducted at room

temperature. It consists of immersing a plant in a

liquid (water, oil, alcohol, etc.) inside an airtight

container, for a variable time based on the plant

material and liquid used. In maceration (for fluid

extract), whole or coarsely powdered plant-drug is

kept in contact with the solvent in a stoppered

container for a defined period with frequent agitation

until soluble matter is dissolved. At the end of the

process the solvent is drained off and the remaining

miscella is removed from the plant material through

pressing or centrifuging (Pandey and Tripathi, 2014;

Silva et al, 2017).

A total of 50 grams of condensed extracts of

ginger leaves are fractionated consecutively by using

polar, semi-polar, and nonpolar solvents. The

ethanol extract was fractionated with water and n-

hexane to obtain semi-polar fraction. The water

layer was fractionated with ethyl acetate solvent to

obtain semi-polar fraction of ethyl acetate and polar

water fraction. In principle, the polar solvents

dissolve polar solutes and nonpolar solvents dissolve

non polar solutes that are also called “like dissolve

like” (Harborne, 1987; Mariana, Andayani, &

Gunawan, 2013). The amount of viscous fraction

obtained is n-hexane 4.22 gram, ethyl acetate 5.51

gram, and water remaining 27.5 gram with a yield

percentage of 8.44%; 11.01% and 55% respectively.

Hyperuricemia is an elevated uric acid level

in the blood. This elevated level is the result of

increased production, decreased excretion of uric

acid, or a combination of both processes.

Hyperuricemia can lead to gout and nephrolithiasis

(George and Minter, 2019). Uric acid is formed

when purines break down in your body. Purines are

chemicals found in certain foods include all meats

but spesifically organ meats, game meats and some

seafood.

For hyperuricemic condition, the mice were

given chicken liver juice as inducers because

chicken liver contain high level of purine (≥300

mg/100 g). Chicken liver juice used as inducer of

uric acid with the dose is 0.5 mL/20g of body weight

for animal experiments until the level of uric acid

increase (Juwita et al., 2014).

Allopurinol used as standard in this study

because allopurinol is widely known as a synthetic

drug widely used for hyperuricemic. Allopurinol is

an alternative compound which used to increase uric

acid excretion through inhibition of the xanthine

oxidase enzyme and 80% is absorbed after oral

administration. Like uric acid, allopurinol itself is

metabolized by xanthine oxidase to allantoxanthine,

maintains the capacity to prevent xanthine oxidase

and has along enough effect duration so that the

treatment is sufficient once a day (Katzung, 2007).

This study using 42 male white mice with

average weight 20-30 grams and average age 3-4

months. The acclimatization procedurs was carried

out in 7 days so that the animals can adaptation with

the environment. The mice must be healthy, showing

normal behaviour and have shining clear eyes.

During maintenance mice were feed and drinking

enough (Malole, 1989).

After acclimation, treatments animals divided

into six groups with each groups consisting of seven

mice. Three groups animals given variation of types

fraction such as n-hexane, ethyl acetate, and residual

water with doses 100mg/kgBB in seven days as

testing groups. One group animals as negative

control which were not received any treatment, one

ICHIMAT 2019 - International Conference on Health Informatics and Medical Application Technology

470

group as positive control which were induced by

chicken liver juice 0.5 ml/20g bw, and one group

given chemical drugs allopurinol as standard.

Fraction was given 1 hour after induction process of

hyperuricemic, and then uric acid level measured

everyday using NESCO

Multi Check Digital tools

it done 2 hour after fraction was given.

Table 2. Effects of Zingiber officinale Rosc fractions on

level of uric acid serum in mice induced chicken liver

juice

Grou

p/day

1 2 3 4 5 6 7

Nega

tive

6,8

2,3

6,01

2,0

6,3

1,9

4,4

1,7

5,8

1,4

5,0

1,5

5,3

1,9

Positi

9,4

2,9

9,3 ±

2,8

9,2

2,6

7,4

3,9

6,5

3,3

7,4

2,8

7,1

2,0

Heks

6,9

2,2

6,5 ±

1,6

5,6

1,7

4,4

1,3

4,1

1,0

4,2

1,0

3,9

0,6

Ethyl

Aseta

5,7

2,1

5,3 ±

1,2

4,8

1,0

4,1

0,8

3,7

0,5

3,8

0.6

3,9

0,4

Wate

6,0

2,4

5 ±

1,5

5,6

0,9

4,7

1,7

4,2

1,7

4,1

1,2

4,4

0,9

Allop

urino

6,7

2,4

5,5 ±

1,6

5,7

1,3

9,1

4,5

5,1

2,2

5,8

2,1

5 ±

1,3

From the above table it can be concluded that

the ethyl acetate fraction is the best fraction that can

reduce uric acid levels in mice compared to the n-

hexane fraction and residual water.

Figure 1. The effect of ginger (Zingiber officinale Rosc)

fractionation in decreasing uric acid level

The effect of ginger (Zingiber officinale

Rosc) fractionation in decreasing uric acid level of

hyperuricemic white mice show at figure 1. In the

Figure 1, we can see the level of uric acid decrease

in every fraction.

Ginger (Zingiber officinale Rosc) contains

over 400 different compounds. The mayor

constituents are carbohydrates (50-70%), lipids (3-

8%), terpens, and phenolic compounds (Prasad and

Tyagi, 2015). Flavonoid is a group of plant phenolic

compound that act as antioxidant such as quercetion,

rutin, catechin, epicatechin, kaempferol and

naringenin (Ghasemzadeh et al, 2010). Due to their

importance in human health, ginger can be used to

pharmacological activites like anti inflammation,

anticancer, antioxidant, antiplatelet, and can be used

to reduce cholesterol and uric acid level (Rehman,

2011).

Flavonoid functions as an inhibitor in uric

acid formation and able to reduce the level of uric

acid by blocking xanthine oxidase, the enzyme

responsible for regulating uric acid formation.

In this study, variation of fraction used to

knowing which the best fraction to lowering level of

uric acid. The fractionation process was carried out

in stages based on level of polarity, from polar, semi

polar and nonpolar solvents. From the experiment,

Duncan’s Multiple Range Test used to determine the

best fraction for lowering uric acid level.

Table 3. Duncan’s Multiple Range Test of Uric Acid

Level

Uric Acid Activity

Group N

Subset

1 2 3 4

Duncan

Ethyl Acetate

100mg/kgBB

49 4.451

Water 100mg/kgBB 49 4.865 4.865

n-Hexane 100mg/kgBB 49 5.067 5.067

Negative Control 49 5.667 5.667

Allupurinol 10mg/kgBB 49 6.135

Positive Control 49 8.031

Sig. .150 .060 .247 1.000

Test results from analysis Duncan’s

Multiple Range Test showed that the best fraction

for lowering level of uric acid serum is ethyl acetate

fraction, because the statistical value of ethyl acetate

has different subset with other test groups. It means,

suspected active compounds that are given can lower

the best of uric acid levels in the blood is in the

semi-polar fraction. While on the allupurinol showed

that the effect is not different significantly with ethyl

acetate. It because the dose of the fraction that used

in this study is greater than the dose of Allupurinol.

The Effect of Ginger (Zingiber Ofﬁcinale Roscoe) Fractionation in Decreasing Uric Acid Level of Hyperuricemic White Mice

471

4 CONCLUSIONS

A total of 600 grams of rhizomes have been dried,

refined and then extracted with ethanol 70%

producing a condensed extract of 160.5 grams. A

total of 50 grams of condensed extracts of ginger

leaves are fractionated consecutively by using n-

hexane, ethyl acetate, and residual water. The

amount of viscous fraction obtained is n-hexane 4.22

gram, ethyl acetate 5.51 gram, and water remaining

27.5 gram with a yield percentage of 8.44%; 11.01%

and 55% respectively. From the study can conclude

that ethyl acetate fraction of Zingiber officinale Rosc

is the best fraction for lowering level of uric acid

serum. For the future study we can use variation of

doses, pathology with other diseases or isolation of

pure compound from ginger.

ACKNOWLEDGEMENTS

We thanks to RISTEKDIKTI was funded this series

of research through a beginner lecturer research

program. We hope this series of research can be

continued to the next stage.

REFERENCES

Andriani, A. (2018). Pengaruh Pemberian Air Rebusan

Daun Salam (Syzygium Polyanthum) Terhadap

Penurunan Kadar Asam Urat. Jurnal Ipteks Terapan,

12(3), 222. https://doi.org/10.22216/jit.2018.v12i3.430

Arifin, H., Fahrefi, M., & Dharma, S. (2013). Pengaruh

Fraksi Air Herba Seledri (Apium graveolens L.)

Terhadap Kadar Kolesterol Total Mencit Putih Jantan

Hiperkolesterol. In Prosiding Seminar Nasional

Perkembangan Terkini Sains Farmasi dan Klinik III

(pp. 293–304). Padang.

Azis, T., Febrizky, S., & Mario, D. A. (2014) “Pengaruh

Jenis Pelarut tehadap Persen Yield Alkaloid dari

Daun Salam India”. Universitas Sriwijaya.

Chen, Yu-Chen, Huang, Chang-Chi, Tsai, Chang-Keng,

Huang, Jan-Wei, Huang, Ching-Wen, Hsu, Chen-Yu,

and Hsu, Lin-Feng. (2014). Evaluation of the

Antihyperuricemic Activity of Phytochemicals from

Davallia formosana by Enzyme Assay and

Hyperuricemic Mice Model. Evidence-Based

Complementary and Alternative Medicine.

Departemen Kesehatan Republik Indonesia. Parameter

Standar Umum Ekstrak Tumbuhan Obat. Jakarta:

Direktorat Jendral Pengawasan Obat dan Makanan;

2000:10-11.

Departemen Kesehatan. (2008). Farmakope Herbal

Indonesia (Edisi 1). Jakarta: Departemen Kesehatan.

Departemen Kesehatan. (2017). Farmakope Herbal

Indonesia (Edisi 2). Jakarta: Departemen Kesehatan.

Endarini, L. H. (2016). Farmakognosi dan Fitokimia.

Jakarta : Pusdik SDM Kesehatan Badan

Pengembangan dan Pemberdayaan Sumber Daya

Manusia Kesehatan.

Facchini, F., Chen, Y. D., Hollenbeck, C. B., & Reaven,

G. M. (1991). Relationship between resistance to

insulin-mediated glucose uptake, urinary uric acid

clearance, and plasma uric acid concentration. Jama,

266(21), 3008–3011.

https://doi.org/10.1001/jama.266.21.3008

Efendi Juniar Ikhsan. (2018). Uji Aktivitas

Antihiperurisemia ekstrak daun kemangi (ocimum

sanctum) dan daun salam (Syzygium polyanthum)pada

tikus yang diinduksi hati ayam. Naskah publikasi.

George, Christina and Minter, A., D. (2019).

Hyperuricemia. MSU-Mclaren Oakland.

Ghasemzadeh A, Jaafar HZ, Rahmat A. 2010. Antioxidant

activities, total phenolic and flavonoids content in two

varieties of Malaysia young ginger (Zingiber officinale

Roscoe). Molecules. 15(6): 4324-4333.

Hamzah, L., Arifin, H., & Ahmad, A. (2014). Pengaruh

Ekstrak Etanol Rambut Jagung (Zea Mays, L)

Terhadap Kadar Asam Uratdarah Mencit Putih Jantan

Hiperurisemia. In Perkembangan Terkini Sains

Farmasi dan Klinik IV (pp. 282–293). Padang.

Harborne, J. (1987). Metode Fitokimia, Penentun Cara

Modern Menganalisis Tumbuhan. (S. I. Padmawinata

K, Trans.) (2nd ed.). Bandung: ITB.

Hassan F. Al-Azzawie and Samah A.Abd. 2015. Effects

of Crude Flavonoids from Ginger (

Zingiber

officinale), on Serum Uric Acid Levels, Biomarkers of

Oxidative Stress and Xanthine Oxidase Activity in

Oxonate-Induced Hyperuricemic Rats. Dept. of

Biotechnology/College of Science/Baghdad

University/Iraq

Hayani, M., Widyaningsih, W. (2011). Efek Ekstrak

Etanol Herba Putri Malu (Mimosa pudica) sebagai

Penurun Kadar Asam Urat Serum Mencit Jantan Galur

Swiss. Prosiding Seminar Nasional "Home Care".

Hawking, D. W., & Rahn, D. W. (2005).

Pharmacotherapy: A Pathophysiologic Approach. (J.

T. DiPiro, R. L. Talbert, G. C. Yee, G. R. Matzke, B.

G.Wells, & L. M. Posey, Eds.) (6th Editio). United

States of America: The McGraw-Hill Companies, Inc.

Hernani dan E. Hayani. Identification of chemical

components on red ginger (Zingiber officinale var.

Rubrum) by GC-MS. Proc. International Seminar on

natural products chemistry and utilization of natural

resources. Jakarta: UI-Unesco; 2001 :501-505

Indriawan.(2010).Penyakit.asamurat/gout.unikom.ac.id/re

po/sector/kampus/view/blog/key/.../Penyakit.

Jolad, S. D., Lantz, R. C., Solyom, A. M., Chen, G. J.,

Bates, R. B. and Timmerman,B. N. (2004) Fresh

organically grown ginger (Zingiber officinale)

(composition and effects on LPS-induced PGE2

production, Phytochem., vol. 65 : 1937–1954.

Juwita, D. A., Arifin, H., & Popy Handayani. (2014).

Pengaruh Fraksi Air Herba Seledri (Apium graveolens

ICHIMAT 2019 - International Conference on Health Informatics and Medical Application Technology

472

L.) Terhadap Kadar Asam Urat Mencit Putih Jantan

Hiperurisemia. In Seminar Nasional dan Workshop

“Perkembangan Terkini Sains Farmasi dan Klinik IV”

(pp. 187–191).

Katzung BG, Masters SB, Trevor AJ. (2007). Basic and

clinical pharmacology. 10

ed. New York: McGraw

Hill Press.

Kristiani, R.D., Rahayu, D dan Subarnas, A. 2013.

Aktivitas Antihiperurisemia Ekstrak Etanol Akar Pakis

Tamgkur (Polypodium feei) Pada Mencit Jantan.

Bionatura-Jurnal Ilmuilmu Hayati dan Fisik. Vol 15

(3):156-159.

Lallo, S., Mirwan, M., Palino, A., Nursamsiar, &

Hardianti, B. (2018). Aktifitas Ekstrak Jahe Merah

Dalam Menurunkan Asam Urat Pada Kelinci Serta

Isolasi Dan Identifikasi Senyawa Bioaktifnya. Jurnal

Fitofarmaka Indonesia, 5(1), 271–278.

Lembaga Ilmu Pengetahuan Indonesia. (2016) Jumlah

Usia Produktif Besar,

Indonesia

Berpeluang

Tingkatkan Produktivitas. Diakses pada tanggal 1

Agustus 2018

dari http://lipi.go.id/berita/jumlah-usia-

produktif-besar-indonesia-berpeluang-tingkatkan-

produktivitas/15220.

Manurung, R. V, Kurniawan, E. D., Hidayat, J., &

Risdian, C. (2012). Desain dan Fabrikasi Elektroda

Biosensor : Metode Teknologi Film Tebal. Jurnal

Ilmiah Elite Elektro, 3(1), 65–70.

Mariana, L., Andayani, Y., & Gunawan, R. (2013).

Analisis Senyawa Flavonoid Hasil Fraksinasi Ekstrak

Diklorometana Daun Keluwih (Artocarpus camansi),

6(2), 50–55.

Masuda T, Jitoe A, Mabry TJ. Isolation and structure

determination of cassumunarins A, B, C: new

antiinflammatory antioxidants from a tropical ginger,

Zingible cassumunar. J Am Oil Chem Soc.

1995;72:1053-57.

Misnadiarly. (2017). Rematik (1st ed.). Jakarta : Pustaka

Obor Popouler.

Muhtadi, Suhendi, A., W., N., & Sutrisna, E. (2013).

Potensi Daun Salam (Syzigium Polyanthum Walp.)

Dan Biji Jinten Hitam (Nigella Sativa Linn) Sebagai

Kandidat Obat Herbal Terstandar Asam Urat. Journal

of Chemical Information and Modeling, 53(9), 1689–

1699.

https://doi.org/10.1017/CBO9781107415324.004

Ningdyah, A. W., Alimuddin, A. H., & Jayuska, A.

(2015). Uji Toksisitas Dengan Metode BSLT (Brine

Shrimp Lethality Test) Terhadap Hasil Fraksinasi

Ekstrak Buah Tampoi (Baccaurea macrocarpa). Jurnal

Kimia Khatulistiwa, 4(1), 75–83.

Pandey, Amita and Tripathi, Shalini. (2014). Concept of

standardization, extraction and pre phytochemical

screening strategies for herbal drug. Journal of

Pharmacognosy and Phytochemistry. 2(5):115-119.

Parwata, I. M. O. A., Rita, W. S., & Yoga, R. (2009).

Isolasi dan uji antiradikal bebas minyak atsiri pada

daun sirih (Piper betle Linn) Secara Spektroskopi

Ultra Violet-Tampak. Jurnal Kimia, 3(1), 7–13.

Pokhrel, K., Yadav, BK., Jha, B., Parajuli, K., Pokharel,

RK. (2011). Estimation of Serum Uric Acid in Cases

of Hyperuricaemia and Gout. Journal of Nepal

Medical Association. 51(181):15-20.

Prasad, Sahdeo and Tyagi, K Amit. 2015. Ginger and Its

Constituent: Role in Prevention and Treatment of

Gastrointestinal Cancer. Gastroenterology Research

and Practice. http://dx.doi.org/10.1155/2015/142979

Quy Diem Do, Artik Elisa Angkawijaya, Phuong Lan

TranNguyen, Lien Huong Hyunh, Felycia Edi

Soetardjo, Suryadi ISmadji, Yi-Hsu Ju. (2014). Effect

of extraction solvent on total phenol content, total

flavonoid content, and antioxidant activity of

Limnophila aromatica. Journal of Food and Drug

Analysis. 22(30:296-302.

Rahman, H., Arifin, H., Dewi, G. K., & Rizal, Z. (2014).

Pengaruh Pemberian Jus Buah Sirsak (Annona

muricata, L) Terhadap Kadar Asam Urat Darah Mencit

Putih Jantan Hiperurisemia. In Perkembangan Terkini

Sains Farmasi dan Klinik IV (pp. 228–232). Padang.

Raji Y, Udoh US, Oluwadara OO, Akinsomisoye OS,

Awobajo O, Adeshoga K. Anti-Inflammatory and

Analgesic Properties of The Rhizome Extract of

Zingiber officinale. Departments of Physiology,

College of Medicine, Universitas of Ibadan.

Ravindran, P.N., Babu, K.N. 2005. Ginger The Genus

Zingiber. CRC Press : New York.

Rehman Riazur, Akram, M, Akhtar Naveed, Jabeen

Qaiser, Saeed Tariq, Shah, Ali MS, Ahmed Khalil,

Shaheen Ghazala, and Asif, MH. 2011. Zingiber

officinale Roscoe (pharmacological activity). Journal

of Medicinal Plants Research. 5(3): 344-348.

Sholihah, F. M. (2014). Diagnosis and Treatment Gout

Arthritis. J Majority, 3(7), 39–45.

Silva, De, O., G., Abeysundara, T., A., and Aponso, W.,

M., M. (2017). Extraction methods, qualitative and

quantitative technique for screening phytochemical

from plants. American Journal of Essential Oils and

Natural Products. 5(2):29-32.

Stoilova IA, Krastanov A, Stoyanova P Denev, Gargova S.

Antioxidant activity of a ginger extract (Zingiber

officinale). Food Chemistry. 2007;102:764–70.

Sruthi, D. R., and Indira, G. (2016). A comparative

evaluation of maceration, soxhlation and ultra sound

assisted extraction for the phytochemical screening of

the leaves of Nephelium lappaceum. L. Journal of

Pharmacognosy and Phytochemistry.5(5):386-389.

Suhendi, A., Nurcahyanti, Muhtadi, & Sutrisna, E. (2011).

Antihyperurisemia activity of water extract of black

seed (Coleus ambonicus Lour) in balb-c mice and its

standardization. Majalah Farmasi Indonesia, 22(2),

77–84.

Thayibah, R., Ariyanto, Y., & Ramani, A. (2018).

Hiperurisemia Pada Remaja di Wilayah Kerja

Puskesmas Arjasa Kabupaten Situbondo

Hyperuricemia in Adolescents ( 16-24 Years Old ) in

Arjasa Primary Health Center , Situbondo Regency,

6(1), 38–45.

Tahir, B., Saleh, C., & Pasaribu, S. P. (2013). Uji

Fitokimia, Toksisitas Dan Aktivitas Antioksidan

Alami Daun Tumbuhan Kelakai (Stenochlaena

The Effect of Ginger (Zingiber Ofﬁcinale Roscoe) Fractionation in Decreasing Uric Acid Level of Hyperuricemic White Mice

473

palustris) Dengan Metode DPPH. In Prosiding

Seminar Nasional Kimia 2013 (pp. 141–146).

Tolistiawaty, I., Widjaja, J., Sumolang, P., Octaviani.

(2014). “Gambara Kesehatan pada Mencit di Instalasi

Hewan Coba”.Jurnal Vektor Penyakit. Sulawesi

Tengah.

Vogel, H. G. (2008). Drug Discovery and Evaluation:

Pharmacological Assays. Journal of Chemical

Information and Modeling (Third, Vol. 53). New

York: Springer-Verlag Berlin Heidelberg.

https://doi.org/10.1017/CBO9781107415324.004

Wahyuni, T., Widuri, A., Abdul, M., & Katrin. (2011).

“Uji Aktivitas Penghambatan Xantin Oksidase Ekstrak

Etanol 80% dari Tanaman Famili Combretaceae,

Lauraceae, Lythraceae, Oxalidaceae, Piperaceae,

Plumbaginaceae, dan

Smilacaceae,” 77–88.

Wall, G. (2010). Pharmacotherapy : Principles &

Practice. (M. A. Chisholm-Burns, B. G.Wells, T. l.

Schwinghammer, P. M.Malone, J. m. Kolesar, J. C.

Rotschafer, & J. t. Dipiro, Eds.). United States of

America: McGraw-Hill Companies, Inc.

https://doi.org/10.1036/0071448802

WHO. (2015). A Global Brief On Uric Acid. Geneva.

Wilmana, P.F. 2005. Farmakologi dan Terapi. Edisi ke-4.

Gaya Baru, Jakarta.

Yulion, R., Suhatri, & Arifin, H. (2017). Pengaruh Hasil

Fraksinasi Ekstrak Etanol Daun Lado-lado (Litsea

cubeba, Pers) Terhadap Kadar Asam Urat Serum

Darah Mencit Putih Jantan Tinggi Asam Urat. Jurnal

Sains Dan Teknologi Farmasi, 19(Desember).

ICHIMAT 2019 - International Conference on Health Informatics and Medical Application Technology

474