The Role Of Boiled Water Of Syzygium Polyanthum Leaves In Decreasing Hyperuricemia Levels

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2 The Role Of Boiled Water Of Syzygium Polyanthum Leaves In Decreasing Hyperuricemia Levels Miftafu Darussalam, Dwi Kartika Rukmi Lecturers of Nursing Department at Stikes Jenderal Achmad Yani Yogyakarta, Indonesia Abstract Hyperuricemia is either a final product or a waste product that results from the metabolism or the breakdown of purines. It will become an antioxidant if its excessive amount in the blood undergoes efflorescence engendering gouty arthritis. The syzygium polyanthum leaves contain tannins, essential oils, sesquiterpenes, triterpenoids, phenols, steroids, sitral, lactones, selenium, saponins, and carbohydrates, in additon to several vitamins including vitamin C, vitamin A, Thiamin, Riboflavin, Niacin, Vitamin B6, vitamin B12 and folate. Most importantly, they contain bioactive substances that affect the levels of hyperuricemia (uric acid) in blood. This study used a design of pretest and posttest without control group. The population consisted of all hyperuricemia patients in the target extensive area of Bantul Community Health Center in Yogyakarta. The sample used in this study was regarded as a concecutive sampling with a total number of 24 respondents. To analyze the data, the researchers used the Wilcoxon test. The dose of bolied water of syzygium polyanthum leaves intake was 0.36 g / KgBW, and once a day for 14 days. The research result shows that the boiled water of syzygium polyanthum leaves can decrease hyperuricemia (uric acid) levels, along with the significancy value of (p <0.05). Before respondents took the boiled water of syzygium polyanthum leaves, the level of their hyperuricemia (uric acid) reached 7279 mg/dl, but after the treatment using the same boiled water, the average level of their hyperuricemia (uric acid) decreased to 6.76 mg/dl. This study proves that the boiled water of syzygium polyanthum leaves can decrease hyperuricemia (uric acid) levels from 7279 mg/dl to 6.76 mg/dl. Keywords: syzygium polyanthum, boiled water of syzygium polyanthum leaves, hyperuricemia 1

3 INTRODUCTION Hyperuricemia has been considered as gout, but it has also been identified as a marker for a number of metabolic and hemodynamic abnormalities for several years (Waring, Webb, & Maxwell, 2002). Under a normal circumstance, there is a balance between the formation and degradation of purine nukleutida and the ability of the kidney to excrete the uric acid. If there is an excess of formation or a hindrance expenditure or both, there will be an increase in the concentration of uric acid in the blood commonly called hyperuricaemia (Edward, 2001). Hyperuricemia is defined as increased levels of uric acid in the blood. The definition of hyperuricemia for men and women is different considerably. A man is said to be suffering from hyperuricemia when his uric acid serum levels exceed 7.0 mg/dl. Meanwhile, hyperuricemia in a woman occurs when her uric acid serum is above 6.0 mg/dl (Berry et al., 2004; Hediger et al., 2005; Putra, 2006 As stated in the western literature, the hyperuricemia incidence in the community widely varies between 2.3% %, whereas the gout incidence varies between %. In 2006, China reached 25.3% of its hyperuricemia prevalence and its gout prevalence was 0.36% in adults aged years (Nan et al, 2006) There have been no definitive data related to the hyperuricemia incidence in Indonesian society, but a research conducted by Indrawan (2005) on the population of Denpasar City s residents, Bali showed 18.2% of the hyperuricemia prevalence. In fact, hyperuricemia can lead to a vascular inflammation, a smooth muscle proliferation, an increased renin production, and vascular lesions of the kidney. Furthermore, hyperuricemia will result ini microvascular changes in the kidney similar to the image of arteriosclerosis in the essential hypertension. Vascular lesions engender ischemia resulting from the release of lactate and it ended with an increased production of uric acid (Heinig and Johnson, 2006; Feig et al., 2008). Indonesia is a country that has the second highest biodiversity in the world after Brazil. Of the species of flora that exist in the world, as many as of them can be found in Indonesia and 940 types of which are known to have medicinal properties that have been used in the folk medicine for generations by various Indonesian ethnic groups. The ubiquitous herbal plants cover about 90% of the number of medicinal plants found in the Asian regions (Muhtadi et al, 2012) The use of traditional medicine (herbal medicine) in Indonesia has long been an integral part of cultures. The advantage of using traditional medicine is mainly concerned with a relatively low side effect compared to modern medicine. Although traditional medicine empirically can cure various diseases, its efficacy and ability have not been proven scientifically and clinically. Besides, chemical compounds can be found in the herbal plants responsible for the efficacy of traditional medicine (Wijayakusuma, 2002). The World Health Orgaization (WHO) has recommended the use of traditional medicine, including herbs to maintain the public health, prevention and treatment of diseases in particular chronic diseases, degenerative diseases, and cancers. In general, the use of traditional medicine is considered safer than the use of modern medicine. In 2003, the Bogor Agricultural Institute (IPB) cooperated with the Ministry of Agriculture and from 2004 to 2005 it continued its cooperation with the Food and Drug Monoitoring Agency (BPOM) to analyze the land suitability for 9 Indonesian medicinal plants (curcume, Centella asiatica, kumis kucing, Netherlands hardwood tree, Tempuyung, Brotowali, Kepel leaf, kemuning, and syzygium polyanthum), which are further added to meniran commodities. Syzygium polyanthum also belongs to the target commodity of Directorate General of Horticulture (listed in the Ministry of Agriculture Decree NO. 511/Kpts/PD. 310/9/2006). The Ministry of 2

4 Health has also published a book entitled Buku Formularium Obat Asli Indonesia (A Book of Native Medicinal Formulae of Indonesia) containing 60 species of plants that are beneficial to the public health and one of them is syzygium polyanthum and the book is planned to be distributed to hospitals and community health centers. This book is based on a reference of the Vademekum of Medicinal Plants, Ministry of Health. It was explained that 60 types of plants will be used for 20 portions of different diseases treatments (Abdibiof, 2012). Syzygium polyanthum leaves contain tannins, essential oils, sesquiterpenes, triterpenoids, phenols, steroids, sitral, lactones, saponins, and carbohydrates (BPOM, 2004), in addition to several vitamins, including vitamin C, vitamin A, Thiamin, Riboflavin, Niacin, Vitamin B6, vitamin B12, and folate, even minerals such as selenium (Pidrayanti, 2008). Syzygium polyanthum is one of the plants that contains bioactive substances influencing the levels of hyperuricemia in the blood. Handadari s research results (2007) proved that syzygium polyanthum leaves intaking at a dose of 1.25 g/kg of body weight could decrease hyperuricemia levels in the blood of white male mice effectively. The minimum toxicity test of syzygium polyanthum leaves (through animal experiments in mice at a dose of 9.6 mg/kg, or even at a dose of 4200 mg/kg) did not show any acute or sub-acute toxicity in mice (Ngestiningsih et al, 2012). Other research show that the boiled water of syzygium polyanthum leaves at a dose of 2.5 g/kg of body weight can decrease hyperuricemia levels in white male mice equivalent to an allopurinol dose of 10 mg / kg (Ariyanti, 2007). As a pro-inflammatory agent, the hyperuricemia plasma will spur human macrophages to produce the interleukin-1 (IL-1), the interleukin 6 (IL-6), the interleukin 8 (IL-8), and tumor necrosis factor-α (TNF-α) (Putra, 2006). TNF-α and IL-1 that release peripheral blood monocytes will trigger the expression of E-selectin, the intercellular adhesion molecule 1 (ICAM-1) and the vascular cell adhesion molecule 1 (VCAM-1) and vascular endothelial cells which would then lead to the withdrawal of leukocytes into local deposits of hyperuricemia crystals, so the response to inflammation increases (Becker & Menaaskshi, 2005). Based on the research of Ngestiningsih et al (2012), the herbal extract containing leaves can reduce levels of interleukin-1 (IL-1) and tumor necrosis factor-α (TNF-α) and serum of hyperuricemia patients and this reduction can reduce the pain of hyperuricemia patients. LITERATURE REVIEW A Syzygium polyanthum leaf has a scientific name called Eugenia polyantha wight and it has other scientific names, Syzygium polyantha wight. and Eugenia lucidula Miq. These plants are categorized as Myrtaceae family. The syzygium polyanthum in the form of a tree has a height of about 20 meters and well-cultivated at high altitude of meters above the sea level (Kurniawati, 2010). Some studies mention that Eugenia polyantha wight has chemical ingredients such as essential oils (0.05%) containing citral, eugenol, tannins and flavonoids. The ethanol extract of the leaves serves as an antifungal and antibacterial agent, while the methanol extract is efficaciously used as an anti-worming agent. The research on the leaves also showed that the boiled water of Eugenia polyantha wight could reduce the number of Streptococcus sp (Sumono and Wulan, 2009). In addition, it also contains several vitamins, including vitamin C, vitamin A, Thiamin, Riboflavin, Niacin, Vitamin B6, vitamin B12, and folate, even minerals such as selenium (Pidrayanti, 2008). Hyperuricemia is the final product or a waste product resulting from the metabolism or breakdown of purines. It is actually an antioxidant from humans and animals, but when its excessive amounts in the blood undergo crystallization, it can engender gout. Hyperuricemia 2

5 (uric acid) has a role as an antioxidant when blood levels are not excessive, but when uric acid levels are excessive, it will act as a prooxidant (McCrudden Francis H. 2000). The name of hyperuricemia is 2,6,8-trioksipurin. The oxidation of hyperuricemia in neutral or alkaline solution can produce carbon dioxide and allantoin, whereas the oxidation of hyperuricemia in the acid solution will produce alloxan. In humans, a purine nucleoside adenosine and guanosine are mainly converted to hyperuricemia as a final product that is excreted out of the body. First, adenosine undergoes deamination into inosine by adenosine deamonase. Phosphorolysis (fosforolisis) will release the compound ribose 1-phosphate and the purine base. Hypoxanthine and xanthine guanine are subsequently formed in a reaction catalyzed by xanthine oxidase and guanase. Xanthine is then oxidized to hyperuricemia through the reaction catalyzed by the same enzyme. The reaction mechanism of hyperuricemia is formed through the purine nucleosides and purine-based hypoxanthine, xanthine, and guanine. The normal hyperuricemia in the human serum ranges from 3-6 mg/dl. The normal value of the hyperuricemia serum in men is 5.1 ± 1.0 mg/dl, while in women 4.0 ± 1.0 mg/dl. The value can be increased to 9-10 mg/dl in someone with gout circumstances (Price and Wilson, 2006). Humans do not have urikase like animals, an enzyme that outlines allantonin hyperuricemia soluble in water. Hyperuricemia formed every day is excreted through the digestive tract or kidneys. In normal circumstances, the amount of hyperuricemia accumulated in men is approximately 1200 mg and 600 mg for women. The accumulated amount is increased several times in hyperuricemia patients. An excessive accumulation can be derived from the excretion of excessive or less production. The excessive purine intake, in normal circumstances, should be excreted through kidneys. In most hyperuricemia patients (75-90%), the clearance of hyperuricemia by the kidneys is decreased (Hediger et al., 2005). A person is said to be affected if he or she has hyperuricemia levels above the normal figure. The hyperuricemia levels can be determined by measuring the serum of hyperuricemia levels. To know whether someone is having hyperuricemia or not, certain indicators are used as the lower limit, whereas the woman is said to have hyperuricemia when her uric acid levels exceed 6 mg/dl and men more than 7 mg/dl (Lingga, 2012). RESEARCH METHODS This study includes a quantitative research, which is a quasi-experiment by using a design of pretest and posttest without control group. The research was conducted in the target area of Pandak I Bantul Community Health Center in Yogyakarta on September 1 to 30, The independent variable in this study was the boiled water of Syzygium polyanthum leaves, while the dependent variable was the level of hyperuricemia (uric acid). Syzygium polyanthum leaves in this study weighed at a dose of 0.36 g/kgbw. Afterwards, ± 1,500 cc of water was added to the pot and heated it. Once the water in the pot was boiling, add Syzygium polyanthum leaves that had been weighed into the pan to boil for ± 15 minutes with a boiling point of 90 degrees Celsius. Then the researchers cooled down the boiled water of Syzygium polyanthum leaves. After that, it was measured by using a measuring cup of 100 cc, so that each of the respondents took the boiled water 100 cc every morning for 14 days. The measurement of hyperuricemia (uric acid) levels was undertaken 2 times, before taking the boiled water of Syzygium polyanthum leaves, and on the 14 th day or the last day of treatment. The population of this study was all hyperuricemia patients in the target area of the Community Health Center. The sampling used in this study was a consecutive sampling. The inclusion criteria were male uric acid levels> 7.0 mg/dl and female> 6.0 mg/dl, who were 3

6 willing to be respondents and signed an informed consent. The exclusion criteria were the respondents requests to stop due to impaired kidneys, and respondents were taking gout medication. The sample size was 24 respondents. Data analysis was performed by the Wilcoxon test. RESULTS AND DISCUSSION Univariate analysis The Distribution of Respondents by Age and Weight Loss in Pandak 1 Community Health Center, Bantul Regency, Yogyakarta (N: 24). Variable Mean Median SD Minmax Age Body weight 95 95%CI The results of the data analysis of respondents by age showed that the average age was years, median 60 years with a standard deviation of years. The lowest age was 33 years old and 80 year old was the oldest age. The results of an interval estimate proved that 95% of the average age was between years to years. While the results of the data analysis of respondents by weight indicated that the average weight was kg, median 53 kg with a standard deviation of kg. The lowest body weight was 34 kg and the highest 95 kg. The results of an interval estimate showed that 95% of the average weight was between kg to kg. The Distribution of Respondents by Gender in Pandak 1 Community Health Center, Bantul Regency, Yogyakarta (N:24) Gender Frequency Percentage Variable Male % Female % Total % The respondents' gender included 83.3% of women (n = 20) and 16.7% of men (n = 4). The Distribution of Respondents by Hyperuricemia Levels before Taking the Boiled Water of Syzygium polyanthum Leaves in Pandak 1 Community Health Center, Bantul Regency, Yogyakarta (N: 24) 95%CI Variable Mean Median SD Minmak Preintervention

7 The results of the analysis of the data on the respondents before taking the boiled water of Syzygium polyanthum leaves showed that the average hyperuricemia levels was 7279 mg/dl (95% CI: ), a median of 7 mg/dl with a standard deviation of 1:24 mg/dl. The hyperuricemia levels varied. The lowest was 6 mg/dl and the highest 11.2 mg/dl. The results of the interval estimate showed 95% of the average hyperuricemia levels before the intervention ranging from 6.75 to 7.8 mg/dl. The Distribution of Respondents by Hyperuricemia Levels after Taking the Boiled Water of Syzygium polyanthum Leaves in Pandak 1 Community Health Center, Bantul Regency, Yogyakarta (N:24) Varia ble Post interv ention Mean Median SD Min - mak Preintervention Postintervention % CI The results of the analysis of data on the respondents after taking the boiled water of Syzygium polyanthum leaves showed that the average level of hyperuricemia was 6.76 mg/dl (95% CI: ), median 6:55 mg/dl with a standard deviation of 1:51 mg/dl. The lowest level of hyperuricemia was 4.3 mg/dl and the highest level was 11.4 mg/dl. The results of the interval estimate showed 95% of the average hyperuricemia levels after the intervention ranging from 6124 to 7401 mg/dl. The Bivariat Analysis The Normality Test Data of Hyperuricemia Levels before and after Taking the Boiled Water of Syzygium polyanthum Leaves. Shapiro-Wilk Statistic Df Sig The analysis of data of normality in hyperuricemia levels before the intervention showed p value: Because the value of p <0.05, then it can be concluded the distribution is not normal. The analysis of data of normality in hyperuricemia levels after the intervention indicated p value: Because the value of p <0.05, then it can be concluded the distribution is not normal. 5

8 Wilcoxon Test Results Analysis of Hyperuricemia Levels Before and After taking the Boiled Water of Syzygium polyanthum Leaves Post- Pre Mean Rank Sum of Ranks Negative 19 a Ranks Positive 5 b Ranks Ties 0 c Total 24 a. Post<pre b. Post>pre c. Post=pre Z Asymp.Sig. (2- tailed) POST-PRE a The results of the data analysis show a comparison of hyperuricemia levels before and after taking the boiled water of Syzygium polyanthum leaves. In fact, 19 respondents hyperuricemia levels, after taking the boiled water of Syzygium polyanthum leaves, were lower than before the intervention. Meanwhile, 5 respondents experienced an increase in hyperuricemia levels after taking the boiled water of Syzygium polyanthum leaves and no respondents had higher levels of hyperuricemia (uric acid) before and after the intervention. The results of the Wilcoxon test analysis showed significancy value of (p <0.05), therefore, it can be concluded that there is a significant difference of hyperuricemia (uric acid) levels before and after taking the boiled water of Syzygium polyanthum leaves. DISCUSSION This research was conducted on 24 hyperuricemia respondents with uric acid levels in the blood. The screening of respondents was performed at the integrated health services posts for the elderly (Posyandu Lansia) located in in a village where this research was conducted namely Krekah, Gesikan IV and Bergan in the target area of Pandak I Community Health Center. Patients who complained of aches and pains were examined particularly their hyperuricemia (uric acid ) levels by using a measuring instrument of gout called Easy Touch. Patients who had the criteria of uric acid> 7 mg/dl in men and> 6 mg/dl in women were taken as prospective respondents. After all of them were selected, potential respondents were given an explanation of the processes and procedures for the research and further agreed to sign an informed consent and recorded the weight, sex, age. After all the data were obtained, a day before starting the treatment, the researchers came to the house of each respondent to provide the boiled water of Syzygium polyanthum leaves that had been packaged in 100 cc dose adjusted to each patient's weight of 0.36 grams/kgbw. When the researchers were giving each of them granting the boiled water of Syzygium polyanthum leaves, they also measured all respondents levels of uric acid and the 6

9 results were regarded as uric acid levels before the treatment (a pre-test). Hyperuricemia respondents were required to drink the boiled water of Syzygium polyanthum leaves according to the dose for 14 days every morning and then the uric acid level were checked on the 14 th day (a post-test). The results showed that as many as 19 respondents levels of uric acid decreased and the Wilcoxon test analysis showed a significant result, that is, (p <0.05), which means that there is a significant difference of hyperuricemia levels before and after respondents took the boiled water of Syzygium polyanthum leaves for 14 days. Hyperuricemia is a risk factor for the occurrence of gouty arthritis, a formation of kidney stones, and atherosclerosis. The prevalence of hyperuricemia in Indonesia varies from 2-18% of the population. The hyperuricemia plasma is a pro-inflammatory agent that will spur human macrophages to produce interleukin - 1 (IL-1), the interleukin - 6 (IL-6), the interleukin - 8 (IL-8), and tumor necrosis factor -α (TNF-α ). TNF-α and IL-1 released peripheral blood monocytes will trigger the expression of E-selectin, intercellular adhesion of molecule 1 (ICAM-1), and vascular cell adhesion of molecule 1 (VCAM-1) of vascular endothelial cells which lead to the withdrawal of leukocytes into local deposits of hyperuricemia crystals (monosodium urate monohydrate), so that the response to inflammation increases. The IL-6 has been known as a pluripotent mediator in the inflammatory and immunological response, and it is a factor that stimulates primary hepatocytes. Crystals of monosodium urate (MSU) and calcium pyrophosphate dyhidrat (CPPD) crystals of hydroxyphalite will increase the production of IL-6 by synoviocyte and monocytes in vitro. The high levels of IL-6 can be found in the synovial fluid of hyperuricemia patients. Drugs used to decrease hyperuricemia are commonly called allopurinol, but at times these drugs are reported to cause effects such as allergies as much as 13-21%. The extract of Syzygium polyanthum leaves has proven preclinical that can decrease blood hyperuricemia (uric acid) levels in hyperuricaemia mice and increase urinary excretion of uric acid, so that researchers applied the influence of decoction of Syzygium polyanthum to decrease uric acid levels in humans respondents. Other pertinent studies related to a decoction of Syzygium polyanthum had been done by Pangaribuan, Soedarmono and Rantung (2013) to decrease cholesterol levels and these studies had shown meaningful results. Other studies related to the use of Syzygium polyanthum leaves had also been done by Muflikhatur and Murwani (2014) in which the expected result concerning the decoction of Syzygium polyanthum leaves can withstand the increasing rate of total cholesterol after respondents took the simvastatin and the extract of Syzygium polyanthum leaves. Syzygium polyanthum is one of the plants whose leaves contain bioactive substances such as flavonoids, tannins and niacin. Several studies have also mentioned that the leaves contain chemicals such as essential oils (0.05%), citral, eugenol. The Syzygium polyanthum content of the active ingredient is thought to have a pharmacological effect. Tannins and flavonoids are active ingredients that have anti-inflammatory and antimicrobial effects, while the essential oils have an analgesic effect. The tannins in the leaves are suspected to have pharmacological and physiological effects of compounds derived from their complexities. Tannins are active compounds that possess an antibacterial activity. Tannins are phenolic compounds that function to inhibit the growth of bacteria with a protein denaturation to increase and decrease the surface tension, so that permeability of bacteria increased. Essential oils in several plants, including the Syzygium polyanthum leaves have a biological activity of antibacterial and antifungal domains, so the oils can be importantly used 7

10 as a food preservative and a natural antimicrobial. Essential oils have an antiseptic and antioxidant activity. Flavonoids have a biological and pharmacological activity, among other things such as antibacterials because flavonoids have hydroxyl groups, anti-inflammatory, enzyme inhibition, activity allergies, an antitumor activity of cytotoxic mechanism of flavonoids to inhibit the inflammation which at high concentrations can inhibit the release of arachidonic acid and secretion of lysosomal enzymes from the membrane by blocking the cyclooxygenase pathway, lipoxygenase pathway, and phospholipase A2, while low concentrations only block the lipoxygenase pathway. The results of research conducted by Wientarsih et al (2005) showed that the herbal extract of Syzygium polyanthum leaves could decrease uric acid levels in hyperuricemia mice. The boiled water of Syzygium polyanthum leaves can also reduce the hyperuricemia patients pain because it could lower the levels of IL-6 and TNF-α as as the research conducted by Ngestiningsih et al (2012) also reported, and according to research conducted by Azaki et al (2007), hyperuricemia herbal extracts proved to reduce pain in patients with symptomatic hyperuricaemia on the 28 th day compared to the placebo group because of an allegedly decrease in the release of pro-inflammatory cytokines (TNF-α, IL-6, IL-1β). The decrease in uric acid levels was significant on 19 hyperuricemia respondents who levels of hyperuricaemia levels ranged from 6124 to 7,401 mg/dl, while other 5 respondents experienced a rise in hyperuricaemia levels because in this research, researchers did not control the risk factors in addition to the use of the gout medication. Consequently, it is necessary to control the other risk factors in the future studies with a larger sample. CONCLUSIONS AND RECOMMENDATIONS CONCLUSION 1. The boiled water of Syzygium polyanthum leaves can decrease hyperuricaemia (uric acid) levels, evidently proven by the Wilcoxon test that showed significancy value of (p <0.05). Thus, there is a significant difference of hyperuricaemia (uric acid) levels before and after the patients took boiled water of Syzygium polyanthum leaves. 2. Respondents by age showed that the average age was years, median 60 years with a standard deviation of years. The lowest age was 33 years old and the highest was 80 years old. Respondents by weight showed that the average weight was kg, median 53 kg with a standard deviation of kg. The lowest body weight was 34 kg and the highest was 95 kg. The comparison of respondents' gender showed 83.3% men (n = 20) and 16.7% women (n = 4). 3. Before taking the boiled water of Syzygium polyanthum leaves, the respondents showed the average hyperuricaemia (uric acid) levels of 7279 mg/dl (95% CI: ), a median of 7 mg/dl with a standard deviation of 1:24 mg/dl. The lowest level of hyperuricaemia (uric acid) was 6 mg/dl and the highest level was 11.2 mg/dl. 4. After taking the boiled water of Syzygium polyanthum leaves, respondents showed the average hyperuricaemia (uric acid) levels of 6.76 mg/dl (95% CI: ), median 6:55 mg/dl with a standard deviation of 1:51 mg/dl. The lowest hyperuricaemia (uric acid) level was 4.3 mg/dl and the highest level was 11.4 mg/dl. Six (6) respondents had normal hyperuricaemia (uric acid) levels. RECOMMENDATIONS 1. For the Pandak The boiled water of Syzygium polyanthum leaves can be used to decrease hyperuricaemia 8

11 (uric acid) levels. Residents can have this complementary therapy according to the weight dose and and control hyperuricaemia (uric acid) levels in the Community Health Center as a therapy. evaluation Pandak. 2. For Puskesmas Pandak 1 This research is expected to be a material considered important for the healthcare workers and hyperuricaemia patients as a complementary therapy in addition to a pharmacological therapy. 3. For other researchers Taking the boiled water of Syzygium polyanthum leaves has shown a significant difference of hyperuricaemia (uric acid) levels. Other researchers can do further research involving more respondents as well as the control groups. REFERENCES Abdibiof Penyusunan Pedoman Bahan Saintifikasi Jamu. Didownload di Pada tanggal 23 Mei Ariyanti, R Pengaruh Pemberian Infusa Daun Salam (Eugenia polyantha Wight.)Terhadap Penurunan Kadar Asam Urat dalam Darah Mencit Putih Jantan hiperurisemia, Skripsi, Fakultas Farmasi Universitas Muhammadiyah Surakarta, Surakarta. Becker & Menaaskshi Clinical gout dan pathogenesis of hyperuricemia. Arthritis and allied condition, A textbook of rheumatology. 13 ed vol.2 editor WJ koopman, Baltimore: William & Wilkin Company, Berry CE and JM Hare Xanthine Oxidoreductase and Cardiovascular Disease: Molecular Mechanism and Pathophysiological Implications. Am J Physiol, pp: Edward NL Management of hyperuricemia. In: Koopman WJ, editor. Arthritis and allied condition. 14th ed Philadelphia: Lippincot William & Wilkins; 2001.p Feig DI, Kang DH, Johnson RJ Uric Acid and Cardiovascular Risk. N Eng J Med, pp: Handadari, H. R., 2007, Efek Decocta Daun Salam (Eugenia polyantha Wight.) Terhadap Penurunan Kadar Asam Urat dalam Darah Mencit Putih (Mus muculus) Jantan hiperurisemia, Skripsi, Fakultas Farmasi Universitas Muhammadiyah Surakarta, Surakarta. Hediger MA, Johnson RJ, Miyazaki H, Endou H Molecular Physiology of Urate Transport. Am J Physiol, pp: Heinig M and RJ Johnson Role of Uric Acid in Hypertension, Renal Disease, and Metabolic Syndrome. Cleveland Clinic Journal of Medicine, pp: Indrawan IGNB Hubungan Konsumsi Purin Tinggi dengan Hiperurisemia Studi Potong Lintang Analitik pada Penduduk Suku Bali di Kota Denpasar.Denpasar: In Press. Muhtadi, Suhendi. A, Nurcahyanti. W. & Sutrisna, E.M Potensi daun salam (syzigium polyanthum walp.) dan biji jinten hitam (nigella sativa linn) sebagai kandidat obat herbal terstandar asam urat. Pharmacon,vol.13 no 1. Nan H, Qing Qiao, Yanhu Dong, Weiguo Gao, Bin Tang, Rongli Qian The prevalence of hyperuricemia in a population of the Coastal City of Qingdao, China. J Rheumatol 2006;33:

12 Ngestiningsih, D., Widiastuti, I.,Wahyu,T.,Hadi,S., & Suntoko,B Perbedaan Pemberian Ekstrak Herbal (Daun Salam, Jintan Hitam, Dan Daun Seledri) Dengan Allopurinol Terhadap Kadar Il-6 Dan Tnf-Α Serumpenderita Hiperurisemia. Medica hospitalia. Vol.1.,No.1 Mei Pangaribuan, E.M., Sudharmono, U. & Rantung, G.A.J Uji Penggunaan Daun Salam (Syzygium Polyanthum) Untuk Menurunkan Kadar Kolesterol Pada Laki-Laki Usia Tahun. Bandung : Prosiding Seminar Kontribusi Fisika 2013 ISBN Pidrayanti, L.T.M Pengaruh Pemberian Ekstrak Daun Salam (Eugenia Polyantha) Terhadap Kadar Ldl Kolesterol Serum Tikus Jantan Galur Wistar Hiperlipidemia. Semarang : karya tulis ilmiah fakultas kedokteran Universitas Diponegoro,Semarang (tidak dipublikasikan). Price SA, Wilson LM Pathophysiology Clinical Concepts of Disease Processes 4th Edition. Philadelphia: Mosby Year Book. Putra,T.R Hiperurisemia. In: Sudoyo dkk (ed). Buku Ajar Ilmu Peyakit Dalam Jilid II Edisi IV. Jakarta: FKUI, pp: Waring WS, Webb DJ, Maxwell SRJ Uric Acid As A Factor For Cardiovascular Disease. Q J Med 2000;93: Wijayakusuma, H., 2002, Tumbuhan Berkhasiat Obat Indonesia Rempah, Rimpang dan Umbi. Prestasi Instan Indonesia, Jakarta. 10

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