JURNAL KEDOKTERAN DIPONEGORO (DIPONEGORO MEDICAL JOURNAL) Online http://ejournal3.undip.ac.id/index.php/medico E-ISSN : 2540-8844 DOI : https://doi.org/10.14710/jkd (dmj).v12i1.37579 JKD (DMJ), Volume 12, Number 1, January 2023 : 10-15 Al Ghiffari Muhammad Rayhan, Nani Maharani, Endang Mahati, Yora Nindita 10 EFFECT OF MELINJO SEED EXTRACT ON URIC ACID LEVELS OF HYPERURICEMIC MALE WISTAR RATS Al Ghiffari Muhammad Rayhan 1 , Nani Maharani 2 , Endang Mahati 2 , Yora Nindita 2 * 1 Undergraduate Program, Faculty of Medicine, Universitas Diponegoro, Semarang, Indonesia 2 Departement of Pharmacology and Therapy, Faculty of Medicine, Universitas Diponegoro, Semarang, Indonesia *Corresponding Author : E-mail : nindita.yora@fk.undip.ac.id ABSTRACK Background : Uric acid is the end product of purine catabolism carried out in the liver. Increased level of uric acid in blood is called hyperuricemia, which might cause gout if it is not treated properly. Melinjo ( Gnetum gnemon L.) plant is a native plant of Indonesia that contains flavonoids and stilbenoid potential as antihyperuricemia. Aim : This paper aimed to study the effect of melinjo seed extract on uric acid levels. Methods : Thirty-six male wistar rats were randomly divided into 6 groups, consists of healthy control group, hyperuricemic control, Allopurinol control, and treatment groups (3 groups). Hyperuricemia was induced by the administration of block broth and potassium oxonate for 4 weeks. Melinjo seed extract doses of 250, 500, and 2000 mg/kg BW, and allopurinol 90 mg/kg BW was given orally for 2 weeks. Statistical analysis was conducted to evaluate differences among groups before and after the intervention. Results : Three doses could significantly reduce uric acid levels (p<0.05) from 5.61±0.95 to 2.45±1.21; 5.86±1.84 to 2.04±1.11; and 5.95±0.91 to 3.59±1.58, respectively. However, there is no significant difference between the three doses. The effectiveness of melinjo seed extract at a dose of 500 mg/kg BW reduced uric acid levels by 65%, a dose of 250 mg/kg BW by 56%, and allopurinol 90 mg/kg BW by 10%. Conlusion : Melinjo seed extract can reduce uric acid levels even though there is no effect of graded dose. Keywords : Gnetum gnemon,, Hyperuricemia, Melinjo seeds, Uric Acid INTRODUCTION People's lifestyles can contribute to the occurrence of health problems in Indonesia such as smoking habits, lack of activity, less nutritious drinks and food, and unhealthy environmental factors. This causes Indonesia to face not only a high number of infectious diseases, but also to face an increase in chronic degenerative diseases. Degenerative chronic diseases generally occur in the elderly. One of the most common health complaints among the elderly is the buildup of uric acid. 1 Uric acid is the end product of purine mononucleotides catabolism into hypoxanthine and guanine which is carried out in the liver. In mammals other than primates, uric acid is further degraded by the uricase enzyme to allantoin, which is more water soluble than uric acid and can be efficiently excreted in the urine. This enzyme is not possessed by higher primates. Between 300 and 400 mg of purines are created and broken down every day. The kidneys normally expel roughly two-thirds of the body's uric acid load each day. 2 If uric acid is not metabolized and excreted properly, there will be an increase in blood uric acid levels, this is called hyperuricemia. 3 Hyperuricemia occurs when uric acid levels exceed >7 mg/dl in men and >6 mg/dl in women. 4 Massive data on hyperuricemia in Indonesia is not yet known for certain, but several regions in Indonesia have conducted surveys on hyperuricemia data. In a study conducted in Depok, 18.6% of people experienced hyperuricemia and the prevalence of hyperuricemia in Denpasar City was 18.2%. 5 There are many factors thath influence hyperuricemia, these include the consumption of food high in purines and impaired excretion on the kidneys. Hyperuricemia that is not followed up will lead to deposits of uric acid crystals in the joint fluid called gout. 6,7 Gout is an inflammation of the joints, bones, and soft tissues triggered by the release of lysosomal enzymes and the production of inflammatory chemokines by the activity of synovial phagocytic cells. 8 Based on the purpose of therapy, there are 2 groups of gout drugs. First, drugs that stop the acute inflammatory process such as colchicine, phenylbutazone, oxyfentabutazone, and indomethacin, and NSAIDs. The second is drugs that affect uric acid levels such as probenecid, sulfinpyrazone, and allopurinol. Allopurinol competitively inhibits the enzyme xanthine oxidase, an important enzyme that plays a role in the uric acid synthesis, at low concentrations and is a noncompetitive inhibitor at