International Journal of Human and Health Sciences Vol. 05 No. 01 January’21 22 Original article: Benefcial role of Stevia rebaudiana dry extract on the blood glucose reduction in the chronic diabetes mellitus Flori R. Sari 1 , Hari Hendarto 1 , Djamal Alfan 2 , Saiful Anwar 3 , Chris Adhiyanto 1 , Rizkiani Juleshodia Wulandari 1 Abstract Introduction: Prolonged hyperglycemia may lead to several detrimental microvascular or macrovascular complications in the chronic diabetes mellitus. Thus, achieving normal glycemic condition remains the most important strategy in the diabetes mellitus. Stevia rebaudiana plays an important role on the blood glucose reduction, however, its role in the chronic diabetes mellitus has not been fully elucidated yet. Method: Stevia rebaudiana dry extract (400 mg/kg BW) were given daily by oral gavage for 84 days in rat with diabetes. The measurement of blood glucose concentration were done monthly during the study. Urine output was analyzed on the day 1 and 84. Additionally, lipid profle were measured on the day 84. Results: Compared to the normal rat, signifcant hyperglycemia were observed in the diabetic rat. Blood glucose concentration tends to decrease in the rat received Stevia rebaudiana extract (St), however, signifcant diference was achieved on the day 84 of the study confronted to the diabetic rats. Moreover, lower concentration of plasma cholesterol concentration and urine output reduction was signifcantly observed in the St rat compared to the D rat on the day 84. Discussion: Daily intake of Stevia rebaudiana extract on its therapeutic doses may play benefcial role in the chronic diabetes mellitus by gradually reduced blood glucose concentration, urine output and plasma cholesterol concentration. However, further cellular analysis were required to explicate the exact mechanism. Keyword: Stevia rebaudiana, diabetes mellitus, hyperglycemia, hyperlipidemia, urine output Correspondence to: Flori R. Sari, Department of Pharmacology, Faculty of Medicine, Universitas Islam Negeri Syarif Hidayatullah Jakarta, Jakarta, Indonesia. Email: forirsari@uinjkt.ac.id 1. Faculty of Medicine, Universitas Islam Negeri Syarif Hidayatullah Jakarta, Jakarta, Indonesia. 2. Department of Research and Development, PT. Agro Jabar Bandung, Jawa Barat, Indonesia 3. Post-Graduate Program, Institut Teknologi dan Bisnis Ahmad Dahlan, Banten, Indonesia International Journal of Human and Health Sciences Vol. 05 No. 01 January’21 Page : 22-26 DOI: http://dx.doi.org/10.31344/ijhhs.v5i1.227 Introduction: Persistent hyperglycemia due to either insulin defciency or insulin resistance has become the main culprit of several diabetic complications including diabetic heart and kidney. 1 Hyperglycemia and glucotoxicity may stimulate advanced glycation end products (AGE) that contributes in the fbrosis, cardiac stifness and impaired diastolic relaxation. 2 Furthermore, intraluminal glucose accumulation in the tubulus proximal of the kidney along with the AGE accumulation result in the hyper- reabsorption which further contributes to the renal injury. 3 Therefore, chronic hyperglycemia directly elicits specifc complications through the cell injury due to impaired glucose metabolism. Thus, targeting euglycemia still remain the most important strategy in the diabetes mellitus in concomitant with multiple risk factor treatment including blood pressure, cholesterol, body weight and smoking. 4 Stevia rebaudiana, from the Asteraceae family, is a nutrient-rich plants that has a sweeter along with a bitter taste compared to the ordinary sugar. Steviol glycosides, including stevioside and rebaudioside, play important roles in the bitter but sweet taste of Stevia. Steviol glycosides has been reported to be safe and not related to any teratogenic, mutagenic or carcinogenic risks. 5 Accumulating evidences have shown that the active compound of Stevia rebaudiana including stevioside and minor glycoside (dulcoside A, rebaudioside B, C, D, steviolbioside) possess an anti-diabetic as well as an insulinomimetic properties by regulating GLUT4 receptors, 6,7 increasing insulin