VOL 34 (1) 2023: 36–44 | RESEARCH ARTICLE 36 Indonesian Journal of Pharmacy Indonesian J Pharm 34(1), 2023, 36-44 | journal.ugm.ac.id/v3/IJP Copyright © 2023 by Indonesian Journal of Pharmacy (IJP). The open access articles are distributed under the terms and conditions of Creative Commons Attribution 2.0 Generic License (https://creativecommons.org/licenses/by/2.0/). Basil (Ocimum basilicum L.) Extract Exhibits Antidiabetic and Hepatoprotective Effects via Sirtuin 1 (SIRT1) and Peroxisome Proliferator-Activated Receptors (PPARγ) on Gestational Diabetes Mellitus Rats Model Liganda Endo Mahata 1 *, Hirowati Ali 2 , Arina Widya Murni 3 and Tofrizal Alimuddin 4 1. Department of Pharmacology and Therapy, Faculty of Medicine, Universitas Andalas, Indonesia, Limau Manis, Pauh, Padang City, West Sumatra 25175 2. Department of Biochemistry, Faculty of Medicine, Universitas Andalas, Padang, Indonesia, Limau Manis, Pauh, Padang City, West Sumatra 25175 3. Department of Internal Medicine, Faculty of Medicine, Universitas Andalas, Padang, Indonesia, Limau Manis, Pauh, Padang City, West Sumatra 25175 4. Departement of Pathology Anatomy, Faculty of Medicine, Universitas Andalas, Padang, Indonesia, Limau Manis, Pauh, Padang City, West Sumatra 25175 Article Info ABSTRACT Submitted: 24-03-2022 Revised: 23-07-2022 Accepted: 02-12-2022 *Corresponding author Liganda Endo Mahata Email: ligandaendomahata@med.u nand.ac.id Gestational Diabetes Mellitus (GDM) is a disorder of carbohydrate metabolism that causes hyperglycemia and insulin resistance during pregnancy. Sirtuin 1 (SIRT1) and Peroxisome Proliferator-Activated Receptor γ (PPARγ) are genes that play an important role in glucose metabolism. Dysregulation of SIRT1 and PPARγ is associated with GDM. Hyperglycemia in GDM causes a lipolysis process, which induces inflammation and oxidative stress in hepatocytes causing liver damage. Basil extract (O. basilicum L) is one of the Indonesian medicinal plants that has been used as traditional medicine in diabetic disorders. This study aims to investigate the hypoglycemic activity of basil (O. basilicum) extract by evaluating the effect of basil extract on the expression of SIRT1 and PPARγ in GDM rats and investigate the potential hepatoprotective effect of basil extract by analyzing the rat’s liver histology. Twenty-four pregnant rats were divided into four groups; negative control, positive group induced by streptozotocin 40 mg/kg BW intraperitoneally, and two groups of GDM rats treated with 100 mg/kg BW and 200 mg/kg BW of basil extract for 14 days. Blood glucose levels were examined with a blood glucose meter. The expression of SIRT1 and PPARγ was assessed by the RT-PCR. Histological analysis of the rat`s liver was conducted to determine the percentage of cell damage and tissue edema. The data were statistically processed using SPSS. The results showed the extract of Basil (O. basilicum) at a dose of 200 mg/kg BW showed an anti-diabetic effect which decreased the glucose level concentration by about two times compared to the untreated rat. It enhanced the expression of SIRT significantly with a value of p= 0.035 (p <0.05). Basil extract-treated group showed a trend of increasing PPARγ expression, but not statistically significant. In addition, HE staining on the liver showed a tendency to improve in the group given basil extract. The percentage of liver cell damage decreased significantly from 70.0% in the GDM rat group to 45.2% in group III (p < 0.05) and 44.3% in group IV (p < 0, 05). The percentage of tissue edema also tends to decrease from 49.5% in the GDM group to 38.9% in P1 (p < 0.05) and 38.8% in P2 (p < 0.05). The treatment of basil extract at a dose of 100mg/kg BW and 200mg/kg BW did not show a significant difference (p>0.05). This study concluded that basil extract could increase SIRT1 and potential to be an anti-hyperglycemic therapy with a hepatoprotective effect. Keywords: Gestational Diabetes Mellitus, Anti-diabetic, Hyperglycemia, SIRT1, PPAR γ, O. basilicum, Basil, Hepatoprotective.