Indones. J. Chem., 2022, 22 (2), 501 - 514 Faizal Maulana et al. 501 Profiling Metabolites through Chemometric Analysis in Orthosiphon aristatus Extracts as α-Glucosidase Inhibitory Activity and In Silico Molecular Docking Faizal Maulana 1 , Alfari Andiqa Muhammad 2 , Ali Umar 1 , Fachrur Rizal Mahendra 2 , Muhammad Musthofa 2 , and Waras Nurcholis 2,3* 1 Department of Chemistry, Faculty of Mathematics and Natural Sciences, IPB University, Jl. Tanjung Kampus IPB Dramaga, Bogor 16680, Indonesia 2 Department of Biochemistry, Faculty of Mathematics and Natural Sciences, IPB University, Jl. Tanjung Kampus IPB Dramaga, Bogor 16680, Indonesia 3 Tropical Biopharmaca Research Center, IPB University, Jl. Taman Kencana Kampus IPB Taman Kencana, Bogor 16128, Indonesia * Corresponding author: tel: +62-8179825145 email: wnurcholis@apps.ipb.ac.id Received: December 18, 2021 Accepted: January 26, 2022 DOI: 10.22146/ijc.71334 Abstract: Orthosiphon aristatus (called kumis kucing in Indonesia) is a valuable herb for diabetes mellitus treatment. In this study, LC-MS/MS and PCA analyses were used to investigate the metabolite profile, classify O. aristatus extracts, and assess the inhibitory activity of -glucosidase and the probable bioactive compounds through in silico study. Results showed that the methanol and ethanol extracts of O. aristatus were active in α- glucosidase inhibitory activity. Both extracts contained 86 compounds as known from the LC-MS/MS analysis. PCA analysis identified 10 metabolites that correlated with α- glucosidase inhibitory activity. Results of in silico analysis obtained rosmarinic acid compound potentially act as anti-diabetic activity, which can be developed for further research. Keywords: diabetic; in silico; Orthosiphon aristatus; metabolomics; PCA ■ INTRODUCTION The International Diabetes Federation reported that in 2019, 463 million people were suffering from diabetes mellitus (DM) in the world. It is predicted that this number will continue to increase to reach 700 million people by 2045 [1]. Indonesia's position is in the top 10 under China, America, Pakistan, Brazil, and Mexico. The population of Indonesian people affected by DM is 10.7 million people. According to the Ministry of Health of the Republic of Indonesia, DM is the number 3 cause of death in Indonesia [2]. Even so, about 30–50% of diabetics are not aware of it [3], so the disease condition develops into complications, such as nephropathy [4], cardiovascular [5], gangrene, or impaired wound healing, to stroke [6]. DM is divided into two, namely, type 1 DM and type 2 DM. Type 1 DM occurs due to damage to the β-pancreatic cells that cannot produce insulin properly. In contrast, type 2 DM is caused by the ineffectiveness of the insulin hormone production process. DM conditions can be determined by calculating blood sugar levels that exceed normal conditions (hyperglycemia). The chronic phase of hyperglycemia causes some of the glucose to undergo auto-oxidation. Glucose auto-oxidation creates reactive oxygen species that act as free radicals, significantly affecting vascular endothelial disorders and leading to complications [7- 8]. One way to prevent hyperglycemia is to inhibit the α- glucosidase enzyme [9]. Determination of the target of α-glucosidase enzymes has been commonly used, and several drugs that have been developed are acarbose and voglibose. However, there are reported adverse effects from the usage of the standard drugs, namely gastrointestinal disturbances in diarrhea, dizziness, nausea, vomiting, liver disorders, and central nervous system disorders [10-11]. Therefore, alternative