Vol.:(0123456789) 1 3 Arabian Journal for Science and Engineering https://doi.org/10.1007/s13369-020-04584-6 RESEARCH ARTICLE-CHEMICAL ENGINEERING Supercritical Carbon Dioxide Extraction of Sinensetin, Isosinensetin, and Rosmarinic Acid from Orthosiphon stamineus Leaves: Optimization and Modeling Ahmad Hazim Abdul Aziz 1,2  · Nicky Rahmana Putra 1,2  · Helen Kong 2  · Mohd Azizi Che Yunus 2 Received: 25 August 2019 / Accepted: 26 April 2020 © King Fahd University of Petroleum & Minerals 2020 Abstract Due to the health benefts such as anti-diabetic, antioxidant, and anti-infammatory agents, the extraction of bioactive compounds from natural plants becomes signifcant. One of the favored extraction processes is supercritical carbon dioxide (SC-CO 2 ). SC-CO 2 is known as a green method with a high-selectivity process. Therefore, this study aims to determine the best parameters and mass transfer process to extract the bioactive compounds, viz. sinensetin, isosinensetin, and rosmarinic acid, in the leaves of Orthosiphon stamineus using the SC-CO 2 extraction technique. Response surface methodology was applied to optimize the operating temperature and pressure of 40–80 °C and 10–30 MPa, respectively. Meanwhile, to quantify the concentration of sinensetin, isosinensetin, and rosmarinic acid, a high-performance liquid chromatography was used. Results showed that the level of sinensetin, isosinensetin, and rosmarinic acid varied signifcantly at each extraction condi- tion from 122.98 to 469.54 mg/kg sample, 50.60 to 419.07 mg/kg sample, and 17.43 to 931.44 mg/kg, respectively. Based on the optimization study, the optimum pressure and temperature were 10 MPa and 80 °C, respectively, with 440.3 mg/g sinensetin, 392.9 mg/g isosinensetin, and 752.0 mg/g of rosmarinic acid concentration obtained. Meanwhile, the single- sphere model showed a signifcant correlation with sinensetin, isosinensetin, and rosmarinic acid extraction, with an average AARD of 12.31%, 13.72%, and 18.90%, respectively. The range of difusivity coefcient, D e , of sinensetin, isosinensetin, and rosmarinic acid was 5.47E−13–1.81E−12 m 2 /s, 8.26E−13–1.89E−12 m 2 /s, and 2.64E−13–2.28E−12 m 2 /s, respectively. Keywords Supercritical carbon dioxide · Orthosiphon stamineus · Optimization · Difusivity · Sinensetin · Isosinensetin · Rosmarinic acid 1 Introduction Orthosiphon stamineus (O. stamineus) is a genus of Lami- aceae and a popular traditional herbal medicine among Asians. It can treat various diseases, including bacterial infections, infuenza, and angiogenesis-related problems such as cancer. Few studies have been conducted on the medicinal properties of O. stamineus. O. stamineus is proven to act as an anti-diabetic [1, 2], anti-obesity [3, 4], antibacte- rial [5], antifungal [6], antihypertensive [7], antioxidant [8], and anti-arthritis [9] and has a hepatoprotective and anti- hyperglycemic efect [10, 11]. To date, phytochemical and pharmacological studies of O. stamineus are still underway due to its popularity and efcacy. Orthosiphon stamineus contains several bioactive com- pounds that contribute to its medicinal properties, such as sinensetin, isosinensetin, and rosmarinic acid. Sinensetin is a potent polymethoxyfavones (PMF) due to its vigorous antiangiogenesis activity [12]. Isosinensetin is a sinensetin PMF-type isomer that reported stronger antiproliferative activity compared to sinensetin against human ovarian and breast cancer cell line of HO8910 and MCF-7, respectively [13]. It also has an antiproliferative efect on human cervi- cal carcinoma HeLa cells [14] and high inhibition to HIV-1 * Ahmad Hazim Abdul Aziz ahazim3@graduate.utm.my * Mohd Azizi Che Yunus azizi@cheme.utm.my 1 Centre of Lipids Engineering and Applied Research (CLEAR), Ibnu Sina Institute for Scientifc and Industrial Research, Universiti Teknologi Malaysia, 81310 UTM Johor Bahru, Johor, Malaysia 2 School of Chemical and Energy Engineering, Universiti Teknologi Malaysia, 81310 UTM Johor Bahru, Johor, Malaysia