Sabah Snake Grass (Clinacanthus nutans) is an interesting traditional medicine because of pharmacology characteristics that contain rich in phenolic content. The aim of the study was to determine the optimum flavonoid compound on the antioxidant activities. The optimum extraction parameters for optimum recovery of phenolic content from Clinachantus nutans leaves were determined using response surface methodology (RSM). A central composite rotatable design (CCRD) was employed to investigate the effects of ultrasonic frequency (X1: 25 - 40 kHz), temperature (X2: 40 - 80 °C) and solid-to-solvent ratio (X3: 10 - 30 ml/g) on the recovery of flavonoid vitexin (Y1) and orientin (Y2). The optimal parameter achieved based on combination of the extraction parameters are as follows: X1 = 25 kHz, X2 = 40 °C and X3 = 15 g/ml. These optimum conditions yielded vitexin (2.25 mg/g) and orientin (3.75 mg/g). Our results revealed that distilled water may be a good choice for extracting the phenolic compound of Clinacanthus nutans due to costing and environmental issue. Vitexin and orientin have potential of antiproliferate activity on the cancer cell. The concentration of extracted compound (orientin and vitexin) from the optimum parameters had produced high in phenolic content. In conclusion, the application of response surface method successfully provide the high extraction parameters with high total phenolic content and antioxidant activity.

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