It is estimated that 80% of all synthetic drugs are derived from medicinal plants, and nowadays, many synthetic drugs are derived from medicinal plants. Valeriana officinalis can treat many diseases of the nervous system. A crucial aspect of valerian extract is that it inhibits the proliferation of breast cancer cells. To optimize the yield of bioactive compounds in the V. officinalis root extraction, a response surface methodology-based D-optimal design was used. To fulfill this aim, the effects of various factors such as solvent type and concentration, mixing temperature, ultrasound time, and drying method were examined. The optimal conditions for solvent percentages, mixing temperature, ultrasound time, solvent type, and drying methods were determined to be 94.88%, 25 °C, 48.95 min, methanol, and microwave, respectively, with a desirability of 0.921. The predicted valerenic acid, total phenols, total flavonoids, and antioxidant activity in V. officinalis extract were 1.19 (mg/g DW), 8.22 (mg/g DW), 5.27 (mg/g DW), and 92.64%, respectively. In optimal conditions, the extracted amounts of valerenic acid, total phenols, total flavonoids, and antioxidant activity were 2.07 mg/g DW, 7.96 mg/g DW, 5.52 mg/g DW, and 78.68%, respectively, which were consistent with the model predicted amounts (based on 95% prediction interval). This study could be useful as a model for demonstrating the efficacy of microwave drying to maximize the biochemical content of V. officinalis, as well as the antioxidant activity of the root extracts of V. officinalis on industrial scale.
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