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A series of citrate salts were tested as hydrogen bond acceptors to synthesize deep eutectic solvents (DES) based on lactic acid and glycerol, used as hydrogen bond donors. The DES produced were then screened to identify the highest performing system for the effective extraction of polyphenolic phytochemicals from the medicinal plant Salvia fruticosa Mill. (Greek sage). The most efficacious DES was the one composed of lactic acid and sodium citrate dibasic, at a molar ratio of 15:1 (LA-SCDB15). Furthermore, for the first time there has been evidence concerning DES pH and extraction efficiency. Using this solvent, a batch, stirred-tank extraction process was developed, by employing ultrasonication pretreatment and response surface methodology. The optimal settings determined were stirring speed 900 rpm, proportion of DES/water 77% (w/v), and ultrasonication pretreatment time 15 min. By adjusting these optimal settings, the predicted maximum total polyphenol yield was calculated to be 79.93 ± 1.92 mg gallic acid equivalents g−1 dry mass. The examination of temperature effects demonstrated that the batch, stirred-tank extraction stage was very energy-efficient, with a barrier of 7.64 kJ mol−1. Comparison of the extraction of Salvia fruticosa polyphenols with other green processes previously developed, illustrated the high extraction capacity of LA-SCDB15. The major polyphenols identified in the extracts produced under optimized settings were chlorogenic acid, luteolin 7-O-glucuronide and rosmarinic acid.

S. fruticosa, collectively known as Cretan sage, is a medicinal plant to which a number of bioactivities have been attributed. In spite of its importance in nutrition and pharmacy, reports on the extraction of major polyphenols using sustainable processes are particularly limited. In this study, three common cyclodextrins, namely, methyl β-cyclodextrin (m-β-CD), hydroxypropyl β-cyclodextrin (HP-β-CD), and β-cyclodextrin (β-CD), were tested as green boosters of aqueous extraction of polyphenols from aerial parts of S. fruticosa. To examine simultaneously important extraction parameters, including the concentration of cyclodextrins (CCD), pH, and liquid-to-solid ratio (RL/S), a Box–Behnken design was chosen, with three central points. Temperature effects on the extraction yield were also considered, by carrying out kinetics. The results showed that m-β-CD was the most effective extraction booster, providing total polyphenols yields that amounted to 98.39 mg gallic acid equivalents g−1 dry mass. The kinetic assay demonstrated that extraction was highly effective at 80 °C, increasing significantly polyphenol yield, as well as the ferric-reducing power and antiradical activity of the extracts. It was also proven that extraction with m-β-CD was the least energy-demanding process. Liquid chromatography-tandem mass spectrometry examination revealed that m-β-CD might possess higher affinity for luteolin 7-O-glucuronide extraction, but β-CD for rosmarinic acid extraction.

Salvia fruticosa Miller, also known as Cretan or Greek sage, is a medicinal plant with significant biological properties, which are largely ascribed to its polyphenolic composition, but there is to-date a scarcity of green and sustainable processes for efficient polyphenol extraction from this plant. The objective of this study was the implementation of an extraction process that would combine a green solvent based on glycerol, a biodiesel industry by-product, and ultrasonication pretreatment. Ultrasonication for 40 min followed by stirred-tank extraction was shown to provide significantly higher total polyphenol yield than mere stirred-tank extraction, while kinetics indicated 50 °C as the most favorable temperature, with the yield being 92 mg gallic acid equivalents (GAE) per g dry mass. Comparison of this method with a previously developed one that used methyl β-cyclodextrin revealed that the extracts obtained had similar antioxidant activity, and yield in major polyphenols including luteolin 7-O-glucuronide and rosmarinic acid was virtually equal. The current process is proposed as a sustainable and effective methodology for the generation of polyphenol-enriched extracts from S. fruticosa, which could be used as effective food antioxidants/antimicrobials and/or cosmetic constituents.

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