Natural products from plants were extracted and widely studied for their activities against many disease conditions. The selection of the extracting solvent is crucial to develop selective and effective methods for the extraction and isolation of target compounds in the plant matrices. Pharmacological properties of plant extracts and their bioactive principles are related to their excellent solubility, stability, and bioavailability when administered by different routes. This review aims to critically analyze natural deep eutectic solvents (NADES) as green solvents in their application to improve the extraction performance of plant metabolites in terms of their extractability besides the stability, bioactivity, solubility, and bioavailability. Herein, the opportunities for NADES to be used in pharmaceutical formulations development including plant metabolites-based nutraceuticals are discussed.

Indonesian cassia (Cinnamomum burmannii Blume) is commonly used as a condiment. It reportedly contains a number of major phytochemical constituents such as trans-cinnamaldehyde and coumarin. Sappan wood (Caesalpinia sappan) is a native plant of Southeast Asia that contains brazilin, a widely known red pigment. This study aimed to determine the optimal extraction conditions using a choline chloride-glycerol (ChCl-glycerol)-based natural deep eutectic solvent (NADES) to obtain greater trans-cinnamaldehyde and brazilin levels from Indonesian cassia and sappan wood. The powders of Indonesian cassia and sappan wood were extracted using ChCl-glycerol-based NADES varied at three different levels: ratio of ChCl to glycerol, ratio of powder to NADES, and the amount of water in NADES. All variables were designed using the Box-Behnken design of response surface methodology to provide 15 extraction conditions. The extraction was performed using ultrasonication-assisted extraction for 30 and 50 min for Indonesian cassia and sappan wood, respectively. Determination of the active compound contents was performed using a high-performance liquid chromatography system equipped with a UV-VIS detector at λmax = 280 nm. The optimization results revealed that the highest levels of trans-cinnamaldehyde, coumarin, and brazilin in NADES extracts were 1907.32, 1735.68, and 368.67 μg/ml, respectively, whereas the lowest levels of these compounds were 453.59, 616.76, and 74.21 μg/ml, respectively. The maximal levels exceeded those obtained using a conventional extraction method, in which 5000 μg/ml Indonesian cassia reflux extract contained only 108.45 μg/ml trans-cinnamaldehyde. Similarly, 1000 μg/ml sappan wood contained only 124.64 μg/ml brazilin. ChCl-glycerol-based NADES was suitable for extracting active compounds from Indonesian cassia and sappan wood; moreover, this solvent is more effective than organic ethanolic coventional solvent.

The high demand for cosmetics has had a great impact on the development of innovative products in the cosmetic industry. The availability of raw materials has become a common problem in the cosmetic industry. Materials from nature can act as alternative sources, such as Ixora javanica. Several studies have shown the potential of I. javanica as an antioxidant and skin lightening agent. The objectives of the present study were to develop and optimize a green ultrasound-assisted deep eutectic solvent extraction of I. javanica. Eleven deep eutectic solvents were evaluated based on extraction efficiency parameters; that is, flavonoid and anthocyanin yields; the antioxidant and tyrosinase inhibitory activities of the extracts. The combination of choline chloride and propylene glycol (1:1) was shown to be the optimal deep eutectic solvent for I. javanica extraction. The extraction parameters of temperature, extraction time, and solid-to-liquid ratio were also optimized using response surface methodology. The total flavonoid compound obtained was 33 mg quercetin equivalent/g dried sample under the optimum extraction condition (extraction time of 5 min, temperature of 57 °C, solid-to-liquid ratio of 0.02 g/mL). In sum, this work demonstrates the potential of natural deep eutectic solvent as an organic solvent replacement to obtain high quality Ixora javanica extract, which is a potential new source of skin-lightening cosmetic materials.

Mitragyna is a genus belonging to the Rubiaceae family and is a plant endemic to Asia and Africa. Traditionally, the plants of this genus were used by local people to treat some diseases from generation to generation. Mitragyna speciosa (Korth.) Havil. is a controversial plant from this genus, known under the trading name “kratom”, and contains more than 40 different types of alkaloids. Mitragynine and 7-hydroxymitragynine have agonist morphine-like effects on opioid receptors. Globally, Mitragyna plants have high economic value. However, regulations regarding the circulation and use of these commodities vary in several countries around the world. This review article aims to comprehensively examine Mitragyna plants (mainly M. speciosa) as potential pharmacological agents by looking at various aspects of the plants. A literature search was performed and information collected using electronic databases including Scopus, ScienceDirect, PubMed, directory open access journal (DOAJ), and Google Scholar in early 2020 to mid-2021. This narrative review highlights some aspects of this genus, including historical background and botanical origins, habitat, cultivation, its use in traditional medicine, phytochemistry, pharmacology and toxicity, abuse and addiction, legal issues, and the potential of Mitragyna species as pharmaceutical products.

Natural deep eutectic solvents (NADES) have been shown to be more effective in extracting plant marker compounds than are organic solvents. In this study, mixtures of choline chloride or betaine with three combinations of sugar molecules (glycerol, xylitol, and sorbitol) and three combinations of organic acids (lactic acid, citric acid, and malic acid) were used as solvents in ultrasonic-assisted extraction (UAE) of trans-cinnamaldehyde and coumarin from cinnamon bark [Cinnamomum burmannii (Nees & T. Nees) Blume]. Optimization of extraction conditions to obtain the optimal trans-cinnamaldehyde content was performed by varying the percentage of water in NADES and extraction time. Efficiency of extraction was determined by conventional extraction performed by maceration, reflux, and the soxhlet method using 96% ethanol for comparison. Trans-cinnamaldehyde and coumarin contents were determined by high-performance liquid chromatography. The surfaces of samples before and after extraction were observed by scanning electron microscopy (SEM). The study results showed that choline chloride-citric acid (1:2) with 40% water addition for 30 minutes produced the highest trans-cinnamaldehyde content of 9.24 ± 0.01 mg/g dry weight. The highest trans-cinnamaldehyde content from conventional extraction using the maceration method was 1.93 ± 0.01 mg/g dry weight. SEM analysis of sample surfaces showed that the ruptured cells in the NADES-UAE method gave a higher trans-cinnamaldehyde yield than that from the shrunken and damaged cells in the conventional extraction. NADES-UAE provided higher extraction efficiency for trans-cinnamaldehyde and coumarin from C. burmannii than that of the conventional methods using 96% ethanol as solvent.

In this study, an environmentally friendly extraction method for flavonoid compound from Ixora javanica , as a new raw material candidate for herbal medicine and cosmetics, was developed. The objectives of the present work were to provide recommendations for the optimal extraction conditions and to investigate the effects of any extraction parameters on flavonoid yields from the I. javanica flower. The extraction process was performed using deep eutectic solvent (DES) (choline chloride and propylene glycol at molar ratio of 1 : 1) and the ultrasound-assisted extraction method. Both single-factor and response surface analyses using three-level and three-factor Box Behnken designs were conducted to obtain the optimum flavonoid concentrations. The results showed that the optimum extraction conditions for total flavonoids featured an extraction time of 40 min, 25% water content in DES and a solid-to-liquid ratio of 1 : 25 g ml ⁻¹ . An extract obtained under optimum extraction conditions showed higher total flavonoid yields than an ethanolic extract which was used for comparison. Scanning electron microscope images demonstrated that both of the solvents also showed different effects on the outer surface of the I. javanica flower during the extraction process. In summary, our work succeeded in determining the optimum conditions for total flavonoids in the I. javanica flower using a green extraction method.