Natural Product Extracts Research Articles

Total Biosynthesis for Milligram-Scale Production of Etoposide Intermediates in a Plant Chassis.

Etoposide is a plant-derived drug used clinically to treat several forms of cancer. Recent shortages of etoposide demonstrate the need for a more dependable production method to replace the semisynthetic method currently in place, which relies on extraction of a precursor natural product from Himalayan mayapple. Here we report milligram-scale production of (-)-deoxypodophyllotoxin, a late-stage biosynthetic precursor to the etoposide aglycone, using an engineered biosynthetic pathway in tobacco. Our strategy relies on engineering the supply of coniferyl alcohol, an endogenous tobacco metabolite and monolignol precursor to the etoposide aglycone. We show that transient expression of 16 genes, encoding both coniferyl alcohol and main etoposide aglycone pathway enzymes from mayapple, in tobacco leaves results in the accumulation of up to 4.3 mg/g dry plant weight (-)-deoxypodophyllotoxin, and enables isolation of high-purity (-)-deoxypodophyllotoxin after chromatography at levels up to 0.71 mg/g dry plant weight. Our work reveals that long (>10 step) pathways can be efficiently transferred from difficult-to-cultivate medicinal plants to a tobacco plant production chassis, and demonstrates mg-scale total biosynthesis for access to valuable precursors of the chemotherapeutic etoposide.

Solid-Supported Proteins in the Liquid Chromatography Domain to Probe Ligand-Target Interactions.

Ligand-target interactions play a central role in drug discovery processes because these interactions are crucial in biological systems. Small molecules-proteins interactions can regulate and modulate protein function and activity through conformational changes. Therefore, bioanalytical tools to screen new ligands have focused mainly on probing ligand-target interactions. These interactions have been evaluated by using solid-supported proteins, which provide advantages like increased protein stability and easier protein extraction from the reaction medium, which enables protein reuse. In some specific approaches, precisely in the ligand fishing assay, the bioanalytical method allows the ligands to be directly isolated from complex mixtures, including combinatorial libraries and natural products extracts without prior purification or fractionation steps. Most of these screening assays are based on liquid chromatography separation, and the binding events can be monitored through on-line or off-line methods. In the on-line approaches, solid supports containing the immobilized biological target are used as chromatographic columns most of the time. Several terms have been used to refer to such approaches, such as weak affinity chromatography, high-performance affinity chromatography, on-flow activity assays, and high-performance liquid affinity chromatography. On the other hand, in the off-line approaches, the binding event occurs outside the liquid chromatography system and may encompass affinity and activity-based assays in which the biological target is immobilized on magnetic particles or monolithic silica, among others. After the incubation step, the supernatant or the eluate from the binding assay is analyzed by liquid chromatography coupled to various detectors. Regardless of the selected bioanalytical approach, the use of solid supported proteins has significantly contributed to the development of automated and reliable screening methods that enable ligands to be isolated and characterized in complex matrixes without purification, thereby reducing costs and avoiding time-laborious steps. This review provides a critical overview of recently developed assays.

Role of Natural Products in Aging Skin

Aging is an unavoidable progression in everyone's life and influenced by lifestyle, genetic as well as environmental factors. Herbal and plant extracts are used as antiaging since ancient times, but the evidence are still limited. Recent developments in antiaging investigation anticipated the use of natural products as the main ingredient in the formulations. Hence, this presentation focused to highlight the importance of twelve most popular medicinal plant extracts that have reported to have skin aging prevention potential. All these natural product extracts have a capacity to scavenge free radicals and defend skin matrix over the inhibition of enzymatic degradation. Some of the extracts promotes collagen synthesis in the skin and also affect the skin tightness and elasticity. However, the use of natural product extracts as an antiaging and anti-wrinkling it should be further explored using a wide range of in-vitro and in-vivo models to confirm its safety and efficacy before proceeding into the development of cosmetic products.

Antifibrotic and tumor microenvironment modulating effect of date palm fruit (Phoenix dactylifera L.) extracts in pancreatic cancer

Date palm fruit (Phoenix dactylifera L.) is an endemic functional food, with great nutritional and economic importance due to its phytochemical compositions. The microenvironment of pancreatic cancer consists of cellular and acellular components, including fibroblasts, myofibroblasts, pancreatic stellate cells (PSCs), immune cells, blood vessels, extracellular matrix (ECM) and soluble proteins, such as cytokines and growth factors. The ECM represents a physical barrier that protects the tumor cell from active therapeutic compounds. In this study, four different solvents; water, ethanol, acetone, and ethyl acetate have been used to extract natural products from date palm fruit using a maceration method. The prepared extracts were investigated for antifibrotic (expression of fibronectin-1 and alpha-smooth muscle actin) and antiproliferative activity in tumor necrosis factor (TNF) stimulated PSCs in vitro. Based on the pharmacological test results, the ethyl acetate extract was subsequently partitioned into nine fractions based on polarity using silica gel column chromatography. These nine collective fractions were further evaluated for their activity. Ethanol, ethyl acetate and acetone, but not water extract significantly reduced PSC proliferation (p < 0.05). Date fruit fractions reduced fibrosis, decreased PSC activity and reversed the PSCs’ fibrotic phenotype. The findings suggest a new approach for targeting pancreatic cancer through the modulation of PSC activity, thereby possibly enhancing the effect of known anticancer drugs. Moreover, date palm fruit appears to have chemopreventive activity protecting from pancreatic and probably other types of cancer, and thereby might be useful candidate to the pharmaceutical and nutraceutical industries in the development of natural compound-based industrial anticancer product.

Antibiotic Dereplication Using the Antibiotic Resistance Platform.

One of the main challenges in the search for new antibiotics from natural product extracts is the re-discovery of common compounds. To address this challenge, dereplication, which is the process of identifying known compounds, is performed on samples of interest. Methods for dereplication such as analytical separation followed by mass spectrometry are time-consuming and resource-intensive. To improve the dereplication process, we have developed the antibiotic resistance platform (ARP). The ARP is a library of approximately 100 antibiotic resistance genes that have been individually cloned into Escherichia coli. This strain collection has many applications, including a cost-effective and facile method for antibiotic dereplication. The process involves the fermentation of antibiotic-producing microbes on the surface of rectangular Petri dishes containing solid medium, thereby allowing for the secretion and diffusion of secondary metabolites through the medium. After a 6 day fermentation period, the microbial biomass is removed, and a thin agar-overlay is added to the Petri dish to create a smooth surface and enable the growth of the E. coli indicator strains. Our collection of ARP strains is then pinned onto the surface of the antibiotic-containing Petri dish. The plate is next incubated overnight to allow for E. coli growth on the surface of the overlay. Only strains containing resistance to a specific antibiotic (or class) grow on this surface enabling rapid identification of the produced compound. This method has been successfully used for the identification of producers of known antibiotics and as a means to identify those producing novel compounds.

Subcritical water extraction, identification, antioxidant and antiproliferative activity of polyphenols from lotus seedpod

In this study, polyphenols from lotus seedpod were extracted by subcritical water. Based on single factor experiments, the extraction conditions were optimized by response surface methodology (RSM). Under optimal conditions [temperature of 140 °C, time of 20 min, liquid-solid ratio of 70 mL/g and 4‰ (W/V) NaHSO3], the maximal yeild of lotus seedpod polyphenols (LSPP) was 178.32 mg of gallic acid equivalents (mg GAE) per gram dry weight (g DW), significantly higher than that of hot water extraction (HWE). This study further investigated antioxidant activity of LSPP. The results showed that, compared with HWE, LSPP extracted by SWE had better reducing power and ability to scavenge DPPH, ABTS*+ and NO2−, (P < 0.05). In addition, the antiproliferative ability on human hepatoma G2 (HepG2) cells of LSPP extracted by SWE was also evaluated to be significant (P < 0.05). Moreover, the antioxidant and antiproliferative activity of LSPP were found to be positively correlated with the polyphenols concentration. Detailed HPLC-ESI-MSn analyses with literatures and contrasted with authentic standards allowed the identification of 8 compounds (proanthocyanidin dimer 1, proanthocyanidin dimer 2, catechin, cyanidin-3-O-glucoside, quercetin-3-O-glucuronoside, isoquercetin, kaempferol-3-O-glucuronide and isorhamnetin) in LSPP (SWE). This work can provide a reference for the utilization of subcritical water extraction in the field of natural product extraction and the development and utilization of lotus seedpod as bioactive materials.

Knowledge Management for Rural Industries using Cloud Computing

About more than two decades ago, the practice of Knowledge Management (KM) was started. Also their importance was understood by the many growing and developed organizations. Now it becomes as an importantly integral and inherent component of any business units. Knowledge management (KM) is actually the process of creating, sharing, using and managing the knowledge and information of any organisation. Actually to achieving organisational objectives, it refers to a multidisciplinary approach. This is by making the best use of knowledge. KM efforts focus on organisational many of the objectives. Some of these are like improved performance, competitive advantage, innovation, the sharing of lessons learned, integration and continuous improvement of the organisation. “Rural industries” refers to the small-scale activities that took place in communities where the dominant economic pursuits revolved around agriculture or natural product extraction. Such industry supported these activities and processed their output. Cloud computing is defined as “the practice of using a network of remote servers hosted on the Internet to store, manage, and process data, rather than a local server/personal computer.” Because of Information and Computer Technologies (ICT), it is possible to put many innovative fruitful ideas into KM practices. In reality this expresses the new trends in KM. This also justifies that, various newly developed technologies have impacted on, how the knowledge is managed? One of advanced, most predominant technology is Cloud Computing, ofcourse within the ICT. The way IT services are provisioned, it has significantly impacted. The rural industries can now get the advantage of such hosted services for major IT activities. This is nothing but KM through the means of Cloud Computing. Before the advent of Cloud Computing, earlier it was beyond their budget.

Extraction of Natural Fragrance Ingredients: History Overview and Future Trends.

For centuries, perfumes consisted in a combination of natural ingredients, mainly of plant origin. From the 19th century on, the advent of organic synthesis enabled the deployment of multiple synthetic olfactory notes, enriching significantly the perfumers' portfolio. Chemistry is ever since the foundation of modern perfumery. However, sustainable-minded consumers, massively rejecting synthetics for safety and ecological issues, engaged a global return to nature in numerous sectors, and the fragrance industry is not outdone. Sustainable extraction of natural products, making use of innovative technologies, process intensification and agro-based solvents, constitutes the answer to develop eco-conceived fragrant ingredients covering every olfactory family without endangering biodiversity any further. The objective of this review is to draw a clear picture of where those technological advances are today and to assess the ones that may be effectively transposed at the industrial scale tomorrow.

New High-Throughput Screening Identifies Compounds That Reduce Viability Specifically in Liver Cancer Cells That Express High Levels of SALL4 by Inhibiting Oxidative Phosphorylation

Some oncogenes encode transcription factors, but few drugs have been successfully developed to block their activity specifically in cancer cells. The transcription factor SALL4 is aberrantly expressed in solid tumor and leukemia cells. We developed a screen to identify compounds that reduce the viability of liver cancer cells that express high levels of SALL4, and we investigated their mechanisms. We developed a stringent high-throughput screening platform comprising unmodified SNU-387 and SNU-398 liver cancer cell lines and SNU-387 cell lines engineered to express low and high levels of SALL4. We screened 1597 pharmacologically active small molecules and 21,575 natural product extracts from plant, bacteria, and fungal sources for those that selectively reduce the viability of cells with high levels of SALL4 (SALL4hi cells). We compared gene expression patterns of SALL4hi cells vs SALL4-knockdown cells using RNA sequencing and real-time polymerase chain reaction analyses. Xenograft tumors were grown in NOD/SCID gamma mice from SALL4hi SNU-398 or HCC26.1 cells or from SALL4lo patient-derived xenograft (PDX) cells; mice were given injections of identified compounds or sorafenib, and the effects on tumor growth were measured. Our screening identified 1 small molecule (PI-103) and 4 natural compound analogues (oligomycin, efrapeptin, antimycin, and leucinostatin) that selectively reduced viability of SALL4hi cells. We performed validation studies, and 4 of these compounds were found to inhibit oxidative phosphorylation. The adenosine triphosphate (ATP) synthase inhibitor oligomycin reduced the viability of SALL4hi hepatocellular carcinoma and non-small-cell lung cancer cell lines with minimal effects on SALL4lo cells. Oligomycin also reduced the growth of xenograft tumors grown from SALL4hi SNU-398 or HCC26.1 cells to a greater extent than sorafenib, but oligomycin had little effect on tumors grown from SALL4lo PDX cells. Oligomycin was not toxic to mice. Analyses of chromatin immunoprecipitation sequencing data showed that SALL4 binds approximately 50% of mitochondrial genes, including many oxidative phosphorylation genes, to activate their transcription. In comparing SALL4hi and SALL4-knockdown cells, we found SALL4 to increase oxidative phosphorylation, oxygen consumption rate, mitochondrial membrane potential, and use of oxidative phosphorylation-related metabolites to generate ATP. In a screening for compounds that reduce the viability of cells that express high levels of the transcription factor SALL4, we identified inhibitors of oxidative phosphorylation, which slowed the growth of xenograft tumors from SALL4hi cells in mice. SALL4 activates the transcription of genes that regulate oxidative phosphorylation to increase oxygen consumption, mitochondrial membrane potential, and ATP generation in cancer cells. Inhibitors of oxidative phosphorylation might be used for the treatment of liver tumors with high levels of SALL4.

Review of Alternative Solvents for Green Extraction of Food and Natural Products: Panorama, Principles, Applications and Prospects.

In recent years, almost all extraction processes in the perfume, cosmetic, pharmaceutical, food ingredients, nutraceuticals, biofuel and fine chemical industries rely massively on solvents, the majority of which have petroleum origins. The intricate processing steps involved in the industrial extraction cycle makes it increasingly difficult to predict the overall environmental impact; despite the tremendous energy consumption and the substantial usage of solvents, often the yields are indicated in decimals. The ideal alternative solvents suitable for green extraction should have high solvency, high flash points with low toxicity and low environmental impacts, be easily biodegradable, obtained from renewable (non-petrochemical) resources at a reasonable price and should be easy to recycle without any deleterious effect to the environment. Finding the perfect solvent that meets all the aforementioned requirements is a challenging task, thus the decision for the optimum solvent will always be a compromise depending on the process, the plant and the target molecules. The objective of this comprehensive review is to furnish a vivid picture of current knowledge on alternative, green solvents used in laboratories and industries alike for the extraction of natural products focusing on original methods, innovation, protocols, and development of safe products.

Highly efficient and selective extraction of minor bioactive natural products using pure ionic liquids: Application to prenylated flavonoids in licorice

Lots of minor constituents in herbal medicines have shown great potential to devolve into lead compounds, and their extraction is attracting more and more attention in pharmaceutical industry. This study provided an example that showed efficient and selective extraction of minor bioactive natural products (prenylated flavonoids with anti-cancer activities) from an herbal medicine (licorice) using pure ionic liquids as green solvents. After investigation of a variety of hydrophobic ionic liquids with ultrasonic-assisted extraction, we found that [C8MIM]BF4 (1-octyl-3-methylimidazolium tetrafluoroborate) was the most effective one for extraction of five representative compounds (isoangustone A, glycycoumarin, licoisoflavanone, licoricidin and glabridin), and solvent to solid ratio, extraction time, extraction temperature and soaking time were then optimized through single-factor experiments and response surface methodology. As a result, the established method had significantly higher extraction selectivity than conventional organic solvents, which could be attributed to significant physical change of licorice microstructures after extraction, as well as strong interactions (especially hydrogen bond interactions) between [C8MIM]BF4 and prenylated flavonoids by mechanism study. In addition, 78.92% of the extracted prenylated flavonoids could be readily recovered from [C8MIM]BF4 by using reversed-phase solid phase extraction, and the recyclability of [C8MIM]BF4 was also confirmed.

Affinity measurement of ligands in Perilla frutescens extract towards α-glucosidase using affinity-based ultrafiltration-high-performance liquid chromatography

It is a time-consuming and challenging task for affinity measurement of drug lead compounds from a plant extract because of its chemical complexity. In this research, a strategy of ultrafiltration-high-performance liquid chromatography (HPLC) was developed to directly measure dissociation constant (Kd) of compounds from natural product extract to target protein, and the Kd measurement of α-glucosidase ligands from the ethyl acetate fraction of Perilla frutescens (L.) Britt. (PFEA) was performed. The recovery value, binding degree, and signal-to-noise ratio of α-glucosidase ligands from PFEA were first determined according to the ultrafiltration-HPLC results; the Kd values were then calculated using proposed equilibrium. Finally, oleanolic acid (4) and apigenin (8) from PFEA were determined as the high affinity ligands for α-glucosidase, and their Kds were calculated as 44.9 μM and 88.5 μM, respectively, which agreed with the isothermal titration calorimetry analysis, kinetic analysis, and computer simulation of molecular docking. These results suggested that the proposed strategy is a simple and convenient method for the direct Kd determination of compounds from natural product extract without using any internal calibrants or internal standards.

The Application of Aqueous Two-phase System in the Extraction of Natural Products from Chinese Herbal Medicine: A Review

Background: In the past decades, Chinese herbal medicine has attracted worldwide attention because they contain a variety of active ingredients which are beneficial to human health. As a result, there is a growing interest in the extraction of these substances. However, traditional extraction methods not only need a large amount of extractant, but are also time-consuming, moreover, the extraction efficiency is extremely poor and tedious purification steps are required to purify the crude extract. Thus, researchers hope to find an alternative method for the extraction of these components and the aqueous two-phase system (ATPS) seems to be one. Objective: This review focuses on introducing the properties of the aqueous two-phase system and summarizing the application of ATPS in the extraction of natural products. Meanwhile, this review also provided a guideline to researchers who wish to design a suitable ATPS for a specific target and how to amplify it to industrial-scale.

Quantifying cell disruption as an integral part of natural product extraction

Cell disruption is a basic yet often overlooked step in the extraction of valuable substances from plants. A simple and easily applicable method is presented to assess cell membrane stability as an integral part of phytoextraction by measuring electric conductivity (EC) and calculating the Index of Injury (Id). In this paper, a wide range of industrially applicable methods is evaluated including mechanical disruption, heat, a combination of both, extreme pH-values, application of microwaves, ultrasound and pulsed electric field (PEF). Moreover, the approach via Id is compared to an alternative method using HPLC analysis of a marker substance to show the method’s limitations as well as to provide further applications of this basic system. For the feedstock used, heavy mechanical processing such as grinding, temperatures above 50°C as well as acidic condition below pH 2.5 were equally potent methods for complete cell disruption. Alternatively, moderate mechanical treatment like chopping or cutting could be combined with temperatures above 40°C for maximal cell damage. Although PEF application showed merely moderate effects applied alone, it may be combined with mechanical pre-treatment in order to achieve high cell disruption at low temperatures, making it ideal for the extraction of thermolabile compounds.

Evaluation of the phenolic antioxidants of olive (Olea europaea) leaf extract obtained by a green approach: Use of reduced graphene oxide for electrochemical analysis

Deep Eutectic Liquids (DELs) have been specially designed, and used for the extraction of bioactive natural products from a bio-waste, since they have attracted much attention from economic and ecological aspects. In this study, an easy, accurate and sensitive detection method has been developed towards a trace amount of oleuropein which is one of the most significant components of the olive leaf extract. TiOx-modified reduced graphene oxide electrode (TiOx-RGO@GCE) has been used as the sensing electrode for the quantitative detection of oleuropein. The structural characterization of TiOx-RGO@GCE has been performed using diffuse reflectance infrared Fourier transform spectroscopy (DRIFT) and atomic force microscopy (AFM) techniques. Cyclic voltammetry (CV) and square wave voltammetry (SWV) techniques have been implemented to investigate the electrochemical behavior of oleuropein. The electrochemical experiments revealed that the quasi-reversible reaction is the dominant mechanism on the electrode/electrolyte interface. The linear concentration range of 1–12 µM was obtained with the detection limit of 18.7 nM for oleuropein.

Design and Application of a High-Throughput, High-Content Screening System for Natural Product Inhibitors of the Human Parasite Trichomonas vaginalis.

It is estimated that Trichomonas vaginalis affects an astonishing 3.9% of the world's population, and while many of those infected are asymptomatic, progression of the disease can lead to serious health problems. Currently, the nitroimidazoles constitute the only drug class approved to treat trichomoniasis in the United States, which makes the spread of drug resistance a realistic concern. We developed a new image-based, high-throughput, and high-content assay for testing natural products (purified compounds and extracts) for antitrichomonal activity. Applying this assay system to a library of fungal natural product extracts led to the identification of three general classes of natural product inhibitors that exhibited moderate to strong activities against T.vaginalis: anthraquinones, xanthone-anthraquinone heterodimers, and decalin-linked tetramic-acid-containing metabolites. The tetramate natural products emerged as the most promising candidate molecules with pyrrolocin A (51) exhibiting potent activity against the parasite (EC50 = 60 nM), yet this metabolite showed limited toxicity to mammalian cell lines (selectivity index values of 100 and 167 versus 3T3 fibroblast and Ect1 normal cervical cells, respectively). The imaging-based assay system is a powerful tool for the bioassay-guided purification of single-component antitrichomonal biomolecules from complex natural product mixtures.

Non-Ionic Deep Eutectic Liquids: Acetamide-Urea Derived Room Temperature Solvents.

A family of non-ionic deep eutectic liquids has been developed based upon mixtures of solid N-alkyl derivatives of urea and acetamide that in some cases have melting points below room temperature. The eutectic behaviour and physical characteristics of a series of eleven eutectic mixtures are presented, along with a molecular dynamics study-supported hypothesis for the origin of the non-ideal mixing of these substances. Their use as solvents in applications ranging from natural product extraction to organic and polymer synthesis are demonstrated.

Natural-Product-Inspired Compounds as Countermeasures against the Liver Carcinogen Aflatoxin B1.

Aflatoxin B1 (AfB1) ranks among the most potent liver carcinogens known, and the accidental or intentional exposure of humans and livestock to this toxin remains a serious global threat. One protective measure that had been proposed is employing small-molecule therapeutics capable of mitigating the toxicity of AfB1; however, to date, these efforts have had little clinical success. To identify molecular scaffolds that reduce the toxicity of AfB1, we developed a cell-based high-throughput high-content imaging assay that enabled our team to test natural products (pure compounds, fractions, and extracts) for protection of monolayers and spheroids composed of HepG2 liver cells against AfB1. The spheroid assay showed notable potential for further development, as it afforded greater sensitivity of HepG2 cells to AfB1, which is believed to better mimic the in vivo response of hepatocytes to the toxin. One of the most bioactive compounds to arise from this investigation was alternariol-9-methyl ether (1, purified from an Alternaria sp. isolate), which inspired the synthesis and testing of several structurally related molecules. Based on these findings, it is proposed that several types of natural and synthetic polyarene molecules that have undergone oxidative functionalization (e.g., compounds containing 3-methoxyphenol moieties) are promising starting points for the development of new agents that protect against AfB1 toxicity.

Hibiscus flower extract selectively induces apoptosis in breast cancer cells and positively interacts with common chemotherapeutics

BackgroundCurrent therapeutic approaches to treat metastatic breast cancer, although effective, have shown many inadvertent side effects such as genotoxicity due to a lack of selectivity. Thus, these treatment plans are not suitable for long-term usage. Natural health product extracts are safe for long-term consumption and some have shown to be medicinally active containing multiple bioactive compounds able target multiple vulnerabilities in cancer. One of which, Hibiscus rosa-sinesis (hibiscus) extract, has been reported to have many medicinal and anticancer properties due to its antioxidant and hypolipidemic effects. However, its efficacy against breast cancer has not been fully investigated and characterized. If effective against cancer, hibiscus extract could potentially be combined with chemotherapeutic treatments in adjuvant therapy to reduce chemotherapy-inducing side effects.MethodWe have investigated aqueous hibiscus flower extract anticancer efficacy, selectivity, and interactions with chemotherapeutics taxol, cisplatin, and tamoxifen in estrogen-receptor positive breast cancer cells, triple-negative human breast cancer cells, and normal non-cancerous cells. Apoptotic morphology and biochemical marker expression were assessed to determine the extent anticancer efficacy of hibiscus. Mitochondrial membrane potential reduction and reactive oxygen species generation were quantified using fluorogenic dyes to determine the mechanism of hibiscus extract action.ResultsHibiscus extract was able to selectively induce apoptosis in both triple-negative and estrogen-receptor positive breast cancer cells in a dosage-dependent manner. Most importantly, addition of hibiscus extract was found to enhance the induction of apoptosis of chemotherapy treatments (taxol and cisplatin) in triple-negative breast cancer cells when compared to treatment alone. Moreover, hibiscus extract addition to chemotherapy treatment was able to increase oxidative stress and decrease mitochondrial membrane potential compared to individual treatments.ConclusionHibiscus extract is effective on breast cancer, most notably on generally resistant triple-negative breast cancer, while being selective for normal healthy cells. Hibiscus extract could supplement chemotherapeutic regimens as an adjuvant and lead to a more efficacious treatment approach to reduce chemotherapy dosages and related toxicity.

Effective extraction of flavonoids from Lycium barbarum L. fruits by deep eutectic solvents-based ultrasound-assisted extraction

The efficient extraction of natural products from biomass is deemed an essential area of interest using green technology in the pharmaceutical and biochemical industries. In recent years, deep eutectic solvents (DESs) have been paying broad interest as compatible, safe, and inexpensive solvents. In this study, we addressed, for the first time, to give a fruitful illustration to extract bioactive compounds from favourite Lycium barbarum L. fruits using DESs as green designer solvents, and displaying the tuneability of DESs to extract bioactive compounds from biomass efficiently. Among the studied DESs, the 1 : 2 M mixture of choline chloride and p-toluene sulfonic acid (DESs-6) with an ultra-sound assisted extraction (UAE) method was more efficient to get high extraction yields of flavonoids including myricetin (57.2 mg/g), morin (12.7 mg/g), and rutin (9.1 mg/g) in net DESs. The resulting extraction method in which 50 mg of sample powder was extracted by UAE for 1.5 h using DESs-6 was found to be a more efficient process than conventional extraction methods such as heating plus stirring. Operational conditions including the extractant to sample solid ratio, the effect of water content, the effect of temperature, recycling of DESs, and the effect of ultra-sound irradiation time were investigated. The proposed DESs based extraction procedure attained recovery for flavonoids were in the range 75.6%–96.9%. Therefore, p-toluenesulfonic acid-based DESs may have strong potential as promising materials for the green and efficient extraction of pharmaceutical compounds from other plants or fruits.