Natural Product Extracts Research Articles

Natural products and polysorbates: Potential Inhibitors of biofilm formation in Pseudomonas aeruginosa.

With all the challenges super bugs are imposing, biofilm formation opens the door against various more complicated challenges. Such issue may be highlighted with the ability of the latter to render the antibiotics hardly accessible to bacterial cells and sheds the light on the importance of finding antibiofilm formers. Therefore, we assessed the inhibitory effect of natural product extracts (ginger, wild blueberry) and polysorbates (PS20, PS80) on biofilm formation at the molecular level. Growth inhibition assay was performed to test the effect of ginger (Zingiber Officinale), wild blueberry (Vaccinium Angustifolium), and polysorbates on Pseudomonas aeruginosa (PAN14) growth. Transcription levels of biofilm exopolysaccharides encoding genes (ndvB, pelC, algC) and quorum sensing genes (lasI, lasR, rhlI, rhlR) for LasI/LasR and RhlI/ RhlR systems were evaluated by RT qPCR. The polysorbates and the extracts of both ginger and wild blueberry had no effect on the growth of P. aeruginosa. Biofilms' examination has unraveled the effectiveness of treatments used in reducing its formation. Moreover, a significant reduction in the expression of all genes tested for biofilm exopolysaccharides and its quorum sensing system was observed. The decrease in the relative gene expression of the exopolysaccharides and quorum sensing encoding genes sheds the light on the mechanism of action of ginger and wild blueberry's constituents as well as polysorbates 20 and 80 on P. aeruginosa biofilm formation. Future studies need to assess the antibiofilm effect of each fraction of herbal extracts separately.

Trapping multiple dual mode liquid-liquid chromatography: Preparative separation of nootkatone from a natural product extract

Trapping multiple dual mode (trapping MDM) is a preparative liquid-liquid chromatography (LLC) technique well-suited to difficult separations of intermediately-eluting components from similarly structured impurities. In this demonstrative study, a design approach for high process throughput is applied for the trapping MDM separation of a target component, nootkatone (NK), initially comprising 16.7% of an industrial side stream mixture with over 90 impurities. This design approach, previously developed and validated using ternary mixtures of model solutes, is applied to a complex real mixture for the first time. The approach consists of five steps: (1) determination of the maximum starting mixture concentration for feed preparation; (2) determination of the maximum flow rate for maintenance of the pre-set stationary phase fraction; (3) determination of the partition coefficients of the target and main impurities; (4) selection of step durations and number of cycles using an established short-cut method; (5) execution of the trapping MDM separation. The target, NK, was obtained along with a co-eluting component at 78.7% purity and 84.6% yield, demonstrating the effectiveness of trapping MDM for the separation of intermediately-eluting natural product target components from complex starting mixtures.

Are Ionic Liquids Better Extracting Agents Than Toxic Volatile Organic Solvents? A Combination of Ionic Liquids, Microwave and LC/MS/MS, Applied to the Lichen Stereocaulon glareosum.

We report a green strategy for the extraction of lichen substances from Stereocaulon glareosum. This sustainable alternative does not use volatile toxic organic solvents, but it is assisted by microwave and is checked by UHPLC/ESI/MS/MS. Ionic liquids may provide a better alternative in the extraction of natural products from lichens.

Supercritical Fluid Technology and its Pharmaceutical Applications: A Revisit with Two Decades of Progress

Over the past two decades, supercritical fluid technology has emerged as one of the most important technologies applied in many fields such as cosmetic, food and pharmaceutical. Supercritical fluid extraction process offers numerous advantages such as easy, effective, inexpensive, high quality of solute extraction and environmentally friendly. This mini-review describes the fundamentals of supercritical fluid technology, the function of supercritical fluid as solvent and anti-solvent, mechanism of supercritical fluid, advantages and disadvantages and revisit the application of supercritical fluid technology in pharmaceutical sciences. In-depth discussion with recent examples of extraction of natural products, particle design in drug delivery, preparation on pharmaceutical powder, drug solubilization, inclusion complex, polymer impregnation, liposomal formulations, purification and polymorphism as well as drug extraction analysis are also presented. Key aspects and processing considerations of supercritical fluid technologies are reviewed to assist scientists to generate other related experimental works. © 2020, Association of Pharmaceutical Teachers of India. All rights reserved.

30Years of sonochemistry links with China.

Most scientists consider that sonochemistry became recognised as a discrete subject in the 1980's - some 40years ago which coincidentally is when my own interests in the subject began. This review briefly outlines how I first became involved in sonochemistry and then in its development. However its main theme is the way in which my links with China through sonochemistry have developed from their beginnings in 1990. This was the subject of my presentation at AOSS4 and involves a range of topics which started with the extraction of natural products and surface treatment but later expanded to include therapeutic ultrasound and environmental protection.

Extraction and purification of triterpenoid saponins from licorice by ionic liquid based extraction combined with in situ alkaline aqueous biphasic systems

Triterpenoid saponins in licorice are important lead compounds for nutraceutical and pharmaceutical applications. This study developed a novel method for extraction and purification of triterpenoid saponins from licorice by ionic liquid based ultrasonic-assisted extraction combined with in situ alkaline aqueous biphasic systems (IL-UAE-AABS). IL-UAE was firstly used to efficiently extract triterpenoid saponins from licorice, which were further purified using in situ IL-AABS formed by adding NaOH into the extraction solution. We screened out the best-performing IL, namely 1-butyl-3-methylimidazolium tetrafluoroborate ([C4MIM]BF4), from various ILs able to form AABS with NaOH, and established the optimal conditions (extraction time, [C4MIM]BF4 concentration and solvent to solid ratio for IL-UAE, and NaOH concentration and temperature for IL-AABS). The established method could achieve high extraction efficiency (26.0 mg/g for glycyrrhizin) and total purify (more than 81.5%) for triterpenoid saponins, which was far superior to conventional IL-ABS. In addition, [C4MIM]BF4 could be easily recovered and reused for the IL-UAE-AABS process for at least three times without apparent worse performance. This is the first report on extraction and purification of natural products by IL-UAE-AABS, which was shown to be able to efficiently and selectively obtain triterpenoid saponins from herbal medicines with good prospects.

Extraction and bioprocessing with supercritical fluids

Abstract Supercritical fluid (SCF) technologies have emerged as a real alternative to various natural product extraction processes and pharmaceutical production to obtain micronized particles, coprecipitates, nanocomposite polymer structures and liposomes, in addition to other increasingly larger applications described in literature. In the present work, a brief literature review of the application of supercritical fluid extraction (SFE) is presented. This is evidenced by several publications and patents, contributions from several countries and the increase of industries around the world dedicated to this technique. Next, we aim to focus the analysis of SFE on a review of the literature applied to microalgae as a substitute primitive feedstock due to its high growth rate, valuable biologically active lipophilic substances, and photosynthetic efficiency without competition with food sources or needs of arable lands. We finally discussing an SCF bioprocess with a very new perspective for liposome production focalized on its potential at industrial scale.

Bioactive Compounds in Diabetic Cardiomyopathy: Current Approaches and Potential Diagnostic and Therapeutic Targets.

Diabetic Cardiomyopathy (DCM) has an adverse effect on health and occurs with or without concurrent vascular disease. Although several pathological mechanisms have been implicated in DCM, oxidative stress is widely thought to be the foremost cause for DCM pathogenesis. In this review, we focused on the role of bioactive compounds from different sources such as plant and marine products in cardiomyopathy. Natural Products (NPs) and their constituents were traditionally considered implausible as therapeutic agents. In the last few decades, studies on the use of NPs in the pharmaceutical field have reduced due to problems such as the requirement of compatibility of conventional NP extract libraries with high-throughput selection. The characteristics of NP structures such as high chemical variety, biochemical specificity, and other molecular properties that make them favorable as direct structures for drug synthesis and that distinguish them from combinatorial and synthetic compound libraries have been documented since ancient times. Consequently, the aim of this review was to provide an overview on the recent progress and development of bioactive compounds in DCM and to focus on the cellular mechanisms underlying cardiomyocyte dysfunction in their therapeutic targets.

Industrial Application of Supercritical Carbon Dioxide for Natural Products Extraction, and Decaffeination Technology for Coffee Beans

Industrial Application of Supercritical Carbon Dioxide for Natural Products Extraction, and Decaffeination Technology for Coffee Beans

Comparison of the Extraction Efficiency of Isoflavone Compounds from Puerariae lobatae by Ionic Liquids with 11 Anions and 8 Imidazolium-Based Cations.

Although the field of natural product extraction with ionic liquids (ILs) is already a crowded one, the guiding rules regarding the selection of suitable ILs for extraction are still lacking. In this study, the extraction capacity of 32 ILs was investigated using Puerariae lobatae as a testing material, namely, 11 [BMIM]-based, 9 [CMIM]-based, 8 [CnMIM][Br] and 8 [CnMIM][BF4] ILs (n = 2, 4, 6, 8, 10, 12, 14, 16) were studied. Three series of concentrations (0.02, 0.50, 2.00 M) were investigated, and the results demonstrated that the extraction capacity increased with the rising IL concentrations except for 1-butyl-3-methyl-imidazolium tosylate ([BMIM][Tos]). Generally, all the 0.50 and 2.00 M ILs led to the best extraction results. At low concentrations, the IL extraction capacity is strongly dependent on the anions and cations. However, the relationship between extraction capacity and anions or cations gradually becomes weak as increasing IL concentrations. Finally, the solution of ILs was prepared in aqueous or 60% methanol depending on the solubility. The pH can vary from strong acid to weak alkaline. Extraction capacity of 32 ILs varying in concentrations has a good negative correlation with the pH, except for five [BMIM]-ILs.

Partial and Total Solvent-Free Limonene’s Hydrogenation: Metals, Supports, Pressure, and Water Effects

Bio-based solvents menthene and menthane were obtained through limonene’s partial and total hydrogenation under various catalytic conditions. Heterogeneous catalysts based on different active metals and supports (carbon, alumina, and silica) were systematically tested for solvent-free total and partial hydrogenation of limonene under high and low hydrogen pressure. Influences of these catalysts on the formation of menthene, menthane, and cymene, a dehydrogenated product, were determined. The impact of water addition on the conversion and selectivity of the catalysts was also investigated. Amongst all tested catalysts, Rh/Alumina which was never tested for total and partial hydrogenation of limonene was the most effective as 1-menthene was quantitatively produced at low pressure (0.275 MPa) while menthane was mostly obtained at a higher pressure (2.75 MPa). Water addition on Rh/Alumina favoured menthene production even at high pressure. To propose menthane, menthene, and menthane/menthene mixture as an alternative to fossil-based solvents such as n-hexane for the extraction of natural products, β-carotene, vanillin, and rosmarinic acid solubilizations have been investigated. If a modeling approach using COSMO-RS software predicted a comparable solubilization of these 3 compounds for the 3 solvents, experimental assays revealed that menthene solubilizes β-carotene, vanillin, and rosmarinic acid three to five times better than n-hexane.

Targeting tRNA-synthetase interactions towards novel therapeutic discovery against eukaryotic pathogens.

The development of chemotherapies against eukaryotic pathogens is especially challenging because of both the evolutionary conservation of drug targets between host and parasite, and the evolution of strain-dependent drug resistance. There is a strong need for new nontoxic drugs with broad-spectrum activity against trypanosome parasites such as Leishmania and Trypanosoma. A relatively untested approach is to target macromolecular interactions in parasites rather than small molecular interactions, under the hypothesis that the features specifying macromolecular interactions diverge more rapidly through coevolution. We computed tRNA Class-Informative Features in humans and independently in eight distinct clades of trypanosomes, identifying parasite-specific informative features, including base pairs and base mis-pairs, that are broadly conserved over approximately 250 million years of trypanosome evolution. Validating these observations, we demonstrated biochemically that tRNA:aminoacyl-tRNA synthetase (aaRS) interactions are a promising target for anti-trypanosomal drug discovery. From a marine natural products extract library, we identified several fractions with inhibitory activity toward Leishmania major alanyl-tRNA synthetase (AlaRS) but no activity against the human homolog. These marine natural products extracts showed cross-reactivity towards Trypanosoma cruzi AlaRS indicating the broad-spectrum potential of our network predictions. We also identified Leishmania major threonyl-tRNA synthetase (ThrRS) inhibitors from the same library. We discuss why chemotherapies targeting multiple aaRSs should be less prone to the evolution of resistance than monotherapeutic or synergistic combination chemotherapies targeting only one aaRS.

Evaluation of Natural and Botanical Medicines for Activity Against Growing and Non-growing Forms of B. burgdorferi.

Lyme disease is the most common vector-borne disease in the US and Europe. Although the current recommended Lyme antibiotic treatment is effective for the majority of Lyme disease patients, about 10–20% of patients continue to suffer from persisting symptoms. There have been various anecdotal reports on the use of herbal extracts for treating patients with persisting symptoms with varying degree of improvements. However, it is unclear whether the effect of the herb products is due to their direct antimicrobial activity or their effect on host immune system. In the present study, we investigated the antimicrobial effects of 12 commonly used botanical medicines and three other natural antimicrobial agents for potential anti-Borrelia burgdorferi activity in vitro. Among them, 7 natural product extracts at 1% were found to have good activity against the stationary phase B. burgdorferi culture compared to the control antibiotics doxycycline and cefuroxime. These active botanicals include Cryptolepis sanguinolenta, Juglans nigra (Black walnut), Polygonum cuspidatum (Japanese knotweed), Artemisia annua (Sweet wormwood), Uncaria tomentosa (Cat's claw), Cistus incanus, and Scutellaria baicalensis (Chinese skullcap). In contrast, Stevia rebaudiana, Andrographis paniculata, Grapefruit seed extract, colloidal silver, monolaurin, and antimicrobial peptide LL37 had little or no activity against stationary phase B. burgdorferi. The minimum inhibitory concentration (MIC) values of Artemisia annua, Juglans nigra, and Uncaria tomentosa were quite high for growing B. burgdorferi, despite their strong activity against the non-growing stationary phase B. burgdorferi. On the other hand, the top two active herbs, Cryptolepis sanguinolenta and Polygonum cuspidatum, showed strong activity against both growing B. burgdorferi (MIC = 0.03–0.06% and 0.25–0.5%, respectively) and non-growing stationary phase B. burgdorferi. In subculture studies, only 1% Cryptolepis sanguinolenta extract caused complete eradication, while doxycycline and cefuroxime and other active herbs could not eradicate B. burgdorferi stationary phase cells as many spirochetes were visible after 21-day subculture. Further studies are needed to identify the active constituents of the effective botanicals and evaluate their combinations for more effective eradication of B. burgdorferi in vitro and in vivo. The implications of these findings for improving treatment of persistent Lyme disease are discussed.

Potential carcinogenic heterocyclic aromatic amines (HAAs) in foodstuffs: Formation, extraction, analytical methods, and mitigation strategies.

During the heat treatment of proteinaceous food, heterocyclic aromatic amines (HAAs), a kind of strong mutagens/carcinogens are formed. HAAs can be classified into two major groups based on the heating temperature, which are thermic HAAs generally formed in 150 to 300°C and pyrolytic HAAs produced above 300°C. This review focuses on the formation mechanisms of HAAs and identifies different mechanisms of the formation of HAAs in foodstuffs. Moreover, an overview of the available extraction, purification methods, and instrumental analytical methods in the last two decades is shown to determine the HAAs in various foodstuffs. Finally, based on the factors that affect the formation of HAAs in heat-processed foodstuffs, such as the cooking method, food type, the recipe, and the content of substances with enhancing or inhibiting effects on the formation of HAAs, this review also highlights the most promising strategies for mitigating HAAs, which include adjusting cooking methods or process conditions, adding natural product extracts, antioxidants or other compounds, or reasonable selection of types of foodstuff. The review intends to provide a broad but comprehensive understanding of the formation, extraction, purification, analytical methods, and possible mitigation strategies for isolated and identified HAAs.

High-Speed Countercurrent Chromatography-Based Method for Simultaneous Recovery and Separation of Natural Products from Deep Eutectic Solvent Extracts

The use of deep eutectic solvents (DESs) to extract natural products has attracted considerable attention in recent years. However, the recovery of extracted compounds and DES from DES extracts is ...

A review of sustainable and intensified techniques for extraction of food and natural products

This review presents innovative extraction techniques and their role in promoting sustainable ingredients for the food, cosmetic and pharmaceutical industries.

LEGO MINDSTORMS Fraction Collector: A Low-Cost Tool for a Preparative High-Performance Liquid Chromatography System.

Preparative high-performance liquid chromatographic (prep-HPLC) systems are used in many research schemes including purifying products from reaction mixtures, fractionating natural product extracts, and isolating compounds. Manual fraction collection from a prep-HPLC is a common method; however, it often lacks the reproducibility of automated fraction collectors due to human error. Automated fraction collectors for prep-HPLC systems can add thousands of dollars to the cost of prep-HPLC and are thus not always available to budgetary constrained research programs. Nevertheless, an automated fraction collector is a tremendous resource for any lab that employs prep-HPLC methods. Using LEGO MINDSTORMS pieces and easily obtained lumber and a steel C-channel, we were able to deploy an automated fraction collector for only a fraction of the cost of a commercial instrument. The programming software allows for a simple interface to create fraction collection programs tailored to individual HPLC methods. This fraction collector can be connected to any LC system and tailored to collect fractions in nearly any size or shaped container. This fraction collector was designed to provide maximum versatility and will make automated fraction collection more accessible to all researchers. The simple interface allows for quickly adapting the fraction collector method to any liquid chromatographic separation, no matter how complex.

Examination of in Vitro Anticancer Activity of Crude Extracts Obtained from Two Bacterial Strains Isolated from Kodiyampalayam, Tamil Nadu

Extracts of natural products, especially microorganisms, have been a valuable source of various molecules in many drug discovery efforts and led to the discovery of many important drugs. The identification of microbial strains with promising biological activities and the purification of biomolecules responsible for activities led to the discovery of many biologically active molecules.Crude extracts of two marine bacterial isolates isolated from marine sediment samples, were studied for their in vitro anticancer activity against human oral squamous carcinoma (KB) cell line. Morphological studies and biochemical tests of the two bacterial extracts were also carried out. Cytotoxic, intracellular ROS, nuclear staining and apoptotic morphological alteration studies were carried out to assess the anticancer potential of each extract. The crude ethyl acetate extract of KP-9 isolate showed promising results by MTT assay with IC50 as low as 7.9 μg/ml while as KP-7 showed an IC50 value of 21.1μg/ml in KB cells. The crude extract of KP-9 augmented higher levels of ROS and displayed higher potential by inducing higher levels of nuclear and morphological alterations when compared with KP-7 bacterial extract in KB cells.

Adipostatins E-J, new potent antimicrobials identified as inhibitors of coenzyme-A biosynthesis

Phosphopantetheine is a key structural element in biological acyl transfer reactions found embedded within coenzyme A (CoA). Phosphopantothenoylcysteine synthetase (PPCS) is responsible for installing a cysteamine group within phosphopantetheine. Therefore, it holds considerable potential as a drug target for developing new antimicrobials. In this study, we adapted a biochemical assay specific for bacterial PPCS to screen for inhibitors of CoA biosynthesis against a library of marine microbial derived natural product extracts (NPEs). Analysis of the NPE derived from Streptomyces blancoensis led to the isolation of novel antibiotics (10–12, and 14) from the adipostatin class of molecules. The most potent molecule (10) displayed in vitro activity with IC50 = 0.93 µM, against S. pneumoniae PPCS. The whole cell antimicrobial assay against isolated molecules demonstrated their ability to penetrate bacterial cells and inhibit clinically relevant pathogenic strains. This establishes the validity of PPCS as a pertinent drug target, and the value of NPEs to provide new antibiotics.

Raphanus sativus L. seed extracts induce apoptosis and reduce migration of oral squamous cell carcinoma KB and KBCD133+cells by downregulation of β-catenin

Although, oral cancer therapies have been developed for decades, patient survival rates have not changed. Side effects of chemotherapy and radiotherapy reduce quality of life of patients and it remains difficult to treat oral cancers due to the presence of cancer stem cells (CSCs) that cause recurrence and metastasis. Therefore, we search for natural products that affect oral cancer cells including oral cancer stem cells. In the present study, we investigated the anticancer effects of Raphanus sativus L. seed (RSLS) extracts on oral squamous cell carcinoma KB cells and CSC-like KBCD133+ cells. CD133 plays an important role in CSCs and physically binds to β-catenin to activate the β-catenin signaling targets. Therefore, a natural extract that can inhibit β-catenin act in may be effective anticancer drug acquiring CSC. Of the natural product extract candidates, RSLS extracts induced apoptosis in KB and KBCD133+ cells and inhibited nuclear translocation of β-catenin cell migration and invasion rates. Treatment of RSLS extracts resulted in increases of Axin and it leds to reductions of β-catenin in KB and KBCD133+ cells. Hence, the result suggests that RSLS are potential candidate for anticancer drug against oral cancer cells and CSCs.AbbreviationsCSCcancer stem cellsOSCCsquamous cell carcinoma cellsRSLSRaphanus sativus L. seed.