Natural Product Extracts Research Articles

Extraction and Counter-Current Separation of Phenylpropanoid Glycosides from Pedicularis oederi Vahl by Deep Eutectic Solvent

Deep eutectic solvents (DESs) are mixtures of organic compounds displaying excellent solvent properties while keeping an ecofriendly character. In this study, DESs have been applied to the extraction of phenylpropanoid glycosides from Pedicularis oederi Vahl, successively separated by means of counter-current chromatography. Firstly, the ultrasonic-assisted extraction conditions were optimized by response surface methodology, and the results showed phenylpropanoid glycosides could be well extracted under the optimized extraction conditions with deep eutectic solvents. Then, the sample was separated by counter-current chromatography using ethyl acetate/aqueous solution of choline chloride and glycerol (6:6, v/v) as the solvent system. In about 360 min, four phenylpropanoid glycosides, including 31.6 mg of echinacoside, 65.3 mg of Jionoside A1, 28.9 mg of Forsythoside B, 74.1 mg of verbascoside, and 21.2 mg of kaempferol-3-O-rutinoside were obtained from about 900 mg of the sample. It revealed deep eutectic solvents could be well employed as a green solvent for the extraction and counter-current separation of natural products.

Ionic Liquid-Based Green Solvents for Extraction and Purification of Natural Plant Products

Introduction: This research paper explores the environmental sustainability of ionic liquid-based green solvents in the extraction and purification of natural plant products, with a focus on their entire life cycle. The objectives of the study were to assess the environmental impact of ionic liquid synthesis, energy consumption, water usage, emissions, recycling rates, policy effects, and stakeholder perceptions. Methods: Methodologically, we conducted a comprehensive Life Cycle Assessment (LCA) that involved primary data collection through field surveys and interviews with key stakeholders in the ionic liquid production and usage industry across various regions in India. The data were analyzed using specialized LCA software tools to quantify environmental impacts. Key findings include the identification of synthesis as a major contributor to environmental impact, emphasizing the need for greener synthesis methods. Results: The study revealed the significant carbon footprint, energy consumption, and water usage during production, highlighting opportunities for improvement. Emissions data underscored the importance of emission control measures, particularly for greenhouse gases and volatile organic compounds. Recycling and reuse were identified as environmentally friendly disposal methods. Policy compliance varied among stakeholders, indicating room for stricter regulations. Stakeholder perceptions varied, with researchers having the most positive outlook. Implications of the findings extend to sustainable chemistry practices, emphasizing interdisciplinary collaboration and the importance of considering the entire life cycle of chemical processes. Conclusion: This research contributes to a deeper understanding of green solvents and provides a foundation for promoting sustainable practices in industrial processes in India and globally.

Natural Products with Potential for the Treatment of Pain: Global Evidence from the NAPRALERT Database.

Natural products (NPs) continue to inform the discovery and development of a diversity of drugs, both marketed and investigational. Pain, one of the most common of human experiences and profound challenges in medicine and biology, has emerged at the core of an urgent societal problem, in the United States and globally. The present study employs a retrospective analysis of an extensive set of published literature curated in the NAPRALERT database to identify NPs with experimental evidence of bioactivity supporting the selection and prioritization of NP leads with promise in pain management. The NAPRALERT pain data set currently documents >38,000 pain-relevant experiments reported in >1,750 distinct journals. The evidence presented here was annotated from >10,000 distinct scientific publications identifying NP extracts and isolates with experimental biological data indicating positive mitigation of pain, inflammation, and/or modulation of nociceptive signaling targets. Correlation of ethnomedical uses with experimental data represents a value-added approach to the selection and prioritization of leads. Dissemination of this unique NP/pain data set, with experimental data and information applicable to basic, translational, and clinical science stakeholders alike, furnishes practical evidence in support of a rational selection of NPs for directed pain research. A large portion of the NAPRALERT pain-relevant data set, along with a set of query tools designed to assist user-directed selection and prioritization of leads, are presented as Supporting Information in order to mitigate the limitations inherent in presenting such a large data set in (print) format. To support user efforts, this report involves explication of NAPRALERT data organization and the articulation of rational approaches to user-guided selection of evidence-based NP leads.

Enhanced Extraction of Tanshinones from Salvia miltiorrhiza Using Natural-Surfactant-Based Cloud Point Extraction

Salvia miltiorrhiza (SM) contains the tanshinones, a compound with various pharmacological effects, and has been extensively studied as a pharmaceutical material. However, conventional methods for extracting tanshinones face challenges such as environmental hazards and high cost. In this study, we aimed to effectively extract tanshinones from SM using cloud point extraction (CPE) with lecithin, a natural surfactant. By optimizing various extraction conditions including the solid-to-liquid ratio, lecithin concentration, NaCl concentration, pH, and equilibrium temperature, the optimal extraction efficiency was achieved using 20 mL of solvent per 1 g of sample, 3% lecithin (w/v), 2% NaCl (w/v), pH 6, and room temperature (25 ± 2 °C). The CPE method, which minimizes the use of organic solvent and is eco-friendly, demonstrated improvements in extraction efficiency, with a 4.55% increase for dihydrotanshinone I, 8.32% for cryptotanshinone, 15.77% for tanshinone I, and 6.81% for tanshinone IIA compared to the conventional water extraction method. These results suggest that CPE is a promising, environmentally friendly, and efficient approach for extracting hydrophobic components from pharmacologically active materials such as SM, with potential applications across various fields of natural product extraction.

Machine Learning Accelerates Screening of Osteoclast Differentiation Inhibitors from Natural Products.

Natural products that inhibit osteoclast differentiation are promising therapeutic and preventive agents for osteoporosis. Conventionally, identifying osteoclast differentiation involves visual inspection of the microscope images of stained osteoclasts. In this study, a supervised machine learning model was developed to classify bright-field microscope images of osteoclasts without staining. The model was used to screen a compound library, and osteoclast differentiation inhibitors were identified, demonstrating the validity of our method. Next, an in-house library of fungal extracts was screened, and pinolidoxin was revealed as an inhibitor of osteoclast differentiation. Our machine learning method enabled accurate, objective, and high-throughput evaluation of osteoclast differentiation and efficient screening of the inhibitors from natural product extracts. This study represents the first machine learning classification developed to evaluate the inhibitory activity of natural products in osteoclast differentiation.

Ionic strength regulates IFT in microemulsion for extraction of botanical natural products

Microemulsion, an emerging environmentally friendly medium, has demonstrated significant potential in botanical natural products (BNP) extraction. We found suitable ionic strength could enhance the BNP extraction capability of microemulsion. However, this mechanism remains unclear. Elucidating this mechanism will help to develop extraction strategies to increase BNP yields. Therefore, this mechanism was explored through scanning electron microscope, 2D NOESY, and molecular dynamics simulation. Ionic strength was quantified by Na+ concentration. BNP was represented by acteoside, hyperoside, luteolin and apigenin in Rehmannia glutinosa Libosch. Leaves. The results revealed the position of coordination ring shift forward when ionic strength regulated IFT. This reduced the electrostatic repulsion among surfactants’ head groups. Head groups are thus closely arranged at interface. This improves the pool capacity, hydrogen bonding interaction between head group and cellulose, as well as the interaction between head group and BNP. These provide guarantees for effective microemulsion-mediated cell wall disruption and BNP extraction.

Parallel Plate Capacitor Model at the Nanoscale for Stable and Gigantic SERS Activity of the 4-MBA@R-AuNP-4-MBA@R-AuNP System.

Selective use of ingredients out of a specific natural product (e.g., fruit, leaf, flower, or honey extract) or their mixture (e.g., bacteria, viruses, fungi, plants, etc.) by smart manipulation of precursors and reaction conditions to synthesize nanoparticles can provide us a low-cost, environmentally friendly route for their industrial-scale production. The presence of more than one active ligand (sourced natural product extract) on the surface not only makes them the most stable (electrostatically) and monodispersed (controlled kinetics) but also devoid of any external ligand-assisted aggregation. This empowered us to modify the surface of the nanoparticles in a monolayered fashion or to couple between nanoparticles through a ligand-assisted chemical coupling pathway to avoid their aggregation and hence to keep their nanoscale property intact. A metal-to-ligand charge transfer (MLCT) trajectory combined with electromagnetic field-induced coherent capacitive coupling between two nanoparticles was introduced to explain the gigantic Raman enhancement observed from these nanoparticles. As a model system, we have synthesized the nanoparticles from rose extract as the active ligand ingredient source for 2-phenyl ethanol, linalool, citronellol, nerol, geraniol, pyrogallol (C6H3(OH)3), and quercetin (3,3',4',5,7-pentahydroxyflavone) and the surface of the synthesized nanoparticles has been modified by 4-mercaptobenzoic acid (4-MBA) acting as a Raman tag. The obtained structural and spectroscopic data correlate well between our numerical and density functional theory (DFT)-based calculations to justify their gigantic SERS activity, which may lead us to propose an unexplored coherent capacitive coupling-based Raman enhancement mechanism.

Electron beam irradiation coupled ultrasound-assisted natural deep eutectic solvents extraction: A green and efficient extraction strategy for proanthocyanidin from walnut green husk

Proanthocyanidin (PAC) is recognized as a potent natural antioxidant that prevents various diseases. As societal awareness increases, eco-friendly and efficient natural product extraction technologies are gaining more attention. In this study, an electron beam irradiation (EBI) coupled with ultrasound-assisted natural deep eutectic solvents (NADES) extraction method was developed to enable the green and highly efficient extraction of PAC from walnut green husk (WGH). NADES, prepared with choline chloride and ethylene glycol, demonstrated excellent extraction capacity and storage stability for PAC. Molecular dynamics simulations elucidated the high compatibility between NADES and PAC, attributed mainly to a higher SASA value (207.85 nm2), a greater number of hydrogen bonds (330.99), an extended hydrogen bonding lifetime (4.54 ps), and lower inter-molecular interaction energy. Based on these findings, the optimal conditions (13 kGy EBI, 42 mL/g liquid-solid ratio, 38 °C extraction temperature, 70 min extraction time) resulted in a maximum PAC extraction yield of 56.34 mg/g. Notably, this yield was 32.93 % higher than that observed in samples not treated with EBI and ultrasound-assisted extraction (UAE). Analysis of tissue morphology, extract functional groups and thermal behavior suggested a possible mechanism for the synergistically enhanced PAC extraction by the EBI-NADES-UAE method. Additionally, the PAC extracted using the NADES by the EBI coupled with ultrasound-assisted method exhibited outstanding antioxidant activity (comparable to Vc), digestive enzyme inhibition (IC50: 17–0.61 mg/mL), and anti-glycation capacity (IC50: 86.49 μg/mL). Overall, this work provided a green and efficient strategy for PAC extraction from WGH, elucidated the extraction mechanism and bioactivities, and offered valuable insights for potential industrial applications.

Carbon-Dots-Mediated Improvement of Antimicrobial Activity of Natural Products.

The development of new microbicidal compounds has become a top priority due to the emergence and spread of drug-resistant pathogenic microbes. In this study, blue-emitting and positively charged carbon dots (CDs), called Du-CDs, were fabricated for the first time utilizing the natural product extract of endophyte Diaporthe unshiuensis YSP3 as raw material through a one-step solvothermal method, which possessed varied functional groups including amino, carboxyl, hydroxyl, and sulfite groups. Interestingly, Du-CDs exhibited notably enhanced antimicrobial activities toward both bacteria and fungi as compared to the natural product extract of YSP3, with low minimum inhibitory concentrations. Moreover, Du-CDs significantly inhibited the formation of biofilms. Du-CDs bound with the microbial cell surface via electronic interaction or hydrophobic interaction entered the microbial cells and were distributed fully inside the cells. Du-CDs caused cell membrane damage and/or cell division cycle interruption, resulting in microbial cell death. Moreover, Du-CDs exhibited an improved antimicrobial effect and accelerated wound healing ability with good biocompatibility in the mouse model. Overall, we demonstrate that the formation of CDs from fungal natural products presents a promising and potential means to develop novel antimicrobial agents with great fluorescence, improved microbiocidal effect and wound healing capacity, and good biosafety for combating microbial infections.

The effect of Artemisia capillaris leaf extract as a benign corrosion inhibitor on the performance of Al–air batteries

The self-corrosion of the aluminum anode reduces largely the performance of Al-air batteries. Herein, we report on the effect of Artemisia capillaris leaf extract (ACLE) as a benign corrosion inhibitor on the performance of Al-air batteries in 4 M NaOH electrolyte. The hydrogen evolution tests, electrochemical measurements, and surface analysis show that ACLE can markedly reduce the corrosion current density of the Al electrode in 4 M NaOH, which is due to the adsorption of the active components in ACLE inhibitor on the Al electrode surface. The presence of ACLE in 4 M NaOH greatly reduces the self-corrosion of the Al anode, and thus improves the utilization rate of the Al electrode. Fourier transform infrared (FT-IR) spectroscopy and X-ray photoelectron spectroscopy (XPS) are employed to determine the chemical composition of the adsorption layers on the surface of the Al electrode. When the concentration of ACLE in 4 M NaOH is 5 g/L, the Al-air battery has a high practical capacity density of 3545 Wh kg−1, and the fuel efficiency also increases to a high value of 44 % from 14 % without ACLE. This work presents a novel approach to enhance the performance of Al-air batteries through the utilization of natural product extracts as corrosion inhibitors.

Natural products from food sources can alter the spread of antimicrobial resistance plasmids in Enterobacterales.

Antimicrobial resistance (AMR) poses a significant threat to global public health. Notably, resistance to carbapenem and extended-spectrum β-lactam antibiotics in Gram-negative bacteria is a major impediment to treating infections. Genes responsible for antibiotic resistance are frequently carried on plasmids, which can transfer between bacteria. Therefore, exploring strategies to prevent this transfer and the prevalence of AMR plasmids is timely and pertinent. Here, we show that certain natural product extracts and associated pure compounds can reduce the conjugation of AMR plasmids into new bacterial hosts. Using our established high-throughput fluorescence-based flow cytometry assay, we found that the natural products were more active in reducing transmission of the IncK extended-spectrum β-lactamase-encoding plasmid pCT in Escherichia coli EC958c, compared to Klebsiella pneumoniae Ecl8 carrying the IncFII carbapenemase-encoding plasmid pKpQIL. The exception was the natural product rottlerin, also active in K. pneumoniae. In classical conjugation assays, rottlerin also reduced the conjugation frequency of the IncFII bla NDM-1 carrying plasmid pCPE16_3 from a clinical K. pneumoniae isolate. Our data indicate that the natural products tested here, in their current molecular structure, reduced conjugation by a small amount, which is unlikely to achieve a large-scale reduction in AMR in bacterial populations. However, certain natural products like rottlerin could provide a foundation for further research into compounds with effective anti-plasmid activity.

Correlation between Chemical Fertilization Practices, Phytochemical Response, and Biological Activities of Cannabis sativa L.

The plant kingdom offers a wealth of molecules with potential efficacy against various human, animal, and plant crop infections and illnesses. Cannabis sativa L. has garnered significant attention in recent decades within the scientific community due to its broad biological activity. Key bioactive compounds such as cannabinoids and phenolic compounds have been isolated from this plant, driving its bioactivity. Numerous studies have highlighted the impact of different agronomic practices, particularly fertilization, on the phytochemical composition, notably altering the percentage of various chemical groups. This review aims to present updated fertilization recommendations, crop requirements, and their implications for the chemical composition of C. sativa plants, along with major biological properties documented in the literature over the past five years. Various databases were utilized to summarize information on fertilization and crop requirements, chemical composition, bioassays employed, natural products (extracts or isolated compounds), and bioactivity results. Through this review, it is evident that C. sativa holds promise as a source of novel molecules for treating diverse human diseases. Nonetheless, careful consideration of agronomic practices is essential to optimize chemical composition and maximize therapeutic potential.

Application of Molecularly Imprinted Polymers Towards Efficient Extraction and Chromatographic Detection of Natural Products

Application of Molecularly Imprinted Polymers Towards Efficient Extraction and Chromatographic Detection of Natural Products

Study on efficient extraction of saponins from Polygonatum sibiricum by enzyme assisted cold isostatic pressing technology

Saponin is one of the main active ingredients of Polygonatum sibiricum. In this study, the method of enzyme-assisted cold isostatic pressure extraction (EACIP) of Polygonatum sibiricum saponins was established. The effects of different cold isostatic extraction pressures, pressure-maintaining time times, enzymatic temperatures and enzymatic pH on the yield of saponin were investigated, and the factors were simplified by single factor experiments and Box-benhken design (BBD). Under the best extraction conditions, the EACIP method achieved the best possible results and extraction rate was 11.45 % ± 0.017. In addition, SEM-Mapping, XRD analysis and FTIR analysis proved that EACIP treatment increased the extent of cell deformation and improved the mass transfer system between solvent and active substance. Furthermore, by comparing different extraction methods, EACIP was found to have a higher extraction rate due to the synergistic effect of cold isostatic pressure extraction (CIP) and enzymatic hydrolysis extraction (EH). In vitro antioxidant and anti-inflammatory assays demonstrated that EACIP extracts have good antioxidant and anti-inflammatory capacity. Therefore, EACIP is a method to extract natural products from plants with increased extraction rate.

Pressurized Hot Water Extraction as Green Technology for Natural Products as Key Technology with Regard to Hydrodistillation and Solid-Liquid Extraction.

Hydrodistillation and solid-liquid extraction with organic solvents or supercritical CO2 are standard technologies for natural product manufacturing. Within this technology, portfolio pressurized hot water technology is ranked as a green, sustainable, resilient, kosher and halal manufacturing process. Essential for sustainability is energy integration for heating and cooling the auxiliary water as well as product concentration without evaporation but with the aid of low energy consuming ultra- and nanofiltration membrane technology. The incorporation of modern unit operations, such as pressurized hot water extraction, along with inline measurement devices for Process Analytical Technology approaches, showcases a shift in traditional extraction processes. Traditional equipment and processes still dominate the manufacturing of plant extracts, yet leveraging innovative chemical process engineering methods offers promising avenues for the economic and ecological advancement of botanicals. Techniques such as modeling and process intensification with green technology hold potential in this regard. Digitalization and Industry 4.0 methodologies, including machine learning and artificial intelligence, play pivotal roles in sustaining natural product extraction manufacturing and can profoundly impact the future of human health.

RSM-based optimization of microwave- and ultrasound-assisted green extraction of iron-chelating and antioxidant natural products from Azadirachta indica leaves

Azadirachta indica is an abundantly available plant and known for its medicinal properties. Some studies showed its iron chelating activity (ICA) with possible implications for iron overload disorders. The present study aimed to discover efficient and green methods for obtaining ICA-rich extract from A. indica leaves. Microwave-assisted extraction (MAE) and ultrasound-assisted extraction (UAE) methods were optimized using response surface methodology (RSM). Four-factor Box-Behnken designs were used (with 29 runs) with five response factors for each technique. Aqueous choline chloride-glycerol (CCG) DES was employed as an extractant. ICA, total phenolic content (TPC), total flavonoid content (TFC), radical scavenging activity (RSA), and ferric-reducing antioxidant power (FRAP) were the responses. The optimal conditions discovered for MAE were 30 mL/g solvent-to-solid ratio (SSR), 38 % DES concentration, 330 W power and 15 s time with predicted ICA, TPC, TFC, FRAP, and RSA as 127.64 mg EDTAE/g d.w., 23.55 mg GAE/g d.w., 19.94 RE/g d.w., 26.77 mg AAE/g d.w. and 5.37 mg AAE/g d.w., respectively. For UAE, the optimal parameters were 30 mL/g SSR, 39 % DES concentration, 54.8 ͦ C temperature and 17.48 min time with predicted ICA, TPC, TFC, FRAP, and RSA as 127.80 mg EDTAE/g d.w., 18.58 mg GAE/g d.w., 23.36 RE/g d.w., 23.33 mg AAE/g d.w., and 5.79 mg AAE/g d.w., respectively. The models were efficient and supported by statistical and validation studies. MAE, however, used far less time than UAE. The outcomes of the study have important implications for iron overload syndrome and oxidative stress. The developed methods can, thus, be proposed as strong candidates for industrial applications obtaining bioactive compounds from abundantly available leaves of A. indica.

Comparing the Efficacy of Select Natural and Synthetic Corrosion Inhibitors on Copper and Iron

Six corrosion inhibitors were evaluated for their effectiveness at preventing corrosion on copper and mild steel in a short-term experiment lasting two weeks. Half of the inhibitors tested were alcohol extracts of natural products (ginger, garlic, and black pepper), and the others were standard chemical reagents including benzotriazole (BTA), cysteine, and 5-amino-1,3,4-thiadiazole-2-thiol (AMT). Metal coupons of both mild steel and copper were immersed in a 0.007M dilute HCl solution with one of the six inhibitors or a combination of two inhibitors. The pH of each solution was monitored to track the corrosion rate and this method proved to be remarkably sensitive and nuanced, allowing for the subtleties of the decay mechanisms to be determined.

Screening and Validation of Natural Products for Drug Discovery: Key Points and Approaches

This article highlights the key points and approaches involved in the screening and validation of natural products for drug discovery. Screening assays play a vital role in evaluating the biological activities of natural product extracts or fractions, targeting specific diseases, pathways, or cellular processes of interest. In vitro studies provide further insights into the efficacy, safety, and mechanism of action of promising candidates, using isolated cells or cellular components. Cell-based assays offer a more realistic cellular environment to assess natural product effects on cell viability, proliferation, and specific functions. Animal models bridge the gap between in vitro and clinical evaluations, providing a comprehensive understanding of therapeutic effects, pharmacokinetics, and toxicity profiles. Pharmacokinetic studies examine the absorption, distribution, metabolism, and excretion of natural products, optimizing dosage regimens and predicting human efficacy. Safety evaluation encompasses toxicity studies to determine safe dosage ranges and identify potential risks. Promising candidates progress to clinical trials, where efficacy, safety, dosage, and interactions are assessed in human subjects. This comprehensive screening and validation process contributes to the development of effective and safe natural product-based drugs.

Ultrasound-Assisted Extraction of Phenolic Compounds from Celtuce (Lactuca sativa var. augustana) Leaves Using Natural Deep Eutectic Solvents (NADES): Process Optimization and Extraction Mechanism Research.

Natural deep eutectic solvents (NADESs), as emerging green solvents, can efficiently extract natural products from natural resources. However, studies on the extraction of phenolic compounds from celtuce (Lactuca sativa var. augustana) leaves (CLs) by NADESs are still lacking. This study screened the NADES L-proline-lactic acid (Pr-LA), combined it with ultrasound-assisted extraction (UAE) to extract phenolic compounds from CLs, and conducted a comparative study on the extraction effect with traditional extraction solvents. Both SEM and FT-IR confirmed that Pr-LA can enhance the degree of fragmentation of cell structures and improve the extraction rate of phenolic compounds. Molecular dynamics simulation results show that Pr-LA can improve the solubility of phenolic compounds and has stronger hydrogen bonds and van der Waals interactions with phenolic compounds. Single-factor and Box-Behnken experiments optimized the process parameters for the extraction of phenolic compounds from CLs. The second-order kinetic model describes the extraction process of phenolic compounds from CLs under optimal process parameters and provides theoretical guidance for actual industrial production. This study not only provides an efficient and green method for extracting phenolic compounds from CLs but also clarifies the mechanism of improved extraction efficiency, which provides a basis for research on the NADES extraction mechanism.

PHYTOCHEMICALS SCREENING, ANTIOXIDANT AND ANTIMICROBIAL ACTIVITY OF CARICA PAPAYA LEAF EXTRACTS

Objective: The objective of the present study aimed at investigating the phytochemical antioxidant and anti-microbial properties of Carica papaya leaf extracts. Methods: As phytochemicals are biologically active compounds and a powerful group of plant chemicals believed to stimulate the immune system along with antioxidants, the molecules which hinder oxidation of other molecules by the process of inhibiting or by generating the oxidizing chain reactions and preventing diseases. The anti-microbial activity on various gram-positive and gram-negative bacteria were determined using zone of inhibition and antioxidant by the 2,2,1-diphenyl-1-picrylhydrazyl method. Results: Phytochemical screening, antioxidant and antibacterial potential were determined using different aqueous and organic solvents in addition to the determination of trace element in leaves of C. papaya. Antioxidant activity using DPPH free radical scavenging assay indicated leaves extracts leaves showed inhibition of per oxidation. The result showed that the ethanolic extract of C. papaya possessed a significant antioxidant activity as compared to methanol and aqueous extract. The antibacterial study showed leaves extract is the best to cope infectious action of bacteria. Conclusion: This study was conducted to test the medicinal profile of C. papaya by extracting secondary metabolites with organic and aqueous solvents. Ethanol was found to be the best solvents of choice to extract natural products to get maximum medicinal benefits and could be used to medicinal formulation against different infectious diseases.