Intra-Herb Interactions: Primary Metabolites in Coptidis Rhizoma Extract Improved the Pharmacokinetics of Oral Berberine Hydrochloride in Mice

Primary plant metabolites can be used for artificial preparation of natural deep eutectic solvents (NADESs), which have strong dissolving capacity, good biocompatibility, and biodegradability. In this study, for the first time, we verified that NADESs were present in Coptidis Rhizoma extract and systematically investigated its effects and mechanisms on the pharmacokinetics of oral berberine hydrochloride (BBR), a co-existing bioactive constituent. First, three LC-MS/MS based methods were established and fully validated to determine the levels of 11 primary metabolites in Coptidis Rhizoma extract. According to the weight ratio of four major primary metabolites in the Coptidis Rhizoma extract, a stable “endogenous” NADES was prepared using the heating method by the addition of 350 μl of water to 1,307.8 mg of the mixture of malic acid (490.5 mg), glucose (280.6 mg), sucrose (517.7 mg), and choline chloride (19.0 mg). The prepared NADES showed significant acute toxicity in mice and cytotoxicity in MDCK-MDR1 cells. However, after being diluted 10 times or 100 times, the NADES had no significant acute toxicity or cytotoxicity, respectively. The dilutions of the NADES significantly increased the water solubility of BBR, reduced its efflux in gut sacs and MDCK-MDR1 cell monolayer, and improved its metabolic stability in intestinal S9. In addition, the NADES dilutions reversibly opened the tight junctions between the enterocytes in the gut sacs. Moreover, the NADES dilutions significantly improved the exposure levels of BBR in the portal vein and livers of mice that were administered oral BBR. Malic acid was identified as a major component in the NADES in terms of solubility, acute toxicity, cytotoxicity, and pharmacokinetic-improving effects on oral BBR. In conclusion, the primary metabolites of Coptidis Rhizoma extract could form “endogenous” NADES, and its dilutions improve the pharmacokinetics of oral BBR. This study demonstrates the synergistic interaction of the constituents of Coptidis Rhizoma extract and the potential use of the NADES dilutions in oral BBR delivery.

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Extracts of medicinal plants with natural deep eutectic solvents: enhanced antimicrobial activity and low genotoxicity

BMC Chemistry ◽

10.1186/s13065-020-00726-x ◽

2020 ◽

Vol 14 (1) ◽

Author(s):

Tsvetinka Grozdanova ◽

Boryana Trusheva ◽

Kalina Alipieva ◽

Milena Popova ◽

Lyudmila Dimitrova ◽

...

Keyword(s):

Antimicrobial Activity ◽

Medicinal Plants ◽

Total Phenolics ◽

Choline Chloride ◽

Deep Eutectic Solvents ◽

Bioactive Constituents ◽

Primary Metabolites ◽

E Coli ◽

Natural Deep Eutectic Solvents ◽

Toxic Organic Solvents

AbstractNatural deep eutectic solvents (NADES) are a new alternative to toxic organic solvents. Their constituents are primary metabolites, non-toxic, biocompatible and sustainable. In this study four selected NADES were applied for the extraction of two medicinal plants: Sideritis scardica, and Plantago major as an alternative to water-alcohol mixtures, and the antimicrobial and genotoxic potential of the extracts were studied. The extraction efficiency was evaluated by measuring the extracted total phenolics, and total flavonoids. Best extraction results for total phenolics for the studied plants were obtained with choline chloride-glucose 5:2 plus 30% water; but surprisingly these extracts were inactive against all tested microorganisms. Extracts with citric acid-1,2-propanediol 1:4 and choline chloride-glycerol 1:2 showed good activity against S. pyogenes, E. coli, S. aureus, and C. albicans. Low genotoxicity and cytotoxicity were observed for all four NADES and the extracts with antimicrobial activity. Our results confirm the potential of NADESs for extraction of bioactive constituents of medicinal plants and further suggest that NADES can improve the effects of bioactive extracts. Further studies are needed to clarify the influence of the studied NADES on the bioactivity of dissolved substances, and the possibility to use such extracts in the pharmaceutical and food industry.

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The effect of plant metabolites on coronaviruses: A comprehensive review focusing on their IC50 values and molecular docking scores

Mini-Reviews in Medicinal Chemistry ◽

10.2174/1389557521666210831152511 ◽

2021 ◽

Vol 21 ◽

Author(s):

Parastou Farshi ◽

Eda Ceren Kaya ◽

Fataneh Hashempour-Baltork ◽

Kianoush Khosravi-Darani

Keyword(s):

Molecular Docking ◽

Inhibitory Effect ◽

Organosulfur Compounds ◽

Amino Acid Residues ◽

Plant Metabolites ◽

Primary Metabolites ◽

Secondary Plant Metabolites ◽

Protein Receptors ◽

Ic50 Values ◽

Natural Drugs

: Coronaviruses have caused worldwide outbreaks in different periods. SARS (severe acute respiratory syndrome), was the first emerged virus from this family, followed by MERS (Middle East respiratory syndrome) and SARS-CoV-2 (2019-nCoV or COVID 19), which is newly emerged. Many studies have been conducted on the application of chemical and natural drugs for treating these coronaviruses and they are mostly focused on inhibiting the proteases of viruses or blocking their protein receptors through binding to amino acid residues. Among many substances which are introduced to have an inhibitory effect against coronaviruses through the mentioned pathways, natural components are of specific interest. Secondary and primary metabolites from plants, are considered as potential drugs to have an inhibitory effect on coronaviruses. IC50 value (the concentration in which there is 50% loss in enzyme activity), molecular docking score and binding energy are parameters to understand the ability of metabolites to inhibit the specific virus. In this study we did a review of 154 papers on the effect of plant metabolites on different coronaviruses and data of their IC50 values, molecular docking scores and inhibition percentages are collected in tables. Secondary plant metabolites such as polyphenol, alkaloids, terpenoids, organosulfur compounds, saponins and saikosaponins, lectins, essential oil, and nicotianamine, and primary metabolites such as vitamins are included in this study.

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Experimental investigation and modeling of thermophysical and extraction properties of choline chloride + DL-malic acid based deep eutectic solvent

Journal of the Serbian Chemical Society ◽

10.2298/jsc170316054v ◽

2017 ◽

Vol 82 (11) ◽

pp. 1287-1302 ◽

Cited By ~ 1

Author(s):

Jelena Vuksanovic ◽

Nina Todorovic ◽

Mirjana Kijevcanin ◽

Slobodan Serbanovic ◽

Ivona Radovic

Keyword(s):

Malic Acid ◽

Atmospheric Pressure ◽

Choline Chloride ◽

Deep Eutectic Solvent ◽

Ternary Mixtures ◽

Extraction Ability ◽

Experimental Phase ◽

Liquid Liquid Extraction ◽

Equilibrium Data ◽

Extraction Properties

The ability of non-toxic and biodegradable deep eutectic solvent (DES) choline chloride + DL-malic acid in mole ratio 1:1, for the breaking of the azeotropes heptane + methanol and toluene + methanol by means of liquid? ?liquid extraction was evaluated. Ternary liquid?liquid equilibrium experiments were performed at 298.15 K and at atmospheric pressure. Densities, viscosities and refractive indices of DES + methanol and water + DES systems were experimentally determined over a wide temperature range and at atmospheric pressure. Additionally, the viscosities of DES + glycerol mixture were - determined at temperatures up to 363.15 K to check how much the addition of glycerol decreases high viscosities of DES. The results indicate that the addition of small amounts of water or glycerol as a third component significantly decreases the viscosity of the investigated deep eutectic solvent. Based on the selectivity and distribution ratio values, the extraction ability of the investigated deep eutectic solvent, in comparison with the conventionally used solvents, yields promising results. Non-random two-liquid (NRTL) and universal quasichemical (UNIQUAC) models were satisfactorily applied for correlation of experimental phase equilibrium data for two ternary mixtures.

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Green Extraction of Alkaloids and Polyphenols from Peumus boldus Leaves with Natural Deep Eutectic Solvents and Profiling by HPLC-PDA-IT-MS/MS and HPLC-QTOF-MS/MS

Plants ◽

10.3390/plants9020242 ◽

2020 ◽

Vol 9 (2) ◽

pp. 242 ◽

Cited By ~ 4

Author(s):

Jeniffer Torres-Vega ◽

Sergio Gómez-Alonso ◽

José Pérez-Navarro ◽

Edgar Pastene-Navarrete

Keyword(s):

Mass Spectrometry ◽

Phenolic Compounds ◽

High Resolution Mass Spectrometry ◽

Choline Chloride ◽

Deep Eutectic Solvents ◽

Total Phenolic ◽

Array Detector ◽

Green Extraction ◽

Medicinal Tree ◽

Natural Deep Eutectic Solvents

Peumus boldus Mol., is a Chilean medicinal tree used for gastrointestinal and liver diseases. Such medicinal properties are associated with the presence of bioactive flavonoids and aporphine alkaloids. In this study, a new green and efficient extraction method used seven natural deep eutectic solvents (NADES) as extraction media. The extraction efficiency of these NADES was assessed, determining the contents of boldine and total phenolic compounds (TPC). Chemical profiling of P. boldus was done by high-performance liquid chromatography coupled to photo diode array detector and electrospray ion-trap mass spectrometry (HPLC-PDA-ESI-IT/MS) and electrospray ionization quadrupole time-of-flight high-resolution mass spectrometry (HPLC-ESI-QTOF-MS). Among the NADES tested, NADES4 (choline chloride-lactic acid) and NADES6 (proline-oxalic acid) enable better extraction of boldine with 0.427 ± 0.018 and 2.362 ± 0.055 mg of boldine g−1 of plant, respectively. Extraction of boldine with NADES4 and NADES6 was more efficient than extractions performed with methanol and water. On the other hand, the highest TPC were obtained using NADES6, 179.442 ± 3.79 mg of gallic acid equivalents (GAE g−1). Moreover, TPC in extracts obtained with methanol does not show significant differences with NADES6. The HPLC-PAD-MS/MS analysis enable the tentative identification of 9 alkaloids and 22 phenolic compounds. The results of this study demonstrate that NADES are a promising green extraction media to extract P. boldus bioactive compounds and could be a valuable alternative to classic organic solvents.

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Natural Deep Eutectic Solvents for Simultaneous Extraction of Multi-Bioactive Components from Jinqi Jiangtang Preparations

Pharmaceutics ◽

10.3390/pharmaceutics11010018 ◽

2019 ◽

Vol 11 (1) ◽

pp. 18 ◽

Cited By ~ 2

Author(s):

Lele Yang ◽

Ling Li ◽

Hao Hu ◽

Jianbo Wan ◽

Peng Li

Keyword(s):

High Performance ◽

Choline Chloride ◽

Deep Eutectic Solvents ◽

Bioactive Components ◽

Operational Parameters ◽

Ultrasound Assisted Extraction ◽

Assisted Extraction ◽

Natural Deep Eutectic Solvents ◽

Quantification Analysis ◽

Chemical Profiles

Natural deep eutectic solvents (NADESs), composed of natural primary metabolites, are now widely used as green and sustainable extraction solvents of bioactive components. In the present study, various NADESs were prepared to extract multi-components from different preparations of an herbal formula (Chinese name: Jinqi Jiangtang, JQJT) using ultrasound-assisted extraction (UAE). Results showed that most prepared NADESs provided more effective extraction of phenolic acids and alkaloids from JQJT preparations than conventional solvents. Among the tested NADESs, the solvent formed by choline chloride and laevulinic acid was selected to optimize the operational parameters using response surface methodology. The optimized extraction method was successfully applied to extract six major components in four commercial JQJT products, and quantification analysis was performed by the validated high-performance liquid chromatography with ultraviolet detection (HPLC-UV) method. The quantitative results indicated that preparations from different manufacturers showed different chemical profiles. In conclusion, NADESs-based UAE shows considerable potential as an efficient and green method for extraction of multi-bioactive components from commercial herbal preparations.

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Inhibition of the calcium paradox in isolated rat hearts by high perfusate sucrose concentrations

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1994.266.5.h1729 ◽

1994 ◽

Vol 266 (5) ◽

pp. H1729-H1737

Author(s):

A. Omachi ◽

R. A. Kleps ◽

T. O. Henderson ◽

R. J. Labotka

Keyword(s):

Pressure Gradient ◽

Sucrose Concentration ◽

Choline Chloride ◽

Weight Ratio ◽

Dry Weight ◽

Calcium Paradox ◽

Oncotic Pressure ◽

Rat Hearts ◽

The Moment ◽

Langendorff Hearts

If a colloid osmotic (oncotic) pressure gradient develops across the myocyte membrane during the calcium paradox, adding an oncotic agent to the perfusate should be inhibitory. After 10-min perfusion with Ca(2+)-free Krebs-Henseleit (KH) buffer under constant flow at 34 degrees C, myoglobin release was measured from Langendorff hearts reperfused with Ca(2+)-containing KH buffer. When the Ca(2+)-free medium contained 200 mM sucrose, myoglobin release was reduced to 5% of that observed in the absence of sucrose, a change that was not seen when 200 mosM NaCl, choline chloride, LiCl, or glycerol was added. Replacement of 75 mM NaCl in the perfusate with 150 mM sucrose resulted in myoglobin release values that were 4% of the control. Plots of myoglobin release against sucrose concentration under these hypertonic and isotonic conditions yielded similar though separate curves. Sucrose also inhibited increases in wet weight-to-dry weight ratio and decreases in ATP and phosphocreatine contents. These results support the hypothesis that an oncotic pressure gradient arises during the calcium paradox at the moment of increased membrane permeability and plays a major role in its development.

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Preparation and adsorption characteristics of rosin-based polymer microspheres for berberine hydrochloride and separation of total alkaloids from coptidis rhizoma

Chemical Engineering Journal ◽

10.1016/j.cej.2019.123707 ◽

2020 ◽

Vol 392 ◽

pp. 123707 ◽

Cited By ~ 2

Author(s):

Pengfei Li ◽

Liting Qin ◽

Ting Wang ◽

Lanxiang Dai ◽

Hua Li ◽

...

Keyword(s):

Polymer Microspheres ◽

Berberine Hydrochloride ◽

Adsorption Characteristics ◽

Total Alkaloids ◽

Coptidis Rhizoma

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Crustacean shell bio-refining to chitin by natural deep eutectic solvents

Green Processing and Synthesis ◽

10.1515/gps-2020-0002 ◽

2019 ◽

Vol 9 (1) ◽

pp. 13-25 ◽

Cited By ~ 15

Author(s):

Bojana Bradić ◽

Uroš Novak ◽

Blaž Likozar

Keyword(s):

Choline Chloride ◽

Deep Eutectic Solvents ◽

Extraction Yield ◽

Added Value ◽

Biomass Waste ◽

Complete Evaluation ◽

Natural Deep Eutectic Solvents ◽

Shrimp Shell ◽

Chitin Extraction ◽

On Line

AbstractThis study provides a complete evaluation of a sustainable zero-waste process for the recovery of added value biomaterials from the abundant shrimp shell biomass waste using natural deep eutectic solvents (NADES). The process parameters for the fractionation of α-chitin, minerals and protein was followed using on-line measurements. Furthermore, the quantitative analysis of isolated chitin, minerals and solvent waste streams were examined. The dominant fractionation mechanisms are explained through the analysis of the liquid and solid fractions. Four of the most promising, and commercially available, NADES consisting on mixtures of Choline Chloride-Lactic Acid (CCLA), Choline Chloride-Malonic Acid (CCMA), Choline Chloride-Urea (CCUR) and Choline Chloride-Citric Acid (CCCA), were tested. The highest chitin extraction yield obtained was < 90% using CCLA, leading to purity higher than 98%. Moreover, it is possible to recycle this particular NADES several times, while having no loss in the shrimp shell fractionation capability.

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