Molecules

20 pages, 6490 KiB

Open AccessFeature PaperArticle

Hydroxytyrosol and Oleuropein-Enriched Extracts Obtained from Olive Oil Wastes and By-Products as Active Antioxidant Ingredients for Poly (Vinyl Alcohol)-Based Films

by Francesca Luzi, Elisa Pannucci, Mariangela Clemente, Edoardo Grande, Silvia Urciuoli, Annalisa Romani, Luigi Torre, Debora Puglia, Roberta Bernini and Luca Santi

Molecules 2021, 26(7), 2104; https://doi.org/10.3390/molecules26072104 - 6 Apr 2021

Cited by 30 | Viewed by 4648

Abstract

Oxidative stability of food is one of the most important parameters affecting integrity and consequently nutritional properties of dietary constituents. Antioxidants are widely used to avoid deterioration during transformation, packaging, and storage of food. In this paper, novel poly (vinyl alcohol) (PVA)-based films [...] Read more.

Oxidative stability of food is one of the most important parameters affecting integrity and consequently nutritional properties of dietary constituents. Antioxidants are widely used to avoid deterioration during transformation, packaging, and storage of food. In this paper, novel poly (vinyl alcohol) (PVA)-based films were prepared by solvent casting method adding an hydroxytyrosol-enriched extract (HTyrE) or an oleuropein-enriched extract (OleE) in different percentages (5, 10 and 20% w/w) and a combination of both at 5% w/w. Both extracts were obtained from olive oil wastes and by-products using a sustainable process based on membrane technologies. Qualitative and quantitative analysis of each sample carried out by high performance liquid chromatography (HPLC) and nuclear resonance magnetic spectroscopy (NMR) proved that the main components were hydroxytyrosol (HTyr) and oleuropein (Ole), respectively, two well-known antioxidant bioactive compounds found in Olea europaea L. All novel formulations were characterized investigating their morphological, optical and antioxidant properties. The promising performances suggest a potential use in active food packaging to preserve oxidative-sensitive food products. Moreover, this research represents a valuable example of reuse and valorization of agro-industrial wastes and by-products according to the circular economy model. Full article

(This article belongs to the Special Issue Natural and Synthetic Phenolic Compounds for Food Applications)

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12 pages, 1661 KiB

Open AccessArticle

Interaction of Squid (Dosidicus giga) Mantle Protein with a Mixtures of Potato and Corn Starch in an Extruded Snack, as Characterized by FTIR and DSC

by José Luis Valenzuela-Lagarda, Ramón Pacheco-Aguilar, Roberto Gutiérrez-Dorado, Jaime Lizardi Mendoza, Jose Ángel López-Valenzuela, Miguel Ángel Mazorra-Manzano and María Dolores Muy-Rangel

Molecules 2021, 26(7), 2103; https://doi.org/10.3390/molecules26072103 - 6 Apr 2021

Cited by 7 | Viewed by 3119

Abstract

The majority of snacks expanded by extrusion (SEE) are made with vegetable sources, to improve their nutritional content; it has been proposed to incorporate squid (Dosidicus gigas), due to its high protein content, low price and high availability. However, the interaction [...] Read more.

The majority of snacks expanded by extrusion (SEE) are made with vegetable sources, to improve their nutritional content; it has been proposed to incorporate squid (Dosidicus gigas), due to its high protein content, low price and high availability. However, the interaction of proteins of animal origin with starch during extrusion causes negative effects on the sensory properties of SEE, so it is necessary to know the type of protein–carbohydrate interactions and their effect on these properties. The objective of this research was to study the interaction of proteins and carbohydrates of SEE elaborated with squid mantle, potato and corn. The nutritional composition and protein digestibility were evaluated, Fourier transform infrared (FTIR) and Differential Scanning Calorimetry (DSC) were used to study the formation of protein–starch complexes and the possible regions responsible for their interactions. The SEE had a high protein content (40–85%) and biological value (>93%). The melting temperature (Tm) was found between 145 and 225 °C; the Tm values in extruded samples are directly proportional to the squid content. The extrusion process reduced the amine groups I and II responsible for the protein–protein interaction and increased the O-glucosidic bonds, so these bonds could be responsible for the protein–carbohydrate interactions. Full article

(This article belongs to the Section Food Chemistry)

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15 pages, 1539 KiB

Open AccessArticle

The Presence of a Cyclohexyldiamine Moiety Confers Cytotoxicity to Pentacyclic Triterpenoids

by Sophie Hoenke, Martin A. Christoph, Sander Friedrich, Niels Heise, Benjamin Brandes, Hans-Peter Deigner, Ahmed Al-Harrasi and René Csuk

Molecules 2021, 26(7), 2102; https://doi.org/10.3390/molecules26072102 - 6 Apr 2021

Cited by 13 | Viewed by 2709

Abstract

Pentacyclic triterpenoids oleanolic acid, ursolic acid, betulinic acid, and platanic acid were acetylated and converted into several amides 9–31; the cytotoxicity of which has been determined in sulforhodamine B assays employing seral human tumor cell lines and nonmalignant fibroblasts. Thereby, [...] Read more.

Pentacyclic triterpenoids oleanolic acid, ursolic acid, betulinic acid, and platanic acid were acetylated and converted into several amides 9–31; the cytotoxicity of which has been determined in sulforhodamine B assays employing seral human tumor cell lines and nonmalignant fibroblasts. Thereby, a betulinic acid/trans-1,4-cyclohexyldiamine amide showed excellent cytotoxicity (for example, EC₅₀ = 0.6 μM for HT29 colon adenocarcinoma cells). Full article

(This article belongs to the Special Issue Triterpenoids and Derivatives with Anticancer Activity)

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21 pages, 10223 KiB

Open AccessArticle

β-Sitosterol Circumvents Obesity Induced Inflammation and Insulin Resistance by down-Regulating IKKβ/NF-κB and JNK Signaling Pathway in Adipocytes of Type 2 Diabetic Rats

by Selvaraj Jayaraman, Nalini Devarajan, Ponnulakshmi Rajagopal, Shyamaladevi Babu, Senthil Kumar Ganesan, Vishnu Priya Veeraraghavan, Chella Perumal Palanisamy, Bo Cui, Vijayalakshmi Periyasamy and Kirubhanand Chandrasekar

Molecules 2021, 26(7), 2101; https://doi.org/10.3390/molecules26072101 - 6 Apr 2021

Cited by 67 | Viewed by 6632

Abstract

β-sitosterol (SIT), the most abundant bioactive component of vegetable oil and other plants, is a highly potent antidiabetic drug. Our previous studies show that SIT controls hyperglycemia and insulin resistance by activating insulin receptor and glucose transporter 4 (GLUT-4) in the adipocytes of [...] Read more.

β-sitosterol (SIT), the most abundant bioactive component of vegetable oil and other plants, is a highly potent antidiabetic drug. Our previous studies show that SIT controls hyperglycemia and insulin resistance by activating insulin receptor and glucose transporter 4 (GLUT-4) in the adipocytes of obesity induced type 2 diabetic rats. The current research was undertaken to investigate if SIT could also exert its antidiabetic effects by circumventing adipocyte induced inflammation, a key driving factor for insulin resistance in obese individuals. Effective dose of SIT (20 mg/kg b.wt) was administered orally for 30 days to high fat diet and sucrose induced type-2 diabetic rats. Metformin, the conventionally used antidiabetic drug was used as a positive control. Interestingly, SIT treatment restores the elevated serum levels of proinflammatory cytokines including leptin, resistin, tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) to normalcy and increases anti-inflammatory adipocytokines including adiponectin in type 2 diabetic rats. Furthermore, SIT decreases sterol regulatory element binding protein-1c (SREBP-1c) and enhances Peroxisome Proliferator–activated receptor-γ (PPAR-γ) gene expression in adipocytes of diabetic rats. The gene and protein expression of c-Jun-N-terminal kinase-1 (JNK1), inhibitor of nuclear factor kappa-B kinase subunit beta (IKKβ) and nuclear factor kappa B (NF-κB) were also significantly attenuated in SIT treated groups. More importantly, SIT acts very effectively as metformin to circumvent inflammation and insulin resistance in diabetic rats. Our results clearly show that SIT inhibits obesity induced insulin resistance by ameliorating the inflammatory events in the adipose tissue through the downregulation of IKKβ/NF-κB and c-Jun-N-terminal kinase (JNK) signaling pathway. Full article

(This article belongs to the Special Issue From Ethnobotany to Ecopharmacognosy: Chemical Characterization and Bioactivity Evaluation of Medicinal and Aromatic Plants)

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13 pages, 1784 KiB

Open AccessArticle

UHPLC-DAD Characterization of Origanum vulgare L. from Atacama Desert Andean Region and Antioxidant, Antibacterial and Enzyme Inhibition Activities

by Claudio Parra, Patricio Muñoz, Luis Bustos, Felipe Parra, Mario J. Simirgiotis and Hugo Escobar

Molecules 2021, 26(7), 2100; https://doi.org/10.3390/molecules26072100 - 6 Apr 2021

Cited by 16 | Viewed by 3110

Abstract

The Lamiaceae family is an important source of species among medicinal plants highly valued for their biological properties and numerous uses in folk medicine. Origanum is one of the main genera that belong to this family. The purpose of the study was to [...] Read more.

The Lamiaceae family is an important source of species among medicinal plants highly valued for their biological properties and numerous uses in folk medicine. Origanum is one of the main genera that belong to this family. The purpose of the study was to determine the phenolic composition of the Origanum vulgare extract and evaluate the antimicrobial, antioxidant, and inhibitory activities of this species that grows in the Andean region of the Atacama Desert. High-performance liquid chromatography was performed to determine the main phenols. Rosmarinic acid was identified as the predominant phenolic compound in this species (76.01 mg/100 g DW), followed by protocatechuic acid, which to our knowledge, no previous study reported similar concentrations in O. vulgare. The oregano extract exhibited a content of total phenolic (3948 mg GAE/100 g DW) and total flavonoid (593 mg QE/100 g DW) with a higher DPPH antioxidant activity (IC₅₀ = 40.58 µg/mL), compared to the same species grown under other conditions. Furthermore, it was found to inhibit α-glucosidase activity with an IC₅₀ value (7.11 mg/mL) lower than acarbose (129.32 mg/mL). Pseudomonas syringae and Pantoea agglomerans (both MIC 0.313 mg/mL and MBC 1.25 mg/mL) were the bacteria most susceptible to oregano extract with the lowest concentration necessary to inhibit bacterial growth. These results open the door for the potential use of this plant to manage chronic diseases, and they expand the knowledge of the species cultivated in arid environmental conditions. Full article

(This article belongs to the Special Issue Bioactive Compounds and Antioxidant Activity of Extracts from Different Natural Plants)

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17 pages, 681 KiB

Open AccessArticle

Health Beneficial Properties of Grapevine Seed Extract and Its Influence on Selected Biochemical Markers in the Blood, Liver and Kidneys of Rattus norvegicus

by Lenka Sochorova, Mojmir Baron, Katerina Dadakova, Tomas Kasparovsky and Jiri Sochor

Molecules 2021, 26(7), 2099; https://doi.org/10.3390/molecules26072099 - 6 Apr 2021

Cited by 3 | Viewed by 2100

Abstract

Cadmium (Cd) is a heavy metal that occurs in all areas of the environment, including the food chain. In the body, it causes oxidative stress by producing free radicals that are harmful to the cells. Grape seed extract (GSE) contains a wide range [...] Read more.

Cadmium (Cd) is a heavy metal that occurs in all areas of the environment, including the food chain. In the body, it causes oxidative stress by producing free radicals that are harmful to the cells. Grape seed extract (GSE) contains a wide range of biologically active components that help to neutralize the adverse effects of free radicals. In this study, the effects of GSE prepared form semi-resistant grapevine cultivar Cerason, which is rich in phenolics, on biochemical markers of brown rats exposed to the effects of cadmium were monitored. GSE increased the plasma antioxidant activity and, in the kidneys and the liver, Cd content was significantly lowered by GSE co-administration. Accordingly, the increase in creatinine content and alanine aminotransferase activity and the decrease of catalase and superoxide dismutase activities caused by cadmium were slowed down by GSE co-administration. The results of this work reveal that grape seed extract offers a protective effect against the intake of heavy metals into the organism. Full article

(This article belongs to the Special Issue Natural Antioxidants: Chemistry, Health Beneficial Properties, and Potential Application)

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13 pages, 1498 KiB

Open AccessArticle

MetaTREE, a Novel Database Focused on Metabolic Trees, Predicts an Important Detoxification Mechanism: The Glutathione Conjugation

by Angelica Mazzolari, Luca Sommaruga, Alessandro Pedretti and Giulio Vistoli

Molecules 2021, 26(7), 2098; https://doi.org/10.3390/molecules26072098 - 6 Apr 2021

Cited by 3 | Viewed by 2740

Abstract

(1) Background: Data accuracy plays a key role in determining the model performances and the field of metabolism prediction suffers from the lack of truly reliable data. To enhance the accuracy of metabolic data, we recently proposed a manually curated database collected by [...] Read more.

(1) Background: Data accuracy plays a key role in determining the model performances and the field of metabolism prediction suffers from the lack of truly reliable data. To enhance the accuracy of metabolic data, we recently proposed a manually curated database collected by a meta-analysis of the specialized literature (MetaQSAR). Here we aim to further increase data accuracy by focusing on publications reporting exhaustive metabolic trees. This selection should indeed reduce the number of false negative data. (2) Methods: A new metabolic database (MetaTREE) was thus collected and utilized to extract a dataset for metabolic data concerning glutathione conjugation (MT-dataset). After proper pre-processing, this dataset, along with the corresponding dataset extracted from MetaQSAR (MQ-dataset), was utilized to develop binary classification models using a random forest algorithm. (3) Results: The comparison of the models generated by the two collected datasets reveals the better performances reached by the MT-dataset (MCC raised from 0.63 to 0.67, sensitivity from 0.56 to 0.58). The analysis of the applicability domain also confirms that the model based on the MT-dataset shows a more robust predictive power with a larger applicability domain. (4) Conclusions: These results confirm that focusing on metabolic trees represents a convenient approach to increase data accuracy by reducing the false negative cases. The encouraging performances shown by the models developed by the MT-dataset invites to use of MetaTREE for predictive studies in the field of xenobiotic metabolism. Full article

(This article belongs to the Special Issue Data and Low-Data Tools for Artificial Intelligence in Medicinal Chemistry)

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18 pages, 2527 KiB

Open AccessArticle

Physical, Chemical and Rheological Characterization of Tuber and Starch from Ceiba aesculifolia subsp. parvifolia

by Lizette Suastegui-Baylón, Ricardo Salazar, Yanik I. Maldonado-Astudillo, Manuel O. Ramírez-Sucre, Gerónimo Arámbula-Villa, Verónica Flores-Casamayor and Javier Jiménez-Hernández

Molecules 2021, 26(7), 2097; https://doi.org/10.3390/molecules26072097 - 6 Apr 2021

Cited by 4 | Viewed by 3074

Abstract

This work aimed to evaluate the physical, chemical and antioxidant properties of Ceiba aesculifolia subsp. parvifolia (CAP) tuber and determinate rheological, thermal, physicochemical and morphological properties of the starch extracted. The CAP tuber weight was 3.66 kg; the edible yield was 82.20%. The [...] Read more.

This work aimed to evaluate the physical, chemical and antioxidant properties of Ceiba aesculifolia subsp. parvifolia (CAP) tuber and determinate rheological, thermal, physicochemical and morphological properties of the starch extracted. The CAP tuber weight was 3.66 kg; the edible yield was 82.20%. The tuber presented a high hardness value (249 N). The content of carbohydrates (68.27%), crude fiber (15.61%) and ash (9.27%) from the isolated starch, reported in dry weight, were high. Phenolic compounds and flavonoid content of CAP tuber peel were almost 3-fold higher concerning the pulp. CAP tuber starch exhibited a pseudoplastic behavior and low viscosity at concentrations of 5–15%. Purity percentage and color parameters describe the isolated starch as high purity. Thermal characteristics indicated a higher degree of intermolecular association within the granule. Pasting properties describes starch with greater resistance to heat and shear. CAP tuber starch has X-ray diffraction patterns type A. The starch granules were observed as oval and diameters ranging from 5 to 30 µm. CAP tuber could be a good source of fiber and minerals, while its peel could be used for extracting bioactive compounds. Additionally, the starch separated from this tuber could be employed as a thickening agent in food systems requiring a low viscosity and subjected to high temperatures. Full article

(This article belongs to the Special Issue Physicochemical Properties of Food)

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11 pages, 2159 KiB

Open AccessArticle

The Annealing of Acetylated Potato Starch with Various Substitution Degrees

by Tomasz Zięba, Aleksandra Wilczak, Justyna Kobryń, Witold Musiał, Małgorzata Kapelko-Żeberska, Artur Gryszkin and Marta Meisel

Molecules 2021, 26(7), 2096; https://doi.org/10.3390/molecules26072096 - 6 Apr 2021

Cited by 10 | Viewed by 2752

Abstract

This study aimed to determine the effect of “annealing” acetylated potato starch with a homogenous granule size and various degrees of substitution on the thermal pasting characteristics (DSC), resistance to amylases, rheology of the prepared pastes, swelling power and dynamics of drug release. [...] Read more.

This study aimed to determine the effect of “annealing” acetylated potato starch with a homogenous granule size and various degrees of substitution on the thermal pasting characteristics (DSC), resistance to amylases, rheology of the prepared pastes, swelling power and dynamics of drug release. A fraction of large granules was separated from native starch with the sedimentation method and acetylated with various doses of acetic anhydride (6.5, 13.0 or 26.0 26 cm³/100 g starch). The starch acetates were then annealed at slightly lower temperatures than their pasting temperatures. The annealing process caused an almost twofold increase in the resistance to amylolysis and a threefold increase in the swelling power of the modified starch preparations. The heat of phase transition decreased almost two times and the range of starch pasting temperatures over two times, but the pasting temperature itself increased by ca. 10 °C. The 40 g/100 g addition of the modified starch preparation decreased the rate of drug release from a hydrogel by ca. one-fourth compared to the control sample. Full article

(This article belongs to the Special Issue Starch: Chemistry, Technology and Application)

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16 pages, 504 KiB

Open AccessArticle

Caffeine Health Claims on Sports Supplement Labeling. Analytical Assessment According to EFSA Scientific Opinion and International Evidence and Criteria

by Pedro Estevan Navarro, Isabel Sospedra, Alejandro Perales, Cristina González-Díaz, Rubén Jiménez-Alfageme, Sonia Medina, Angel Gil-Izquierdo and José Miguel Martínez-Sanz

Molecules 2021, 26(7), 2095; https://doi.org/10.3390/molecules26072095 - 6 Apr 2021

Cited by 3 | Viewed by 3415

Abstract

Caffeine is a food supplement widely consumed by athletes, but it has not been established. So far, the veracity of their labeling in terms of the dosage and cause/effect relationship aimed at the consumer. The aim is to analyze the health claims and [...] Read more.

Caffeine is a food supplement widely consumed by athletes, but it has not been established. So far, the veracity of their labeling in terms of the dosage and cause/effect relationship aimed at the consumer. The aim is to analyze the health claims and the dosage presented on the labeling of caffeine supplements and to evaluate if they follow the European Food Safety Authority (EFSA) and international criteria. A descriptive cross-sectional study of a sample of caffeine supplements was carried out. The search was done through the Amazon and Google Shopping web portals. In order to assess the adequacy of the health claims, the guidelines of reference established by European Food Safety Authority were compared to the Academy of Nutrition and Dietetics, International Olympic Committee, and Australian Institute of Sport guidelines; in addition, recent systematic reviews were addressed. A review of labels of 42 caffeine supplements showed that, in less than 3% of the products were the health claims supported by the recommendations and by the labeled quantity of caffeine. The claims that fully complied the recommendations were, “improves or increases endurance performance”, “improves strength performance”, or “improves short-term performance”. In most cases, the recommended dosage was 200 mg/day for these products, which is the minimum for the caffeine effects to be declared. The rest of the health claims were not adequate or need to be modified. Most of the health claims identified indicated an unproven cause and effect, which constitutes consumer fraud, and so must be modified or eliminated. Full article

(This article belongs to the Section Food Chemistry)

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15 pages, 51199 KiB

Open AccessArticle

Bioactivity Performance of Pure Mg after Plasma Electrolytic Oxidation in Silicate-Based Solutions

by Yevheniia Husak, Joanna Michalska, Oleksandr Oleshko, Viktoriia Korniienko, Karlis Grundsteins, Bohdan Dryhval, Sahin Altundal, Oleg Mishchenko, Roman Viter, Maksym Pogorielov and Wojciech Simka

Molecules 2021, 26(7), 2094; https://doi.org/10.3390/molecules26072094 - 6 Apr 2021

Cited by 17 | Viewed by 3209

Abstract

The biodegradable metals, including magnesium (Mg), are a convenient alternative to permanent metals but fast uncontrolled corrosion limited wide clinical application. Formation of a barrier coating on Mg alloys could be a successful strategy for the production of a stable external layer that [...] Read more.

The biodegradable metals, including magnesium (Mg), are a convenient alternative to permanent metals but fast uncontrolled corrosion limited wide clinical application. Formation of a barrier coating on Mg alloys could be a successful strategy for the production of a stable external layer that prevents fast corrosion. Our research was aimed to develop an Mg stable oxide coating using plasma electrolytic oxidation (PEO) in silicate-based solutions. 99.9% pure Mg alloy was anodized in electrolytes contained mixtures of sodium silicate and sodium fluoride, calcium hydroxide and sodium hydroxide. Scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDX), contact angle (CA), Photoluminescence analysis and immersion tests were performed to assess structural and long-term corrosion properties of the new coating. Biocompatibility and antibacterial potential of the new coating were evaluated using U2OS cell culture and the gram-positive Staphylococcus aureus (S. aureus, strain B 918). PEO provided the formation of a porous oxide layer with relatively high roughness. It was shown that Ca(OH)₂ was a crucial compound for oxidation and surface modification of Mg implants, treated with the PEO method. The addition of Ca²⁺ ions resulted in more intense oxidation of the Mg surface and growth of the oxide layer with a higher active surface area. Cell culture experiments demonstrated appropriate cell adhesion to all investigated coatings with a significantly better proliferation rate for the samples treated in Ca(OH)₂-containing electrolyte. In contrast, NaOH-based electrolyte provided more relevant antibacterial effects but did not support cell proliferation. In conclusion, it should be noted that PEO of Mg alloy in silicate baths containing Ca(OH)₂ provided the formation of stable biocompatible oxide coatings that could be used in the development of commercial degradable implants. Full article

(This article belongs to the Special Issue Electrochemistry of Thin Films and Nanostructured Materials)

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14 pages, 1653 KiB

Open AccessArticle

Preparation of Co-Processed Excipients for Controlled-Release of Drugs Assembled with Solid Lipid Nanoparticles and Direct Compression Materials

by Luis Eduardo Serrano-Mora, María L. Zambrano-Zaragoza, Néstor Mendoza-Muñoz, Gerardo Leyva-Gómez, Zaida Urbán-Morlán and David Quintanar-Guerrero

Molecules 2021, 26(7), 2093; https://doi.org/10.3390/molecules26072093 - 6 Apr 2021

Cited by 2 | Viewed by 4187

Abstract

The purpose of the study was to develop a novel, directly compressible, co-processed excipient capable of providing a controlled-release drug system for the pharmaceutical industry. A co-processed powder was formed by adsorption of solid lipid nanoparticles (SLN) as a controlled-release film onto a [...] Read more.

The purpose of the study was to develop a novel, directly compressible, co-processed excipient capable of providing a controlled-release drug system for the pharmaceutical industry. A co-processed powder was formed by adsorption of solid lipid nanoparticles (SLN) as a controlled-release film onto a functional excipient, in this case, dicalcium phosphate dihydrate (DPD), for direct compression (Di-Tab^®). The co-processed excipient has advantages: easy to implement; solvent-free; industrial scaling-up; good rheological and compressibility properties; and the capability to form an inert platform. Six different batches of Di-Tab^®:SLN weight ratios were prepared (4:0.6, 3:0.6, 2:0.6, 1:0.6, 0.5:0.6, and 0.25:0.6). BCS class III ranitidine hydrochloride was selected as a drug model to evaluate the mixture’s controlled-release capabilities. The co-processed excipients were characterized in terms of powder rheology and dissolution rate. The best Di-Tab^®:SLN ratio proved to be 2:0.6, as it showed high functionality with good flow and compressibility properties (Carr Index = 16 ± 1, Hausner Index = 1.19 ± 0.04). This ratio could control release for up to 8 h, so it fits the ideal profile calculated based on biopharmaceutical data. The compressed systems obtained using this powder mixture behave as a matrix platform in which Fickian diffusion governs the release. The Higuchi model can explain their behavior. Full article

(This article belongs to the Special Issue Nano-particulate Drug Delivery System: Current Status and Future Perspective)

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17 pages, 13864 KiB

Open AccessArticle

Simultaneous Quantitative Analysis of Ginsenosides Isolated from the Fruit of Panax ginseng C.A. Meyer and Regulation of HO-1 Expression through EGFR Signaling Has Anti-Inflammatory and Osteogenic Induction Effects in HPDL Cells

by Eun-Nam Kim, Oryon Kaygusuz, Hyun-Su Lee and Gil-Saeng Jeong

Molecules 2021, 26(7), 2092; https://doi.org/10.3390/molecules26072092 - 6 Apr 2021

Cited by 13 | Viewed by 2977

Abstract

Periodontitis is a set of chronic inflammatory diseases caused by the accumulation of Gram-negative bacteria on teeth, resulting in gingivitis, pocket formation, alveolar bone loss, tissue destruction, and tooth loss. In this study, the contents of ginsenosides isolated from Panax ginseng fruit extract [...] Read more.

Periodontitis is a set of chronic inflammatory diseases caused by the accumulation of Gram-negative bacteria on teeth, resulting in gingivitis, pocket formation, alveolar bone loss, tissue destruction, and tooth loss. In this study, the contents of ginsenosides isolated from Panax ginseng fruit extract were quantitatively analyzed, and the anti-inflammatory effects were evaluated in human periodontal ligament cells. The major ginsenosides, Re, Ra8, and Rf, present in ginseng fruit were simultaneously analyzed by a validated method using high-performance liquid chromatography with a diode-array detector; Re, Ra8, and Rf content per 1 g of P. ginseng fruit extract was 1.01 ± 0.03, 0.33 ± 0.01, and 0.55 ± 0.04 mg, respectively. Ginsenosides-Re, -Ra8, and -Rf inhibited the production of pro-inflammatory factors and the expression of important cytokines in periodontitis by inducing the expression of heme oxygenase 1 (HO-1), promoting osteoblast differentiation of periodontal ligament cells, suppressing alveolar bone loss, and promoting the expression of osteoblast-specific genes, such as alp, opn, and runx2. An inhibitory effect of these ginsenosides on periodontitis and alveolar bone loss was observed via the regulation of HO-1 and subsequent epidermal growth factor receptor (EGFR) signaling. Silencing EGFR with EGFR siRNA confirmed that the effect of ginsenosides on HO-1 is mediated by EGFR. In conclusion, this study evaluated the contents of ginsenosides-Re, -Ra8, and -Rf isolated from P. ginseng fruit extract. Therefore, these results provide important basic data for future P. ginseng fruit component studies and suggest that ginsenosides Re, Ra8, and Rf have potential as future treatment options for periodontitis. Full article

(This article belongs to the Special Issue Bioactive Compounds from Roots, Stems, Leaves, Flowers, Fruits, and Seeds)

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14 pages, 7386 KiB

Open AccessArticle

Development and Validation of a Chiral Liquid Chromatographic Assay for Enantiomeric Separation and Quantification of Verapamil in Rat Plasma: Stereoselective Pharmacokinetic Application

by Mostafa S. Mohammed, Mohamed M. Hefnawy, Abdulrhman A. Al-Majed, Haitham K. Alrabiah, Nasser A. Algrain, Ahmad J. Obaidullah, Abdulmalik S. Altamimi, Yousef A. Bin Jardan and Abdullah M. Al-Hossaini

Molecules 2021, 26(7), 2091; https://doi.org/10.3390/molecules26072091 - 6 Apr 2021

Cited by 8 | Viewed by 2793

Abstract

A novel, fast and sensitive enantioselective HPLC assay with a new core–shell isopropyl carbamate cyclofructan 6 (superficially porous particle, SPP) chiral column (LarihcShell-P, LSP) was developed and validated for the enantiomeric separation and quantification of verapamil (VER) in rat plasma. The polar organic [...] Read more.

A novel, fast and sensitive enantioselective HPLC assay with a new core–shell isopropyl carbamate cyclofructan 6 (superficially porous particle, SPP) chiral column (LarihcShell-P, LSP) was developed and validated for the enantiomeric separation and quantification of verapamil (VER) in rat plasma. The polar organic mobile phase composed of acetonitrile/methanol/trifluoroacetic acid/triethylamine (98:2:0.05: 0.025, v/v/v/v) and a flow rate of 0.5 mL/min was applied. Fluorescence detection set at excitation/emission wavelengths 280/313 nm was used and the whole analysis process was within 3.5 min, which is 10-fold lower than the previous reported HPLC methods in the literature. Propranolol was selected as the internal standard. The S-(−)- and R-(+)-VER enantiomers with the IS were extracted from rat plasma by utilizing Waters Oasis HLB C18 solid phase extraction cartridges without interference from endogenous compounds. The developed assay was validated following the US-FDA guidelines over the concentration range of 1–450 ng/mL (r² ≥ 0.997) for each enantiomer (plasma) and the lower limit of quantification was 1 ng/mL for both isomers. The intra- and inter-day precisions were not more than 11.6% and the recoveries of S-(−)- and R-(+)-VER at all quality control levels ranged from 92.3% to 98.2%. The developed approach was successfully applied to the stereoselective pharmacokinetic study of VER enantiomers after oral administration of 10 mg/kg racemic VER to Wistar rats. It was found that S-(−)-VER established higher C_max and area under the concentration-time curve (AUC) values than the R-(+)-enantiomer. The newly developed approach is the first chiral HPLC for the enantiomeric separation and quantification of verapamil utilizing a core–shell isopropyl carbamate cyclofructan 6 chiral column in rat plasma within 3.5 min after solid phase extraction (SPE). Full article

(This article belongs to the Collection Advances in Liquid Separation Techniques for Food and Pharmaceutical Analysis)

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18 pages, 1956 KiB

Open AccessReview

Gastroprotective Effects of Polyphenols against Various Gastro-Intestinal Disorders: A Mini-Review with Special Focus on Clinical Evidence

by Hui-Fang Chiu, Kamesh Venkatakrishnan, Oksana Golovinskaia and Chin-Kun Wang

Molecules 2021, 26(7), 2090; https://doi.org/10.3390/molecules26072090 - 6 Apr 2021

Cited by 50 | Viewed by 8049

Abstract

Polyphenols are classified as an organic chemical with phenolic units that display an array of biological functions. However, polyphenols have very low bioavailability and stability, which make polyphenols a less bioactive compound. Many researchers have indicated that several factors might affect the efficiency [...] Read more.

Polyphenols are classified as an organic chemical with phenolic units that display an array of biological functions. However, polyphenols have very low bioavailability and stability, which make polyphenols a less bioactive compound. Many researchers have indicated that several factors might affect the efficiency and the metabolism (biotransformation) of various polyphenols, which include the gut microbiota, structure, and physical properties as well as its interactions with other dietary nutrients (macromolecules). Hence, this mini-review covers the two-way interaction between polyphenols and gut microbiota (interplay) and how polyphenols are metabolized (biotransformation) to produce various polyphenolic metabolites. Moreover, the protective effects of numerous polyphenols and their metabolites against various gastrointestinal disorders/diseases including gastritis, gastric cancer, colorectal cancer, inflammatory bowel disease (IBD) like ulcerative colitis (UC), Crohn’s disease (CD), and irritable bowel syndrome (IBS) like celiac disease (CED) are discussed. For this review, the authors chose only a few popular polyphenols (green tea polyphenol, curcumin, resveratrol, quercetin), and a discussion of their proposed mechanism underpinning the gastroprotection was elaborated with a special focus on clinical evidence. Overall, this contribution would help the general population and science community to identify a potent polyphenol with strong antioxidant, anti-inflammatory, anti-cancer, prebiotic, and immunomodulatory properties to combat various gut-related diseases or disorders (complementary therapy) along with modified lifestyle pattern and standard gastroprotective drugs. However, the data from clinical trials are much limited and hence many large-scale clinical trials should be performed (with different form/metabolites and dose) to confirm the gastroprotective activity of the above-mentioned polyphenols and their metabolites before recommendation. Full article

(This article belongs to the Special Issue Plant Polyphenols and Gut Health)

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16 pages, 4106 KiB

Open AccessFeature PaperArticle

A Theoretical Model for Release Dynamics of an Antifungal Agent Covalently Bonded to the Chitosan

by Luminita Marin, Marcel Popa, Alexandru Anisiei, Stefan-Andrei Irimiciuc, Maricel Agop, Tudor-Cristian Petrescu, Decebal Vasincu and Loredana Himiniuc

Molecules 2021, 26(7), 2089; https://doi.org/10.3390/molecules26072089 - 6 Apr 2021

Cited by 7 | Viewed by 2525

Abstract

The aim of the study was to create a mathematical model useful for monitoring the release of bioactive aldehydes covalently bonded to the chitosan by reversible imine linkage, considered as a polymer–drug system. For this purpose, two hydrogels were prepared by the acid [...] Read more.

The aim of the study was to create a mathematical model useful for monitoring the release of bioactive aldehydes covalently bonded to the chitosan by reversible imine linkage, considered as a polymer–drug system. For this purpose, two hydrogels were prepared by the acid condensation reaction of chitosan with the antifungal 2-formyl-phenyl-boronic acid and their particularities; influencing the release of the antifungal aldehyde by shifting the imination equilibrium to the reagents was considered, i.e., the supramolecular nature of the hydrogels was highlighted by polarized light microscopy, while scanning electron microscopy showed their microporous morphology. Furthermore, the in vitro fungicidal activity was investigated on two fungal strains and the in vitro release curves of the antifungal aldehyde triggered by the pH stimulus were drawn. The theoretical model was developed starting from the hypothesis that the imine-chitosan system, both structurally and functionally, can be assimilated, from a mathematical point of view, with a multifractal object, and its dynamics were analyzed in the framework of the Scale Relativity Theory. Thus, through Riccati-type gauges, two synchronous dynamics, one in the scale space, associated with the fungicidal activity, and the other in the usual space, associated with the antifungal aldehyde release, become operational. Their synchronicity, reducible to the isomorphism of two SL(2R)-type groups, implies, by means of its joint invariant functions, bioactive aldehyde compound release dynamics in the form of “kink–antikink pairs” dynamics of a multifractal type. Finally, the theoretical model was validated through the experimental data. Full article

(This article belongs to the Special Issue Drug Delivery Systems Based on Polysaccharides)

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16 pages, 7066 KiB

Open AccessCommunication

Ratiometric Near-Infrared Fluorescent Probes Based on Hemicyanine Dyes Bearing Dithioacetal and Formal Residues for pH Detection in Mitochondria

by Yunnan Yan, Yibin Zhang, Shuai Xia, Shulin Wan, Tara Vohs, Marina Tanasova, Rudy L. Luck and Haiying Liu

Molecules 2021, 26(7), 2088; https://doi.org/10.3390/molecules26072088 - 6 Apr 2021

Cited by 11 | Viewed by 3745

Abstract

Ratiometric near-infrared fluorescent probes (AH⁺ and BH⁺) have been prepared for pH determination in mitochondria by attaching dithioacetal and formal residues onto a hemicyanine dye. The reactive formyl group on probe BH⁺ allows for retention inside mitochondria as [...] Read more.

Ratiometric near-infrared fluorescent probes (AH⁺ and BH⁺) have been prepared for pH determination in mitochondria by attaching dithioacetal and formal residues onto a hemicyanine dye. The reactive formyl group on probe BH⁺ allows for retention inside mitochondria as it can react with a protein primary amine residue to form an imine under slightly basic pH 8.0. Probes AH⁺ and BH⁺ display ratiometric fluorescent responses to pH changes through the protonation and deprotonaton of a hydroxy group in hemicyanine dyes with experimentally determined pKa values of 6.85 and 6.49, respectively. Calculated pK_a values from a variety of theoretical methods indicated that the SMD_BONDI method of accounting for solvent and van der Waals radii plus including a water molecule located near the site of protonation produced the closest overall agreement with the experimental values at 7.33 and 6.14 for AH⁺ and BH⁺ respectively. Full article

(This article belongs to the Special Issue Exclusive Papers of the Editorial Board Members (EBMs) of the Bioorganic Chemistry Section of Molecules)

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19 pages, 8666 KiB

Open AccessArticle

Pore Development during the Carbonization Process of Lignin Microparticles Investigated by Small Angle X-ray Scattering

by Harald Rennhofer, Janea Köhnke, Jozef Keckes, Johannes Tintner, Christoph Unterweger, Thomas Zinn, Karl Deix, Helga Lichtenegger and Wolfgang Gindl-Altmutter

Molecules 2021, 26(7), 2087; https://doi.org/10.3390/molecules26072087 - 6 Apr 2021

Cited by 9 | Viewed by 2691

Abstract

Application of low-cost carbon black from lignin highly depends on the materials properties, which might by determined by raw material and processing conditions. Four different technical lignins were subjected to thermostabilization followed by stepwise heat treatment up to a temperature of 2000 °C [...] Read more.

Application of low-cost carbon black from lignin highly depends on the materials properties, which might by determined by raw material and processing conditions. Four different technical lignins were subjected to thermostabilization followed by stepwise heat treatment up to a temperature of 2000 °C in order to obtain micro-sized carbon particles. The development of the pore structure, graphitization and inner surfaces were investigated by X-ray scattering complemented by scanning electron microscopy and FTIR spectroscopy. Lignosulfonate-based carbons exhibit a complex pore structure with nanopores and mesopores that evolve by heat treatment. Organosolv, kraft and soda lignin-based samples exhibit distinct pores growing steadily with heat treatment temperature. All carbons exhibit increasing pore size of about 0.5–2 nm and increasing inner surface, with a strong increase between 1200 °C and 1600 °C. The chemistry and bonding nature shifts from basic organic material towards pure graphite. The crystallite size was found to increase with the increasing degree of graphitization. Heat treatment of just 1600 °C might be sufficient for many applications, allowing to reduce production energy while maintaining materials properties. Full article

(This article belongs to the Special Issue Lignin for Energy, Chemicals and Materials II)

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19 pages, 1705 KiB

Open AccessArticle

Traumatic Stress, Chronic Ethanol Exposure, or the Combination, Alter Cannabinoid System Components in Reward and Limbic Regions of the Mouse Brain

by Veronica M. Piggott, Scott C. Lloyd, James I. Matchynski, Shane A. Perrine and Alana C. Conti

Molecules 2021, 26(7), 2086; https://doi.org/10.3390/molecules26072086 - 6 Apr 2021

Cited by 7 | Viewed by 2761

Abstract

The cannabinoid system is independently affected by stress and chronic ethanol exposure. However, the extent to which co-occurrence of traumatic stress and chronic ethanol exposure modulates the cannabinoid system remains unclear. We examined levels of cannabinoid system components, anandamide, 2-arachidonoylglycerol, fatty acid amide [...] Read more.

The cannabinoid system is independently affected by stress and chronic ethanol exposure. However, the extent to which co-occurrence of traumatic stress and chronic ethanol exposure modulates the cannabinoid system remains unclear. We examined levels of cannabinoid system components, anandamide, 2-arachidonoylglycerol, fatty acid amide hydrolase, and monoacylglycerol lipase after mouse single-prolonged stress (mSPS) or non-mSPS (Control) exposure, with chronic intermittent ethanol (CIE) vapor or without CIE vapor (Air) across several brain regions using ultra-high-performance liquid chromatography tandem mass spectrometry or immunoblotting. Compared to mSPS-Air mice, anandamide and 2-arachidonoylglycerol levels in the anterior striatum were increased in mSPS-CIE mice. In the dorsal hippocampus, anandamide content was increased in Control-CIE mice compared to Control-Air, mSPS-Air, or mSPS-CIE mice. Finally, amygdalar anandamide content was increased in Control-CIE mice compared to Control-Air, or mSPS-CIE mice, but the anandamide content was decreased in mSPS-CIE compared to mSPS-Air mice. Based on these data we conclude that the effects of combined traumatic stress and chronic ethanol exposure on the cannabinoid system in reward pathway regions are driven by CIE exposure and that traumatic stress affects the cannabinoid components in limbic regions, warranting future investigation of neurotherapeutic treatment to attenuate these effects. Full article

(This article belongs to the Special Issue Endocannabinoid System Modulators in a Medicinal Chemistry Perspective)

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11 pages, 1364 KiB

Open AccessArticle

Comparison of the In Vitro Bioavailability of Selected Minerals from Gluten-Free Breads Enriched with Grains and Synthetic Organic and Non-Organic Compounds

by Anna Rogaska, Julita Reguła, Joanna Suliburska and Zbigniew Krejpcio

Molecules 2021, 26(7), 2085; https://doi.org/10.3390/molecules26072085 - 6 Apr 2021

Cited by 2 | Viewed by 2316

Abstract

Introduction: Despite the constant efforts of scientists to improve the texture, sensory properties, and nutritional value of gluten-free bread, obtaining high bioavailability of minerals is still a huge challenge. Gluten-free bakery products are characterized by a low bioavailability of minerals. The aim of [...] Read more.

Introduction: Despite the constant efforts of scientists to improve the texture, sensory properties, and nutritional value of gluten-free bread, obtaining high bioavailability of minerals is still a huge challenge. Gluten-free bakery products are characterized by a low bioavailability of minerals. The aim of this study was to design gluten-free bread with high bioavailability of minerals commonly found in deficiencies in people struggling with gluten intolerance. Material and methods: The material consisted of gluten-free breads designed to obtain the highest possible content of minerals in the bread while maintaining a good structure and taste. Results: Higher contents of all the analyzed minerals were obtained in breads with natural and synthetic additives, both in rice and buckwheat bread, compared to basic bread. There was also a higher content of the analyzed minerals in buckwheat bread in comparison to rice bread for each type of additive. Higher bioavailability of iron, copper, calcium, and magnesium was noted in rice bread, while the bioavailability of zinc was higher in buckwheat bread. Conclusion: The additives used increased the bioavailability of the analyzed minerals from the gluten-free breads. The use of various variants of flour (rice, buckwheat) influenced the bioavailability of iron, zinc, copper, calcium, and magnesium. The release of minerals from gluten-free bread depends on the element and added components (seeds or synthetic additives). Full article

(This article belongs to the Section Food Chemistry)

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12 pages, 2916 KiB

Open AccessArticle

Photocytotoxic Activity of Ruthenium(II) Complexes with Phenanthroline-Hydrazone Ligands

by Priscila Pereira Silva-Caldeira, Antônio Carlos Almendagna de Oliveira Junior and Elene Cristina Pereira-Maia

Molecules 2021, 26(7), 2084; https://doi.org/10.3390/molecules26072084 - 6 Apr 2021

Cited by 7 | Viewed by 3159

Abstract

This paper reports on the synthesis and characterization of two new polypyridyl-hydrazone Schiff bases, (E)-N′-(6-oxo-1,10-phenanthrolin-5(6H)-ylidene)thiophene-2-carbohydrazide (L¹) and (E)-N′-(6-oxo-1,10-phenanthrolin-5(6H)-ylidene)furan-2-carbohydrazide (L²), and their two Ru(II) complexes of [...] Read more.

This paper reports on the synthesis and characterization of two new polypyridyl-hydrazone Schiff bases, (E)-N′-(6-oxo-1,10-phenanthrolin-5(6H)-ylidene)thiophene-2-carbohydrazide (L¹) and (E)-N′-(6-oxo-1,10-phenanthrolin-5(6H)-ylidene)furan-2-carbohydrazide (L²), and their two Ru(II) complexes of the general formula [RuCl(DMSO)(phen)(Lⁿ)](PF6). Considering that hydrazides are a structural part of severa l drugs and metal complexes containing phenanthroline derivatives are known to interact with DNA and to exhibit antitumor activity, more potent anticancer agents can be obtained by covalently linking the thiophene acid hydrazide or the furoic acid hydrazide to a 1,10-phenanthroline moiety. These ligands and the Ru(II) complexes were characterized by elemental analyses, electronic, vibrational, ¹H NMR, and ESI-MS spectroscopies. Ru is bound to two different N-heterocyclic ligands. One chloride and one S-bonded DMSO in cis-configuration to each other complete the octahedral coordination sphere around the metal ion. The ligands are very effective in inhibiting cellular growth in a chronic myelogenous leukemia cell line, K562. Both complexes are able to interact with DNA and present moderate cytotoxic activity, but 5 min of UV-light exposure increases cytotoxicity by three times. Full article

(This article belongs to the Special Issue Hybrid Compounds, Multitarget Ligands, and Conjugate Derivatives as New Targeted Anticancer Agents)

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21 pages, 5503 KiB

Open AccessArticle

Strength of the [Z–I···Hal]⁻ and [Z–Hal···I]⁻ Halogen Bonds: Electron Density Properties and Halogen Bond Length as Estimators of Interaction Energy

by Maxim L. Kuznetsov

Molecules 2021, 26(7), 2083; https://doi.org/10.3390/molecules26072083 - 5 Apr 2021

Cited by 12 | Viewed by 2611

Abstract

Bond energy is the main characteristic of chemical bonds in general and of non-covalent interactions in particular. Simple methods of express estimates of the interaction energy, E_int, using relationships between E_int and a property which is easily accessible from experiment [...] Read more.

Bond energy is the main characteristic of chemical bonds in general and of non-covalent interactions in particular. Simple methods of express estimates of the interaction energy, E_int, using relationships between E_int and a property which is easily accessible from experiment is of great importance for the characterization of non-covalent interactions. In this work, practically important relationships between E_int and electron density, its Laplacian, curvature, potential, kinetic, and total energy densities at the bond critical point as well as bond length were derived for the structures of the [Z–I···Hal]⁻ and [Z–Hal···I]⁻ types bearing halogen bonds and involving iodine as interacting atom(s) (totally 412 structures). The mean absolute deviations for the correlations found were 2.06–4.76 kcal/mol. Full article

(This article belongs to the Special Issue 25th Anniversary of Molecules—Recent Advances in Computational and Theoretical Chemistry)

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22 pages, 9303 KiB

Open AccessArticle

In Silico Mining of Terpenes from Red-Sea Invertebrates for SARS-CoV-2 Main Protease (M^pro) Inhibitors

by Mahmoud A. A. Ibrahim, Alaa H. M. Abdelrahman, Tarik A. Mohamed, Mohamed A. M. Atia, Montaser A. M. Al-Hammady, Khlood A. A. Abdeljawaad, Eman M. Elkady, Mahmoud F. Moustafa, Faris Alrumaihi, Khaled S. Allemailem, Hesham R. El-Seedi, Paul W. Paré, Thomas Efferth and Mohamed-Elamir F. Hegazy

Molecules 2021, 26(7), 2082; https://doi.org/10.3390/molecules26072082 - 5 Apr 2021

Cited by 40 | Viewed by 5043

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent for the COVID-19 pandemic, which generated more than 1.82 million deaths in 2020 alone, in addition to 83.8 million infections. Currently, there is no antiviral medication to treat COVID-19. In the search [...] Read more.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent for the COVID-19 pandemic, which generated more than 1.82 million deaths in 2020 alone, in addition to 83.8 million infections. Currently, there is no antiviral medication to treat COVID-19. In the search for drug leads, marine-derived metabolites are reported here as prospective SARS-CoV-2 inhibitors. Two hundred and twenty-seven terpene natural products isolated from the biodiverse Red-Sea ecosystem were screened for inhibitor activity against the SARS-CoV-2 main protease (M^pro) using molecular docking and molecular dynamics (MD) simulations combined with molecular mechanics/generalized Born surface area binding energy calculations. On the basis of in silico analyses, six terpenes demonstrated high potency as M^pro inhibitors with ΔG_binding ≤ −40.0 kcal/mol. The stability and binding affinity of the most potent metabolite, erylosides B, were compared to the human immunodeficiency virus protease inhibitor, lopinavir. Erylosides B showed greater binding affinity towards SARS-CoV-2 M^pro than lopinavir over 100 ns with ΔG_binding values of −51.9 vs. −33.6 kcal/mol, respectively. Protein–protein interactions indicate that erylosides B biochemical signaling shares gene components that mediate severe acute respiratory syndrome diseases, including the cytokine- and immune-signaling components BCL2L1, IL2, and PRKC. Pathway enrichment analysis and Boolean network modeling were performed towards a deep dissection and mining of the erylosides B target–function interactions. The current study identifies erylosides B as a promising anti-COVID-19 drug lead that warrants further in vitro and in vivo testing. Full article

(This article belongs to the Special Issue Computational Answers to Biomolecular Recognition Problems)

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18 pages, 2608 KiB

Open AccessArticle

Synthesis, Characterization and Biological Evaluation of New 3,5-Disubstituted-Pyrazoline Derivatives as Potential Anti-Mycobacterium tuberculosis H37Ra Compounds

by Kok Tong Wong, Hasnah Osman, Thaigarajan Parumasivam, Unang Supratman, Mohammad Tasyriq Che Omar and Mohamad Nurul Azmi

Molecules 2021, 26(7), 2081; https://doi.org/10.3390/molecules26072081 - 5 Apr 2021

Cited by 16 | Viewed by 3621

Abstract

A total of fourteen pyrazoline derivatives were synthesized through cyclo-condensation reactions by chalcone derivatives with different types of semicarbazide. These compounds were characterized by IR, 1D-NMR (¹H, ¹³C and Distortionless Enhancement by Polarization Transfer - DEPT-135) and 2D-NMR (COSY, HSQC [...] Read more.

A total of fourteen pyrazoline derivatives were synthesized through cyclo-condensation reactions by chalcone derivatives with different types of semicarbazide. These compounds were characterized by IR, 1D-NMR (¹H, ¹³C and Distortionless Enhancement by Polarization Transfer - DEPT-135) and 2D-NMR (COSY, HSQC and HMBC) as well as mass spectroscopy analysis (HRMS). The synthesized compounds were tested for their antituberculosis activity against Mycobacterium tuberculosis H37Ra in vitro. Based on this activity, compound 4a showed the most potent inhibitory activity, with a minimum inhibitory concentration (MIC) value of 17 μM. In addition, six other synthesized compounds, 5a and 5c–5g, exhibited moderate activity, with MIC ranges between 60 μM to 140 μM. Compound 4a showed good bactericidal activity with a minimum bactericidal concentration (MBC) value of 34 μM against Mycobacterium tuberculosis H37Ra. Molecular docking studies for compound 4a on alpha-sterol demethylase was done to understand and explore ligand–receptor interactions, and to hypothesize potential refinements for the compound. Full article

(This article belongs to the Special Issue Synthetic Heterocyclic Chemistry)

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19 pages, 2494 KiB

Open AccessArticle

In Vitro and In Silico Screening and Characterization of Antimicrobial Napin Bioactive Protein in Brassica juncea and Moringa oleifera

by Sangeeta Chandrashekar, Raman Vijayakumar, Ramachandran Chelliah, Eric Banan-Mwine Daliri, Inamul Hasan Madar, Ghazala Sultan, Momna Rubab, Fazle Elahi, Su-Jung Yeon and Deog-Hwan Oh

Molecules 2021, 26(7), 2080; https://doi.org/10.3390/molecules26072080 - 5 Apr 2021

Cited by 6 | Viewed by 3604

Abstract

The study aimed to investigate the antibacterial activity of Mustard (Brassica juncea) and Moringa (Moringa oleifera) leaf extracts and coagulant protein for their potential application in water treatment. Bacterial cell aggregation and growth kinetics studies were employed for thirteen [...] Read more.

The study aimed to investigate the antibacterial activity of Mustard (Brassica juncea) and Moringa (Moringa oleifera) leaf extracts and coagulant protein for their potential application in water treatment. Bacterial cell aggregation and growth kinetics studies were employed for thirteen bacterial strains with different concentrations of leaf extracts and coagulant protein. Moringa oleifera leaf extract (MOS) and coagulant protein showed cell aggregation against ten bacterial strains, whereas leaf extract alone showed growth inhibition of five bacterial strains for up to 6 h and five bacterial strains for up to 3 h. Brassica juncea leaf extract (BJS) showed growth inhibition for up to 6 h, and three bacterial strains showed inhibition for up to 3 h. The highest inhibition concentration with 2.5 mg/mL was 19 mm, and furthermore, the minimum inhibitory concentration (MIC) (0.5 mg/mL) and MBC (1.5 mg/mL) were determined to have a higher antibacterial effect for <3 KDa peptides. Based on LCMS analysis, napin was identified in both MOS and BJS; furthermore, the mode of action of napin peptide was determined on lipoprotein X complex (LpxC) and four-chained structured binding protein of bacterial type II topoisomerase (4PLB). The docking analysis has exhibited moderate to potent inhibition with a range of dock score −912.9 Kcal/mol. Thus, it possesses antibacterial-coagulant potential bioactive peptides present in the Moringa oleifera purified protein (MOP) and Brassica juncea purified protein (BJP) that could act as an effective antimicrobial agent to replace currently available antibiotics. The result implies that MOP and Brassica juncea purified coagulant (BJP) proteins may perform a wide degree of antibacterial functions against different pathogens. Full article

(This article belongs to the Special Issue Natural Plants Extracts–Content, Composition and Identification to Enhance Their Applications)

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14 pages, 3226 KiB

Open AccessArticle

Natural Deep Eutectic Solvents for the Extraction of Bioactive Steroidal Saponins from Dioscoreae Nipponicae Rhizoma

by Gui-Ya Yang, Jun-Na Song, Ya-Qing Chang, Lei Wang, Yu-Guang Zheng, Dan Zhang and Long Guo

Molecules 2021, 26(7), 2079; https://doi.org/10.3390/molecules26072079 - 5 Apr 2021

Cited by 42 | Viewed by 4317

Abstract

In the present study, a simple and environmentally friendly extraction method based on natural deep eutectic solvents (NADESs) was established to extract four bioactive steroidal saponins from Dioscoreae Nipponicae Rhizoma (DNR). A total of twenty-one types of choline chloride, betaine, and L-proline based [...] Read more.

In the present study, a simple and environmentally friendly extraction method based on natural deep eutectic solvents (NADESs) was established to extract four bioactive steroidal saponins from Dioscoreae Nipponicae Rhizoma (DNR). A total of twenty-one types of choline chloride, betaine, and L-proline based NADESs were tailored, and the NADES composed of 1:1 molar ratio of choline chloride and malonic acid showed the best extraction efficiency for the four steroidal saponins compared with other NADESs. Then, the extraction parameters for extraction of steroidal saponins by selected tailor-made NADES were optimized using response surface methodology and the optimal extraction conditions are extraction time, 23.5 min; liquid–solid ratio, 57.5 mL/g; and water content, 54%. The microstructure of the DNR powder before and after ultrasonic extraction by conventional solvents (water and methanol) and the selected NADES were observed using field emission scanning electron microscope. In addition, the four steroidal saponins were recovered from NADESs by D101 macroporous resin with a satisfactory recovery yield between 67.27% and 79.90%. The present research demonstrates that NADESs are a suitable green media for the extraction of the bioactive steroidal saponins from DNR, and have a great potential as possible alternatives to organic solvents for efficiently extracting bioactive compounds from natural products. Full article

(This article belongs to the Special Issue Natural Deep Eutectic Solvents (NADES) for Isolation of Biological Active Compounds)

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15 pages, 2420 KiB

Open AccessArticle

Protease Inhibitors Purified from the Canola Meal Extracts of Two Genetically Diverse Genotypes Exhibit Antidiabetic and Antihypertension Properties

by Saira Hussain, Ata ur Rehman, David J. Luckett, Syed Muhammad Saqlan Naqvi and Christopher L. Blanchard

Molecules 2021, 26(7), 2078; https://doi.org/10.3390/molecules26072078 - 4 Apr 2021

Cited by 4 | Viewed by 2929

Abstract

Valorization of vegetable oil waste residues is gaining importance due to their high protein and polyphenol contents. Protease inhibitors (PIs), proteins from these abundantly available waste residues, have recently gained importance in treating chronic diseases. This research aimed to use canola meal of [...] Read more.

Valorization of vegetable oil waste residues is gaining importance due to their high protein and polyphenol contents. Protease inhibitors (PIs), proteins from these abundantly available waste residues, have recently gained importance in treating chronic diseases. This research aimed to use canola meal of genetically diverse Brassica napus genotypes, BLN-3347 and Rivette, to identify PIs with diverse functionalities in therapeutic and pharmacological applications. The canola meal PI purification steps involved: native PAGE and trypsin inhibition activity, followed by ammonium sulfate fractionation, anion exchange, gel filtration, and reverse-phase chromatography. The purified PI preparations were characterized using SDS-PAGE, isoelectric focusing (IEF), and N terminal sequencing. SDS-PAGE analysis of PI preparations under native reducing and nonreducing conditions revealed three polymorphic PIs in each genotype. The corresponding IEF of the genotype BLN-3347, exhibited three acidic isoforms with isoelectric points (pI) of 4.6, 4.0, and 3.9, while Rivette possessed three isoforms, exhibiting two basic forms of pI 8.65 and 9.9, and one acidic of pI 6.55. Purified PI preparations from both the genotypes displayed dipeptidyl peptidase-IV (DPP-IV) and angiotensin-converting enzyme (ACE) inhibition activities; the BLN-3347 PI preparation exhibited a strong inhibitory effect with lower IC₅₀ values (DPP-IV 37.42 µg/mL; ACE 129 µg/mL) than that from Rivette (DPP-IV 67.97 µg/mL; ACE 376.2 µg/mL). In addition to potential human therapy, these highly polymorphic PIs, which can inhibit damaging serine proteases secreted by canola plant pathogens, have the potential to be used by canola plant breeders to seek qualitative trait locus (QTLs) linked to genes conferring resistance to canola diseases. Full article

(This article belongs to the Section Natural Products Chemistry)

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16 pages, 1491 KiB

Open AccessArticle

Increase in Autoantibodies-Abzymes with Peroxidase and Oxidoreductase Activities in Experimental Autoimmune Encephalomyelitis Mice during the Development of EAE Pathology

by Anna S. Tolmacheva, Kseniya S. Aulova, Andrey E. Urusov, Irina A. Orlovskaya and Georgy A. Nevinsky

Molecules 2021, 26(7), 2077; https://doi.org/10.3390/molecules26072077 - 4 Apr 2021

Cited by 4 | Viewed by 2457

Abstract

The exact mechanisms of multiple sclerosis (MS) development are still unknown, but the development of experimental autoimmune encephalomyelitis (EAE) in C57BL/6 mice is associated with the violation of bone marrow hematopoietic stem cells (HSCs) differentiation profiles associated with the production of harmful for [...] Read more.

The exact mechanisms of multiple sclerosis (MS) development are still unknown, but the development of experimental autoimmune encephalomyelitis (EAE) in C57BL/6 mice is associated with the violation of bone marrow hematopoietic stem cells (HSCs) differentiation profiles associated with the production of harmful for human’s autoantibodies hydrolyzing myelin basic protein, myelin oligodendrocyte glycoprotein (MOG_35–55), and DNA. It was shown that IgGs from the sera of healthy humans and autoimmune patients oxidize many different compounds due to their H₂O₂-dependent peroxidase and oxidoreductase activity in the absence of H₂O₂. Here we first analyzed the change in the relative redox activities of IgGs antibodies from the blood of C57BL/6 mice over time at different stages of the EAE development. It was shown that the peroxidase activity of mice IgGs in the oxidation of ABTS (2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) is on average 6.9-fold higher than the oxidoreductase activity. The peroxidase activity of IgGs increased during the spontaneous development of EAE during 40 days, 1.4-fold. After EAE development acceleration due to mice immunization with MOG_35–55 (5.3-fold), complexes of bovine DNA with methylated bovine serum albumin (DNA-metBSA; 3.5-fold), or with histones (2.6-fold), the activity was increased much faster. The increase in peroxidase activity after mice immunization with MOG_35–55 and DNA-metBSA up to 40 days of experiments was relatively gradual, while for DNA-histones complex was observed its sharp increase at the acute phase of EAE (14–20 days). All data show that IgGs’ redox activities can play an important role in the protection of mice from toxic compounds and oxidative stress. Full article

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14 pages, 8496 KiB

Open AccessArticle

From Colloidal Dispersions of Zeolite Monolayers to Effective Solid Catalysts in Transformations of Bulky Organic Molecules: Role of Freeze-Drying and Dialysis

by Katarzyna Kałahurska, Pawel P. Ziemiański, Wieslaw J. Roth and Barbara Gil

Molecules 2021, 26(7), 2076; https://doi.org/10.3390/molecules26072076 - 4 Apr 2021

Cited by 3 | Viewed by 2668

Abstract

We investigated the properties and catalytic activity of zeolites with MWW topology obtained by unprecedented liquid exfoliation of the MCM-56 zeolite into solutions of monolayers and isolation/reassembly of the dispersed layers by various methods, with optional purification by dialysis or ammonium exchange. The [...] Read more.

We investigated the properties and catalytic activity of zeolites with MWW topology obtained by unprecedented liquid exfoliation of the MCM-56 zeolite into solutions of monolayers and isolation/reassembly of the dispersed layers by various methods, with optional purification by dialysis or ammonium exchange. The layers were recovered by flocculation with alcohol or ammonium nitrate and freeze-drying. Flocculation alone, even with ammonium nitrate, did not ensure removal of residual sodium cations resulting in catalysts with low activity. Dialysis of the solutions with dispersed monolayers proved to be efficient in removing sodium cations and preserving microporosity. The monolayers were also isolated as solids by freeze-drying. The highest BET area and pore volume obtained with the freeze-dried sample confirmed lyophilization efficiency in preserving layer structure. The applied test reaction, Friedel–Crafts alkylation of mesitylene, showed high benzyl alcohol conversion due to increased concentration of accessible acid centers caused by the presence of secondary mesoporosity. The applied treatments did not change the acid strength of the external acid sites, which are the most important ones for converting bulky organic molecules. Zeolite acidity was not degraded in the course of exfoliation into monolayers, showing the potential of such colloid dispersions for the formation of active catalysts. Full article

(This article belongs to the Special Issue 25th Anniversary of Molecules—Recent Advances in Applied Chemistry)

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16 pages, 1171 KiB

Open AccessArticle

Bioactivity-Guided Isolation of Phytochemicals from Vaccinium dunalianum Wight and Their Antioxidant and Enzyme Inhibitory Activities

by Tianrui Zhao, Mengxue Sun, Lingpeng Kong, Qingwang Xue, Yudan Wang, Yifen Wang, Afsar Khan, Jianxin Cao and Guiguang Cheng

Molecules 2021, 26(7), 2075; https://doi.org/10.3390/molecules26072075 - 4 Apr 2021

Cited by 20 | Viewed by 2832

Abstract

Vaccinium dunalianum Wight, usually processed as a traditional folk tea beverage, is widely distributed in the southwest of China. The present study aimed to investigate the antioxidant, α-glucosidase and pancreatic lipase inhibitory activities of V.dunalianum extract and isolate the bioactive components. In [...] Read more.

Vaccinium dunalianum Wight, usually processed as a traditional folk tea beverage, is widely distributed in the southwest of China. The present study aimed to investigate the antioxidant, α-glucosidase and pancreatic lipase inhibitory activities of V.dunalianum extract and isolate the bioactive components. In this study, the crude extract (CE) from the buds of V. dunalianum was prepared by the ultrasound-assisted extraction method in 70% methanol and then purified with macroporous resin D101 to obtain the purified extract (PM). Five fractions (Fr. A–E) were further obtained by MPLC column (RP-C18). Bioactivity assays revealed that Fr. B with 40% methanol and Fr. D with 80% methanol had better antioxidant with 0.48 ± 0.03 and 0.62 ± 0.01 nM Trolox equivalent (TE)/mg extract for DPPH, 0.87 ± 0.02 and 1.58 ± 0.02 nM TE/mg extract for FRAP, 14.42 ± 0.41 and 19.25 ± 0.23 nM TE/mg extract for ABTS, and enzyme inhibitory effects with IC₅₀ values of 95.21 ± 2.21 and 74.55 ± 3.85 for α-glucosidase, and 142.53 ± 11.45 and 128.76 ± 13.85 µg/mL for pancreatic lipase. Multivariate analysis indicated that the TPC and TFC were positively related to the antioxidant activities. Further phytochemical purification led to the isolation of ten compounds (1–10). 6-O-Caffeoylarbutin (7) showed significant inhibitory effects on α-glucosidase and pancreatic lipase enzymes with values of 38.38 ± 1.84 and 97.56 ± 7.53 µg/mL, and had the highest antioxidant capacity compared to the other compounds. Full article

(This article belongs to the Special Issue Medicinal and Aromatic Plants as Source of Bioactive Compounds: Chemical Characterization and Bioactivity)

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Molecules, Volume 26, Issue 7 (April-1 2021) – 289 articles

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