Allicin and Capsaicin Ameliorated Hypercholesterolemia by Upregulating LDLR and Downregulating PCSK9 Expression in HepG2 Cells.

Hypercholesterolemia is a common cause of cardiovascular diseases (CVDs). Although allicin and capsaicin possess hypolipidemic effects through several molecular mechanisms, their effects on LDLR and PCSK9 expression are still unknown. This study aimed to investigate the effects of allicin and capsaicin on LDLR and PCSK9 expression in HepG2 cells. The effects of allicin and capsaicin on cell viability were evaluated by MTT assay and trypan blue exclusion assay. Low-density lipoprotein receptor (LDLR) levels and LDL uptake were determined by flow cytometry and confocal laser scanning microscopy (CLSM), respectively. RT-qPCR and Western blot analyses were performed to evaluate the expression of PCSK9, LDLR, SREBP-2, and HNF1α. ELISA was used to measure PCSK9 levels in culture media. Allicin and capsaicin increased the protein expression levels of LDLR via activation of the transcription factor SREBP2. However, allicin and capsaicin decreased the expression of PCSK9 protein and the secretion of PCSK9 in culture media via the suppression of HNF1α. Moreover, allicin and capsaicin increased LDL uptake into HepG2 cells. The efficacies of the hypolipidemic effects of allicin (200 µM) and capsaicin (200 µM) were comparable to that of atorvastatin (10 µM) in this study. In conclusion, allicin and capsaicin possessed hypolipidemic effects via the upregulation of LDLR and downregulation of PCSK9 expression, thereby enhancing LDL uptake into HepG2 cells. This indicates that allicin and capsaicin should be used as potent supplements to ameliorate hypercholesterolemia.

Computational Screening of Phenylamino-Phenoxy-Quinoline Derivatives against the Main Protease of SARS-CoV-2 Using Molecular Docking and the ONIOM Method.

In the search for new anti-HIV-1 agents, two forms of phenylamino-phenoxy-quinoline derivatives have been synthesized, namely, 2-phenylamino-4-phenoxy-quinoline and 6-phenylamino-4-phenoxy-quinoline. In this study, the binding interactions of phenylamino-phenoxy-quinoline derivatives and six commercially available drugs (hydroxychloroquine, ritonavir, remdesivir, S-217622, N3, and PF-07321332) with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) main protease (Mpro) were investigated using molecular docking and the ONIOM method. The molecular docking showed the hydrogen bonding and hydrophobic interactions of all the compounds in the pocket of SARS-CoV-2 main protease (Mpro), which plays an important role for the division and proliferation of the virus into the cell. The binding free energy values between the ligands and Mpro ranged from -7.06 to -10.61 kcal/mol. The molecular docking and ONIOM results suggested that 4-(2',6'-dimethyl-4'-cyanophenoxy)-2-(4″-cyanophenyl)-aminoquinoline and 4-(4'-cyanophenoxy)-2-(4″-cyanophenyl)-aminoquinoline have low binding energy values and appropriate molecular properties; moreover, both compounds could bind to Mpro via hydrogen bonding and Pi-Pi stacking interactions with amino acid residues, namely, HIS41, GLU166, and GLN192. These amino acids are related to the proteolytic cleavage process of the catalytic triad mechanisms. Therefore, this study provides important information for further studies on synthetic quinoline derivatives as antiviral candidates in the treatment of SARS-CoV-2.

Structural Basis of 2-Phenylamino-4-phenoxyquinoline Derivatives as Potent HIV-1 Non-Nucleoside Reverse Transcriptase Inhibitors.

New target molecules, namely, 2-phenylamino-4-phenoxyquinoline derivatives, were designed using a molecular hybridization approach, which was accomplished by fusing the pharmacophore structures of three currently available drugs: nevirapine, efavirenz, and rilpivirine. The discovery of disubstituted quinoline indicated that the pyridinylamino substituent at the 2-position of quinoline plays an important role in its inhibitory activity against HIV-1 RT. The highly potent HIV-1 RT inhibitors, namely, 4-(2',6'-dimethyl-4'-formylphenoxy)-2-(5″-cyanopyridin-2″ylamino)quinoline (6b) and 4-(2',6'-dimethyl-4'-cyanophenoxy)-2-(5″-cyanopyridin-2″ylamino)quinoline (6d) exhibited half-maximal inhibitory concentrations (IC50) of 1.93 and 1.22 µM, respectively, which are similar to that of nevirapine (IC50 = 1.05 µM). The molecular docking results for these two compounds showed that both compounds interacted with Lys101, His235, and Pro236 residues through hydrogen bonding and interacted with Tyr188, Trp229, and Tyr318 residues through π-π stacking in HIV-1 RT. Interestingly, 6b was highly cytotoxic against MOLT-3 (acute lymphoblastic leukemia), HeLA (cervical carcinoma), and HL-60 (promyeloblast) cells with IC50 values of 12.7 ± 1.1, 25.7 ± 0.8, and 20.5 ± 2.1 µM, respectively. However, 6b and 6d had very low and no cytotoxicity, respectively, to-ward normal embryonic lung (MRC-5) cells. Therefore, the synthesis and biological evaluation of 2-phenylamino-4-phenoxyquinoline derivatives can serve as an excellent basis for the development of highly effective anti-HIV-1 and anticancer agents in the near future.

Characterization of essential oil from Ocimum gratissimum leaves: Antibacterial and mode of action against selected gastroenteritis pathogens.

Essential oil of fresh leaves of Ocimum gratissimum (OGEO) was water-steam distilled and analyzed by GC-MS. Thirty-seven compounds were identified, with eugenol (55.6%) as the major component followed by cis-ocimene (13.9%), γ-muurolene (11.6%), (Z,E)-α-farnesene (5.6%), α-trans-bergamotene (4.1%), and ß-caryophyllene (2.7%). Antimicrobial activity of OGEO was tested against four gastroenteritis pathogens (Staphylococcus aureus, Escherichia coli, Salmonella Typhimurium, and Shigella flexneri). OGEO exhibited antibacterial effect, with MICs of 1-2 mg ml-1, against the tested species. OGEO also displayed rapid killing effect within 5 s at four times of MIC against both E. coli and S. Typhimurium. Various assays were performed to investigate the mode of action of the oil. OGEO increased the permeability of microbial cell membrane as evidenced by LIVE/DEAD BacLight assay. Analyses of the release of absorbing materials at 260 nm, protein leakage, SDS-PAGE, and SEM strongly suggested the disruptive action of the oil on the cytoplasmic membrane of the tested microorganisms. Results revealed that the antibacterial property of OGEO could be due to membrane disruption.

Synthesis of 3-aminocoumarin-N-benzylpyridinium conjugates with nanomolar inhibitory activity against acetylcholinesterase.

A series of 3-amino-6,7-dimethoxycoumarins conjugated with the N-benzylpyridinium moiety through an amide-bond linkage was synthesized and evaluated for their acetylcholinesterase inhibitory activity. A number of the benzylpyridinium derivatives exhibited potent activities with inhibitory concentration (IC50) values in the nanomolar concentration range. Among them, the 2,3-difluorobenzylpyridinium-containing compound was the most potent inhibitor with an IC50 value of 1.53 ± 0.01 nM. Docking studies revealed that the synthesized compounds inhibit the target enzyme by a dual binding site mechanism whereby the coumarin portion binds with the peripheral anionic site while the N-benzylpyridinium residue binds with the catalytic anionic site of the enzyme.

Synthesis and anti-acetylcholinesterase activity of scopoletin derivatives.

A series of scopoletin derivatives incorporated with the pyridinium moiety was synthesized and evaluated for their acetylcholinesterase (AChE) inhibitory activity by the colorimetric Ellman's method. A 2-fluorobenzylpyridinium derivative was the most potent among the tested compounds, with an IC50 value of 0.215±0.015µM, which was greatly improved from that of scopoletin. Docking studies revealed that the scopoletin portion of the mentioned compound was bound to the peripheral anionic site of the AChE, whereas the N-benzylpyridinium residue to the catalytic anionic site.

Synthesis, Antiacetylcholinesterase Activity, and Molecular Dynamics Simulation of Aporphine-benzylpyridinium Conjugates.

A series of aporphines conjugated with an N-benzylpyridinium moiety through an amide-bond linkage were synthesized and evaluated for their acetylcholinesterase (AChE) inhibitory activity. The conjugation of the N-benzylpyridinium group significantly enhanced the AChE inhibitory activity of the core aporphine. The halogen substituents on the benzyl group affected the activity of the conjugates. Both (S)- and (R)-enantiomers of three conjugates with low IC50 values were synthesized and evaluated for their activities. All (S)-enantiomers exhibited higher activity than the corresponding (R)-enantiomers. The (S)-enantiomer of 2-chlorobenzylpyridinium-containing aporphine was the most potent inhibitor in this study with an IC50 value of 0.06 ± 0.003 µM. Molecular dynamics simulation analysis revealed that both enantiomers can interact with the AChE binding site, whereas the (S)-enantiomer possessed slightly stronger interaction than the (R)-enantiomer, presumably because of their different orientations, as evidenced by molecular docking. The N-benzylpyridinium dehydroaporphine conjugates were also synthesized but were less active than the corresponding aporphine conjugates.

Dual-functional natural rubber latex foam composites for solar-driven clean water production and heavy metal decontamination.

Solar steam generation (SSG) offers a sustainable approach to fresh water production. Herein, a novel dual-functional natural rubber/carbon black composite foam evaporator is presented for a cost-efficient SSG system that both produces fresh water and eliminates heavy metals present in the water. The composite foam is produced using the Dunlop process, and in its optimized form, it absorbed >96 % of sunlight. The foam evaporator exhibited a thermal conductivity of 0.052 W/m⋅K, a water evaporation rate of 1.40 kg/m2/h, converted 83.38 % of light to heat under 1 sun irradiation, and showed outstanding stability. The technology required to produce this composite foam is already available to make large-scale production feasible, while the natural raw materials are abundant. On the basis of its performance qualities, the rubber foam composite appears to be an excellent candidate for application as a viable solar absorber for SSG to produce fresh, clean water for commercial purposes.

Green magnetic carbon/alginate biocomposite beads from iron scrap waste for efficient removal of textile dye and heavy metal.

The circular economy can help enhance the value of industrial waste and remediate the environment. This study considers the application of iron scrap from steel production as a free resource to produce magnetic adsorbent beads to remove methylene blue dye and lead (II) ions from wastewater. Composite beads were prepared by incorporating iron scrap and activated carbon into a calcium alginate gel using a simple 'mix and drop' synthesis. The optimized magnetic beads were stable and offered a large specific surface area. The maximum adsorption capacity of the adsorbent, calculated from the Langmuir isotherm model, was 476.19 mg g-1 for methylene blue and 163.93 mg g-1 for lead (II) ions. This study places emphasis upon the zero-waste principle and employs a scalable synthetic approach for the conversion of waste iron scrap into an adsorbent material capable of delivering significant environmental benefits.

Grewiifopenes A-K, bioactive clerodane diterpenoids from Casearia grewiifolia Vent.

Eleven novel clerodane-type diterpenoids, grewiifopenes A-K (1-4 and 12-18), along with nine known compounds (5-11, 19, and 20) were purified from the dichloromethane extract of the twigs and stems of Casearia grewiifolia Vent. (Salicaceae). Their spectroscopic data, including the NMR, HRESIMS, and electronic circular dichroism calculations were employed to completely characterize and elucidate the chemical structures and absolute configurations. The clerodane diterpenoids possessing a 6-OH group and no substitution at C-7 exhibited greater cytotoxic activity than others, with their IC50 values ranging from 0.3 to 2.9 µM. Isocaseamembrin E (7) exhibited antibacterial activity against Staphylococcus aureus, while isocaseamembrin E (7), corymbulosin X (8), caseargrewiin A (9), kurzipene A (10), and balanspene F (11) exhibited antibacterial activity against Bacillus cereus.

Albiflorenes A-L, polyoxygenated cyclohex(a/e)ne diterpene esters from Kaempferia albiflora.

Twelve polyoxygenated cyclohex(a/e)ne diterpene esters, named albiflorenes A-L (1-12), were isolated from the whole plants of Kaempferia albiflora, known as "Prao Mang Mum." Their structures and relative stereochemistry were determined by extensive spectroscopic analysis. Furthermore, the comparison of experimental electronic circular dichroism (ECD) curves with the curves predicted by TDDFT was used to determine the absolute configurations. Albiflorenes contain polyoxygenated cyclohexane (or cyclohexene) derivatives, which are linked to either isopimarane or abietane diterpene acid units. The discovery marks the first occurrence of a conjugate between polyoxygenated cyclohexane (or cyclohexene) rings and diterpenoids. Among the isolates, albiflorene C specifically exhibited antibacterial activity against Bacillus cereus with MIC and MBC values of 3.13 and 6.25 µg/mL, respectively.

Influence of a Transparent and Edible Coating of Encapsulated Cannabidiol Nanoparticles on the Quality and Shelf Life of Strawberries.

Cannabidiol (CBD) has been shown to have antioxidant and antibacterial effects. The investigation into CBD's potential as an antioxidant and antibacterial agent, meanwhile, is still in its initial stages. The study goals were to prepare encapsulated cannabidiol isolate (eCBDi), evaluate the effect of eCBDi edible active coatings on the physicochemical properties of strawberries, and determine whether CBD and sodium alginate coatings could be used as a postharvest treatment to promote antioxidation and antimicrobial activity and prolong the strawberry shelf life. A well-designed edible coating on the strawberry surface was achieved using eCBDi nanoparticles in combination with a sodium alginate polysaccharide-based solution. Strawberries were examined for their visual appearance and quality parameters. In the results, a significantly delayed deterioration was observed in terms of weight loss, total acidity, pH, microbial activity, and antioxidant activity for coated strawberries compared to the control. This study demonstrates the capability of eCBDi nanoparticles as an efficient active food coating agent.

Acetylcholinesterase modified inkjet-printed graphene/gold nanoparticle/poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) hybrid electrode for ultrasensitive chlorpyrifos detection.

This study successfully created a portable acetylcholinesterase sensor on a printed hybrid electrode capable of detecting chlorpyrifos in the field. While a screen-printed electrode was chosen herein to enable a single-use and portable platform for the in-field application, the hybrid material was incorporated to ensure ultrasensitive detection at lower electrode potentials. The hybrid ink of gold nanoparticles (AuNPs) decorated on graphene (GP) sheets in poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) was synthesized through a simple completely-green one-pot process. The subsequent characterization was carried out via transmission electron microscopy (TEM), X-ray diffraction (XRD), scanning electron microscopy (SEM), and Fourier-transform infrared spectroscopy (FTIR). The synergy resulting from the greater surface area and enhanced transfer of electrons combined with high levels of electrocatalytic activity and superb conductivity offered by GP, AuNP, and PEDOT:PSS allows the sensor to exhibit ultrasensitive chlorpyrifos detection at the relatively low detection limit of 0.07 nM. The sensor demonstrated in this study also exhibits good reproducibility, desirable stability, and a successful application for the real sample with satisfactory recovery results of around 106 %, indicating its potential for use as a tool in the analysis of pesticides.

Turmeric Herb Extract-Incorporated Biopolymer Dressings with Beneficial Antibacterial, Antioxidant and Anti-Inflammatory Properties for Wound Healing.

Bacterial infection and inflammation caused by excess oxidative stress are serious challenges in chronic wound healing. The aim of this work is to investigate a wound dressing based on natural- and biowaste-derived biopolymers loaded with an herb extract that demonstrates antibacterial, antioxidant, and anti-inflammatory activities without using additional synthetic drugs. Turmeric extract-loaded carboxymethyl cellulose/silk sericin dressings were produced by esterification crosslinking with citric acid followed by freeze-drying to achieve an interconnected porous structure, sufficient mechanical properties, and hydrogel formation in situ in contact with an aqueous solution. The dressings exhibited inhibitory effects on the growth of bacterial strains that were related to the controlled release of the turmeric extract. The dressings provided antioxidant activity as a result of the radical scavenging effect on DPPH, ABTS, and FRAP radicals. To confirm their anti-inflammatory effects, the inhibition of nitric oxide production in activated RAW 264.7 macrophages was investigated. The findings suggested that the dressings could be a potential candidate for wound healing.

One-Pot and Green Preparation of Phyllanthus emblica Extract/Silver Nanoparticles/Polyvinylpyrrolidone Spray-On Dressing.

A spray-on wound dressing has many benefits, including easy and quick administration to broad and uneven wounds, better interface with the wound site, adhesion without additional dressing, and multiple applications in a portable package. By limiting direct contact with the wound site, such a design can prevent wound damage during treatment. This study revealed a simple, one-pot synthesis of spray-on wound dressing relying on polyvinylpyrrolidone solution incorporating silver nanoparticles as a broad-spectrum antibacterial agent and wound-healing antioxidant Phyllanthus emblica extract. Silver nanoparticles were synthesized in situ using Phyllanthus emblica extract as a biogenic reducing agent. Polyvinylpyrrolidone was employed as a film-forming agent to create an adhesive hydrogel-based dressing matrix to provide moisture and establish a shielding barrier for the wound bed as well as to regulate the release of fruit extract. In vitro tests revealed that the produced dressing film had a controlled release of the fruit extract, high antioxidant activity, and a good antibacterial action against S. aureus, P. aeruginosa, E. coli, and MRSA. Additionally, a biocompatibility study has shown that both human fibroblasts and keratinocytes are unaffected by the dressing film. Based on established findings, the current spray-on solution might be a potential option for antibacterial wound dressing.

Quercetin/Hydroxypropyl-ß-Cyclodextrin Inclusion Complex-Loaded Hydrogels for Accelerated Wound Healing.

This study concentrated on developing quercetin/cyclodextrin inclusion complex-loaded polyvinyl alcohol (PVA) hydrogel for enhanced stability and solubility. Quercetin was encapsulated in hydroxypropyl-ß-cyclodextrin (HP-ß-CD) by the solvent evaporation method. The prepared quercetin/HP-ß-CD inclusion complex showed 90.50 ± 1.84% encapsulation efficiency (%EE) and 4.67 ± 0.13% loading capacity (%LC), and its successful encapsulation was confirmed by FT-IR and XRD. The quercetin/HP-ß-CD inclusion complex was well dispersed in viscous solutions of PVA in various amounts (0.5, 1.0, 1.5. 2.5, and 5.0% w/v ratio), and the drug-loaded polymer solution was physically crosslinked by multiple freeze-thaw cycles to form the hydrogel. The cumulative amount of quercetin released from the prepared hydrogels increased with increasing concentrations of the inclusion complex. The introduction of the inclusion complex into the PVA hydrogels had no influence on their swelling ratio, but gelation and compressive strength reduced with increasing inclusion complex concentration. The potential cytotoxicity of quercetin/HP-ß-CD inclusion complex hydrogels was evaluated by MTT assay and expressed as % cell viability. The results show biocompatibility toward NCTC 929 clone cells. The inhibitory efficacy was evaluated with 2, 2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging assay, and the results show a higher level of antioxidant activity for quercetin/HP-ß-CD inclusion complex hydrogels compared with free quercetin. The findings of our study indicate that the developed quercetin/HP-ß-CD inclusion complex hydrogels possess the required properties and can be proposed as a quercetin delivery system for wound-healing applications.

Diterpenoids and p-methoxycinnamic acid diol esters from Kaempferia saraburiensis Picheans. (Zingiberaceae): Structural assignment of saraburol and their biological activities.

Five undescribed compounds, including three diterpenoids namely, saraburol, saraburanes A and B, and two p-methoxycinnamic acid monoterpene diol esters, named E/Z-saraburinic esters, together with ten known oxygenated isopimarane diterpenoids, were isolated from the whole plant of Kaempferia saraburiensis Picheans. Among these compounds, saraburol possesses an unusual 6/9/6 tricyclic ring system bearing a 1,3-dioxonane-4-one scaffold, which is rarely found in natural products. The structure of isolated compounds was elucidated by spectroscopic methods, including HRESIMS, FTIR, 1D and 2D-NMR, and by comparison with published data, and their absolute configurations were determined by comparison of experimental with calculated ECD spectra and hydrolysis reaction. Using gauge-independent atomic orbital (GIAO) NMR shift calculations coupled with DP4+ probability analyses, biogenetic considerations, and optical rotation allowed for the complete characterization of saraburol. A plausible biosynthetic pathway for saraburol and saraburane A was proposed. The cytotoxicity result indicated that E-saraburinic ester exhibited the most potent activity with an IC50 value of 12.0 µM against MOLT-3 cells with a selectivity index of 12.5. Saraburane B exhibited the most potent activity against Gram-positive bacteria strain Staphylococcus epidermidis with MIC (MBC) value of 25 (50) µg/mL.

Cytotoxic and antimicrobial activities of aporphine alkaloids isolated from Stephania venosa (Blume) Spreng.

The cytotoxic activity of five alkaloids, namely 4,5-dioxo-dehydrocrebanine (1), dehydrocrebanine (2), crebanine (3), oxostephanine (4), and thailandine (5) isolated from the tuber and leaves of Stephania venosa (Blume) Spreng was investigated. Thailandine showed the strongest activity against lung carcinoma cells (A549) (IC50 of 0.30 µg/mL) with very low cytotoxicity against normal embryonic lung cells (MRC-5). Thailandine also demonstrated strong activity against Plasmodium falciparum, K1 strain (IC50 of 20 ng/mL), and Mycobacterium tuberculosis H(37)Ra (MIC of 6.25 µg/mL) as well as gram-positive bacteria such as Streptococcus pneumoniae and Staphylococcus aureus. Oxostephanine exhibited strong activity against breast cancer (BC) and acute lymphoblastic leukemia cells (MOLT-3) with an IC50 of 0.24 and 0.71 µg/mL, respectively, and exhibited very low cytotoxicity against MRC-5 cells. Dehydrocrebanine demonstrated strong activity against promyelocytic leukemia cells (HL-60) with an IC50 of 2.14 µg/mL whereas crebanine showed weak activity against cancer cell lines. However, both of them showed cytotoxicity against MRC-5 cells.

(-)-crebanine.

THE ASYMMETRIC UNIT OF THE TITLE COMPOUND [SYSTEMATIC NAME: 9,10-dimeth-oxy-7-methyl-6,7,7a,8-tetra-hydro-5H-benzo[g][1,3]benzodioxolo[6,5,4-de]quinoline], C(20)H(21)NO(4), contains two independent mol-ecules with very similar bond lengths and angles. The crystal packing exhibits voids of 131 Å(3).

Injectable eggshell-derived hydroxyapatite-incorporated fibroin-alginate composite hydrogel for bone tissue engineering.

Tissue engineering is a promising approach to repair and regenerate damaged or lost tissues or organs. In dental aspect, reconstruction of the resorbed alveolar bone after tooth extraction plays an important role in the success of dental substitution, especially in dental implant treatment. The hydroxyapatite (HA)-incorporated fibroin-alginate composite injectable hydrogel was fabricated to be used as scaffold for bone regeneration. HA was synthesized from eggshell biowaste. Fibroin was extracted from Bombyx mori cocoon. The synthesized HA, fibroin and alginate hydrogel were characterized. HA-incorporated fibroin-alginate hydrogel had decreased pore size and porosity compared with pure alginate hydrogel. Thermal analysis showed that hydrogel had a degradation peak of approximately 250 °C. Hydrogel could absorb water, with a swelling ratio of around 300% at 24 h. Hydrogel was degraded as time passed and almost completely degraded at day 7. Its compressive Young's modulus was approximately 0.04 ± 0.02 N/mm2 to 0.10 ± 0.02 N/mm2. Primary cytotoxicity test indicated non-toxic potential of the fabricated hydrogel. Increased ALP activity was observed in MC3T3-E1 cultured in HA-incorporated fibroin-alginate hydrogel. Results suggested the potential use of injectable HA fibroin-alginate hydrogel as dental scaffolding material. Further studies including in vivo examinations are needed prior to its clinical application.