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Antioxidants (Basel, Switzerland) Feb 2022An extraction method using 80% EtOH was selected and applied to obtain the total extracts from leaves, flowers, fruits, twigs, and roots of L.f. based on the...
An extraction method using 80% EtOH was selected and applied to obtain the total extracts from leaves, flowers, fruits, twigs, and roots of L.f. based on the antioxidant activity-guided experiments. Subsequently, total extract from each part of . was successfully partitioned into fractions, which were evaluated for their antioxidant and anti-inflammatory properties via DPPH, ABTS, and NO assays, respectively. Among them, EtOAc (E) and -butanol (B) fractions showed the potent antioxidant activity and the methylene chloride (MC) fractions of roots, leaves, and fruits that exhibited strong scavenging activity on DPPH and ABTS radicals. In the anti-inflammatory assay, -hexane (H) and MC fractions of leaves potently inhibited NO production in LPS-stimulated RAW264.7 cells, followed by E fractions derived from fruits, flowers, twigs, and roots, along with B fractions from flowers and twigs. Additionally, a comprehensive HPLC-decoupled MS profiling was established and validated using seven isolated marker compounds (-), which were identified by analysis of their UV, NMR, and MS data. The established method was also applied for quantification of these marker compounds in each organ collected from different locations, and to assess their antioxidant capacity by a screening DPPH-HPLC method. Principal component analysis suggested the botanical organs from this plant correlated with the marker compound contents in association with bioactivity. The study results are a prelude to further studies involving the active fractions and provide a comprehensive insight into the functional products of this plant against oxidative diseases.
PubMed: 35326104
DOI: 10.3390/antiox11030454 -
ACS Omega Oct 2023Eutectic solvent systems are versatile solvents that have found widespread use in numerous applications. Traditional solvents are homogeneous, having only one component,...
Eutectic solvent systems are versatile solvents that have found widespread use in numerous applications. Traditional solvents are homogeneous, having only one component, and their chemistry is relatively simple, with some exceptions. On the other hand, deep eutectic solvents (DESs) comprise binary components, generally a donor and an acceptor in hydrogen bonding with varying ratios. The interaction chemistry among the donor and acceptor involved in hydrogen bonding in DESs is complicated. Although numerous research is focused on the synthesis and application of DESs, few studies are reported to elucidate the complex structure and dynamic and interaction behavior of DESs. In this study, we employed calorimetry, vibrational spectroscopy techniques including FTIR and Raman, and nuclear magnetic resonance to derive insight into the structural feature and noncovalent contact of choline chloride (ChCl) and citric acid (CA) while they formed DESs. The 1:1 ChCl/CA eutectic system showed phase transitions and melting peaks with the most pronounced peak at 156.22 °C, suggesting the DESs melting at a lower temperature than the melting temperatures of ChCl and CA. In addition to IR and Raman findings, H NMR investigations demonstrate hydrogen bonding intermolecular interactions between ChCl and CA, supporting the formation of 1:1 ChCl/CA DESs based on the deshielded chemical shifts of the proton for Ch. The interaction of the chloride anion with the methyl protons (H4) and methylene protons (H3) of ChCl as well as the strong hydrogen bonding interactions between the hydroxyl hydrogen (H1) of ChCl with one of CA's carbonyl oxygens both supported the formation of conformer E. In addition, molecular dynamics followed by the density functional theory (DFT) was employed to visualize the structure and interaction of DESs using the ωB97XD theory and 6-311++G (d,p) basis set. Both experimental and theoretical IR, Raman, and structural analyses provided evidence of the formation of DESs by possessing hydrogen bonds. These multifaceted experimental and computational investigations provide details of structural and intermolecular interactions of ChCl/CA DESs.
PubMed: 37867676
DOI: 10.1021/acsomega.3c04570 -
Journal of Tropical Medicine 2022The elimination of onchocerciasis is hampered by the absence of suitable drugs that are effective against adult filariae. This study is aimed at assessing the...
INTRODUCTION
The elimination of onchocerciasis is hampered by the absence of suitable drugs that are effective against adult filariae. This study is aimed at assessing the anti-onchocercal effects of extracts of and that could serve as drug leads against onchocerciasis.
METHODS
Different parts of the plants ( and ) were extracted with hexane, methylene chloride, and methanol. The extracts were tested against the bovine model parasite, . Adult female worm viability was determined biochemically by MTT/formazan colorimetry, while the adult male and microfilariae viability were determined by microscopy based on % inhibition of worm motility score. Cytotoxicity and acute toxicity of active extracts were tested on monkey kidney epithelial cells (LLC-MK2) and Balb/C mice, respectively.
RESULTS
The hexane extract of recorded the highest activity, with IC of 50.78 g/ml on both adult male and female worms and 3.91 g/ml on microfilariae. For extract, the highest activity was seen with the methylene chloride extract, with IC of 50.78 g/ml, 62.50 g/ml, and 16.28 g/ml on, respectively, adult male, female, and microfilariae. The 50% cytotoxic concentration on the LLC-MK2 cells was 31.25 g/ml for the most active extracts. No acute toxicity was recorded for the extracts. Phytochemical analysis of the extracts revealed the presence of alkaloids, flavonoids, sterols, saponins, phenols, and glycosides.
CONCLUSION
This study validates the traditional use of these plants in treating onchocerciasis and suggests and as new potential sources for the isolation of anti-onchocerca lead compounds.
PubMed: 36438180
DOI: 10.1155/2022/4279689 -
Nature Communications Nov 2019Enzymes provide optimal three-dimensional structures for substrate binding and the subsequent accelerated reaction. Such folding-dependent catalytic behaviors, however,...
Enzymes provide optimal three-dimensional structures for substrate binding and the subsequent accelerated reaction. Such folding-dependent catalytic behaviors, however, are seldom mechanistically explored with reduced structural complexity. Here, we demonstrate that the α-helix, a much simpler structural motif of enzyme, can facilitate its own growth through the self-catalyzed polymerization of N-carboxyanhydride (NCA) in dichloromethane. The reversible binding between the N terminus of α-helical polypeptides and NCAs promotes rate acceleration of the subsequent ring-opening reaction. A two-stage, Michaelis-Menten-type kinetic model is proposed by considering the binding and reaction between the propagating helical chains and the monomers, and is successfully utilized to predict the molecular weights and molecular-weight distributions of the resulting polymers. This work elucidates the mechanism of helix-induced, enzyme-mimetic catalysis, emphasizes the importance of solvent choice in the discovery of new reaction type, and provides a route for rapid production of well-defined synthetic polypeptides by taking advantage of self-accelerated ring-opening polymerizations.
Topics: Amines; Anhydrides; Catalysis; Enzymes; Glutamates; Kinetics; Magnetic Resonance Spectroscopy; Methylene Chloride; Models, Molecular; Polymerization; Polymers; Protein Conformation, alpha-Helical
PubMed: 31784526
DOI: 10.1038/s41467-019-13502-w -
Photodiagnosis and Photodynamic Therapy Jun 2017For deep carious lesions, a more conservative treatment modality ("selective caries removal") has been proposed, where only the heavily contaminated dentine is removed.... (Meta-Analysis)
Meta-Analysis Review
For deep carious lesions, a more conservative treatment modality ("selective caries removal") has been proposed, where only the heavily contaminated dentine is removed. In this regard, effective adjuncts for cavity disinfection such as the antimicrobial photodynamic therapy (aPDT) can be valuable clinically prior to definitive restoration. Therefore, the aim of this study was to systematically assess clinical studies on the effectiveness of aPDT as a supplementary tool in the treatment of deep caries lesions. Searches were performed in four databases (PubMed, EMBASE, ISI Web of Science, ClinicalTrials.gov) from 1st January, 2011 until 21st June, 2016 for search terms relevant to the observed parameters, pathological condition, intervention and anatomic entity. The pooled information was evaluated according to PRISMA guidelines. At first, 1651 articles were recovered, of which 1249 full-text articles were evaluated, 270 articles thereof were reviewed for eligibility and finally 6 articles met all inclusion criteria. The aPDT protocols involved Methylene Blue, Toluidine Blue and aluminium-chloride-phthalocyanine as photosensitizers and diode lasers, light-emitting diodes and halogen light-sources. The data from five reports, utilizing both culture-dependent and -independent methods, disclosed significant reduction of cariogenic bacterial load after mechanical caries removal with adjunct aPDT. As these studies exhibit some methodological limitations, e.g. lack of positive controls, this systematic review can support the application of aPDT to a limited extent only in terms of reducing the microbial load in deep carious lesions before restorative treatment.
Topics: Bacterial Infections; Bacterial Load; Combined Modality Therapy; Dental Caries; Disinfection; Evidence-Based Medicine; Humans; Photochemotherapy; Photosensitizing Agents; Prevalence; Risk Factors; Treatment Outcome
PubMed: 28099873
DOI: 10.1016/j.pdpdt.2017.01.005 -
Biochemistry Research International 2022Herbal medication developed from natural resources has to have antibacterial and antioxidant effects. The aim of this research is to look at the chemical makeup of (. )...
Herbal medication developed from natural resources has to have antibacterial and antioxidant effects. The aim of this research is to look at the chemical makeup of (. ) stem bark essential oil (EO), as well as the effectiveness of EO and extracts (chloroform, ethyl acetate, and methanol) against human pathogenic bacteria and their antioxidant activity. The GC-MS analysis identified 23 components, accounting for 98.7% of the total oil containing Methylene chloride (49.2%), sabinene (10.5%), 1-nonene (11.3%), Terpinen-4-ol (6.9%), Camphene (4.3%), -terpinene (3.6%), -phellandrene (2.9%) -myrcene (2.6%), 1,2,5-Oxadiazol-3-carboxamide, 4,4'-azobis-2,2'-dioxide (2.4%), -terpinene (1.9%), 1-Octanamine, N-methyl- (1.9%), -cymene (1.6%) as major components. The antibacterial efficacy of the EO and extracts (25, 50, 100, and 200 mg/ml) was demonstrated by the inhibitory zones (8.5 ± 0.47-23.3 ± 0.36 and 7.2 ± 0.25-22.0 ± 0.45 mm), respectively. The MIC values of the extracts and the EO were 120-150 and 240 to <1100 g/ml, respectively. The EO also demonstrated a significant antibacterial impact. The EO and methanolic extract had free radical scavenging activities with IC value, 13.8 ± 0.48 and 4.2 ± 0.04 g/ml, respectively. In comparison to the other extracts, the methanolic extract had the greatest phenolics (100.2 ± 0.13 g GAE/mg of dry extract) and flavonoid contents (112.1 ± 0.18 g CE/mg of dry extract).
PubMed: 35855890
DOI: 10.1155/2022/4900917 -
Toxicology and Industrial Health Mar 2023The focus on occupational exposures in the first published risk evaluations of existing chemicals by the Environmental Protection Agency (EPA) under the amended Toxic... (Review)
Review
The focus on occupational exposures in the first published risk evaluations of existing chemicals by the Environmental Protection Agency (EPA) under the amended Toxic Substances Control Act (TSCA) puts a welcome spotlight on protecting the health of workers in the United States. Because new, fit-for-purpose occupational exposure assessment methodologies were developed by EPA, the objective of this analysis was to evaluate these methodologies in light of other existing occupational risk assessment frameworks. We focused our analysis on three chlorinated chemicals (methylene chloride, carbon tetrachloride, perchloroethylene). The EPA's methods were evaluated relative to peer-reviewed and professional organizations' guidelines for conducting site- and facility-based exposure assessment. Analyses of several key phases in the EPA approach were conducted to evaluate the effect of alternative approaches on exposure estimates. The revised exposure estimates using these alternative approaches yielded substantially different exposure estimates from those in the TSCA risk evaluations for these chemicals. The results also demonstrated the importance of utilizing a tiered approach to exposure estimation that includes collecting qualitative data, defining similar exposure groups, and integrating well-parameterized models with empirical data. These approaches aid in preventing mischaracterization of exposures and generating exposure estimates representative of current industrial practices. Collaboration among industry, EPA, and other government agencies to develop a harmonized approach to exposure assessment would improve the methodological rigor of, and increase stakeholder confidence in, the results of TSCA risk evaluations.
Topics: United States; Humans; Inhalation Exposure; United States Environmental Protection Agency; Occupational Exposure; Risk Assessment; Industry
PubMed: 36656073
DOI: 10.1177/07482337221145988 -
RSC Advances Dec 2023Gas sensors are used to detect gas components in human breath to diagnose diseases, such as cancers. However, choosing suitable two-dimensional materials for gas sensors...
Gas sensors are used to detect gas components in human breath to diagnose diseases, such as cancers. However, choosing suitable two-dimensional materials for gas sensors is a challenge. Germanene can be a good candidate because of its outstanding electronic and structural properties. Based on the density functional theory calculations with various schemes, such as PBE + vdW-DF2, HSE06 + PBE, and HSE06 + vdW-DF2, we elucidated the structural and electronic properties of germanene substrates (perfect, vacancy-1, and vacancy-2) while adsorbing hepatocellular carcinoma-related volatile organic compounds (VOCs), , acetone, 1,4-pentadiene, methylene chloride, phenol, and allyl methyl sulfide. These gases have been selected for investigation because of their most frequent occurence in diagnosing the disease. We found that vacancy substrates enhanced the adsorption strength of the VOCs compared to the perfect one, where the phenol adsorbed most strongly and exhibited the most profound influence on the structural deformation of the substrates over the other VOCs. Besides, the adsorbed VOCs significantly modified the energy bandgap of the considered germanene substrates. In particular, the gases, except allyl methyl sulfide, vanished the bandgap of the vacancy-1 germanene and converted this substrate from a semiconductor to a metal, while they widened the bandgap of the vacancy-2 structure compared to the isolated case. Therefore, the perfect and vacancy-2 germanene sheets could maintain their semiconducting state upon gas adsorption, implying that these substrates may be suitable candidates for gas sensing applications. The nature of the interaction between the VOCs and the germanene substrates is a physical adsorption with a weak charge exchange, which mainly comes from the contribution of the p orbital of the VOCs and the p orbital of Ge.
PubMed: 38090092
DOI: 10.1039/d3ra05927h -
BioMed Research International 2016The failure of several Phase II/III clinical trials in Alzheimer's disease (AD) with drugs targeting β-amyloid accumulation in the brain fuelled an increasing interest... (Review)
Review
The failure of several Phase II/III clinical trials in Alzheimer's disease (AD) with drugs targeting β-amyloid accumulation in the brain fuelled an increasing interest in alternative treatments against tau pathology, including approaches targeting tau phosphatases/kinases, active and passive immunization, and anti-tau aggregation. The most advanced tau aggregation inhibitor (TAI) is methylthioninium (MT), a drug existing in equilibrium between a reduced (leuco-methylthioninium) and oxidized form (MT(+)). MT chloride (methylene blue) was investigated in a 24-week Phase II clinical trial in 321 patients with mild to moderate AD that failed to show significant positive effects in mild AD patients, although long-term observations (50 weeks) and biomarker studies suggested possible benefit. The dose of 138 mg/day showed potential benefits on cognitive performance of moderately affected AD patients and cerebral blood flow in mildly affected patients. Further clinical evidence will come from the large ongoing Phase III trials for the treatment of AD and the behavioral variant of frontotemporal dementia on a new form of this TAI, more bioavailable and less toxic at higher doses, called TRx0237. More recently, inhibitors of tau acetylation are being actively pursued based on impressive results in animal studies obtained by salsalate, a clinically used derivative of salicylic acid.
Topics: Alzheimer Disease; Brain; Evidence-Based Medicine; Humans; Methylene Blue; Molecular Targeted Therapy; Neuroprotective Agents; Treatment Outcome; tau Proteins
PubMed: 27429978
DOI: 10.1155/2016/3245935 -
Bioconjugate Chemistry Feb 2020Some heptamethine cyanine dyes accumulate in solid tumors and persist there for several days. The reasons why they accumulate and persist in tumors were incompletely...
Some heptamethine cyanine dyes accumulate in solid tumors and persist there for several days. The reasons why they accumulate and persist in tumors were incompletely defined, but explanations based on uptake into cancer cells via organic anion transporting polypeptides (OATPs) have been widely discussed. All cyanine-based "tumor-seeking dyes" have a chloride centrally placed on the heptamethine bridge (a "-chloride"). We were intrigued and perplexed by the correlation between this particular functional group and tumor uptake, so the following study was designed. It features four dyes (-Cl, -Ph, -Cl, and -Ph) with complementary properties. Dye -Cl is otherwise known as MHI-148, and -Ph is a close analog wherein the -chloride has been replaced by a phenyl group. Data presented here shows that both -Cl and -Ph form noncovalent adducts with albumin, but only -Cl can form a covalent one. Both dyes -Cl and -Ph have a methylene (CH) unit replaced by a dimethylammonium functionality (NMe). Data presented here shows that both these dyes do not form tight noncovalent adducts with albumin, and only -Cl can form a covalent one (though much more slowly than -Cl). In tissue culture experiments, uptake of dyes is more impacted by the albumin in the media than by the pan-OATP uptake inhibitor (BSP) that has been used to connect uptake of tumor-seeking dyes with the OATPs. Uptake of -Cl in media containing fluorescein-labeled albumin gave a high degree of colocalization of intracellular fluorescence. No evidence was found for the involvement of OATPs in uptake of the dyes into cells in media containing albumin. In an tumor model, only the two dyes that can form albumin adducts (-Cl and -Cl) gave intratumor fluorescence that persisted long enough to be clearly discerned over the background (∼4 h); this fluorescence was still observed at 48 h. Tumors could be imaged with a higher contrast if -Cl is used instead of -Cl, because -Cl is cleared more rapidly from healthy tissues. Overall, the evidence is consistent with and results and indicates that the two dyes in the test series that accumulate in tumors and persist there (-Cl and -Cl, true tumor-seeking dyes) do so as covalent albumin adducts trapped in tumor tissue via uptake by some cancer cells and via the enhanced permeability and retention (EPR) effect.
Topics: Albumins; Animals; Carbocyanines; Cell Line, Tumor; Fluorescent Dyes; Hep G2 Cells; Humans; Indoles; Mice, Inbred C57BL; Neoplasms; Optical Imaging; Organic Anion Transporters
PubMed: 31909595
DOI: 10.1021/acs.bioconjchem.9b00771