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1.
Stable encapsulation of medically active compounds can lead to longer storage life and facilitate the slow-release mechanism. In this work, the dynamic and molecular interactions between plumbagin molecule with β-cyclodextrin (BCD) and its two derivatives, which are dimethyl-β-cyclodextrin (MBCD), and 2-O-monohydroxypropyl-β-cyclodextrin (HPBCD) were investigated. Molecular dynamics simulations (MD) with GLYCAM-06 and AMBER force fields were used to simulate the inclusion complex systems under storage temperature (4 °C) in an aqueous solution. The simulation results suggested that HPBCD is the best encapsulation agent to produce stable host–guest binding with plumbagin. Moreover, the observation of the plumbagin dynamic inside the binding cavity revealed that it tends to orient the methyl group toward the wider rim of HPBCD. Therefore, HPBCD is a decent candidate for the preservation of plumbagin with a promising longer storage life and presents the opportunity to facilitate the slow-release mechanism.  相似文献   

2.
A computational study on the origin of the activating effect for Pd-catalyzed directed C–H activation by the concerted metalation-deprotonation (CMD) mechanism is conducted. DFT calculations indicate that strong acids can make Pd catalysts coordinate with directing groups (DGs) of the substrates more strongly and lower the C–H activation energy barrier. For the CMD mechanism, the electrophilicity of the Pd center and the basicity of the corresponding acid ligand for deprotonating the C–H bond are vital to the overall C–H activation energy barrier. Furthermore, this rule might disclose the role of some additives for C–H activation.  相似文献   

3.
Hepatocellular carcinoma (HCC) and type 2 diabetes mellitus (T2DM) are common clinical conditions, and T2DM is an independent risk factor for HCC. Sorafenib and lenvatinib, two multi-targeted tyrosine kinase inhibitors, are first-line therapies for advanced HCC, while canagliflozin, a sodium-glucose co-transporter 2 inhibitor, is widely used in the treatment of T2DM. Here, we developed an ultra-performance liquid chromatography-tandem mass spectrometry method for the simultaneous determination of canagliflozin, sorafenib, and lenvatinib, and investigated the pharmacokinetic drug interactions between canagliflozin and sorafenib or lenvatinib in rats. The animals were randomly divided into five groups. Groups I–III were gavage administrated with sorafenib, lenvatinib, and canagliflozin, respectively. Group IV received sorafenib and canagliflozin; while Group V received lenvatinib and canagliflozin. The area under the plasma concentration-time curves (AUC) and maximum plasma concentrations (Cmax) of canagliflozin increased by 37.6% and 32.8%, respectively, while the apparent volume of distribution (Vz/F) and apparent clearance (CLz/F) of canagliflozin significantly decreased (30.6% and 28.6%, respectively) in the presence of sorafenib. Canagliflozin caused a significant increase in AUC and Cmax of lenvatinib by 28.9% and 36.2%, respectively, and a significant decrease in Vz/F and CLz/F of lenvatinib by 52.9% and 22.7%, respectively. In conclusion, drug interactions exist between canagliflozin and sorafenib or lenvatinib, and these findings provide a reference for the use of these drugs in patients with HCC and T2DM.  相似文献   

4.
Inflammation is the primary pathological process of myocardial ischemia/reperfusion injury (MI/RI). 7-Hydroxyflavone (HF), a natural flavonoid with a variety of bioactivities, plays a crucial role in various biological processes. However, its cardioprotective effects and the underlying mechanisms of MI/RI have not been investigated. This study aimed to explore whether pretreatment with HF could attenuate MI/RI-induced inflammation in rats and investigate its potential mechanisms. The results showed that pretreatment with HF could significantly improve the anatomic data and electrocardiograph parameters, reduce the myocardial infarct size, decrease markers of myocardial injury (aspartate transaminase, creatine kinase, lactate dehydrogenase, and cardiac troponin I), inhibit inflammatory cytokines (IL-1β, IL-6, and TNF-α), suppress oxidative stress, and recover the architecture of the cardiomyocytes. The cardioprotective effect of HF was connected with the regulation of the MAPK/NF-κB signaling pathway. What is more, molecular docking was carried out to prove that HF could be stably combined with p38, ERK1/2, JNK, and NF-κB. In summary, this is a novel study demonstrating the cardioprotective effects of HF against MI/RI in vivo. Consequently, these results demonstrate that HF can be considered a promising potential therapy for MI/RI.  相似文献   

5.
Fatty acid synthase (FASN) is highly expressed in multiple types of human cancers and is recognized as one of the targets for treating cancer metastasis. α-Linolenic acid is an omega-3 essential fatty acid and it possesses various biological activities. The present study was designed to reveal the effects of α-linolenic acid on osteosarcoma and to reveal whether the mechanism of α-linolenic acid in anticancer activity may be related to FASN inhibition. The cytotoxicity of α-linolenic acid was assessed in osteosarcoma MG63, 143B, and U2OS cells. Cell viability was detected by the MTT assay. The protein expression level was detected by western blotting. Flow cytometry, Annexin V/propidium iodide dual staining, and Hoechst 33258 staining were performed to assess the apoptotic effects. Wound healing assay was applied to detect the inhibitory effect of α-linolenic acid on osteosarcoma cells migration. The results showed that α-linolenic acid downregulated FASN expression. α-Linolenic acid inhibited osteosarcoma cell proliferation and migration in a dose-dependent manner. In addition, α-linolenic acid regulated endoplasmic reticulum transmembrane receptors and signal protein expression in osteosarcoma cells. The findings of the present study suggested that α-linolenic acid suppresses osteosarcoma cell proliferation and metastasis by inhibiting FASN expression, which provides a basis as a potential target for osteosarcoma treatment.  相似文献   

6.
Hybrid tannic acid-silica-based porous nanoparticles, TA-SiO2 NPs, have been synthesized under mild conditions in the presence of green and renewable tannic acid biopolymer, a glycoside polymer of gallic acid present in a large part of plants. Tannic acid (TA) was exploited as both a structuring directing agent and green chelating site for heavy metal ions recovery from aqueous solutions. Particles morphologies and porosity were easily tuned by varying the TA initial amount. The sample produced with the largest TA amount showed a specific surface area an order of magnitude larger than silica nanoparticles. The adsorption performance was investigated by using TA-SiO2 NPs as adsorbents for copper (II) ions from an aqueous solution. The effects of the initial Cu2+ ions concentration and the pH values on the adsorption capability were also investigated. The resulting TA-SiO2 NPs exhibited a different adsorption behaviour towards Cu2+, which was demonstrated through different tests. The largest adsorption (i.e., ~50 wt% of the initial Cu2+ amount) was obtained with the more porous nanoplatforms bearing a higher final TA content. The TA-nanoplatforms, stable in pH value around neutral conditions, can be easily produced and their use would well comply with a green strategy to reduce wastewater pollution.  相似文献   

7.
The online preconcentration technique, cyclodextrin-assisted sweeping (CD-sweeping), coupled with micellar electrokinetic chromatography (MEKC) was established to determine 13-cis-retinoic acid (13-cis-RA), all-trans-retinoic acid (all-trans-RA) and 4-oxo-13-cis-retinoic acid (4-oxo-13-cis-RA) in human plasma. A CD-sweeping buffer (45 mM borate (pH 9.2), containing 80 mM sodium dodecyl sulfate (SDS) and 22 mM hydroxypropyl β-CD (HP-β-CD) was introduced into the capillary and, then, the sample dissolved in 70 mM borate (pH 9.2): methanol = 9:1 (v/v) was injected into capillary by pressure. The separation voltage was 23 kV. Compared to the conventional cyclodextrin-micellar electrokinetic chromatography (CD-MEKC) method, the new technique achieved 224–257-fold sensitivity enrichment of analytes. The limits of detection of 13-cis-RA, all-trans-RA were 1 ng/mL, whereas that of 4-oxo-13-cis-RA was 25 ng/mL in plasma. The linear ranges of 13-cis-RA, all-trans-RA were between 15 and 1000 ng/mL, whereas that of 4-oxo-13-cis-RA was between 75 and 1500 ng/mL. The coefficient of correlation between the concentration of analytes and peak area ratio of analytes and internal standard (2, 4-dihydroxy-benzophenone) for intra-day (n = 3) and inter-day (n = 5) analyses were both greater than 0.999. The optimized experimental conditions were successfully applied to determine 13-cis-retinoic acid and its metabolites in plasma samples from a patient during the administration of 13-cis-RA for treating acne.  相似文献   

8.
Pectin and mucilage are polysaccharides from the cactus Opuntia ficus-indica, which are also known as hydrocolloids, with useful properties in industries such as food, pharmaceuticals, and construction, among others. In the present work, cactus hydrocolloids were hydrolyzed characterized using two techniques: first, thin-layer chromatography, to identify the monosaccharides present in the sample, followed by the phenol–sulfuric acid method to determine the monosaccharide content. The hydrolyzing method allowed us to reduce the processing time to 180 min and, considering the identification and quantification procedures, the proposed methodology is much simpler and more cost-effective compared to other methods, such as high-performance liquid chromatography (HPLC), nuclear magnetic resonance (NMR), and mass spectrometry. The analysis of the results revealed that the maximum concentration of monosaccharides was obtained after hydrolyzing for 90 min. Under such conditions, with pectin being the main component contained in the cactus hydrocolloids analyzed here, galacturonic acid was found in the largest quantities.  相似文献   

9.
10.
Salicylic acid is a key compound in nonsteroidal anti-inflammatory drugs that has been recently used for preventing the risk of hospitalization and death among COVID-19 patients and in preventing colorectal cancer (CRC) by suppressing two key proteins. Understanding drug–drug interaction pathways prevent the occurrence of adverse drug reactions in clinical trials. Drug–drug interactions can result in the variation of the pharmacodynamics and pharmacokinetic of the drug. Inhibition of the Cytochrome P450 enzyme activity leads to the withdrawal of the drug from the market. The aim of this paper was to develop and validate an HPLC-UV method for the quantification of 4′-hydroxydiclofenac as a CYP2C9 metabolite using salicylic acid as an inhibitor in rat liver microsomes. A CYP2C9 assay was developed and validated on the reversed phase C18 column (SUPELCO 25 cm × 4.6 mm × 5 µm) using a low-pressure gradient elution programming at T = 30 °C, a wavelength of 282 nm, and a flow rate of 1 mL/min. 4′-hydroxydiclofenac demonstrated a good linearity (R2 > 0.99), good reproducibility, low detection, and quantitation limit, and the inter and intra-day precision met the ICH guidelines (<15%). 4′-hydroxydiclofenac was stable for three days and showed an acceptable accuracy and recovery (80–120%) within the ICH guidelines in a rat liver microsome sample. This method will be beneficial for future applications of the in vitro inhibitory effect of salicylic acid on the CYP2C9 enzyme activity in rat microsomes and the in vivo administration of salicylic acid in clinical trials.  相似文献   

11.
As an important biomarker in urine, the level of uric acid is of importance for human health. In this work, a Cu(II) functionalized metal–organic framework (Cu2+@Tb-MOFs) is designed and developed as a novel fluorescence probe for wide-range uric acid detection in human urine. The study shows that this fluorescence platform demonstrated excellent pH-independent stability, high water tolerance, and good thermal stability. Based on the strong interaction between metal ions and uric acid, the designed Cu2+@Tb-MOFs can be employed as efficient turn-on fluorescent probes for the detection of uric acid with wide detection range (0~104 µM) and high sensitivity (LOD = 0.65 µM). This probe also demonstrates an anti-interference property, as other species coexisted, and the possibility for recycling. The sensing mechanisms are further discussed at length. More importantly, we experimentally constructed a molecular logic gate operation based on this fluorescence probe for intelligent detection of uric acid. These results suggest the Cu(II) functionalized metal–organic framework can act as a prominent candidate for personalized monitoring of the concentration of uric acid in the human urine system.  相似文献   

12.
This study investigated the effects of syringic acid (SA) on renal, cardiac, hepatic, and neuronal diabetic complications in streptozotocin-induced neonatal (nSTZ) diabetic rats. STZ (110 mg/kg i.p) was injected into Wistar rat neonates as a split dose (second and third postnatal day). Diabetes mellitus was diagnosed in adults by measuring fasting blood glucose levels, urine volume, and food and water intake. The treatment of SA (25 mg/kg, 50 mg/kg p.o) was given from the 8th to 18th postnatal week. To assess the development of diabetic complications and the effect of therapy, biochemical indicators in serum and behavioural parameters were recorded at specific intervals during the study period. SA (25 mg/kg, 50 mg/kg p.o) treatment reduced hyperglycaemia, polydipsia, polyphagia, polyuria, relative organ weight, cardiac hypertrophic indices, inflammatory markers, cell injury markers, glycated haemoglobin, histopathological score, and oxidative stress, and increased Na/K ATPase activity. These findings suggest that SA might significantly alleviate diabetic complications and/or renal, neuronal, cardiac, and hepatic damage in nSTZ diabetic rats.  相似文献   

13.
Fatty acid profiling on gas chromatography–mass spectrometry (GC–MS) platforms is typically performed offline by manually derivatizing and analyzing small batches of samples. A GC–MS system with a fully integrated robotic autosampler can significantly improve sample handling, standardize data collection, and reduce the total hands-on time required for sample analysis. In this study, we report an optimized high-throughput GC–MS-based methodology that utilizes trimethyl sulfonium hydroxide (TMSH) as a derivatization reagent to convert fatty acids into fatty acid methyl esters. An automated online derivatization method was developed, in which the robotic autosampler derivatizes each sample individually and injects it into the GC–MS system in a high-throughput manner. This study investigated the robustness of automated TMSH derivatization by comparing fatty acid standards and lipid extracts, derivatized manually in batches and online automatically from four biological matrices. Automated derivatization improved reproducibility in 19 of 33 fatty acid standards, with nearly half of the 33 confirmed fatty acids in biological samples demonstrating improved reproducibility when compared to manually derivatized samples. In summary, we show that the online TMSH-based derivatization methodology is ideal for high-throughput fatty acid analysis, allowing rapid and efficient fatty acid profiling, with reduced sample handling, faster data acquisition, and, ultimately, improved data reproducibility.  相似文献   

14.
A hydrogen-bonded (H-bonded) amide macrocycle was found to serve as an effective component in the host–guest assembly for a supramolecular chirality transfer process. Circular dichroism (CD) spectroscopy studies showed that the near-planar macrocycle could produce a CD response when combined with three of the twelve L-α-amino acid esters (all cryptochiral molecules) tested as possible guests. The host–guest complexation between the macrocycle and cationic guests was explored using NMR, revealing the presence of a strong affinity involving the multi-point recognition of guests. This was further corroborated by density functional theory (DFT) calculations. The present work proposes a new strategy for amplifying the CD signals of cryptochiral molecules by means of H-bonded macrocycle-based host–guest association, and is expected to be useful in designing supramolecular chiroptical sensing materials.  相似文献   

15.
In this study, we developed a novel cerium/ascorbic acid/iodine active species to design a redox flow battery (RFB), in which the cerium nitrate hexahydrate [Ce(NO3)3·6H2O] was used as a positive Ce3+/Ce4+ ion pair, and the potassium iodate (KIO3) containing ascorbic acid was used as a negative I2/I ion pair. In order to improve the electrochemical activity and to avoid cross-contamination of the redox pair ions, the electroless plating and sol–gel method were applied to modify the carbon paper electrode and the Nafion 117 membrane. The electrocatalytic and electrochemical properties of the composite electrode using methanesulfonic acid as a supporting electrolyte were assessed using the cyclic voltammetry (CV) test. The results showed that the Ce (III)/Ce (IV) active species presented a symmetric oxidation/reduction current ratio (1.09) on the C–TiO2–PdO composite electrode. Adding a constant amount of ascorbic acid to the iodine solution led to a good reversible oxidation/reduction reaction. Therefore, a novel Ce/ascorbic acid/I RFB was developed with C–TiO2–PdO composite electrodes and modified Nafion 117–SiO2–SO3H membrane using the staggered-type flow channel, of which the energy efficiency (EE%) can reach about 72%. The Ce/ascorbic acid/I active species can greatly reduce the electrolyte cost compared to the all-vanadium redox flow battery system, and it therefore has greater development potential.  相似文献   

16.
Isospongian diterpenes are a small but growing family of natural tetracyclic secondary metabolites isolated from marine organisms, primarily sponges and nudibranchs. A palladium-catalyzed domino Heck–Suzuki reaction sequence for the synthesis of the tetracyclic skeleton of marginatafuran-type isospongian diterpenoids with a wide variety of substituents in the C-17 position is reported. The proposed approach was based on selective transformations of the accessible plant diterpenoid lambertianic acid and includes an intramolecular Heck reaction of 16-bromolambertianic and arylation of the palladium intermediate with arylboronic acid. The influence of the nature of the substituent both in arylboronic acids and in the furan ring of 16-bromolambertianic acid on the direction and chemoselectivity of the reaction has been studied. The described derivatization of natural furanolabdanoid lambertianic acid produced new functionalized molecules for biological study and gave novel insights into the reactivity of complex molecular structures.  相似文献   

17.
Sorafenib (SOR), an inhibitor of multiple kinases, is a classic targeted drug for advanced hepatocellular carcinoma (HCC) which often coexists with type 2 diabetes mellitus (T2DM). Dapagliflozin (DAPA), a sodium–glucose cotransporter-2 inhibitor (SGLT2i), is widely used in patients with T2DM. Notably, co-administration of SOR with DAPA is common in clinical settings. Uridine diphosphate-glucuronosyltransferase family 1 member A9 (UGT1A9) is involved in the metabolism of SOR and dapagliflozin (DAPA), and SOR is the inhibitor of UGT1A1 and UGT1A9 (in vitro). Therefore, changes in UGT1A9 activity caused by SOR may lead to pharmacokinetic interactions between the two drugs. The objective of the current study was to develop an ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for the simultaneous determination of SOR and DAPA in plasma and to evaluate the effect of the co-administration of SOR and DAPA on their individual pharmacokinetic properties and the mechanism involved. The rats were divided into four groups: SOR (100 mg/kg) alone and co-administered with DAPA (1 mg/kg) for seven days, and DAPA (1 mg/kg) alone and co-administered with SOR (100 mg/kg) for seven days. Liquid–liquid extraction (LLE) was performed for plasma sample preparation, and the chromatographic separation was conducted on Waters XSelect HSS T3 column with a gradient elution of 0.1% formic acid and 5 mM ammonium acetate (Phase A) and acetonitrile (Phase B). The levels of Ugt1a7 messenger RNA (mRNA) were determined in rat liver and intestine using quantitative real-time polymerase chain reaction (qRT-PCR). The method was successfully applied to the study of pharmacokinetic interactions. DAPA caused a significant decrease in the maximum plasma concentrations (Cmax) and the area under the plasma concentration–time curves (AUC0–t) of SOR by 41.6% and 50.5%, respectively, while the apparent volume of distribution (Vz/F) and apparent clearance (CLz/F) significantly increased 2.85- and 1.98-fold, respectively. When co-administering DAPA with SOR, the AUC0–t and the elimination half-life (t1/2Z) of DAPA significantly increased 1.66- and 1.80-fold, respectively, whereas the CLz/F significantly decreased by 40%. Results from qRT-PCR showed that, compared with control, seven days of SOR pretreatment decreased Ugt1a7 expression in both liver and intestine tissue. In contrast, seven days of DAPA pretreatment decreased Ugt1a7 expression only in liver tissue. Therefore, pharmacokinetic interactions exist between long-term use of SOR with DAPA, and UGT1A9 may be the targets mediating the interaction. Active surveillance for the treatment outcomes and adverse reactions are required.  相似文献   

18.
Co-administered medicinal herbs can modify a drug’s pharmacokinetics (PK), effectiveness, and toxicity. Andrographis paniculata (Burm. f.) ethanolic extract (APE) and andrographolide (AND) (a potent CYP2C9 inducer/inhibitor) can alter the pharmacokinetic parameters of glipizide (GLZ). This study aimed to determine the potential pharmacokinetics of herb–drug interactions between GLZ and APE/AND in the plasma of normal and diabetic rats using the HPLC bioanalysis method. The glipizide bioanalytical method established with RP-HPLC/UV instrument was validated following the EMA guidelines. GLZ was administered alone and in combination with APE or AND to normal and diabetic rats. The GLZ pharmacokinetic parameters were estimated according to the correlation between concentration and sampling time using the PK solver program. A simple and rapid GLZ bioanalysis technique with a lower limit of quantitation of 25 ng/mL was developed and presented the following parameters: accuracy (error ≤ 15%), precision (CV ≤ 15%), selectivity, stability, and linearity (R2 = 0.998) at concentrations ranging 25–1500 ng/mL. APE administration significantly improved the Cmax and AUC0–t/AUC0–∞ GLZ values in normal and diabetic rats (p < 0.05). AND significantly reduced the bioavailability of GLZ in diabetic rats with small values of T 1/2, Cmax, and AUC0–t/AUC0–∞ (p < 0.05). This combination can be considered in administering medications because it can influence the pharmacological effects of GLZ.  相似文献   

19.
Background: There is a growing interest in the correlation between antioxidants and periodontal disease. In this study, we aimed to investigate the effect of oxidative stress and the impact of two antioxidants, curcumin and rutin, respectively, in the etiopathology of experimentally induced periodontitis in diabetic rats. Methods: Fifty Wistar albino rats were randomly divided into five groups and were induced with diabetes mellitus and periodontitis: (1) (CONTROL)—control group, (2) (DPP)—experimentally induced diabetes mellitus and periodontitis, (3) (DPC)—experimentally induced diabetes mellitus and periodontitis treated with curcumin (C), (4) (DPR)—experimentally induced diabetes mellitus and periodontitis treated with rutin (R) and (5) (DPCR)—experimentally induced diabetes mellitus and periodontitis treated with C and R. We evaluated malondialdehyde (MDA) as a biomarker of oxidative stress and reduced glutathione (GSH), oxidized glutathione (GSSG), GSH/GSSG and catalase (CAT) as biomarkers of the antioxidant capacity in blood harvested from the animals we tested. The MDA levels and CAT activities were also evaluated in the gingival tissue. Results: The control group effect was statistically significantly different from any other groups, regardless of whether or not the treatment was applied. There was also a significant difference between the untreated group and the three treatment groups for variables MDA, GSH, GSSG, GSH/GSSG and CAT. There was no significant difference in the mean effect for the MDA, GSH, GSSG, GSH/GSSG and CAT variables in the treated groups of rats with curcumin, rutin and the combination of curcumin and rutin. Conclusions: The oral administration of curcumin and rutin, single or combined, could reduce the oxidative stress and enhance the antioxidant status in hyperglycemic periodontitis rats.  相似文献   

20.
The new homochiral 1D metal–organic coordination polymer [Cu2(EDPB)•H2O]n was synthesized starting from the original 3,3′-ethyne-1,2-diylbis[6-(L-prolylamino)benzoic acid] (H4EDPB). The unique crystal structure of the new compound was established by powder X-ray diffraction. The [Cu2(EDPB)•H2O]n system shows catalytic activity and enantioselectivity in a Henry reaction of p-nitrobenzaldehyde with nitromethane.  相似文献   

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