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1.
Angew Chem Int Ed Engl ; 62(27): e202304023, 2023 07 03.
Article in English | MEDLINE | ID: mdl-37115672

ABSTRACT

Disulfide bonds play an important role in thiol-based redox regulation. However, owing to the lack of analytical tools, little is known about how local O2 mediates the reversible thiol/disulfide cycle under protein confinement. In this study, a protein-nanopore inside a glove box is used to control local O2 for single-molecule reaction, as well as a single-molecule sensor for real-time monitoring of the reversible thiol/disulfide cycle. The results demonstrate that the local O2 molecules in protein nanopores could facilitate the redox cycle of disulfide formation and cleavage by promoting a higher fraction of effective reactant collisions owing to nanoconfinement. Further kinetic calculations indicate that the negatively charged residues near reactive sites facilitate proton-involved oxygen-induced disulfide cleavage under protein confinement. The unexpectedly strong oxidation ability of confined local O2 may play an essential role in cellular redox signaling and enzyme reactions.


Subject(s)
Nanopores , Sulfhydryl Compounds , Sulfhydryl Compounds/chemistry , Disulfides/chemistry , Oxygen , Proteins/chemistry , Oxidation-Reduction
2.
J Org Chem ; 87(6): 4168-4182, 2022 03 18.
Article in English | MEDLINE | ID: mdl-35212524

ABSTRACT

Photoredox neutral decarboxylative hydroxyalkylations of heteroarenes with α-keto acids under mild conditions are described. Stable and readily available α-keto acids were employed as hydroxyalkylating reagents with only CO2 released as the byproduct. A range of aromatic and aliphatic α-keto acids were successfully converted into hydroxyalkylated products with various heteroarenes. This transformation proceeded through a decarboxylation/Minisci addition/SCS sequence, generating a variety of valuable hydroxyalkylated heteroarenes.


Subject(s)
Keto Acids , Catalysis , Indicators and Reagents , Oxidation-Reduction
3.
Nanotechnology ; 32(5): 055603, 2021 Jan 29.
Article in English | MEDLINE | ID: mdl-33059342

ABSTRACT

Silver nanowires are susceptible to degradation under ultraviolet (UV) light illumination. Encapsulating silver nanowire transparent conductive films (AgNW TCFs) with UV shielding materials usually result in the increasing of the sheet resistance or the decrease of the visible light transparency. Herein, we combine a reducing species (FeSO4) and a thin layer (overcoating) of UV shielding material to solve the stability and the optical performance issues simultaneously. The AgNW TCFs show excellent stability under continuous UV light illumination for 14 h, and their sheet resistance varies only 6%. The dramatic enhancement of the stability against UV light illumination for as-obtained TCFs will make them viable for real-world applications in touch panels and displays.

4.
Nanotechnology ; 32(37)2021 Jun 25.
Article in English | MEDLINE | ID: mdl-34111854

ABSTRACT

The fabrication of strain sensors with high sensitivity, large sensing range and excellent stability is highly desirable because of their promising applications in human motion detection, human-machine interface and electric skin, etc. Herein, by introducing a highly conductive silver nanowire (AgNW) layer between two serried silver nanoparticle (AgNP) layers, forming a sandwich structure, a strain sensor with high sensitivity (a large gauge factor of 2.8 × 105), large sensing range (up to 80% strain) and excellent stability (over 1000 cycles) can be achieved. A combination of experimental and mechanism studies shows that the high performance of the obtained strain sensor is ascribed to the synergy of the highly conductive AgNW layer, astatic AgNP layers and the presence of large cracks in stretching. As a proof-of-concept application, the obtained strain sensor can be used for highly effective human motion detection ranging from large scale motions, i.e. kneel bending and wrist flexion, to subtle scale motions, i.e. pulse and swallowing.


Subject(s)
Biosensing Techniques/instrumentation , Silver/chemistry , Humans , Metal Nanoparticles/chemistry , Nanowires/chemistry , Proof of Concept Study , Wearable Electronic Devices
5.
Biogerontology ; 21(5): 669-682, 2020 10.
Article in English | MEDLINE | ID: mdl-32506187

ABSTRACT

Aging is related to the lowered overall functioning and increased risk for various age-related diseases in humans. Tectochrysin is a flavonoid compound and rich in a traditional Chinese Medicine Alpinia oxyphylla Miq., which has antioxidant, anti-inflammatory, anti-cancer, anti-bacterial, anti-diarrhea, hepatoprotective, and neuro-protective effects. Therefore, we tested if tectochrysin had an effect on aging in Caenorhabditis elegans (C. elegans). Our results showed that tectochrysin could extend the lifespan of C. elegans by up to 21.0%, delay the age-related decline of body movement, improve high temperature-stress resistance and anti-infection capacity, and protected worms against Aß1-42-induced toxicity. Tectochrysin could not extend the lifespan of the mutants from genes daf-2, daf-16, eat-2, aak-2, skn-1, and hsf-1. Tectochrysin could increase the expression of DAF-16 regulated genes. The extension of lifespan by tectochrysin requires FOXO/DAF-16 and HSF-1. Overall, our findings suggest that tectochrysin may have a potential effect on extending lifespan and age-related diseases.


Subject(s)
Caenorhabditis elegans Proteins , Caenorhabditis elegans , Flavonoids/pharmacology , Longevity , Animals , Caenorhabditis elegans/drug effects , Caenorhabditis elegans/metabolism , Caenorhabditis elegans Proteins/metabolism , Forkhead Transcription Factors/metabolism , Stress, Physiological , Transcription Factors/metabolism
6.
Drug Dev Ind Pharm ; 45(1): 124-129, 2019 Jan.
Article in English | MEDLINE | ID: mdl-30229685

ABSTRACT

Akebia saponin D (ASD) exhibits a variety of pharmacological activities, such as anti-osteoporosis, neuroprotection, hepatoprotection, but has poor oral bioavailability. A self-nanoemulsifying drug delivery system loaded with akebia saponin D - phospholipid complex (APC-SNEDDS) (composition: Peceol: Cremophor® EL: Transcutol HP: ASD: phospholipid; ratio: 10:45:45:51:12.3, w:w:w:w:w) was first developed to improve the oral absorption of saponins and it was found to significantly enhance ASD's oral bioavailability by 4.3 - fold (p < .01). This study was conducted to elucidate the mechanism of enhanced oral absorption of ASD by the drug delivery system of APC-SNEDDS. The aggregation morphology and particle size of ASD and APC-SNEDDS prepared in aqueous solutions were determined by transmission electron microscope and particle size analyzer, respectively. Stability of ASD and APC-SNEDDS in gastrointestinal luminal contents and mucosa homogenates were also explored. The differences of in situ intestinal permeability of ASD and APC-SNEDDS were compared. APC-SNEDDS reduced the aggregation size from 389 ± 7 nm (ASD) to 148 ± 3 nm (APC-SNEDDS). APC-SNEDDS increased the remaining drug in large intestine luminal contents from 47 ± 1% (ASD) to 83 ± 1% (APC-SNEDDS) during 4 h incubation. APC-SNEDDS provided an 11-fold increase in Ka value and an 11-fold increase in Peff value compared to ASD. In summary, APC-SNEDDS improved ASD's oral bioavailability mainly by increasing membrane permeability, destroying self-micelles and inhibiting the intestinal metabolism.


Subject(s)
Drug Delivery Systems/methods , Emulsifying Agents/metabolism , Gastrointestinal Absorption/physiology , Nanoparticles/metabolism , Phospholipids/metabolism , Saponins/metabolism , Administration, Oral , Animals , Emulsifying Agents/administration & dosage , Emulsifying Agents/chemical synthesis , Gastrointestinal Absorption/drug effects , Male , Nanoparticles/administration & dosage , Nanoparticles/chemistry , Phospholipids/administration & dosage , Phospholipids/chemical synthesis , Rats , Rats, Sprague-Dawley , Saponins/administration & dosage , Saponins/chemical synthesis
7.
Molecules ; 24(7)2019 Apr 01.
Article in English | MEDLINE | ID: mdl-30939835

ABSTRACT

Hyperlipidemia is a major component of metabolic syndrome, and regarded as one of the main risk factors causing metabolic diseases. We have developed a therapeutic drug, akebia saponin D (ASD), and determined its anti-hyperlipidemia activity and the potential mechanism(s) of action by analyzing the metabolome and intestinal microbiota. Male Sprague-Dawley rats were fed a high fat diet to induce hyperlipidemia, and then given ASD orally for 8 weeks. Lipid levels in serum were determined biochemically. Metabolites in serum, urine and feces were analyzed by UPLC-Q/TOF-MS, and the structure of the intestinal microbiota was determined by 16S rRNA sequencing. The ASD treatment significantly decreased the levels of TC, TG and LDL-c and increased the serum level of HDL-c. Metabolomics analysis indicated that the ASD treatment mainly impacted seven differential metabolites in the serum, sixteen differential metabolites in the urine and four differential metabolites in feces compared to the model group. The ASD treatment significantly changed eight bacteria at the genus level compared to the model group. In conclusion, ASD treatment can significantly alleviate HFD-induced hyperlipidemia and the hypolipidemic effect of ASD treatment is certainly associated with a systematic change in the metabolism, as well as dynamic changes in the structure of the intestinal microbiota.


Subject(s)
Diet, High-Fat/adverse effects , Gastrointestinal Microbiome/drug effects , Hyperlipidemias/metabolism , Hyperlipidemias/microbiology , Metabolome/drug effects , Saponins/pharmacology , Animals , Hyperlipidemias/drug therapy , Hyperlipidemias/etiology , Male , Phylogeny , Rats , Rats, Sprague-Dawley
8.
Zhongguo Zhong Yao Za Zhi ; 42(10): 1901-1907, 2017 May.
Article in Zh | MEDLINE | ID: mdl-29090549

ABSTRACT

The aim of this study was to develop a simple, sensitive ultra performance liquid chromatography mass spectrometry (UPLC-MS/MS) method for the determination of syringaresinol, N-trans-feruloyltyramine, chelerythrine chloride, sinomenine, coptisine chloride, sanguinarine, chelidonine, magnolflorine, allocryptopine, protopine, farrerol, stylopine and dihydrosanguin-arine in Tong'an injection (TAI), which could be used for the quality control of TAI. The UPLC analysis was performed on Agilent Zorbax SB-Aq column (2.1 mm×150 mm,3.5 µm), with 0.1% formic acid solution (A) -acetonitrile (B) as the mobile phase for gradient elution (0.01-2 min, 5%B; 2-8 min, 5%-30%B; 8-11 min, 30%-95%B; 11-13 min, 95%B; 13-13.1 min, 95%-5%B; 13.1-14 min, 5%B). The flow rate was 0.5 mL•min⁻¹, and the column temperature was 25 ℃; multiple reaction monitoring (MRM) was performed in electrospray ion source positive ion mode for quantitative determination. The calibration curves for the above thirteen compounds showed good linear relationship in corresponding mass concentration range (r>0.999 0). The average recovery rate of the compounds ranged from 95.70% to 104.8%, with RSD of less than 1.9%. The contents of thirteen active components in 10 batches of TAI were 0.021 2-0.029 0, 0.001 7-0.002 3, 0.000 9-0.001 3, 5.952-6.205 2, 0.195 4-0.240 5, 0.002 0-0.002 9, 0.693-0.798 2, 0.069 3-0.078 2, 0.089 29-0.102 9, 0.386 5-0.420 1, 0.014 3-0.015 9, 0.755 3-0.842 1, and 0.008 2-0.011 2 g•L⁻¹ respectively. Methodology validation proved that this method was simple, rapid, sensitive and accurate, which can be used to provide reference for the comprehensive evaluation of TAI quality. The determination results of 10 batches of TAI showed the content of each batch had no significant difference. The results may provide a basis for the quality control of TAI.


Subject(s)
Chromatography, High Pressure Liquid , Drugs, Chinese Herbal/analysis , Phytochemicals/analysis , Tandem Mass Spectrometry , Quality Control , Reproducibility of Results
9.
J Sep Sci ; 39(19): 3661-3668, 2016 Oct.
Article in English | MEDLINE | ID: mdl-27471121

ABSTRACT

Quality control has been one of the key scientific issues in the modernization of traditional Chinese medicine. This study explored a novel method for quality evaluation of herbal medicines. High-performance liquid chromatography fingerprints and the osteoblast proliferation activity of 18 batches of Achyranthes bidentata, which were prepared with salt, were determined to establish a chromatographic database and an activity database. Correlation analyses of these databases were performed using partial least squares to obtain regression coefficients (positive and negative correlation coefficients). Then, the sums of the products of the positive and negative correlation peak areas and the corresponding coefficients, respectively, were calculated for each sample. The absolute value of the ratios of the sums of the positive and negative products were calculated, our studies showed that this ratio was significantly correlated with the proliferation activity, particularly when the activity was in the best and worst ranges. Therefore, we developed a parameter that was used to evaluate the quality of samples osteoblast proliferation activity. The quality of another ten batches of samples was assessed to verify this method. The results indicated that this method can be used for quality evaluation of herbal medicines according to the dynamic changes in the chemical compounds and activity.


Subject(s)
Chromatography, High Pressure Liquid/methods , Drug Evaluation, Preclinical/methods , Drugs, Chinese Herbal/analysis , Plants, Medicinal/chemistry , Cell Line , Cell Proliferation/drug effects , Drugs, Chinese Herbal/pharmacology , Herbal Medicine , Humans , Quality Control
10.
Pharm Biol ; 54(9): 1857-64, 2016 Sep.
Article in English | MEDLINE | ID: mdl-26760929

ABSTRACT

Context Eucommiae Cortex and Radix Dipsaci, occurring in a ratio of 1:1 in Du-Zhong-Wan (DZW), a Chinese herbal medicine, is available as a water extract followed by ethanol precipitation for the treatment of osteoporosis, fractures and menopausal syndrome. Objective This study investigates the protective effects of DZW in ovariectomy (OVX)-induced bone loss in a rat osteopenia model. Materials and methods Sixty Sprague-Dawley rats were randomly divided into the sham-operated group (SHAM) and five OVX subgroups: OVX with vehicle (OVX), 17ß-estradiol (E2) and with three graded doses of DZW. Daily oral administration of the different samples started on the fifth week and lasted for 12 weeks, respectively. The body weight, uterus wet weight, serum biochemical parameters, bone mineral density (BMD), bone biomechanical properties, bone microarchitecture and immunohistochemistry were examined. Results Compared with the SHAM group, the DZW treatment significantly reversed the osteoporotic changes in OVX rats. The DZW-H group showed that serum tartrate-resistant acid phosphatase 5b (TRACP-5b) levels reduced by 152.25% (p < 0.01) and osteocalein (OCN) levels dose dependently increased by 118.43% (p < 0.01) as compared with the OVX group. Compared with the OVX group, the DZW at different three dosages of DZW evidently increased the right femur BMD by 112.43, 114.56 and 116.45%, and dramatically promoted bone quality and bone strength (p < 0.05). Further, immunohistochemical evaluation also showed that DZW administration increased ER expression in uteri (p < 0.01). Conclusions DZW exhibits an anti-osteoporotic effect, probably mediated via phyto-estrogenic effects. It might be a potential herbal alternative for the management of postmenopausal osteoporosis.


Subject(s)
Bone Density Conservation Agents/pharmacology , Bone Density/drug effects , Bone Diseases, Metabolic/prevention & control , Bone Remodeling/drug effects , Drugs, Chinese Herbal/pharmacology , Femur/drug effects , Osteoporosis, Postmenopausal/prevention & control , Ovariectomy , Absorptiometry, Photon , Animals , Biomarkers/blood , Biomechanical Phenomena , Bone Diseases, Metabolic/blood , Bone Diseases, Metabolic/diagnostic imaging , Bone Diseases, Metabolic/physiopathology , Disease Models, Animal , Female , Femur/diagnostic imaging , Femur/metabolism , Femur/physiopathology , Humans , Immunohistochemistry , Osteoporosis, Postmenopausal/blood , Osteoporosis, Postmenopausal/diagnostic imaging , Osteoporosis, Postmenopausal/physiopathology , Rats , Rats, Sprague-Dawley , Receptors, Estrogen/drug effects , Receptors, Estrogen/metabolism , Up-Regulation , Uterus/drug effects , Uterus/metabolism , X-Ray Microtomography
11.
Planta Med ; 81(4): 279-85, 2015 Mar.
Article in English | MEDLINE | ID: mdl-25760382

ABSTRACT

Hyperuricemia has been considered to be a key risk factor for kidney disease. The formation of uric acid crystals in the kidney further stimulates an intensive inflammatory response. Rhein possesses various pharmacological activities, including anti-inflammatory, antioxidative, antitumor, purgative effects, and so on. To our knowledge, no previous work has been reported about the therapeutic effect of rhein on urate nephropathy. In this study, a model of hyperuricemia and nephropathy induced by adenine and ethambutol in mice was established. Meanwhile, the potential beneficial effects and mechanisms of rhein on hyperuricemia and nephropathy were also investigated. The results demonstrated that rhein significantly decreased the serum uric acid level by inhibiting the xanthine oxidase activity and increasing the excretion of urinary uric acid. In addition, rhein also markedly improved kidney damage related to hyperuricemia. Further investigation indicated that rhein improved the symptoms of nephropathy through decreasing the production of proinflammatory cytokines, including interleukin 1ß, prostaglandin E2, and tumor necrosis factor-α and inhibiting the expression of transforming growth factor-ß1. The present study suggests that rhein may have a considerable potential for development as an anti-hyperuricemic and nephroprotective agent for clinical application.


Subject(s)
Anthraquinones/therapeutic use , Drugs, Chinese Herbal/therapeutic use , Hyperuricemia/drug therapy , Kidney Diseases/drug therapy , Kidney/drug effects , Phytotherapy , Rheum/chemistry , Animals , Anthraquinones/pharmacology , Blood Urea Nitrogen , Creatinine/blood , Disease Models, Animal , Drugs, Chinese Herbal/pharmacology , Hyperuricemia/blood , Interleukin-1beta/blood , Kidney Diseases/blood , Kidney Diseases/pathology , Male , Mice , Organic Anion Transport Protein 1/blood , Organic Anion Transporters/blood , Protective Agents/pharmacology , Protective Agents/therapeutic use , Tumor Necrosis Factor-alpha/blood , Uric Acid/urine
12.
Drug Dev Ind Pharm ; 41(11): 1777-84, 2015.
Article in English | MEDLINE | ID: mdl-25686726

ABSTRACT

CONTEXT: Echinacoside (ECH) has been shown to possess a multitude of pharmacological activities, however, oral administered ECH failed to fulfill its therapeutic potential due to poor absorption and low bioavailability. Thus, there is a pressing need to develop a new oral dosage form to enhance its intestinal absorption and improve bioavailability. OBJECTIVE: The aim of this study was to formulate ECH into phospholipid complex (phytosome, PHY) to enhance intestinal absorption and oral bioavailability of ECH in vivo. METHODS: The PHY was prepared by a solvent evaporation method and was characterized by differential scanning calorimetry (DSC) and infrared spectroscopy (IR), and then the physicochemical properties, intestinal absorption and bioavailability of the PHY were investigated. RESULTS: Compared with the physical mixture (MIX) or ECH alone, the n-octanol/water partition coefficient (P) determination results showed that the lipophilicity of ECH was significantly enhanced by formation of PHY. Accordingly, the intestinal absorption rate (Ka) was improved to 2.82-fold and the effective permeability coefficient (Peff) increased to 3.39-fold. The concentrations of ECH in rat plasma at different times after oral administration of PHY were determined by HPLC. Pharmacokinetic parameters of the PHY in rats were Tmax = 1.500 h, Cmax = 3.170 mg/mL, AUC0-∞ = 9.375 mg/L h and AUC0-24 = 7.712 mg/L h, respectively. CONCLUSIONS: Compared with ECH alone or the MIX group, the relative bioavailability of ECH was increased significantly after formulation into PHY (p < 0.05). This might be mainly due to an improvement of the absorption of PHY.


Subject(s)
Glycosides/administration & dosage , Intestinal Absorption , Phospholipids/chemistry , Administration, Oral , Animals , Area Under Curve , Biological Availability , Calorimetry, Differential Scanning , Chemistry, Pharmaceutical/methods , Chromatography, High Pressure Liquid , Female , Glycosides/pharmacokinetics , Permeability , Rats , Solvents/chemistry , Spectrophotometry, Infrared
13.
Zhongguo Zhong Yao Za Zhi ; 40(10): 1960-4, 2015 May.
Article in Zh | MEDLINE | ID: mdl-26390656

ABSTRACT

According to ICH, Chinese Pharmacopoeia and supplementary requirements on the separation and purification of herbal extract with macroporous adsorption resin by SFDA, hexane, acetidine, ethanol, benzene, methyl-benzene, o-xylene, m-xylene, p-xylene, styrene, diethyl-benzene and divinyl-benzene of residual organic solvents and macroporous resin residues in Akebia saponin D were determined by headspace capillary GC. Eleven residues in Akebia saponin D were completely separated on DB-wax column, with FID detector, high purity nitrogen as the carry gases. The calibration curves were in good linearity (0.999 2-0.999 7). The reproducibility was good (RSD < 10%). The average recoveries were 80.0% -110%. The detection limit of each component was far lower than the limit concentration. The method is simple, reproducible, and can be used to determine the residual organic solvents and macroporous resin residues in Akebia saponin D.


Subject(s)
Chromatography, Gas/methods , Organic Chemicals/analysis , Saponins/isolation & purification , Chromatography, Gas/instrumentation , Drug Contamination/prevention & control , Reproducibility of Results , Resins, Synthetic/chemistry , Saponins/analysis
14.
Planta Med ; 80(4): 269-76, 2014 Mar.
Article in English | MEDLINE | ID: mdl-24535719

ABSTRACT

Diabetic nephropathy, one of the most common and serious vascular complications of both type 1 and type 2 diabetes mellitus, has become a major contributor of end-stage renal failure. The aims of this study were to investigate the effects and possible underlying action mechanism(s) of oxymatrine on renal damage in diabetic rats. Diabetes was induced in male Sprague-Dawley rats by administering a high-fat diet and an intraperitoneal 30 mg/kg streptozotocin injection. The animals were treated orally with saline, metformin hydrochloride, and oxymatrine at 50, 100, and 150 mg/kg/day for 11 weeks. At the end of the treatment, renal tissue, blood, and urine samples were collected for histological and biochemical examination. The results revealed that oxymatrine significantly decreased blood glucose, urinary protein and albumin excretion, serum creatinine, and blood urea nitrogen in diabetic rats, and ameliorated diabetes-induced glomerular and tubular pathological changes. Furthermore, oxymatrine significantly prevented oxidative stress and reduced the contents of renal advanced glycation end products, transforming growth factor-ß1, connective tissue growth factor, and inflammatory cytokines in diabetic rats. All these results indicate that oxymatrine has protective effects on experimental diabetic nephropathy by multiple mechanisms.


Subject(s)
Alkaloids/therapeutic use , Diabetes Mellitus, Experimental/complications , Diabetic Nephropathies/drug therapy , Kidney/drug effects , Phytotherapy , Plant Extracts/therapeutic use , Quinolizines/therapeutic use , Sophora/chemistry , Albuminuria/prevention & control , Alkaloids/pharmacokinetics , Animals , Blood Glucose/metabolism , Blood Urea Nitrogen , Connective Tissue Growth Factor/metabolism , Creatinine/blood , Cytokines/metabolism , Diabetes Mellitus, Experimental/drug therapy , Diabetic Nephropathies/metabolism , Diabetic Nephropathies/pathology , Glycation End Products, Advanced/metabolism , Kidney/metabolism , Kidney/pathology , Kidney Glomerulus/drug effects , Kidney Glomerulus/pathology , Kidney Tubules/drug effects , Kidney Tubules/pathology , Male , Oxidative Stress/drug effects , Plant Extracts/pharmacology , Proteinuria/prevention & control , Quinolizines/pharmacokinetics , Rats , Rats, Sprague-Dawley , Transforming Growth Factor beta1/metabolism
15.
Zhongguo Zhong Yao Za Zhi ; 39(12): 2311-3, 2014 Jun.
Article in Zh | MEDLINE | ID: mdl-25244765

ABSTRACT

In order to study the stability of akebia saponin D (ASD) in biological fluids in vitro, the determination methods of ASD were established in this study. Akebia saponin D was dissolved in artificial gastric juice, intestinal juice and gastrointestinal contents of rats, respectively, then thermostatically maintained at 37 degrees C. At time intervals after degradation, samples were withdrawn and the concentrations of ASD were determined by HPLC, from which stability of it at different biological specimen was evaluated. As a result, ASD was totally degraded in large intestinal contents of rats in 8 hours. ASD was very stable in artificial gastric juice, intestinal juice and gastric contents of rats. All of the above data proved that ASD was easily degraded by coliform bacteria but stable in acid environment and with the presence of digestive enzyme.


Subject(s)
Drugs, Chinese Herbal/pharmacokinetics , Gastrointestinal Tract/metabolism , Saponins/chemistry , Saponins/pharmacokinetics , Animals , Drug Stability , Drugs, Chinese Herbal/administration & dosage , Gastrointestinal Tract/chemistry , Humans , Rats , Saponins/administration & dosage
16.
Nat Nanotechnol ; 2024 Aug 20.
Article in English | MEDLINE | ID: mdl-39164412

ABSTRACT

Heteromeric pore-forming proteins often contain recognition patterns or stereospecific selection filters. However, the construction of heteromeric pore-forming proteins for single-molecule sensing is challenging due to the uncontrollability of producing position isomers and difficulties in purification of regio-defined products. To overcome these preparation obstacles, we present an in situ strategy involving single-molecule chemical modification of a heptameric pore-forming protein to build a stereo- and regio-specific heteromeric nanopore (hetero-nanopore) with a subunit stoichiometric ratio of 3:4. The steric hindrance inherent in the homo-nanopore of K238C aerolysin directs the stereo- and regio-selective modification of maleimide derivatives. Our method utilizes real-time ionic current recording to facilitate controlled voltage manipulation for stoichiometric modification and position-based side-isomer removal. Single-molecule experiments and all-atom molecular dynamics simulations revealed that the hetero-nanopore features an asymmetric stereo- and regio-defined residue structure. The hetero-nanopore produced was characterized by mass spectrometry and single-particle cryogenic electron microscopy. In a proof-of-concept single-molecule sensing experiment, the hetero-nanopore exhibited 95% accuracy for label-free discrimination of four peptide stereoisomers with single-amino-acid structural and chiral differences in the mixtures. The customized hetero-nanopores could advance single-molecule sensing.

17.
Biomed Chromatogr ; 27(11): 1568-73, 2013 Nov.
Article in English | MEDLINE | ID: mdl-23832283

ABSTRACT

A sensitive liquid chromatography-electrospray ionization-mass spectrometry method has been developed and validated for determination of two major bioactive saponins in rat plasma after oral administration of saponins extracted from Rhizoma Panacis Japonici, including chikusetsusaponin V and chikusetsusaponin IV for the first time. Akebia saponin D was used as the internal standard (IS). Plasma samples were prepared by protein precipitation with methanol. A Phenomenex C18 column (150 × 4.6 mm, 4 µm) was used as the analytical column with a mobile phase of acetonitrile and 0.05% aqueous formic acid. Mass spectrometric detection was achieved by single quadrupole mass spectrometer equipped with an electrospray ionization interface operating in negative ionization mode. Calibration curves showed good linearity over the concentration range of 5-500 ng/mL for the two analytes in rat plasma. The lower limit of quantification was 5 ng/mL. The intra- and inter-batch precisions were within 10.3% and accuracy ranged from -3.9 to 5.4%. The method was validated and successfully applied to the preliminary pharmacokinetic study of chikusetsusaponin V and chikusetsusaponin IV in rat plasma after oral administration of saponins extracted from Rhizoma Panacis Japonici.


Subject(s)
Chromatography, High Pressure Liquid/methods , Oleanolic Acid/analogs & derivatives , Saponins/blood , Spectrometry, Mass, Electrospray Ionization/methods , Administration, Oral , Animals , Limit of Detection , Male , Oleanolic Acid/administration & dosage , Oleanolic Acid/blood , Oleanolic Acid/isolation & purification , Panax/chemistry , Rats , Rats, Sprague-Dawley , Rhizome/chemistry , Saponins/administration & dosage , Saponins/isolation & purification , Tandem Mass Spectrometry/methods
18.
Zhongguo Zhong Yao Za Zhi ; 38(14): 2378-83, 2013 Jul.
Article in Zh | MEDLINE | ID: mdl-24199576

ABSTRACT

To study the pharmacokinetics, excretion characteristics and plasma protein binding rate of asperosaponin VI (A-VI) and its active metabolite hederagenin (M1). A-VI and M1 concentrations in plasma, bile, urine and feces were determined by established LC-MS/MS to calculate the pharmacokinetic parameters. The plasma protein binding rate of A-VI was determined by equilibrium dialysis method. the double peaks was observed in the A-VI plasma concentration-time curve, after rats were orally administered with low, medium and high doses of A-VI (0.03, 0.09, 0.27 g x kg(-1)). The Cmax1 and Cmax2 of A-VI were (28.88 +/- 49.78) and (4.480 +/- 1.872) microg x L(-1), (35.19 +/- 23.53) and (22.11 +/- 16.15) microg x L(-1), (73.37 +/- 37.28) and (132.2 +/- 160.7) microg x L(-1), respectively. The AUC0-t, of A-VI were (43.21 +/- 37.32), (133.9 +/- 102.5) and (779.6 +/- 876.9) microg x h x L(-1), respectively. The t1/2 of A-VI were (3.3 +/- 0.8), (3.2 +/- 2.3) and (4.5 +/- 1.2) h, respectively. The Cmax of M1 were (16.03 +/- 9.336), (26.41 +/- 11.95) and (28.71 +/- 5.874) microg x L(-1), respectively. The AUC0-t, of M1 were (105.6 +/- 73.60), (260.0 +/-153.9) and (323.1 +/- 107.9) microg x h x L(-1), respectively. The t1/2 of M1 were (4.1 +/- 3.4), (4.4 +/- 2.3), (3.9 +/- 0.9) h, respectively. No significant gender difference was found in the in vivo pharmacokinetics of A-VI and M1. There was no accumulation of A-VI and M1 after multiple administrations of A-VI (0.09 g x kg(-1)). After oral administration of A-VI, the double peaks were also observed in biliary and urinary excretion rate-time curves for A-VI. M1 was detected in the feces samples at 6 h after oral administration. The average plasma protein binding rate of A-VI was 92. 9% in rats.


Subject(s)
Drugs, Chinese Herbal/pharmacokinetics , Saponins/pharmacokinetics , Administration, Oral , Animals , Area Under Curve , Bile/metabolism , Drugs, Chinese Herbal/metabolism , Female , Male , Plants, Medicinal , Protein Binding/drug effects , Rats , Saponins/blood , Saponins/metabolism , Saponins/urine
19.
ACS Appl Mater Interfaces ; 15(35): 41906-41915, 2023 Sep 06.
Article in English | MEDLINE | ID: mdl-37610108

ABSTRACT

With the rapid development of electronic information technology, composite materials with outstanding performance in terms of electromagnetic interference (EMI) shielding and strain sensing are crucial for next-generation smart wearable electronic devices. However, the fabrication of flexible composite films with dual functionality remains a significant challenge. Herein, multifunctional flexible composite films with exciting EMI shielding and strain sensing properties were constructed using a facile vacuum-assisted filtration process and transfer method. The films consisted of ultrathin AgNW/MXene (Ti3C2Tx)/AgNW conductive networks (1 µm) attached to a flexible polydimethylsiloxane (PDMS) substrate. The obtained AgNW/MXene/PDMS composite film exhibited an exceptional EMI shielding effectiveness of 50.82 dB and good flexibility (retaining 93.67 and 90.18% of its original value after 1000 bending and stretching cycles, respectively), which are attributed to the enhanced multilayer internal reflection network created by the AgNWs and MXene as well as the synergistic effect of PDMS. Besides EMI shielding, the composite films also displayed remarkable strain sensing properties. They exhibited a wide linear range of tensile strain up to 68% with a gauge factor of 468. They also showed fast response, ultralow detection limit, and high mechanical stability. Interestingly, the composite films could also detect motion and voice recognition, demonstrating their potential as wearable sensors. This study highlights the effectiveness of multifunctional flexible AgNW/MXene/PDMS composite films in resisting electromagnetic radiation and monitoring human motion, thereby providing a promising solution for the development of flexible wearable electronic devices in complex electromagnetic environments.

20.
Membranes (Basel) ; 13(6)2023 May 30.
Article in English | MEDLINE | ID: mdl-37367765

ABSTRACT

Aniline is a highly toxic organic pollutant with "carcinogenic, teratogenic and mutagenesis" characteristics. In the present paper, a membrane distillation and crystallization (MDCr) process was proposed to achieve zero liquid discharge (ZLD) of aniline wastewater. Hydrophobic polyvinylidene fluoride (PVDF) membranes were used in the membrane distillation (MD) process. The effects of the feed solution temperature and flow rate on the MD performance were investigated. The results showed that the flux of the MD process was up to 20 L·m-2·h-1 and the salt rejection was above 99% under the feeding condition of 60 °C and 500 mL/min. The effect of Fenton oxidation pretreatment on the removal rate of aniline in aniline wastewater was also investigated, and the possibility of realizing the ZLD of aniline wastewater in the MDCr process was verified.

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