Rheumatoid arthritis(RA)is a prevalent autoimmune disease characterized by chronic inflammation and excessive proliferation of the synovium.Currently,treatment options focus on either reducing inflammation or inhibiti...Rheumatoid arthritis(RA)is a prevalent autoimmune disease characterized by chronic inflammation and excessive proliferation of the synovium.Currently,treatment options focus on either reducing inflammation or inhibiting synovial hyperplasia.However,these modalities are unsatisfactory in achieving the desired therapeutic outcomes.Halofuginone hydrobromide(HF),an herbal active ingredient,has demonstrated pharmacological effects of both anti-inflammation and inhibition of synovial hyperplasia proliferation.However,HF's medical efficacy is limited due to its poor water solubility,short half-life(t_(1/2)),and non-target toxicity.In the current study,by using the advantages of nanotechnology,we presented a novel dual-targeted nanocomplex,termed HA-M@P@HF NPs,which consisted of a hyaluronic acid(HA)-modified hybrid membrane(M)-camouflaged poly lactic-co-glycolic acid(PLGA)nanosystem for HF delivery.These nanocomplexes not only overcame the limitations of HF but also achieved simultaneous targeting of inflammatory macrophages and human fibroblast-like synoviocytes-RA(HFLS-RA).In vivo experiments demonstrated that these nanocomplexes effectively suppressed immune-mediated inflammation and synovial hyperplasia,safeguarding against bone destruction in rats with adjuvant-induced arthritis(AIA).Remarkable anti-arthritic effects of these nanocomplexes were accomplished through promoting repolarization of M1-to-M2 macrophages and apoptosis of HFLS-RA,thereby offering a promising therapeutic strategy for RA.展开更多
The development of tin-based devices with low toxicity is critical for the commercial viability of perovskite solar cells.However because tin halide is a stronger Lewis acid,its crystallization rate is extremely fast,...The development of tin-based devices with low toxicity is critical for the commercial viability of perovskite solar cells.However because tin halide is a stronger Lewis acid,its crystallization rate is extremely fast,resulting in the formation of numerous defects that affect the device performance of tin-based perovskite solar cells.Herein,propylamine hydrobromide(PABr)was added to the perovskite precursor solution as an additive to passivate defects and fabricate more uniform and dense perovskite films.Because propylamine cations are too large to enter the perovskite lattices,they only exist at the grain boundary to passivate surface defects and promote crystal growth in a preferred orientation.The PABr additive raises the average short-circuit current density from 19.45 to 25.47 mA·cm^(-2)by reducing carrier recombination induced by defects.Furthermore,the device’s long-term illumination stability is improved after optimization,and the hysteresis effect is negligible.The addition of PABr results in a power conversion efficiency of 9.35%.展开更多
An isocratic stability-indicating reversed phase high performance liquid chromatographic method (RP-HPLC) was developed for determination of process related impurities and assay of darifenacin hydrobromide (DRF) in bu...An isocratic stability-indicating reversed phase high performance liquid chromatographic method (RP-HPLC) was developed for determination of process related impurities and assay of darifenacin hydrobromide (DRF) in bulk drugs. DRF was subjected to various stress conditions such as hydrolysis (acid, base, and neutral), oxidation, photolysis and thermal degradation as per International Conference on Harmonization (ICH Q1A(R2) and Q1B) prescribed conditions to investigate the stability-indicating ability of the method. Significant degradation was observed during acidic hydrolysis and oxidative stress conditions. The chromatographic separation was accomplished on a Prodigy C8 column (250 × 4.6 mm, 5 μm) with mobile phase consisting of 0.05 M ammonium acetate (pH adjusted to 7.2 by using ammonia solution) and methanol (36% acetonitrile) in 35:65 v/v ratio in an isocratic elution mode at a flow rate of 1.0 mL/min at 25°C. Detection of analytes was carried out using photo diode array detector at a wavelength of 215 nm. The developed LC method was validated with respect to accuracy, linearity, precision, limits of detection and quantitation and robustness as per ICH guidelines.展开更多
Aim To evaluate the time-effect and dose-effect of prasugrel hydrobromide acetic acid compound （PHAAC） inhibiting platelet aggregation. Methods For the time-effect study, 190 Sprague-Dawley （SD） rats were devided ...Aim To evaluate the time-effect and dose-effect of prasugrel hydrobromide acetic acid compound （PHAAC） inhibiting platelet aggregation. Methods For the time-effect study, 190 Sprague-Dawley （SD） rats were devided into 19 groups （n- 10）： the vehicle control group, the PHAAC groups （0.5, 1, 2, 4, 6, 24, 48, 72, 96 h） and the prasugrel hydrochloride groups （0.5, 1, 2, 4, 6, 24, 48, 72, 96 h）. Rats were singly intra- gastic administration of the vehicle, the PHAAC （5 mg·kg^-1） or the prasugrel hydrochloride （5 mg · kg^-1 ）, re- spectively. Blood samples were taken at each time point for the determination of platelet aggregation rate （PAR）. For the dose-effect study, 110 SD rats were devided into 11 groups （n= 10）： the vehicle control group, the PHAAC groups （10, 5, 2.5, 1, 0.5 mg · kg^-1, dosage of prasugrel） and the prasugrel hydrochloride groups （ 10, 5, 2.5, 1, 0.5 mg · kg^-1, dosage of prasugrel） . Blood samples were taken at 4 h after drug administration for the determination of PAR. Results Compared with the vehicle group, PHAAC has significant anti-platelet ag- gregative effects （P 〈 0.05） at the time of 0.5, 1, 2, 4, 6, 24, 48 h, and the effect at the time of 4 h was the strongest. There were no obvious differences between the effect of PHAAC （5 mg · kg^-1） and prasugrel hydrochlo- ride （5 mg · kg^-1） at each time point. Compared with the vehicle group, intragastic administration of PHAAC at the doses of 10, 5, 2.5, 1, 0.5 mg · kg^-1 could obviously inhibite the platelet aggregation, and showed a dose- dependent manner. There were no significant differences between the effect of PHAAC and prasugrel hydrochloride at the same dose. Conclusion PHAAC can inhibit platelet aggregation in a dose-dependent manner, and the effect at 4 h after drug administration is the strongest. The action strength and duration of PHAAC are similar with that of the prasugrel hydrochloride.展开更多
This paper reports that 1-dodecylamine hydrobromide （1 C12H25NH3.Br）（s） has been synthesized using the liquid phase reaction method. The lattice potential energy of the compound 1-C12H25NH3.Br and the ionic vol- u...This paper reports that 1-dodecylamine hydrobromide （1 C12H25NH3.Br）（s） has been synthesized using the liquid phase reaction method. The lattice potential energy of the compound 1-C12H25NH3.Br and the ionic vol- ume and radius of the 1-C12H25NH3＋ cation are obtained from the crystallographic data and other auxiliary ther- modynamic data. The constant-volume energy of combustion of 1 C12H25NH3.Br（s） is measured to be AcUo（1 C12H25NH3.Br, s） = （7369.03-4-3.28） kJ.mo1-1 by means of an RBC-II precision rotating-bomb combustion calorime- ter at T=（298.15~0.001） K. The standard molar enthalpy of combustion of the compound is derived to be △cHo（1- C12H25NH3.Br, s）=- （7384.52±3.28） kJ.mo1-1 from the constant-volume energy of combustion. The standard molar enthalpy of formation of the compound is calculated to be △fHo（1-C12H25NH3.Br, s）=-（1317.86~3.67） kJ.mo1-1 from the standard molar enthalpy of combustion of the title compound and other auxiliary thermodynamic quantities through a thermochemical cycle.展开更多
Background:Anisodine hydrobromide(AT3),an anti-cholinergic agent,could be delivered to the brain across the blood-brain barrier and has been used clinically for the treatment of cerebral ischemia/reperfusion injury.En...Background:Anisodine hydrobromide(AT3),an anti-cholinergic agent,could be delivered to the brain across the blood-brain barrier and has been used clinically for the treatment of cerebral ischemia/reperfusion injury.Endothelial dysfunction can be caused by hypoxia/reoxygenation(H/R)via oxidative stress and metabolic alterations.The present study investigated whether AT3 regulates the production of nitric oxide(NO)and reactive oxygen species(ROS),and the HIF-1αpathway via regulation of muscarinic acetylcholine receptors(mAChRs)in brain microvascular endothelial cells after H/R exposure.Methods:Under H/R conditions,hCMEC/D3 cerebral microvascular endothelial cells were treated with AT3.Specific inhibitors of M2-and M4-mAChRs were used to explore the mechanism by which AT3 influences oxidative stress in endothelial cells.Then,mAChRs expression was detected by western blotting and NO production was detected by Greiss reaction.The intracellular ROS level was measured using DCFH-DA probes.The expression of hypoxia-inducible transcription factor 1α(HIF-1α)was also detected.Results:While H/R induced the expression of M2-and M4-mAChRs,AT3 suppressed the H/R-upregulated M2-and M4-mAChRs.H/R also induced the production of NO,ROS,and apoptosis.AT3 and M4-mAChR inhibitors inhibited the H/R-induced production of NO and ROS and apoptosis.HIF-1αwas induced by H/R,but was suppressed by AT3.Conclusion:Thus,the in vitro evidence shows that AT3 protects against H/R injury in cerebral microvascular endothelial cells via inhibition of HIF-1α,NO and ROS,predominantly through the downregulation of M4-mAChR.The findings offer novel understandings regarding AT3-mediated attenuation of endothelial cell apoptosis and cerebral ischemia/reperfusion injury.展开更多
Two polymorphic forms （forms I and IV） of antidepressant bupropion hydrobro- mides were prepared and characterized by powder X-ray single-crystal diffractometer. Lots of commercial substances may consist of form I. ...Two polymorphic forms （forms I and IV） of antidepressant bupropion hydrobro- mides were prepared and characterized by powder X-ray single-crystal diffractometer. Lots of commercial substances may consist of form I. Form I crystallizes in the triclinic system, space group P1^- with Z= 2, a = 7.6943（8）, b = 7.9347（9）, c = 13.8558（15） A, a = 85.971（3）, β = 85.619（2）, γ = 65.974（3）°, V = 769.66（14） A^3, Dc= 1.384 g/cm^3, formula C13H19C1NOBr, F（000） = 328, p = 2.83 mm^-1, the final R = 0.0579 and wR = 0.1282 for 1756 observed reflections with I 〉 2σ（I）. Another polymorphic form, IV, belongs to the orthorhombic system, space group Pbca with a = 8.6365（3）, b = 12.4167（4）, c = 27.7299（9） A, Z = 8, V= 2973.67（17） A^3, Dc= 1.432 g/cm^3, formula C13H19CINOBr, F（000） = 1312,μ = 2.93 mm^-1, the final R = 0.044 and wR = 0.1093 for 2018 observed reflections with I 〉 2σ（I）. In the crystal structure of the two polymorphic forms, expected proton transfer from HBr to amino group of bupropion molecule occurs and intramolecular and intermolecular hydrogen bonds N-H…Br are formed. These interactions result in hydrogen-bond dimers in these two forms. The bupropion molecule adopts different conformations in the two investigated solid state modifications.展开更多
1 INTRODUCTIONThe drying of fine chemicals and pharmaceuticals is dominated by a number of special factorscompared to the drying of bulk chemicals.These include:very high value of product;lowthroughputs(typically,100 ...1 INTRODUCTIONThe drying of fine chemicals and pharmaceuticals is dominated by a number of special factorscompared to the drying of bulk chemicals.These include:very high value of product;lowthroughputs(typically,100 kg·h<sup>-1</sup>);materials that frequently possess toxic properties andare often sticky,pasty and difficult to handle when wet;the moisture to be evaporated ofteninvolves solvents;and multipurpose processing plants.展开更多
[Objective] To make an objective evaluation about security of a new veterinary drug-arecoline hydrobromide according to the research results and papers in recent years and supply science basis for clinical usage. [ Me...[Objective] To make an objective evaluation about security of a new veterinary drug-arecoline hydrobromide according to the research results and papers in recent years and supply science basis for clinical usage. [ Method] The security of arecoline hydrobromide was evaluated based on acute toxicity tests; the ranges of safe medication, tolerability and toxicity as well as ＂Three-induced＇ effects （carcinogensis, mutagene- sis and teratogenesis） and reproductive toxicity were summarized according to the combinations of experimental results, papers and clinical effects. E Result] The results of acute toxicity tests in mice and rats showed that LD^0 （50% lethal dosages） of arecoline hydrobromide in mice was 691.83 mg/（kg.BW） and 95% incredible range of its LDso was 642.92 -744.47 mg/（ kg. BW）, and LDso of arecoline hydrobromide in rats was 2 054 mg/（kg.BW） and 95% incredible range of its LDso was 1 908 -2 210 mg/（kg.BW）. Its LDso value was hundreds times higher than the recommen- ded clinical dosage [ 1 -5 mg/（kg-BW） ], therefore it is safe to apply in clinic. The research results of ranges of safe medication, tolerability and toxicity showed that arecoline hydrobromide could entirely dispel the dog Diphyllobothrium, Spirometra mansoni, Dipylidium mesocestoides, Linea- tus and Cysticercus at dosages of 2 -3 mg/（ kg.BW）, and the same effects to Railletina tapeworm of chickens and Drepanidotaenia lanceolata of duck and goose at dosages of I -2 mg/（kg.BW）. The arecoline hydrobromide had muscarinic effects as side-effects and could cause vomiting, di- arrhea and other clinical symptoms to discharge the paralyzed worm from livestock body rapidly and completely. The arecoline hydrobromide had ＂Three-induced＂ effects and reproductive toxicity when it was used as antitapeworm drug with long-term, sustained and a large number of drug us- age, rather than used in clinical application with shorter time and lower dosage of administration. [ Conclusion] The arecoline hydrobromide is low- toxic substance and has a certain of toxicity such as ＂Three-induced＂ effects and reproductive toxicity at high-dosages application, and there are good effects on livestock and poultry tapeworm at the clinical recommended dosacles without ＂Three-induced＂ effects and reproductive toxicity.展开更多
Taeniasis and cysticercosis in domestic animals belong to zoonosis and seriously threaten the public health security. Especially the cysticercosis and echinococcosis caused by the tapeworm eggs have great harms to bod...Taeniasis and cysticercosis in domestic animals belong to zoonosis and seriously threaten the public health security. Especially the cysticercosis and echinococcosis caused by the tapeworm eggs have great harms to bodies because they can attack many organs of body. According to the combination of experimental results and literature materials, the morphology and transmission mode of taenia and cysticercus, the prevalence status and monitoring of taeniasis and cysticercosis as well as the antitapeworm mechanism, comparative analysis to other drugs, expelling tapeworm tests in vitro, dose determining tests and usage notes of arecoline hydrobromide were expounded in detail. It provides a theoretical basis for prevention of taeniasis and cysticarcosis and more scientific usage of arecoline hydrobromide and thus relieves the harms of taeniasis and cysticercosis and ensuring the public health security.展开更多
Background The rapidly activating delayed rectifier potassium current （/Kr）, whose pore-forming alpha subunit is encoded by the human ether-a-go-go-related gene （hERG）, is a key contributor to the third phase of a...Background The rapidly activating delayed rectifier potassium current （/Kr）, whose pore-forming alpha subunit is encoded by the human ether-a-go-go-related gene （hERG）, is a key contributor to the third phase of action potential repolarization. The aim of this study was to investigate the effect and mechanism of arecoline hydrobromide induced inhibition of hERG K^＋ current （/hERG）. Methods Transient transfection of hERG channel cDNA plasmid pcDNA3.1 into the cultured HEK293 cells was performed using Lipofectamine. A standard whole-cell patch-clamp technique was used to record the /hI=RG before and after the exposure to arecoline. Results Arecoline decreased the amplitude and the density of the /bERG in a concentration-dependent manner （IC5o=9.55 μmol/L）. At test potential of ＋60 mV, the magnitude of lhERG tail at test pulse of -40 mV was reduced from （151.7±6.2） pA/pF to （84.4±7.6） pA/pF （P 〈0.01, n=20） and the magnitude of IhERG tail at test pulse of -110 mV was reduced from （-187.5±9.8） pA/pF to （-97.6±12.6） pA/pF （P 〈0.01, n=20）. The blockade of arecoline in the open and inactivated state was significant in a state-dependent manner. The maximal blockade was achieved in the inactivated state. Studies of gating mechanism showed that the steady-state activation curve of IhERG was significantly negatively shifted by arecoline. Time constants of activation were shortened. Steady-state inactivation curve and time constants of fast inactivation were not significantly affected by arecoline. Furthermore, the inhibition of IhERG by arecoline was characterized markedly by a frequency-dependent manner from 0.03 to 1.00 Hz pulse. Conclusion Arecoline could potently block IhERG in both frequency and state-dependent manner.展开更多
Kai Xin San(KXS, containing ginseng, hoelen, polygala, and acorus), a traditional Chinese herbal compound, has been found to regulate cognitive dysfunction; however, its mechanism of action is still unclear. In this s...Kai Xin San(KXS, containing ginseng, hoelen, polygala, and acorus), a traditional Chinese herbal compound, has been found to regulate cognitive dysfunction; however, its mechanism of action is still unclear. In this study, 72 specific-pathogen-free male Kunming mice aged 8 weeks were randomly divided into a vehicle control group, scopolamine group, low-dose KXS group, moderate-dose KXS group, high-dose KXS group, and positive control group. Except for the vehicle control group and scopolamine groups(which received physiological saline), the doses of KXS(0.7, 1.4 and 2.8 g/kg per day) and donepezil(3 mg/kg per day) were gastrointestinally administered once daily for 2 weeks. On day 8 after intragastric treatment, the behavioral tests were carried out. Scopolamine group and intervention groups received scopolamine 3 mg/kg per day through intraperitoneal injection. The effects of KXS on spatial learning and memory, pathological changes of brain tissue, expression of apoptosis factors, oxidative stress injury factors, synapse-associated protein, and cholinergic neurotransmitter were measured. The results confirmed the following.(1) KXS shortened the escape latency and increased residence time in the target quadrant and the number of platform crossings in the Morris water maze.(2) KXS increased the percentage of alternations between the labyrinth arms in the mice of KXS groups in the Y-maze.(3) Nissl and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling staining revealed that KXS promoted the production of Nissl bodies and inhibited the formation of apoptotic bodies.(4) Western blot assay showed that KXS up-regulated the expression of anti-apoptotic protein Bcl-2 and inhibited the expression of pro-apoptotic protein Bax. KXS up-regulated the expression of postsynaptic density 95, synaptophysin, and brain-derived neurotrophic factor in the cerebral cortex and hippocampus.(5) KXS increased the level and activity of choline acetyltransferase, acetylcholine, superoxide dismutase, and glutathione peroxidase, and reduced the level and activity of acetyl cholinesterase, reactive oxygen species, and malondialdehyde through acting on the cholinergic system and reducing oxidative stress damage. These results indicate that KXS plays a neuroprotective role and improves cognitive function through reducing apoptosis and oxidative stress, and regulating synapse-associated protein and cholinergic neurotransmitters.展开更多
Objective This study aimed to examine the effects of microcirculatory dysfunction and 654-1intervention after cardiopulmonary resuscitation on myocardial injury.Methods Landrace pigs were divided into a sham operation...Objective This study aimed to examine the effects of microcirculatory dysfunction and 654-1intervention after cardiopulmonary resuscitation on myocardial injury.Methods Landrace pigs were divided into a sham operation group(S group,n=6),ventricular fibrillation control group(VF-C group,n=8)and 654-1 intervention group(VF-I group,n=8).Hemodynamics was recorded at baseline,at recovery of spontaneous circulation(ROSC),and 1 h,2 h,4h and 6 h thereafter.Sidestream dark field(SDF)technology was used to evaluate and monitor the microcirculation flow index,total vessel density,perfusion vessel ratio,De-Backer score,and perfusion vessel density in animal viscera at various time points.Results After administration of 654-1 at 1.5 h post-ROSC,the hemodynamics in the VF-I group,as compared with the VF-C group,was significantly improved.The visceral microcirculation detected by SDF was also significantly improved in the VF-I group.As observed through electron microscopy,significantly less myocardial tissue injury was present in the VF-I group than the VF-C group.Conclusion Administration of 654-1 inhibited excessive inflammatory by improving the state of visceral microcirculation.展开更多
Two simple, rapid, accurate, precise, reliable and economical spectrophotometric methods have been proposed for the determination of galanthamine hydrobromide (GH) in bulk and pharmaceutical formulation. First method ...Two simple, rapid, accurate, precise, reliable and economical spectrophotometric methods have been proposed for the determination of galanthamine hydrobromide (GH) in bulk and pharmaceutical formulation. First method is zero order UV spectrophotometry and second is 1st derivative zero crossing spectrophotometry. The developed methods have shown best results in terms of linearity, accuracy, precision, LOD and LOQ for bulk drugs and marketed formulations. Absorbance was measured at 287 nm for zero order and 277.4 nm for first derivative. It obeyed Lambert-Beer’s law in the range of 30-80 μg mL-1. Both methods have good linearity (r2 = 0.9997) and accuracy found to be 100.5% and 101.2% for both methods respectively.展开更多
The ~3H-labelled belladonna alkaloids obtained by catalysed exchange method with microwave excitation was investigated. The specific activities of the labelled products Were 16—32 TBq/mol. More than 90% labelled posi...The ~3H-labelled belladonna alkaloids obtained by catalysed exchange method with microwave excitation was investigated. The specific activities of the labelled products Were 16—32 TBq/mol. More than 90% labelled positions of these ~3H-tracers were on phenyl rings. The radiochemical purity and chemical purity of crude products were both in 75—80%.展开更多
Ficus infectoria has a wide distribution in Bangladesh, Nepal, Pakistan, Sri Lanka, Southwest China and Indochina and is an enrich source of phytochemicals thereby possess antibacterial, antifungal and hyperglycaemic ...Ficus infectoria has a wide distribution in Bangladesh, Nepal, Pakistan, Sri Lanka, Southwest China and Indochina and is an enrich source of phytochemicals thereby possess antibacterial, antifungal and hyperglycaemic activities. In this study, we attempted to examine the cognitive ability of methanolic and ethanolic extract of F. infectoria fruit extract in scopolamine induced memory impairment in mice by using preliminary phytochemical and antioxidant tests, and the cognitive ability of the methanolic and ethanolic fruit extract of F. infectoria. Fruit extract was analyzed in scopolamine amnesia mice using passive avoidance approach. Piracetam was used as a reference drug (200 mg/Kg). Further confirmation was provided by means of mice brain homogenate biochemical tests. Maximum phytochemical, antioxidant activity and nootropic ability were observed in the ethanolic fruit extract of F. infectoria. Plant extract was used at three doses i.e. 75 mg/Kg, 150 mg/Kg and 300 mg/Kg and exhibited nootropic abilities in all tests used. Enhanced SDL value i.e. (291.2 ± 0.33+++###) was observed by the administration of plant extract at all dose range in comparison to reference drug i.e. piracetam (252.8 ± 1.60###) used in the study. The plant extract utilization has showed increase in total protein (25.08 ± 0.26+++### mg/g of tissue) and reduced glutathione content (33.0 ± 0.46+++### nmoles/mg of protein) and vice versa while low malondialehyde (MDA) (9.18 ± 0.17+++### nmoles/mg of protein) and AChE activity (0.067 ± 0.009+++### M/min/g protein). However, opposite situation was observed in the scopolamine amnesia mice. Hence it was concluded the plant extract possessed neuroprotective activity in the scopolamine induced cognitive decline in mice thereby used as cost effective natural medicines in near future.展开更多
The influence of γ-aminobutyric type-A (GABA<sub>A</sub>) receptors agonist (muscimol hydrobromide, 0.1 μg/0.5 μl) injections into the right or left basolateral amygdala (BLA) on the behavior of high-an...The influence of γ-aminobutyric type-A (GABA<sub>A</sub>) receptors agonist (muscimol hydrobromide, 0.1 μg/0.5 μl) injections into the right or left basolateral amygdala (BLA) on the behavior of high-anxiety (HA) and low-anxiety (LA) rats subjected to the elevated plus-maze (EPM) test was investigated. Anxiolytic-like effects (increase of open-arm entries and open-arm time) was revealed only after administration of muscimol into the left (but not right) amygdala of HA animals. No effect was observed upon administration of muscimol to LA rats. These findings suggest an important role in anxiety regulation of the amygdalar GABA levels, and the assumed GABA hemispheric lateralization.展开更多
基金funded by grants from the National Natural Science Foundation of China(Grant No.:82274506)the China Postdoctoral Science Foundation(Grant No.:2022M721128)+6 种基金the Science and Technology Innovation Program of Hunan,China(Grant No.:2021RC4035)the Natural Science Foundation of Hunan,China(Grant No.:2023JJ40477)the Open-competing Disciple Construction Project of Hunan University of Chinese Medicine(HNUCM),China(Grant No.:22JBZ003)was financially supported by the Furong Distinguished Scholar Program of Hunan,China(Program No.:XJT[2020]58)the 121 Training Project for Innovative Talents of Hunan,China(Project No.:XRSH[2019]192)the Chinese Academy of Engineering Academician Liang Liu's Workstation Project,China(Project No.:KH[2023]3-23YS001)the World First-class Discipline Incubation Project of HNUCM,China(Project No.:XJF[2022]57)。
文摘Rheumatoid arthritis(RA)is a prevalent autoimmune disease characterized by chronic inflammation and excessive proliferation of the synovium.Currently,treatment options focus on either reducing inflammation or inhibiting synovial hyperplasia.However,these modalities are unsatisfactory in achieving the desired therapeutic outcomes.Halofuginone hydrobromide(HF),an herbal active ingredient,has demonstrated pharmacological effects of both anti-inflammation and inhibition of synovial hyperplasia proliferation.However,HF's medical efficacy is limited due to its poor water solubility,short half-life(t_(1/2)),and non-target toxicity.In the current study,by using the advantages of nanotechnology,we presented a novel dual-targeted nanocomplex,termed HA-M@P@HF NPs,which consisted of a hyaluronic acid(HA)-modified hybrid membrane(M)-camouflaged poly lactic-co-glycolic acid(PLGA)nanosystem for HF delivery.These nanocomplexes not only overcame the limitations of HF but also achieved simultaneous targeting of inflammatory macrophages and human fibroblast-like synoviocytes-RA(HFLS-RA).In vivo experiments demonstrated that these nanocomplexes effectively suppressed immune-mediated inflammation and synovial hyperplasia,safeguarding against bone destruction in rats with adjuvant-induced arthritis(AIA).Remarkable anti-arthritic effects of these nanocomplexes were accomplished through promoting repolarization of M1-to-M2 macrophages and apoptosis of HFLS-RA,thereby offering a promising therapeutic strategy for RA.
基金supported by the Talent Fund of Beijing Jiaotong University (No.2019RC058)the National Natural Science Foundation of China (Nos.62205013,62075009,62275013,and 12274020)。
文摘The development of tin-based devices with low toxicity is critical for the commercial viability of perovskite solar cells.However because tin halide is a stronger Lewis acid,its crystallization rate is extremely fast,resulting in the formation of numerous defects that affect the device performance of tin-based perovskite solar cells.Herein,propylamine hydrobromide(PABr)was added to the perovskite precursor solution as an additive to passivate defects and fabricate more uniform and dense perovskite films.Because propylamine cations are too large to enter the perovskite lattices,they only exist at the grain boundary to passivate surface defects and promote crystal growth in a preferred orientation.The PABr additive raises the average short-circuit current density from 19.45 to 25.47 mA·cm^(-2)by reducing carrier recombination induced by defects.Furthermore,the device’s long-term illumination stability is improved after optimization,and the hysteresis effect is negligible.The addition of PABr results in a power conversion efficiency of 9.35%.
文摘An isocratic stability-indicating reversed phase high performance liquid chromatographic method (RP-HPLC) was developed for determination of process related impurities and assay of darifenacin hydrobromide (DRF) in bulk drugs. DRF was subjected to various stress conditions such as hydrolysis (acid, base, and neutral), oxidation, photolysis and thermal degradation as per International Conference on Harmonization (ICH Q1A(R2) and Q1B) prescribed conditions to investigate the stability-indicating ability of the method. Significant degradation was observed during acidic hydrolysis and oxidative stress conditions. The chromatographic separation was accomplished on a Prodigy C8 column (250 × 4.6 mm, 5 μm) with mobile phase consisting of 0.05 M ammonium acetate (pH adjusted to 7.2 by using ammonia solution) and methanol (36% acetonitrile) in 35:65 v/v ratio in an isocratic elution mode at a flow rate of 1.0 mL/min at 25°C. Detection of analytes was carried out using photo diode array detector at a wavelength of 215 nm. The developed LC method was validated with respect to accuracy, linearity, precision, limits of detection and quantitation and robustness as per ICH guidelines.
文摘Aim To evaluate the time-effect and dose-effect of prasugrel hydrobromide acetic acid compound （PHAAC） inhibiting platelet aggregation. Methods For the time-effect study, 190 Sprague-Dawley （SD） rats were devided into 19 groups （n- 10）： the vehicle control group, the PHAAC groups （0.5, 1, 2, 4, 6, 24, 48, 72, 96 h） and the prasugrel hydrochloride groups （0.5, 1, 2, 4, 6, 24, 48, 72, 96 h）. Rats were singly intra- gastic administration of the vehicle, the PHAAC （5 mg·kg^-1） or the prasugrel hydrochloride （5 mg · kg^-1 ）, re- spectively. Blood samples were taken at each time point for the determination of platelet aggregation rate （PAR）. For the dose-effect study, 110 SD rats were devided into 11 groups （n= 10）： the vehicle control group, the PHAAC groups （10, 5, 2.5, 1, 0.5 mg · kg^-1, dosage of prasugrel） and the prasugrel hydrochloride groups （ 10, 5, 2.5, 1, 0.5 mg · kg^-1, dosage of prasugrel） . Blood samples were taken at 4 h after drug administration for the determination of PAR. Results Compared with the vehicle group, PHAAC has significant anti-platelet ag- gregative effects （P 〈 0.05） at the time of 0.5, 1, 2, 4, 6, 24, 48 h, and the effect at the time of 4 h was the strongest. There were no obvious differences between the effect of PHAAC （5 mg · kg^-1） and prasugrel hydrochlo- ride （5 mg · kg^-1） at each time point. Compared with the vehicle group, intragastic administration of PHAAC at the doses of 10, 5, 2.5, 1, 0.5 mg · kg^-1 could obviously inhibite the platelet aggregation, and showed a dose- dependent manner. There were no significant differences between the effect of PHAAC and prasugrel hydrochloride at the same dose. Conclusion PHAAC can inhibit platelet aggregation in a dose-dependent manner, and the effect at 4 h after drug administration is the strongest. The action strength and duration of PHAAC are similar with that of the prasugrel hydrochloride.
基金supported by the National Natural Science Foundation of China (Grant Nos. 20673050 and 20973089)
文摘This paper reports that 1-dodecylamine hydrobromide （1 C12H25NH3.Br）（s） has been synthesized using the liquid phase reaction method. The lattice potential energy of the compound 1-C12H25NH3.Br and the ionic vol- ume and radius of the 1-C12H25NH3＋ cation are obtained from the crystallographic data and other auxiliary ther- modynamic data. The constant-volume energy of combustion of 1 C12H25NH3.Br（s） is measured to be AcUo（1 C12H25NH3.Br, s） = （7369.03-4-3.28） kJ.mo1-1 by means of an RBC-II precision rotating-bomb combustion calorime- ter at T=（298.15~0.001） K. The standard molar enthalpy of combustion of the compound is derived to be △cHo（1- C12H25NH3.Br, s）=- （7384.52±3.28） kJ.mo1-1 from the constant-volume energy of combustion. The standard molar enthalpy of formation of the compound is calculated to be △fHo（1-C12H25NH3.Br, s）=-（1317.86~3.67） kJ.mo1-1 from the standard molar enthalpy of combustion of the title compound and other auxiliary thermodynamic quantities through a thermochemical cycle.
基金funding from the National Natural Science Foundation of China(12272246)the Key Research and Development Projects of Sichuan Province(2023YFS0075).
文摘Background:Anisodine hydrobromide(AT3),an anti-cholinergic agent,could be delivered to the brain across the blood-brain barrier and has been used clinically for the treatment of cerebral ischemia/reperfusion injury.Endothelial dysfunction can be caused by hypoxia/reoxygenation(H/R)via oxidative stress and metabolic alterations.The present study investigated whether AT3 regulates the production of nitric oxide(NO)and reactive oxygen species(ROS),and the HIF-1αpathway via regulation of muscarinic acetylcholine receptors(mAChRs)in brain microvascular endothelial cells after H/R exposure.Methods:Under H/R conditions,hCMEC/D3 cerebral microvascular endothelial cells were treated with AT3.Specific inhibitors of M2-and M4-mAChRs were used to explore the mechanism by which AT3 influences oxidative stress in endothelial cells.Then,mAChRs expression was detected by western blotting and NO production was detected by Greiss reaction.The intracellular ROS level was measured using DCFH-DA probes.The expression of hypoxia-inducible transcription factor 1α(HIF-1α)was also detected.Results:While H/R induced the expression of M2-and M4-mAChRs,AT3 suppressed the H/R-upregulated M2-and M4-mAChRs.H/R also induced the production of NO,ROS,and apoptosis.AT3 and M4-mAChR inhibitors inhibited the H/R-induced production of NO and ROS and apoptosis.HIF-1αwas induced by H/R,but was suppressed by AT3.Conclusion:Thus,the in vitro evidence shows that AT3 protects against H/R injury in cerebral microvascular endothelial cells via inhibition of HIF-1α,NO and ROS,predominantly through the downregulation of M4-mAChR.The findings offer novel understandings regarding AT3-mediated attenuation of endothelial cell apoptosis and cerebral ischemia/reperfusion injury.
基金supported by the Natural Science Foundation of Zhejiang Province (J200801)
文摘Two polymorphic forms （forms I and IV） of antidepressant bupropion hydrobro- mides were prepared and characterized by powder X-ray single-crystal diffractometer. Lots of commercial substances may consist of form I. Form I crystallizes in the triclinic system, space group P1^- with Z= 2, a = 7.6943（8）, b = 7.9347（9）, c = 13.8558（15） A, a = 85.971（3）, β = 85.619（2）, γ = 65.974（3）°, V = 769.66（14） A^3, Dc= 1.384 g/cm^3, formula C13H19C1NOBr, F（000） = 328, p = 2.83 mm^-1, the final R = 0.0579 and wR = 0.1282 for 1756 observed reflections with I 〉 2σ（I）. Another polymorphic form, IV, belongs to the orthorhombic system, space group Pbca with a = 8.6365（3）, b = 12.4167（4）, c = 27.7299（9） A, Z = 8, V= 2973.67（17） A^3, Dc= 1.432 g/cm^3, formula C13H19CINOBr, F（000） = 1312,μ = 2.93 mm^-1, the final R = 0.044 and wR = 0.1093 for 2018 observed reflections with I 〉 2σ（I）. In the crystal structure of the two polymorphic forms, expected proton transfer from HBr to amino group of bupropion molecule occurs and intramolecular and intermolecular hydrogen bonds N-H…Br are formed. These interactions result in hydrogen-bond dimers in these two forms. The bupropion molecule adopts different conformations in the two investigated solid state modifications.
文摘1 INTRODUCTIONThe drying of fine chemicals and pharmaceuticals is dominated by a number of special factorscompared to the drying of bulk chemicals.These include:very high value of product;lowthroughputs(typically,100 kg·h<sup>-1</sup>);materials that frequently possess toxic properties andare often sticky,pasty and difficult to handle when wet;the moisture to be evaporated ofteninvolves solvents;and multipurpose processing plants.
基金supported by Technology Development and Research Projects of Ministry of Science and Scientific Research Institutes(NCSTE-2006-JKZX-293)Science and Technology Major Projects in Gansu Province(2009GS02443)National Science and Technology Support Program of China (2008BADB4B05)
文摘[Objective] To make an objective evaluation about security of a new veterinary drug-arecoline hydrobromide according to the research results and papers in recent years and supply science basis for clinical usage. [ Method] The security of arecoline hydrobromide was evaluated based on acute toxicity tests; the ranges of safe medication, tolerability and toxicity as well as ＂Three-induced＇ effects （carcinogensis, mutagene- sis and teratogenesis） and reproductive toxicity were summarized according to the combinations of experimental results, papers and clinical effects. E Result] The results of acute toxicity tests in mice and rats showed that LD^0 （50% lethal dosages） of arecoline hydrobromide in mice was 691.83 mg/（kg.BW） and 95% incredible range of its LDso was 642.92 -744.47 mg/（ kg. BW）, and LDso of arecoline hydrobromide in rats was 2 054 mg/（kg.BW） and 95% incredible range of its LDso was 1 908 -2 210 mg/（kg.BW）. Its LDso value was hundreds times higher than the recommen- ded clinical dosage [ 1 -5 mg/（kg-BW） ], therefore it is safe to apply in clinic. The research results of ranges of safe medication, tolerability and toxicity showed that arecoline hydrobromide could entirely dispel the dog Diphyllobothrium, Spirometra mansoni, Dipylidium mesocestoides, Linea- tus and Cysticercus at dosages of 2 -3 mg/（ kg.BW）, and the same effects to Railletina tapeworm of chickens and Drepanidotaenia lanceolata of duck and goose at dosages of I -2 mg/（kg.BW）. The arecoline hydrobromide had muscarinic effects as side-effects and could cause vomiting, di- arrhea and other clinical symptoms to discharge the paralyzed worm from livestock body rapidly and completely. The arecoline hydrobromide had ＂Three-induced＂ effects and reproductive toxicity when it was used as antitapeworm drug with long-term, sustained and a large number of drug us- age, rather than used in clinical application with shorter time and lower dosage of administration. [ Conclusion] The arecoline hydrobromide is low- toxic substance and has a certain of toxicity such as ＂Three-induced＂ effects and reproductive toxicity at high-dosages application, and there are good effects on livestock and poultry tapeworm at the clinical recommended dosacles without ＂Three-induced＂ effects and reproductive toxicity.
基金supported by the Technology Development and Research Projects of Ministry of Science and Scientific Research Institutes(NCSTE-2006-JKZX-293)Science and Technology Major Projects in Gansu Province(2009GS02443)the National Science and Technology Support Program of China(2008BADB4B05)
文摘Taeniasis and cysticercosis in domestic animals belong to zoonosis and seriously threaten the public health security. Especially the cysticercosis and echinococcosis caused by the tapeworm eggs have great harms to bodies because they can attack many organs of body. According to the combination of experimental results and literature materials, the morphology and transmission mode of taenia and cysticercus, the prevalence status and monitoring of taeniasis and cysticercosis as well as the antitapeworm mechanism, comparative analysis to other drugs, expelling tapeworm tests in vitro, dose determining tests and usage notes of arecoline hydrobromide were expounded in detail. It provides a theoretical basis for prevention of taeniasis and cysticarcosis and more scientific usage of arecoline hydrobromide and thus relieves the harms of taeniasis and cysticercosis and ensuring the public health security.
基金This study was supported by the grants from the National Natural Science Foundation of China （No. 81170177 and No. 30770901 ）.Acknowledgment： We would like to thank Prof. Priori, University of Pavia in Italy for generously providing the hERG plasmid.
文摘Background The rapidly activating delayed rectifier potassium current （/Kr）, whose pore-forming alpha subunit is encoded by the human ether-a-go-go-related gene （hERG）, is a key contributor to the third phase of action potential repolarization. The aim of this study was to investigate the effect and mechanism of arecoline hydrobromide induced inhibition of hERG K^＋ current （/hERG）. Methods Transient transfection of hERG channel cDNA plasmid pcDNA3.1 into the cultured HEK293 cells was performed using Lipofectamine. A standard whole-cell patch-clamp technique was used to record the /hI=RG before and after the exposure to arecoline. Results Arecoline decreased the amplitude and the density of the /bERG in a concentration-dependent manner （IC5o=9.55 μmol/L）. At test potential of ＋60 mV, the magnitude of lhERG tail at test pulse of -40 mV was reduced from （151.7±6.2） pA/pF to （84.4±7.6） pA/pF （P 〈0.01, n=20） and the magnitude of IhERG tail at test pulse of -110 mV was reduced from （-187.5±9.8） pA/pF to （-97.6±12.6） pA/pF （P 〈0.01, n=20）. The blockade of arecoline in the open and inactivated state was significant in a state-dependent manner. The maximal blockade was achieved in the inactivated state. Studies of gating mechanism showed that the steady-state activation curve of IhERG was significantly negatively shifted by arecoline. Time constants of activation were shortened. Steady-state inactivation curve and time constants of fast inactivation were not significantly affected by arecoline. Furthermore, the inhibition of IhERG by arecoline was characterized markedly by a frequency-dependent manner from 0.03 to 1.00 Hz pulse. Conclusion Arecoline could potently block IhERG in both frequency and state-dependent manner.
基金supported by the National Natural Science Foundation of China,No.81473740,81673627,81673717(to QW)Guangzhou Science Technology and Innovation Commission Technology Research Projects,China,No.2018050100(to QW)+3 种基金the Foundation for Characteristic Innovation of Educational Commission of Guangdong Province,China,Grant No.2016KTSCX011(to SHF)the Open Tending Project for Construction of High-Level University,Guangzhou University of Chinese Medicine,China,No.34 and 118,2017(to SHF)the Technology Platform of Clinical Trials on New Traditional Medicine,China,No.2012ZX09303009-003(to WXL)the Technology Platform of Clinical Evaluation on New Traditional Medicine,China,No.2008ZX09312-021(to WXL)
文摘Kai Xin San(KXS, containing ginseng, hoelen, polygala, and acorus), a traditional Chinese herbal compound, has been found to regulate cognitive dysfunction; however, its mechanism of action is still unclear. In this study, 72 specific-pathogen-free male Kunming mice aged 8 weeks were randomly divided into a vehicle control group, scopolamine group, low-dose KXS group, moderate-dose KXS group, high-dose KXS group, and positive control group. Except for the vehicle control group and scopolamine groups(which received physiological saline), the doses of KXS(0.7, 1.4 and 2.8 g/kg per day) and donepezil(3 mg/kg per day) were gastrointestinally administered once daily for 2 weeks. On day 8 after intragastric treatment, the behavioral tests were carried out. Scopolamine group and intervention groups received scopolamine 3 mg/kg per day through intraperitoneal injection. The effects of KXS on spatial learning and memory, pathological changes of brain tissue, expression of apoptosis factors, oxidative stress injury factors, synapse-associated protein, and cholinergic neurotransmitter were measured. The results confirmed the following.(1) KXS shortened the escape latency and increased residence time in the target quadrant and the number of platform crossings in the Morris water maze.(2) KXS increased the percentage of alternations between the labyrinth arms in the mice of KXS groups in the Y-maze.(3) Nissl and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling staining revealed that KXS promoted the production of Nissl bodies and inhibited the formation of apoptotic bodies.(4) Western blot assay showed that KXS up-regulated the expression of anti-apoptotic protein Bcl-2 and inhibited the expression of pro-apoptotic protein Bax. KXS up-regulated the expression of postsynaptic density 95, synaptophysin, and brain-derived neurotrophic factor in the cerebral cortex and hippocampus.(5) KXS increased the level and activity of choline acetyltransferase, acetylcholine, superoxide dismutase, and glutathione peroxidase, and reduced the level and activity of acetyl cholinesterase, reactive oxygen species, and malondialdehyde through acting on the cholinergic system and reducing oxidative stress damage. These results indicate that KXS plays a neuroprotective role and improves cognitive function through reducing apoptosis and oxidative stress, and regulating synapse-associated protein and cholinergic neurotransmitters.
文摘Objective This study aimed to examine the effects of microcirculatory dysfunction and 654-1intervention after cardiopulmonary resuscitation on myocardial injury.Methods Landrace pigs were divided into a sham operation group(S group,n=6),ventricular fibrillation control group(VF-C group,n=8)and 654-1 intervention group(VF-I group,n=8).Hemodynamics was recorded at baseline,at recovery of spontaneous circulation(ROSC),and 1 h,2 h,4h and 6 h thereafter.Sidestream dark field(SDF)technology was used to evaluate and monitor the microcirculation flow index,total vessel density,perfusion vessel ratio,De-Backer score,and perfusion vessel density in animal viscera at various time points.Results After administration of 654-1 at 1.5 h post-ROSC,the hemodynamics in the VF-I group,as compared with the VF-C group,was significantly improved.The visceral microcirculation detected by SDF was also significantly improved in the VF-I group.As observed through electron microscopy,significantly less myocardial tissue injury was present in the VF-I group than the VF-C group.Conclusion Administration of 654-1 inhibited excessive inflammatory by improving the state of visceral microcirculation.
文摘Two simple, rapid, accurate, precise, reliable and economical spectrophotometric methods have been proposed for the determination of galanthamine hydrobromide (GH) in bulk and pharmaceutical formulation. First method is zero order UV spectrophotometry and second is 1st derivative zero crossing spectrophotometry. The developed methods have shown best results in terms of linearity, accuracy, precision, LOD and LOQ for bulk drugs and marketed formulations. Absorbance was measured at 287 nm for zero order and 277.4 nm for first derivative. It obeyed Lambert-Beer’s law in the range of 30-80 μg mL-1. Both methods have good linearity (r2 = 0.9997) and accuracy found to be 100.5% and 101.2% for both methods respectively.
基金The Project Supported by National Natural Science Foundation of China
文摘The ~3H-labelled belladonna alkaloids obtained by catalysed exchange method with microwave excitation was investigated. The specific activities of the labelled products Were 16—32 TBq/mol. More than 90% labelled positions of these ~3H-tracers were on phenyl rings. The radiochemical purity and chemical purity of crude products were both in 75—80%.
文摘Ficus infectoria has a wide distribution in Bangladesh, Nepal, Pakistan, Sri Lanka, Southwest China and Indochina and is an enrich source of phytochemicals thereby possess antibacterial, antifungal and hyperglycaemic activities. In this study, we attempted to examine the cognitive ability of methanolic and ethanolic extract of F. infectoria fruit extract in scopolamine induced memory impairment in mice by using preliminary phytochemical and antioxidant tests, and the cognitive ability of the methanolic and ethanolic fruit extract of F. infectoria. Fruit extract was analyzed in scopolamine amnesia mice using passive avoidance approach. Piracetam was used as a reference drug (200 mg/Kg). Further confirmation was provided by means of mice brain homogenate biochemical tests. Maximum phytochemical, antioxidant activity and nootropic ability were observed in the ethanolic fruit extract of F. infectoria. Plant extract was used at three doses i.e. 75 mg/Kg, 150 mg/Kg and 300 mg/Kg and exhibited nootropic abilities in all tests used. Enhanced SDL value i.e. (291.2 ± 0.33+++###) was observed by the administration of plant extract at all dose range in comparison to reference drug i.e. piracetam (252.8 ± 1.60###) used in the study. The plant extract utilization has showed increase in total protein (25.08 ± 0.26+++### mg/g of tissue) and reduced glutathione content (33.0 ± 0.46+++### nmoles/mg of protein) and vice versa while low malondialehyde (MDA) (9.18 ± 0.17+++### nmoles/mg of protein) and AChE activity (0.067 ± 0.009+++### M/min/g protein). However, opposite situation was observed in the scopolamine amnesia mice. Hence it was concluded the plant extract possessed neuroprotective activity in the scopolamine induced cognitive decline in mice thereby used as cost effective natural medicines in near future.
文摘The influence of γ-aminobutyric type-A (GABA<sub>A</sub>) receptors agonist (muscimol hydrobromide, 0.1 μg/0.5 μl) injections into the right or left basolateral amygdala (BLA) on the behavior of high-anxiety (HA) and low-anxiety (LA) rats subjected to the elevated plus-maze (EPM) test was investigated. Anxiolytic-like effects (increase of open-arm entries and open-arm time) was revealed only after administration of muscimol into the left (but not right) amygdala of HA animals. No effect was observed upon administration of muscimol to LA rats. These findings suggest an important role in anxiety regulation of the amygdalar GABA levels, and the assumed GABA hemispheric lateralization.
