JOURNAL OF CHEMICAL AND ENGINEERING DATA
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2018
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IF 2.196
Yanxiao Zhao,Haiyan Yang,Zeren Shang,Tingting Gong,Xu Zhang,Songgu Wu
Glibenclamide (GCM) is an oral antihyperglycemic drug and widely used to treat type-II diabetes. The quality of the GCM product impacts the efficacy of the medicine. However, the quality of the product is determined by the crystallization process, in which the solubility property plays a significant role. In this study, GCM solubility in 11 monosolvents (methanol, ethanol, 1-propanol, 2-propanol, 1-butanol, 2-butanol, acetone, acetonitrile, methyl isobutyl ketone, methyl acetate and ethyl acetate) and (acetone + acetonitrile) binary solvents, has been determined through a gravimetric method from 283.15 K to 323.15 K. It elucidates that GCM has the highest solubility in acetone among the 11 monsolvents. Meanwhile, the solubility of GCM in (acetone + acetonitrile) binary solvents increases when the mole fraction of acetone rises. Then, we correlated the solubility data in monosolvents using the modified Apelblat model and nonrandom two-liquid (NRTL) model. Besides, the modified Apelblat model, the CNIBS/R-K model, Jouyban–Acree model, and NRTL model were adopted to fit the data in (acetone + acetonitrile) mixture solvents. Furthermore, thermodynamic properties were calculated on the basis of the NRTL model.
研究领域:
药物化学
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物理化学
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DOI
高影响因子
NEW JOURNAL OF CHEMISTRY
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2017
·Vol. 41
·期 21
·12535-12540
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IF 3.269
Zong-yuan Wu,Xiao-yan Li,Min Liu,Fang Wang,Li Liu,Xue-cai Tan,Fu-hou Lei
Core–shell magnetic polymers were prepared using acrylic acid (AA) as the functional monomer, ethyleneglycol dimethacrylate (EGDMA) as the cross-linking agent, and Fe3O4@GO@SiO2–OH nano particles as the magnetic core. The core–shell materials were investigated by scanning electron microscopy (SEM), fourier transform infrared spectroscopy (FT-IR), vibrating sample strong magnetic analysis (VSM), thermogravimetric analysis (TGA) and re-binding experiments. The results showed that the core–shell materials exhibit a fast adsorption equilibrium and good adsorption capacity. The core–shell materials could be applied for the enrichment and determination of glibenclamide in hypoglycemic health products, with the recoveries of spiked samples ranging from 80.02% to 87.28%, and the RSD being ≤1.97%. The durability test shows that the core–shell materials could be reused more than 3 times through re-binding experiments. On using an external magnetic field, the absorbed analytes were efficiently separated, so it is a promising method to conveniently detect the illegal addition of glibenclamide to hypoglycemic health products.
研究领域:
分析化学
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材料科学
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药物分析
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高影响因子
NEUROPHARMACOLOGY
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2017
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IF 5.012
Zhenzhou Lin,Hua Huang,Yong Gu,Kaibin Huang,Yafang Hu,Zhong Ji,Yongming Wu,Shengnan Wang,Tingting Yang,Suyue Pan
Glibenclamide (GBC), a sulfonylurea receptor 1 blocker, emerges recently as a promising neuron protectant in various neurological disorders . This study aimed to determine whether GBC improves survival and neurological outcome of status epilepticus (SE). Male Sprague-Dawley rats successfully undergoing SE for 2.5 h (n = 134) were randomly assigned to GBC or vehicle group. Rats in the GBC group received a loading dose of 10 μg/kg of GBC, followed by 1.2 μg/6 h for 3 days, while same dose of vehicle was used as control. The 28-day survival rate in the GBC group (11/23) was significantly higher than that in the vehicle group (8/36). In addition, the frequency and duration of spontaneous recurrent seizures in SE rats were profoundly reduced by GBC but not by vehicle treatment. Moreover, cognitive impairment was observed in the SE rats at day 28, which was reversed by GBC treatment. Meanwhile, cerebral edema , as well as neuronal loss, was decreased in several brain areas in the GBC group. Additionally, on the molecular basis, the subunits of sulfonylurea receptor 1/transient receptor potential M4 (SUR1-TRPM4) heterodimer were both strongly upregulated after SE but partly suppressed by GBC treatment. Furthermore, gene knockdown of Trpm4 in SE rats reduced BBB disruption and neuronal loss, similar to the inhibitory effects with GBC treatment. Taken together, GBC treatment markedly improved survival and neurologic outcomes after SE. The salutary effects of GBC were correlated to the alleviation of cerebral edema and reduction in neurological injury via down-regulation of SUR1-TRPM4 channel.
研究领域:
神经病学
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药理学
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神经科学
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DOI
PubMed
高影响因子
JCI Insight
·
2021
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IF 8.315
Kewei Liu,Juan Zhu,Yuan Chang,Zhenzhou Lin,Zhu Shi,Xing Li,Xing Chen,Chuman Lin,Suyue Pan,Kaibin Huang
Status epilepticus (SE) is a neurological emergency usually accompanied by acute cerebral edema and long-term cognitive impairment, and is characterized by neurodegeneration and aberrant hyperphosphorylated tau protein (p-tau) aggregation. The glia-lymphatic (glymphatic) system plays a central role in facilitating the clearance of metabolic waste from the brain, but its relationship with cerebral edema and cognitive dysfunction after SE is unclear. We hypothesized that cerebral edema after SE might impair glymphatic system function through compression, thus leading to impaired removal of metabolic waste, and ultimately affecting long-term cognitive function. Our results showed that glymphatic system function was temporarily impaired, as evidenced by 2-photon imaging, MRI enhancement, imaging of brain sections, and astrocytic water channel aquaporin 4 (AQP4) protein polarization. The severity of cerebral edema on MRI correlated well with glymphatic system dysfunction within 8 days following SE. Moreover, when cerebral edema was alleviated by glibenclamide treatment or genetic deletion of Trpm4 , post-SE glymphatic system function recovered earlier, along with fewer p-tau–deposited neurons and neuronal degeneration and better cognitive function. These findings suggest that SE-induced cerebral edema may cause glymphatic system dysfunction and render the post-SE brain vulnerable to p-tau aggregation and neurocognitive impairment.
研究领域:
神经科学
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神经病学
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药理学
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DOI
PubMed
高影响因子
PHARMAZIE
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2021
·Vol. 76
·期 10
·499-502
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IF 1.267
Tao Lijun,Chen Lina,Pei Yanmin,Ma Ping,Xu Qingbin,Wang Jialing,Yu Yang,Cheng Jiang,Zhou Ru
The aim of this study was to investigate the vasodilatory effects of betaine, an alkaloid isolated from Lycium barbarum, on isolated pulmonary artery rings in rats and its possible mechanisms. Pulmonary vessels of normal Sprague–Dawley rats were isolated and pre-contracted
using norepinephrine. Then, betaine was cumulatively added in differing concentrations (0.02-0.14 mg/mL), and the tension curve was observed and recorded. Changes in the tension of the pulmonary artery rings with an intact endothelium and a dissected endothelium were recorded. The interactions
among betaine and NG-nitro-L-arginine methyl ester, indomethacin, 4-aminopyridine, barium chloride, and glibenclamide were evaluated. The experimental results show that betaine can relax the pulmonary artery rings pre-contracted by norepinephrine. Furthermore, pre-incubation with NG-nitro-L-arginine
methyl ester and indomethacin did not inhibit betaine vasodilation, demonstrating that vasodilation by betaine is endothelium-dependent. Additionally, pretreatment of pulmonary artery rings with 4-aminopyridine and glibenclamide had no effect on betaine. However, pretreatment of pulmonary
artery rings with barium chloride attenuated the effects of betaine. In conclusion, the vasodilatory effects of betaine on pulmonary artery rings is associated with inward rectifier potassium channels.
研究领域:
药理学
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心血管研究
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DOI
PubMed
高影响因子
RSC Advances
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2017
·Vol. 7
·期 55
·34448-34460
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IF 3.108
Bing Wang,Na Li,Teng Liu,Jie Sun,Xiaojing Wang
Various substituted neoflavonoid derivatives were synthesized using sulfated montmorillonite K-10 as a catalyst. This method is environmental friendly, sustainable and economical, convenient in isolation and purification processes, with little byproducts, using earth-abundant catalysts and has relatively high yield. Those neoflavonoid derivatives were screened for antioxidant, a-glucosidase inhibitory, aldose reductase 2 (ALR2) inhibitory and advanced glycation end-product formation inhibitory effects. Most compounds exhibited significant antioxidant and advanced glycation end-product (AGE) formation inhibitory activities. It was interesting to note that out of thirty compounds, 8k and 8l were found to have greater ALR2 inhibitory activity than the standard drug quercetin. The pharmacological studies suggested neoflavonoid with adjacent 7,8-dihydroxy groups were more effective in inhibiting ALR2. Antidiabetic activity studies had shown that compounds 8l and 8m were equipotent to the standard drug glibenclamide in vivo. In summary, the target compound 8l provided a potential drug design concept for the development of therapeutic or prophylactic agents of diabetes and diabetes complications.
研究领域:
药理学
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有机化学
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药物化学
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DOI
高影响因子
Acta Pharmaceutica Sinica B
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2026
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IF 14.6
Xiuneng Zhang,Xiaolin Yu,Longze Sha,Yunfeng Li,Qi Qiao,Xiaoming Yu,Qi Xu
Previous studies have shown that heat shock protein 90 (Hsp90) inhibitors can reduce seizures in temporal lobe epilepsy (TLE) by upregulating excitatory amino acid transporter 2 (EAAT2, also known as GLT-1). While the Hsp90 inhibitor 17-AAG is effective, its long-term use raises toxicity concerns. This study aimed to identify a safer Hsp90 inhibitor by screening benzenoid ansamycin derivatives for higher binding affinity and lower toxicity. Among nine natural benzenoid ansamycins and their derivatives screened, reblastatin emerged as the top candidate, exhibiting the highest binding affinity to Hsp90. Compared to geldanamycin and 17-AAG, reblastatin demonstrated significantly lower cytotoxicity in HEK293 and HepG2 cells. Like 17-AAG, reblastatin upregulated EAAT2 levels by disrupting the association among Hsp90, EAAT2, and the 20S proteasome. In a kainic acid-induced TLE mouse model, reblastatin reduced seizure frequency by 50%, with long-term treatment showing toxicity comparable to vehicle controls. Additionally, behavioral tests revealed neuroprotective effects of reblastatin in mouse models of Alzheimer’s disease and Parkinson’s disease. These findings collectively suggest that reblastatin is a promising Hsp90 inhibitor for treating TLE and excitotoxic conditions associated with neurodegenerative diseases.
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高影响因子
DRUG DELIVERY
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2025
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IF 8.1
Jiming Ke,Shenao Li,Miaomiao Zi,Jing Zhang,Shan Huang,Wenhui Luo,Hailun Han,Jiwen Zhang,Can Peng
Acute lung injury (ALI) is a lung disease characterized by pulmonary edema caused by an excessive inflammatory response within the lungs and disruption of the alveolar capillary barrier, with a high morbidity and mortality rate in critically ill patients. Dry powder inhalers (DPI) are an effective way of administering medication to improve efficacy, and inhalation administration not only improves efficacy but also increases the bioavailability of the drug. Synephrine, a natural ingredient derived from the fruit of the citrus plant in the Brassicaceae family, has anti-inflammatory and antioxidant properties. In the present study, we prepared a synephrine dry powder inhaler (SYN-DPI) by anti-solvent precipitation method and evaluated it in vivo and in vitro. The in vitro results show that SYN-DPI has low hygroscopicity and good aerodynamic properties. The in vitro and in vivo efficacy results showed that SYN-DPI not only had low toxicity but also possessed good anti-inflammatory and antioxidant capacity, which could significantly reduce inflammation, oxidative stress, and lung injury. Pharmacokinetic results showed that inhalation administration significantly increased SYN bioavailability. In conclusion, this study provides inhalation administration of synephrine as an inhalable formulation that can be used to improve ALI.
研究领域:
药理学
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呼吸病学
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药物递送系统
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DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
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2025
·
IF 6.2
Xiaoting Yu,Tao Zhou,Kangliang Pan,Michelle Huiying Fan,Xinfu Yan,Xin-An Huang,Huiling Zhang,Xing Shen,Haihuan Xie,Yong-Gui Gao,Hongtao Lei
The limited understanding of the broad-specific antibody recognition mechanism significantly hinders the development of immunoassays for simultaneously detecting illegal adulterants. Herein, a recombinant antisulfonylureas (SUs) single-chain variable fragment (scFv), which retained the properties of its parental monoclonal antibody, was successfully generated. X-ray crystallography, molecular docking, functional assays, and mutation validation were used to investigate the structure–function relationships underlying antibody-SUs binding. Our study revealed three key mechanisms for broad specificity: (1) the conformational adaptability of the scFv, which enabled various SUs to access the binding pocket; (2) the role of the Trp98 residue in CDR-L3 in modulating binding affinities among multiple SUs; and (3) the design of haptens with common structures and more rigid R substituents, which emerged as a promising strategy for generating broad-specific antibodies. This study provides a comprehensive analysis of the broad-specific recognition mechanism, offering valuable insights for rational hapten design and targeted antibody evolution to advance multitarget immunoassays.
研究领域:
免疫学
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结构生物学
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食品科学
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DOI
PubMed
高影响因子
BIOMEDICINE & PHARMACOTHERAPY
·
2025
·
IF 7.5
Yang Yu,Yurong Wang,Ziqi Yang,Zhanqiang Li,Dianxiang Lu,Xingmei Nan
Pulmonary hypertension is divided into five groups, and chronic exposure to hypoxia causes pulmonary hypertension in the third group -- high altitude pulmonary hypertension, which is commonly seen in patients with chronic obstructive pulmonary disease, sleep-disordered breathing, and interstitial lung disease. Its clinicopathological features include right heart overload and right ventricular hypertrophy, with severe patients potentially experiencing right heart failure or even death. The pathogenesis of high altitude pulmonary hypertension is complex; it includes oxidative stress, mitochondrial dysfunction, apoptosis, and pyroptosis. Pharmacological therapy may alleviate the condition if immediate descent to lower altitudes or supplemental oxygen is not possible. Herein, we preliminarily investigated the effect of methyleugenol on high altitude pulmonary hypertension through in vitro and in vivo experiments. Methyleugenol alleviated pulmonary arteriole constriction by acting on potassium ion channels, and inhibited the proliferation of pulmonary artery smooth muscle cells(PASMCs) by decreasing and reactive oxygen species levels, as well as inhibiting the expression of HIF-1α. The cardiac systolic function improved and mitochondrial structure of pulmonary artery smooth muscle cells in rats with high altitude pulmonary hypertension was significantly improved after methyleugenol gavage intervention, and malondialdehyde levels in serum of rats were decreased while those of superoxide dismutase and glutathione increased, suggesting that the reduction of oxidative stress may be one of the mechanisms to improve mitochondrial function. Western blot experiments showed that methyleugenol regulated the oxidative stress level in rats by activating Nrf2/HO-1 signaling pathway, activate p27Kip1, inhibit CDK4/CCND1/ p-ERK1/2 and inhibited HIF-1α/RASSF1/Ras axis to inhibit cell proliferation, thereby improving the occurrence and development of high altitude pulmonary hypertension in rats. The results of this study reveal that methyl eugenol has the potential to alleviate pulmonary vasoconstriction and remodeling in rat models of high-altitude pulmonary hypertension, providing a scientific basis for the application of this compound in improving pulmonary vascular remodeling.
研究领域:
药理学
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心血管病学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2024
·
IF 4.8
Qiao-Lai Wang,Pei-Xi Zhang,Rui Shen,Meng Xu,Liang Han,Xuan Shi,Zi-Rui Zhou,Jing-Yi Yang,Jie-Qing Liu
Ethnopharmacological relevance Arbutin is a naturally occurring glucoside extracted from plants, known for its antioxidant and tyrosinase inhibiting properties. It is widely used in cosmetic and pharmaceutical industries. With in-depth study of arbutin, its application in disease treatment is expanding, presenting promising development prospects. However, reports on the metabolic stability, plasma protein binding rate, and pharmacokinetic properties of arbutin are scarce. Aim of the study The aim of this study is to enrich the data of metabolic stability and pharmacokinetics of arbutin through the early pre-clinical evaluation, thereby providing some experimental basis for advancing arbutin into clinical research. Materials and methods We developed an efficient and rapid liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay for determining arbutin in plasma. We investigated the metabolic and pharmacokinetic properties of arbutin through in vitro metabolism assay, cytochrome enzymes P450 (CYP450) inhibition studies, plasma protein binding rate analysis, Caco-2 cell permeability tests, and rat pharmacokinetics to understand its in vivo performance. Results In vitro studies show that arbutin is stable, albeit with some species differences. It exhibits low plasma protein binding (35.35 ± 11.03% ∼ 40.25 ± 2.47%), low lipophilicity, low permeability, short half-life (0.42 ± 0.30 h) and high oral bioavailability (65 ± 11.6%). Arbutin is primarily found in the liver and kidneys and is eliminated in the urine. It does not significantly inhibit CYP450 up to 10 μM, suggesting a low potential for drug interactions. Futhermore, preliminary toxicological experiments indicate arbutin's safety, supporting its potential as a therapeutic agent. Conclusion This study provides a comprehensive analysis the drug metabolism and pharmacokinetics (DMPK) of arbutin, enriching our understanding of its metabolism stability and pharmacokinetics properties, It establishes a foundation for further structural optimization, pharmacological studies, and the clinical development of arbutin.
研究领域:
药理学
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分析化学
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临床前研究
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DOI
PubMed
高影响因子
Arabian Journal of Chemistry
·
2024
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IF 5.3
Chuanxi Tian,Jinyue Zhao,Qian Wang,Keke Luo,Shuang Zhao,Li Wan,Jiarui Li,Kaile Ma,Yanyan Zhou,Min Li
Background Huashi Baidu granule (HSBD), an approved herbal formula for treating COVID-19, demonstrates safety and efficacy. Despite its market approval, the detailed methodology and identification of its active components remain unexplored, leaving its bioactive constituents and action mechanisms unclear. Methods This study investigated the potential mechanisms of HSBD’s active ingredient in treating COVID-19. Our approach integrated various techniques, including the UHPLC-QqQ-MS/MS method, analysis of the GEO database, network pharmacology, surface plasmon resonance, molecular docking and molecular dynamics simulations, to formulate a comprehensive research strategy. Results The UHPLC-QqQ-MS/MS method employed for HSBD analysis proved stable, reliable, and reproducible. We identified 25 principal components in HSBD, with 7 compounds detected in plasma, namely Pogostone, P-Hydroxybenzoic acid, Paeoniflorin, Rhein, Emodin, Ephedrine hydrochloride, and Pseudoephedrine hydrochloride. Protein-Protein Interaction (PPI) network analysis identified MMP9 as a pivotal target. Surface plasmon resonance analysis revealed that Paeoniflorin and Rhein exert their antiviral effects by interacting with RBD and ACE2. In contrast, Emodin’s antiviral mechanism predominantly involves binding to MMP9. Molecular docking results indicated strong binding affinities of Rhein and Paeoniflorin to the hACE2 protein, and high binding affinities of Emodin to the MMP9 protein, all of which were corroborated by molecular dynamics simulations. Conclusion We investigated the methodology and identified the active components of HSBD, focusing on those absorbed into the plasma, to elucidate the effective material basis of HSBD in the treatment of COVID-19, our research offered insightful exploration into its mechanisms of action against COVID-19.
研究领域:
药理学
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医学
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生物化学
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分子生物学
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产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）