Antioxidants
·
2021
·Vol. 10
·期 9
·1333
·
IF 6.313
Mengyuan Fang,Tingfeng Zou,Xiaoxiao Yang,Zhen Zhang,Peichang Cao,Jihong Han,Yajun Duan,Ban-Feng Ruan,Qing-Shan Li
Sepsis remains one of the most common life-threatening illnesses that is characterized by a systemic inflammatory response syndrome (SIRS) and usually arises following severe trauma and various septic infections. It is still in urgent need of new effective therapeutic agents, and chances are great that some candidates can be identified that can attenuate oxidative stress and inflammatory responses. Pterostilbene, which exerts attractive anti-oxidative and anti-inflammatory activities, is a homologue of natural polyphenolic derivative of resveratrol. Starting from it, we have made several rounds of rational optimizations. Firstly, based on the strategy of pharmacophore combination, indanone moiety was introduced onto the pterostilbene skeleton to generate a novel series of pterostilbene derivatives (PIF_1–PIF_16) which could possess both anti-oxidative and anti-inflammatory activities for sepsis treatment. Then, all target compounds were subjected to their structure–activity relationships (SAR) screening of anti-inflammatory activity in mouse mononuclear macrophage RAW264.7 cell line, and their cytotoxicities were determined after. Finally, an optimal compound,PIF_9, was identified. It decreased the mRNA levels of lipopolysaccharide (LPS)-induced interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), inducible nitric oxide synthase (iNOS), and cyclooxygenase 2 (COX2). We also found that the anti-inflammatory effects might be contributed by its suppression on the nuclear factor-κB (NF-κB) and MAPKs signaling pathway. Moreover,PIF_9also demonstrated potent anti-oxidative activity in RAW264.7 macrophages and the sepsis mouse model. Not surprisingly, with the benefits mentioned above, it ameliorated LPS-induced sepsis in C57BL/6J mice and reduced multi-organ toxicity. Taken together,PIF_9was identified as a potential sepsis solution, targeting inflammation and oxidative stress through modulating MAPKs/NF-κB.Keywords:antioxidants;anti-inflammatory agents;indanone;pterostilbene;sepsis
研究领域:
药理学
·
传染病学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
MOLECULES
·
2020
·Vol. 25
·期 20
·4815
·
IF 3.267
Minmin Sun,Yaoting Ji,Zhen Li,Rourong Chen,Shuhui Zhou,Chang Liu,Minquan Du
Conventional treatments for chronic periodontitis are less effective in controlling inflammation and often relapse. Therefore, it is necessary to explore an immunomodulatory medication as an adjuvant. Ginsenoside Rb3 (Rb3), one of the most abundant active components of ginseng, has been found to possess anti-inflammatory and immunomodulatory properties. Here, we detected the anti-inflammatory effect of Rb3 onPorphyromonas gingivalisLPS-stimulated human periodontal ligament cells and experimental periodontitis rats for the first time. We found that the expression of pro-inflammatory mediators, including IL-1β, IL-6 and IL-8, upregulated by lipopolysaccharide (LPS) stimulation was remarkably downregulated by Rb3 treatment in a dose-dependent manner at both transcriptional and translational levels. Network pharmacological analysis of Rb3 showed that the mitogen-activated protein kinase (MAPK) signaling pathway had the highest richness and that p38, JNK, and ERK molecules were potential targets of Rb3 in humans. Western blot analysis revealed that Rb3 significantly suppressed the phosphorylation of p38 MAPK and p65 NF-κB, as well as decreased the expression of total AKT. In experimental periodontitis rat models, reductions in alveolar bone resorption and osteoclast generation were observed in the Rb3 treatment group. Thus, we can conclude that Rb3 amelioratedPorphyromonas gingivalisLPS-induced inflammation by inhibiting the MAPK/AKT/NF-κB signaling pathways and attenuated alveolar bone resorption in experimental periodontitis rats.Keywords:anti-inflammatory agents;chronic periodontitis;ginsenoside;lipopolysaccharides
研究领域:
药理学
·
牙科
·
免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MOLECULAR AND CELLULAR BIOCHEMISTRY
·
2015
·Vol. 411
·期 1
·161-171
·
IF 2.393
Peng Haibo,Wu Xia,Zhao Lifang,Feng Yifan
Abstract Through studying the changes of the total phospholipid components in mouse macrophages under the inflammatory status and the drug intervention status, we found the targets of non-steroidal anti-inflammatory drugs on phospholipids, thus providing the basis for the targets of in vitro anti-inflammatory effects of non-steroidal anti-inflammatory drugs. After RAW264.7 cells were pretreated with common non-steroidal anti-inflammatory drugs (aspirin and ibuprofen) and, respectively, stimulated with KLA for various periods (0.5, 4, 12, 16, and 24 h), the phospholipids were extracted. The dynamic changes of phospholipids in cells under various stimulations were analyzed with UPLC-Q-TOF–MS technique. Through the statistical analysis of Simca-P, we explored the potential targets of non-steroidal anti-inflammatory drugs on phospholipids. Through the dynamic analysis of phospholipids, we found two biomarkers (PC(17:1/18:1), PA(18:0/18:4)) which might be in vitro intervention inflammatory response targets of non-steroidal anti-inflammatory drugs. The analysis results show that in anti-inflammatory effects, non-steroidal anti-inflammatory drugs can inhibit COX, induce the cellular fatty acid desaturation and the changes of phospholipid components, stimulate free fatty acids, activate calcium ion channels of endoplasmic reticulum, and promote cell endocytosis, thus controlling inflammation and activating cells. Non-steroidal anti-inflammatory drugs can promote endocytosis, alter cell inflammatory response, and activate the process cells, thus realizing the anti-inflammatory effects. Graphical Abstract
研究领域:
药理学
·
生物化学
·
炎症研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Cleaner Production
·
2023
·
IF 11.1
Yakun Wang,Ziwei Song,Liwen Zhang,Deming Dong,Zhuojuan Li,Heyang Sun,Liting Wang,Zhiyong Guo
In surface waters at middle and high latitudes during winter, the coexistence of ice and water is a natural phenomenon. Nonsteroidal anti-inflammatory drugs (NSAIDs) as emerging contaminants have been found frequently in aquatic environments, including waters that are seasonally covered in ice. However, little is available for the environmental behaviors and fate of NSAIDs in ice, particularly in the system where ice and water coexist. In this study, the distribution and photodegradation of model NSAIDs naproxen (NPX), diclofenac (DCF), and acetaminophen (APAP) in an ice-water system were investigated. The findings demonstrated a 66.7%, 60.5%, and 66.7% increase in the ice-water distribution coefficient K iw of NPX, DCF, and APAP with initial concentrations of 10 ng L −1 relative to 500 ng L −1 . The K iw values were in decreased order of DCF, NPX, and APAP. The photodegradation rate constants of NPX, DCF, and APAP in ice increased by 27.0%, 35.6%, and 56.6% relative to those in water. With the increase in freezing time, the contribution ratios of distribution to the mass loss of NPX, DCF, and APAP increased by 19.9%, 21.1%, and 16.1%, respectively. The ratios of photodegradation to the mass loss of NPX, DCF, and APAP decreased by 5.0%, 5.7%, and 0.9%, respectively. An ice cover as the predominant factor could affect the distribution and photodegradation of drugs in the surface water. This study can close a knowledge gap regarding the transport and transformation of NSAIDs in the ice-water system and provide fresh insights into the behaviors and fate of emerging contaminants in seasonally ice-covered waters.
研究领域:
环境科学
·
药物化学
✓ 已验证
产品关联
DOI
高影响因子
SEPARATION AND PURIFICATION TECHNOLOGY
·
2020
·
IF 5.774
Chaoqun Tan,Kechun Sun,Xinxin Cui,Tianyu Sheng,Tianhu Xu,Haiying Gao
In this study, free active chlorine (HOCl/OCl - , FAC) was employed as an activator of ozone (O 3 ) to remove typical non-steroidal anti-inflammatory drugs of aspirin (ASA) and phenacetin (PNT). The combination of FAC and O 3 significantly improved the removal of pollutants. O 3 molecules, hydroxyl radicals ( OH) and reactive chlorine species (RCS) contributed to the removal of target contaminants in O 3 /FAC system. By fitting the pollutant removal pattern with the experiment and model, the contribution of each oxidative species in O 3 /FAC system was measured. The average removal contribution of O 3 , OH, and RCS to ASA/PNT was 10.3%/8.4%, 53.8%/10.5%, and 35.9%/81.1%, respectively. Compared with O 3 alone system, the average mineralization of pollutant in O 3 /FAC system increased from 20.6% to 34.0%. The formation of five typical CX 3 R-type disinfection by-products (DBPs) was evaluated with post-chlorine system. The maximum concentration of total DBPs was achieved at pH 6.0 of 12.5 μM, in which trichloromethane (TCMs) was the main component (accounting for 55.3%). This study provides a new method to remove contaminants based on the combination of O 3 and FAC disinfectants.
研究领域:
环境科学
·
水处理工程
·
药物化学
✓ 已验证
DOI
高影响因子
ENVIRONMENTAL POLLUTION
·
2021
·
IF 8.071
Jianfeng Tang,Jing Sun,Wendong Wang,Lei Yang,Yaoyang Xu
Pharmaceuticals are of increasing environmental concern due to their potential threat to aquatic ecosystems . Intensive human activities are a major factor influencing the level of pharmaceutical pollution in aquatic ecosystems. In this study, we investigated the occurrence, ecological risks of 31 pharmaceuticals and the possible influence of human activities on pharmaceutical distribution in two watersheds in the Yangtze River Delta, Eastern China. The target compounds were grouped into six categories: three non-steroidal anti-inflammatory drugs, ten antibiotics, six cardiovascular drugs, five hormones, six psychotropic drugs , and one antiparasitic. All target pharmaceuticals were detected in the surface water samples, with dexamethasone (100% of samples), tetracycline (100% of samples), and cefradine (100% of samples) being the dominant compounds (maximum concentrations of 686, 128, and 2280 ng/L, respectively). The total pharmaceutical concentrations were significantly higher in the urban watershed (711–2790 ng/L, mean = 1150 ng/L) than in the peri-urban watershed (467–1525 ng/L, mean = 863 ng/L) (p < 0.05). Distinct variation in the total pharmaceutical concentration also occurred between the dry season (507–2790 ng/L, mean = 1100 ng/L) and the wet season (467–1525 ng/L, mean = 943 ng/L). Ecological risk assessment showed that in the two watersheds, benzylpenicillin potassium, tetracycline hydrochloride, chlormadinone, ampicillin, cefotaxime acid, atorvastatin, sertraline hydrochloride, and oxazepam posed a medium potential risk (0.1 < risk quotient < 1), while norethisterone posed a high potential risk (risk quotient > 1). Redundancy analysis revealed that the concentrations of pharmaceuticals in various categories were positively correlated with land-use type (urban and agricultural land-use percentages), population density, and distance from town in both watersheds. Urban and agricultural activities were likely the main factors influencing the concentrations and composition of pharmaceuticals in these aquatic environments. Positive correlations were also found between total pharmaceutical concentrations and population density in both watersheds, suggesting a significant contribution of human disturbance to pharmaceutical pollution. The results provide useful information for pharmaceutical pollution control , ecological risk assessment, and sustainable water management at the watershed scale.
研究领域:
环境科学
·
生态学
·
公共卫生
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF SEPARATION SCIENCE
·
2020
·Vol. 43
·期 14
·2827-2833
·
IF 2.878
Zichun Liu,Wei Zhou,Chenlu Wang,Wei Hu,Zilin Chen
Cotton fiber is a biodegradable material that possesses properties such as high specific area, adjustable shape, and hygroscopicity. In this work, organic polymer was directly in situ grown on the surface of cotton thread and packed into a poly(ether ether ketone) tube for online in-tube solid-phase microextraction. The novel strategy solves the problems like high backpressure and tedious optimization process of normal monolithic polymer-based in-tube solid-phase microextraction capillary. The quaternary ammonium typed ionic liquid of 1-allyl-methylimidazolium chloride, 4-vinylbiphenyl, and ethylene dimethacrylate were co-polymerized and in situ grown on the surface of cotton thread as extraction phase. The solid-phase microextraction tube showed excellent performance for the extraction of three nonsteroidal anti-inflammatory drugs including ketoprofen, naproxen, and flurbiprofen due to the strong ion exchange and hydrophobic interactions. After online coupling with a high-performance liquid chromatography system by six-port valve, the method was applied for the quantitative analysis of nonsteroidal anti-inflammatory drugs in human plasma samples showing good enrichment performance (enrichment factor between 263 and 279), high sensitivity, good linearity, and good reproducibility.
研究领域:
分析化学
·
材料科学
·
药物分析
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF COLLOID AND INTERFACE SCIENCE
·
2017
·
IF 4.233
Jin Yan,Ji-Lai Gong,Guang-Ming Zeng,Biao Song,Peng Zhang,Hong-Yu Liu,Shuang-Yan Huan,Xiao-Dong Li
Carbon nanotubes (CNTs), usually with a superior affinity with organic chemicals, are expected to ultimately released to the environment through their manufacturing, usage, and eventual disposal, which will influence the mobility and environmental risk of nonsteroidal anti-inflammatory drugs (NSAIDs). In this study, batch and column experiments were performed to examine the effects of two kinds of multi-walled carbon nanotubes (MWCNTs: MWCNT2040, MWCNT0815) and one kind of single-walled carbon nanotubes (SWCNTs) on the environmental fate of two NSAIDs, paracetamol (PA) and diclofenac sodium (DS), in sediments. Impact ways of CNTs including addition in inflow and mixing with sediments were investigated. The adsorption capacity of NSAIDs on sediments increased with increasing CNTs/sediments ratios and in an order of MWCNT2040 < MTWCNT0815 < SWCNT. In column tests, PA showed a higher mobility than DS. With CNTs in inflow, the amounts of NSAIDs leached from sediment columns reduced because of the association with CNTs. For the sediment columns mixed with CNTs, breakthrough of the two NSAIDs was dramatically retarded, and the NSAIDs were hard to separate from CNT-polluted sediments. Our work provides useful insights into fate, transport and risk assessment of NSAIDs in the presence of CNTs.
研究领域:
环境科学
·
药物化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Letters in Drug Design & Discovery
·
2019
·Vol. 16
·期 12
·1378-1386
·
IF 0.953
Cai Xingchen,Huang Weiwei,Huang Yi,Xia Lihua,Liu Miao,Wang Mengke,Wang Wenchao,Li Qingyong
Background: The single-agent therapy was unable to provide an effective control of the malignant process, a well-established strategy to improve the efficacy of antitumor therapy is the rational design of drug combinations aimed at achieving synergistic effects. Objective: The
objective of this study is generating the new potential anticancer agents with synergistic activity. Owing to the unique mechanism of action of Camptothecin (CPT), it has shown abroad spectrum of anti-cancer activity against human malignancies, and growing evidence revealed that Nonsteroidal
Anti-Inflammatory Drugs (NSAIDs) reduce the risk of different kinds of cancers. So four CPT-NSAIDs conjugates were synthesized and evaluated. Methods: In this study, a series of novel CPT - NSAIDs derivatives were synthesized by esterification. These new compounds were evaluated for in
vitro antitumor activity against tumor cell lines A549, Hela, HepG2, HCT116 by MTT assay. To probe the required stabilities as prodrugs, stability tests were studied in human plasma. To further evaluate the stability of Ketoprofen-CPT in vivo, the female SD rats were used to determine the
pharmacokinetics following a single oral dose. Results: In vitro results showed that Ketoprofen-CPT and Naproxen-CPT conjugates possessed nice efficacy. In a molecular docking model, the two conjugates interacted with Topo I-DNA through hydrogen bonds, - stacking and
so on.In human plasma results showed that the prodrug was converted to ketoprofen and another compound. The female SD rats were used to determine the pharmacokinetics following a single oral dose, the half-life (t1/2) of Ketoprofen-CPT was approximately 12 h which was much longer than that
of CPT. Conclusion: Good activity was noted for some compounds will be helpful for the design of dualaction agents with most promising anti-cancer activity.
研究领域:
肿瘤学
·
药物化学
·
药理学
✓ 已验证
DOI
高影响因子
JOURNAL OF HAZARDOUS MATERIALS
·
2020
·
IF 9.038
Yang Wang,Lei Zhang
In this paper, we report a new type of 3D ZIF-8@NiAl-LDHs micro-flowers material consisting of sandwich-like structured 2D nanopetals (highly compact ZIF-8 film anchored on both sides of petals). ZIF-8 was successfully incorporated into NiAl-LDHs (ZIF-8@NiAl-LDHs) via seeding strategy directed growth of ZIFs on the surface of LDHs nanopetals. The coating of ZIF-8 significantly increased the adsorption ability to organic pollutants and inorganic cation. 3D ZIF-8@NiAl-LDHs with excellent enrichment and filtration properties has been exploited for the application in water purification, and exhibit superior high adsorption rate and adsorption efficiency of organic (nonsteroidal anti-inflammatory drugs: ketoprofen, flurbiprofen, indometacin and ibuprofe; anionic dyes: congo red, orange g; cationic dyes: methylene blue, rhodamine b) and inorganic cation (Cu 2+ , Pb 2+ ) residues due to their novel hierarchical and submicroscopic structures. Further, 3D ZIF-8@NiAl-LDHs as filter membrane to extraction four kind of trace anti-inflammatory drugs followed by direct quantification detection of targets with HPLC was demonstrated. The validated method was successfully applied for analysis of four anti-inflammatory drugs in environmental water and human urine samples. This work provided a feasible way to design and construct purification materials for wastewater treatment and contaminant detection.
研究领域:
环境科学
·
材料科学
·
分析化学
✓ 已验证
DOI
高影响因子
RSC Advances
·
2018
·Vol. 8
·期 28
·15459-15470
·
IF 2.936
Rong Hu,Yunping Zhoujin,Meng Liu,Mingtao Zhang,Sean Parkin,Panpan Zhou,Jianzhi Wang,Faquan Yu,Sihui Long
We report the discovery of two new forms (II and III) of a potential non-steroidal anti-inflammatory and thyroid drug, 2-((2,6-dimethylphenyl)amino)benzoic acid (HDMPA) through solution growth and thermal treatment of crystals. Form II has been discovered through crystal growth in a variety of solvents, and characterized by single-crystal X-ray diffraction, powder X-ray diffraction (PXRD), FT-IR, and Raman spectroscopy. Form II converts into form III upon thermal treatment, as indicated by the phase behavior study of form II with differential scanning calorimetry (DSC). Form III has been characterized by IR, Raman and PXRD. Conformational flexibility of the molecule seems to lead to the polymorphism of the system. A conformational scan shows the conformational minima correspond to the conformers in the polymorphs. Lattice energy calculations show energies of −48.14 and −50.31 kcal mol−1 for forms I and II, providing information on the relative stability for each form. Hirshfeld analysis revealed that intermolecular interactions such as C⋯C, H⋯H, C⋯H, and H⋯O contribute to the stability of the crystal forms.
研究领域:
药物化学
·
晶体学
✓ 已验证
DOI
高影响因子
MACROMOLECULAR RAPID COMMUNICATIONS
·
2020
·Vol. 41
·期 14
·2000202
·
IF 4.886
Xuefeng Li,Xueyin Peng,Rongzhe Li,Yikun Zhang,Zuifang Liu,Yiwan Huang,Shijun Long,Haiyan Li
The research on multiple hydrogen bonds (H-bonds) hydrogels have gradually aroused wide interest. In this paper, a multiple H-bonds-reinforced poly(acrylamide- co -2-vinyl-4,6-diamino-2-vinyl-1,3,5-triazine)/tannic acid (P(Am- co -VDT)/TA) hydrogels are prepared. The results suggest that the prepared hydrogel has two types of H-bonds crosslinking regions: A “soft” region of H-bonds between the diaminotriazine (DAT) moieties on the polymer chains and the TA pyrogallol/catechol groups, and a “hard” region of H-bonds forming by DAT moieties with itself. The hard crosslinking region exhibits significantly higher activation energy than the soft region. Such soft and hard dual physically crosslinked networks dramatically enhance the mechanical properties of P(Am- co -VDT)/TA hydrogels in a synergistic manner (tensile strength is 2.34 MPa, elongation at break is 410%). Due to the multiple hydrogen bonds, the hydrogel has good pH sensitivity and rapid response to shape memory within a few minutes. In addition, the hydrogels have the capacity of physical adsorption of the anti-inflammatory drug diclofenac sodium and other molecules with a specific spatially arranged chemical composition. These hydrogels with high mechanical strength, excellent shape memory behavior, and capacity of adsorption of anti-inflammatory drug could be attractive candidates for applications in the fields of biomedicine, tissue engineering, and medical materials.
研究领域:
生物材料
·
组织工程
·
生物医药
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）