EUROPEAN JOURNAL OF PHARMACOLOGY
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2016
·
IF 2.73
Ming Zong,Dan-Dan Fan,Shan Lin,Yan-Ping Song,Ze-Yu Wang,Xiao-Liang Ma,Wei-Hua Qiu,Yu-Hua Bai,Lei Li,Sen Li
Aspirin has been used in the treatment and chemoprevention of many malignant cancers. The mechanism of its anti-cancer activity mainly involves the inhibition of cyclooxygenase-2 (COX-2). However, the application of aspirin is limited by the serious gastric mucosal damage that accompanies its usage. We have previously reported the preparation of a novel aspirin derivative that we named Ca-Asp, and showed that it causes less damage to gastric mucosa of rat and inhibits the expression of COX-2 to higher degree than Asp. However, the anti-cancer effect and mechanism of Ca-Asp was not demonstrated. In this study, the anti-cancer effect of Ca-Asp was investigated and compared with those of Asp and Hydroxyapatite (Hap) at the cell level. The results showed that treatment of SGC-7901 cells (human gastric cancer cell line) with 200–400 μg/ml Ca-Asp resulted in significant reduction in cell viability , compared to treatment with either Asp or Hap, and at a higher concentration (500 μg/ml). Subsequent investigation into the possible underlying mechanism showed that Ca-Asp induced apoptosis and caused cell cycle arrest at the G1 phase . Ca-Asp also up-regulated the levels of caspase-3 and p53, but down regulated the level of cyclin D1 , NF-κB, COX-2 and PGE 2 . Furthermore, simultaneous treatment of SGC-7901 cells with Ca-Asp and exogenous PGE 2 reduced the anti-proliferative effect of Ca-Asp on the cells. Taken together, the results suggested that Ca-Asp might act as a potential anti-cancer drug, and that its suppression of PGE 2 production might constitute an important part of its anti-cancer activity.
研究领域:
肿瘤学
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药理学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
NEW JOURNAL OF CHEMISTRY
·
2022
·Vol. 46
·期 22
·10637-10643
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IF 3.925
Juan-Juan Hu,Zhong-Ying Ma,Xin-Rui He,Yi-Gang Wu,Qian Chen,Xue-Qing Song,Guan-Yuan Wang,Yi-Han Li,Jing-Yuan Xu
Gastric adenocarcinomas present elevated cyclooxygenase-2 (COX-2) expression compared to non-neoplastic mucosa. Four oxaliplatin (L-OHP)-based Pt(IV) complexes, CP-L-OHP (1), ED-L-OHP (2), KP-L-OHP (3), and SL-L-OHP (4), were synthesized with the non-steroidal anti-inflammatory drugs (COX inhibitors) carprofen, etodolac, ketoprofen and sulindac, respectively, as axial ligands to inhibit BGC-823 gastric cancer cells. Complexes 1–4 displayed comparable cytotoxicity to L-OHP, of which 1 displayed the lowest IC50 value and best selectivity in BGC-823 cells compared to normal liver cells (LO2). Complex 1 significantly enhanced Pt accumulation, DNA damage and apoptosis in BGC-823 cells. Overexpression of COX-2 can lead to a more aggressive behavior in gastric cancer, inducing metastatic and invasive processes. The wound-healing assay displayed that 1 could significantly delay BGC-823 cell metastasis with the lowest wound-healing rate compared to L-OHP and carprofen after treatment for 24 h. Interestingly, few 1-treated cells were observed to adhere to Matrigel, while the cell adhesion was hardly affected by the other treatment groups such as carprofen in cell adhesion experiments. Immunofluorescence studies indicated that 1 exhibited a longer-acting COX-2 response than carprofen alone. Carprofen (20 μM) effectively inhibited COX-2 at 1 and 5 h of treatment in BGC-823 cells, but did not work at 24 h. In contrast, 1 could retain the high inhibitory activity against COX-2 up to 24 h at least.
研究领域:
肿瘤学
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药理学
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细胞生物学
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DOI
高影响因子
BIOORGANIC CHEMISTRY
·
2026
·
IF 5.1
Ao Yu,Yunlong Li,Yimei Wang,Jian He,Yong Zhou,Huiming Cai,Yiqing Wang,Bo Dai,Yi Shen
Intraoperative fluorescence-guided imaging has transformed oncological surgery, yet clinically approved probes lack specificity for primary tumors and metastatic lymph nodes. Herein, we developed NY-IND, a near-infrared fluorescent (NIRF) probe targeting cyclooxygenase-2 (COX-2). NY-IND not only has high water solubility, but also boasts higher fluorescence quantum yield and excellent biosafety. NY-IND exhibited high binding affinity for the COX-2 target with a dissociation constant (Kd) of 99.69 nM, thereby endowing it with the capacity to specifically recognize COX-2-overexpressing tumor cells and tissues. Significant tumor-to-background ratio (TBR > 6) was still observed 48 h after injection, allowing for clear differentiation between subcutaneous tumors and surrounding tissues. Furthermore, the probe NY-IND exhibited a long tumor retention time (>72 h) in vivo metabolism and provided a longer imaging window for fluorescence-guided tumor surgery. NY-IND showed significantly superior specificity in detecting metastatic tumor lesions including peritoneal metastasis of lung cancer and lymph node metastasis. This work presents a promising tool for real-time intraoperative visualization of tumors and metastases, advancing surgical precision and improving patient prognosis.
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DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2018
·
IF 3.831
Attiq Ali,Jalil Juriyati,Husain Khairana,Ahmad Waqas
Over the last few decade Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) are the drugs of choice for treating numerous inflammatory diseases including rheumatoid arthritis. The NSAIDs produces anti-inflammatory activity via inhibiting cyclooxygenase enzyme, responsible for the conversation of arachidonic acid to prostaglandins. Likewise, cyclooxegenase-2 inhibitors (COX-2) selectively inhibit the COX-2 enzyme and produces significant anti-inflammatory, analgesic, and anti-pyretic activity without producing COX-1 associated gastrointestinal and renal side effects. In last two decades numerous selective COX-2 inhibitors (COXIBs) have been developed and approved for various inflammatory conditions. However, data from clinical trials have suggested that the prolong use of COX-2 inhibitors are also associated with life threatening cardiovascular side effects including ischemic heart failure and myocardial infection. In these scenario secondary metabolites from natural product offers a great hope for the development of novel anti-inflammatory compounds. Although majority of the natural product based compounds exhibit more selectively toward COX-1. However, the data suggest that slight structural modification can be helpful in developing COX-2 selective secondary metabolites with comparative efficacy and limited side effects. This review is an effort to highlight the secondary metabolites from terrestrial and marine source with significant COX-2 and COX-2 mediated PGE2 inhibitory activity, since it is anticipated that isolates with ability to inhibit COX-2 mediated PGE2 production would be useful in suppressing the inflammation and its classical sign and symptoms. Moreover, this review has highlighted the potential lead compounds including berberine, kaurenoic acid, α-cyperone, curcumin, and zedoarondiol for further development with the help of structure–activity relationship (SAR) studies and their current status.
研究领域:
药理学
·
天然药物化学
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DOI
PubMed
高影响因子
Korean Journal of Pain
·
2024
·
IF 3.4
Kaiwen Lin,Datian Fu,Zhongtao Wang,Xueer Zhang,Canyang Zhu
Background Galangin, commonly employed in traditional Chinese medicine for its diverse medicinal properties, exhibits potential in treating inflammatory pain. Nevertheless, its mechanism of action remains unclear. Methods Mice were randomly divided into 4 groups for 7 days a normal control group, a galangin-treated (25 and 50 mg/kg), and a positive control celecoxib (20 mg/kg). Analgesic and anti-inflammatory effects were evaluated using a hot plate test, acetic acid-induced writhing test, acetic acid-induced vascular permeability test, formalin-induced paw licking test, and carrageenan-induced paw swelling test. The interplay between galangin, transient receptor potential vanilloid 1 (TRPV1), NF-κB, COX-2, and TNF-α proteins was evaluated via molecular docking. COX-2, PGE2, IL-1β, IL-6, and TNF-α levels in serum were measured using ELISA after capsaicin administration (200 nmol/L). TRPV1 expression in the dorsal root ganglion was analyzed by Western blot. The quantities of substance P (SP) and calcitonin gene-related peptide (CGRP) were assessed using qPCR. Results Galangin reduced hot plate-induced licking latency, acetic acid-induced contortions, carrageenan-triggered foot inflammation, and capillary permeability in mice. It exhibited favorable affinity towards TRPV1, NF-κB, COX-2, and TNF-α, resulting in decreased levels of COX-2, PGE2, IL-1β, IL-6, and TNF-α in serum following capsaicin stimulation. Galangin effectively suppressed the upregulation of TRPV1 protein and associated receptor neuropeptides CGRP and SP mRNA, while concurrently inhibiting the expression of NF-κB, TNF-α, COX-2, and PGE2 mRNA. Conclusions Galangin exerts its anti-inflammatory pain effects by inhibiting TRPV1 activation and regulating COX-2, NF-κB/TNF-α expression, providing evidence for the use of galangin in the management of inflammatory pain.
研究领域:
药理学
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生物化学
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分子生物学
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炎症研究
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疼痛管理
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DOI
PubMed
高影响因子
BIOORGANIC CHEMISTRY
·
2020
·
IF 4.831
Bo Zhang,Xiu-Ting Hu,Jin Gu,Yu-Shun Yang,Yong-Tao Duan,Hai-Liang Zhu
As an essential enzyme with a variety of physiological functions, Cyclooxygenase-2 (COX-2) is also closely related to carcinoma due to the observed overexpression. In this work, a novel series of sulfonamide-containing aminophosphonate derivatives ( A1-A25 ) were developed as selective COX-2 inhibitors and anti-cancer candidates. The top hit compound A23 presented applicative COX-2 inhibitory activity (IC 50 = 0.28 µM) and anti-proliferative capability against several cancer cell lines (IC 50 = 2.34–16.43 µM for HeLa, MCF-7, HCT116 and HepG2 cells). Among them, A23 has the most significant inhibitory effect on HCT116 cells, which were comparable with that of the positive controls respectively (eg: IC 50 = 8.73 µM for HCT116). The binding pattern of A23 was inferred by the molecular docking simulation. Moreover, A23 could induce the apoptosis via a mitochondrion-dependent mode and cause the arrest of the cell-cycle in G1 stage. A further investigation in the checkpoints of apoptosis indicated that the node Bcl-2 might connect the selective COX-2 inhibition and the anti-tumor activity. Therefore, this work brought new information for developing COX-2 inhibitors in anti-tumor therapies in future.
研究领域:
药理学
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肿瘤学
·
药物化学
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DOI
PubMed
高影响因子
Molecular Medicine Reports
·
2019
·Vol. 19
·期 6
·5417-5423
·
IF 1.851
Zhimin Wang,Fang Li,Yuan Quan,Junye Shen
Hepatocellular carcinoma (HCC) has become a global public health problem. Therefore, the development of novel and effective therapeutic agents for the treatment of HCC is considered an emergency. Avicularin, a bio‑active flavonoid from plants, has been reported to exhibit diverse pharmacological properties. The aim of the present study was to investigate the role of avicularin in HCC and the underlying mechanism of action. Huh7 cells were treated with avicularin in a concentration‑dependent manner, and the cell proliferation was examined using a 3‑(4, 5‑dimethylthiazol‑2‑yl)‑2, 5‑diphenyltetrazolium bromide assay kit. The cell migration and invasion abilities were detected using wounding‑healing assays and Transwell assays. Flow cytometric analysis was performed to investigate the cell cycle distribution and cell apoptosis. The activity of nuclear factor (NF)‑κB (p65), cyclooxygenase‑2 (COX‑2) and peroxisome proliferator‑activated receptor γ (PPAR‑γ) were measured by reverse transcription‑quantitative polymerase chain reaction and western blot analyses, respectively. The results indicated that avicularin treatment markedly decreased cell proliferation concentration‑dependently in HCC, and inhibited cell migration and invasion in Huh7 cells. It was also found that the treatment of avicularin markedly inhibited the G0/G1‑phase cells and decreased the accumulation of S‑phase cells in the cell cycle and induced cell apoptosis. In addition, it was confirmed that the anticancer efficacy of avicularin in HCC was dependent on the regulation of NF‑κB (p65), COX‑2 and PPAR‑γ activities. In conclusion, the findings suggested that avicularin serves an antineoplastic role in HCC and may provide a potential therapeutic strategy for the treatment of HCC.
研究领域:
肿瘤学
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药理学
·
分子生物学
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产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2024
·
IF 13.3
Ning Zhang,Zijia Wang,Gen Li,Mingzhe Zhang,Quan Liu,Chunxiu Cai,Yanfei Shang,Hailiang Zhu,Hailong An,Shenzhen Ren
The development of multidrug resistance (MDR) is the primary contributor to the failure of cancer treatment, ultimately leading to tumor recurrence and metastasis. Ferroptosis, an iron-dependent cell death form related to the accumulation of lipid peroxidation (LPO), has the potential to circumvent MDR. Furthermore, recent breakthroughs have confirmed that the inhibition of cyclooxygenase-2 (COX-2) not only facilitate LPO and ferroptosis, but also suppress the expression of p-glycoprotein. Therefore, the combination of immunogenic ferroptosis with COX-2 inhibitors may be an enticing approach for overcoming tumor resistance and metastasis. Herein, polyphenolic COX-2 inhibitors are first screened using molecular docking, enzyme-linked immunosorbent assay, and combination index analysis. Then, a carrier-free metal-phenolic networks are constructed based on the coordination between polyphenolic COX-2 inhibitors and Fe 3+ , and DOX and dopamine-modified hyaluronic acid are directly decorated using a one-pot process. The nanosystem can selectively inhibit the COX-2 pathway, thereby suppressing the expression of p-glycoprotein and enhancing Fe 3+ -induced ferroptosis; Additionally, the nanosystem demonstrates excellent photothermal performance, promoting ferroptosis and synergistically triggering strong immune responses against tumor metastasis. The RNA-seq analysis further confirmes the transcriptomic alterations in drug resistance and ferroptosis pathways induced by the nanosystem. Taken together, this study provides a promising strategy for efficient cancer treatment.
研究领域:
肿瘤学
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药理学
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生物医学工程
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产品关联
DOI
高影响因子
ANALYTICAL AND BIOANALYTICAL CHEMISTRY
·
2018
·Vol. 410
·期 15
·3587-3595
·
IF 3.307
Chen Guilin,Wu Jianlin,Li Na,Guo Mingquan
Rhamnus davurica Pall. ( R. davurica ) has been used as a traditional medicine for many years in China and abroad and shown a wide spectrum of biological activities. Previously, we reported the phytochemical fingerprinting profile of R. davurica , its distinct anti-proliferative activities against HT-29 and SGC-7901 cell lines, and the topoisomerase I (Top I) ligands based on bio-affinity ultrafiltration and HPLC-MS (UF-HPLC-MS). Nevertheless, among the 32 peaks detected in the fingerprinting profile, the common bioactive constituents responsible for the anti-inflammatory and anti-proliferative activities in the extracts remain elusive. To further explore the specific responsible components for their diversified activities and their potential action targets/mechanisms, the method based on bio-affinity UF-HPLC-MS using therapeutic targets like Top I and cyclooxygenase 2 (COX-2) was established to rapidly screen and identify the ligands binding to these known target enzymes. As a result, 12 components were revealed as potential Top I ligands along with 11 components as potential COX-2 ligands, where several components were revealed to possess both activities. Further validations of these bioactive components have also been conducted and confirmed their highlighted activities. This integrated method of UF-HPLC-MS exhibits high efficiency in rapidly screening for multi-target bioactive components responsible for multiple pharmacological effects from the complex natural products and could be very useful to explain the complex action mechanisms of herb medicines in a complex multi-component and multi-target mode at the molecular level.
Schematic diagram of UF-HPLC-MS assay to screen for Top I and COX-2 ligands. The principle of the assay usually involves the following steps: incubation, ultrafiltration, and identification.
研究领域:
药理学
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植物化学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
MOLECULES
·
2024
·Vol. 29
·期 23
·5801
·
IF 4.2
Fan Zhang,Fan Sun,Lequan Yu,Fei Li,Lixia Liu,Xiaoyan Cao,Yi Zhang,Lijie Wu
A novel screening platform based on an Fe3O4@C@PDA-Ni2+@COX-2 ligand fishing combination with high-performance liquid chromatography–mass spectrometry was first designed, synthesized, and employed to screen and identify COX-2 inhibitors fromPanax notoginsengleaves. The obtained magnetic nanoparticles exhibit outstanding preconcentration ability that allows for controlling the enzyme orientation to avoid enzyme active site blocking, conformational changes, or denaturing during immobilization. The as-prepared Fe3O4@C@PDA-Ni2+@COX-2 composite was carefully characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), Fourier-transform infrared spectrometry (FT-IR), Xray powder diffraction (XRD), thermal gravimetric analyzer (TGA), vibrating sample magnetometer (VSM), and Zeta potential analysis. The analytical parameters influencing the magnetic solid-phase fishing efficiency were optimized by univariate and multivariate methods (Box–Behnken design) by testing a positive control and celecoxib with active and inactive COX-2. Under the optimized ligand fishing conditions, twelve potential COX-2 inhibitors were screened and characterized inPanax notoginsengleaves. The results indicate that the proposed method provides a simple, feasible, selective, and effective platform for the efficient screening and identification of active compounds from Chinese herbal medicine. It has guiding significance for the synthesis and development of novel anti-inflammatory drugs, and provides a reference for the efficient discovery of anti-inflammatory drugs or lead compounds from the complex system of Chinese herbal medicine.
研究领域:
药理学
·
纳米技术
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中药化学
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产品关联
DOI
PubMed
高影响因子
Food Frontiers
·
2025
·
IF 6.9
Xiaoli Qin,Yan Lu,Yawen Luo,Yafang Cui,Kai Zhao,Yang He,Muhammad Aziz ur Rahman,Shengnan Min,Wenfang Wang,Fuyu Yang,Binghai Cao,Huawei Su
Alfalfa is rich in flavonoid compounds, which are known for their antioxidative and anti-inflammatory properties, suggesting therapeutic potential for alfalfa flavonoids (AF) in inflammation-related diseases. This study investigated the effects of AF on Salmonella -induced colitis, a severe inflammatory bowel disorder characterized by oxidative damage and inflammatory response. In vitro, antioxidant assays revealed AF's concentration-dependent radical scavenging, significantly reducing electron paramagnetic resonance (EPR) signals for HO • and O 2 •− by 42% and 54%, respectively. In vivo, AF treatment significantly mitigated body weight (BW) loss by 6%, increased colon length by 11%, and reduced liver and spleen weights by 19% and 81%, respectively, compared to the colitis group. Mechanistically, AF suppressed inflammation by downregulating the Toll-like receptor 4 (TLR4)/IκB/nuclear factor-κB (NF-κB)/cyclooxygenase-2 (COX-2) pathway and inhibiting nucleotide-binding domain-like receptor protein 3 (NLRP3) inflammasome activation, thereby lowering levels of pro-inflammatory cytokines (tumor necrosis factor alpha [TNF-α], interleukin 6 [IL-6], interleukin 1 beta [IL-1β]). Concurrently, AF enhanced antioxidant defense via the Kelch-like ECH-associated protein 1 (Keap1)-nuclear factor erythroid 2-related factor 2 (Nrf2) pathway, reducing reactive oxygen species (ROS) and malondialdehyde (MDA) levels while increasing catalase (CAT) (69%), glutathione peroxidase (GPx) (83%), and superoxide dismutase (SOD) (21%) activities. Moreover, AF preserved epithelial and mucosal barriers by reducing apoptosis and upregulating tight junction proteins (Claudin1, ZO-1, E-cadherin) and goblet cell marker Ulex europaeus (Gorse) Agglutinin I (UEA-1). Microbiota analysis revealed that AF significantly enriched beneficial bacteria, including Akkermansia , Oscillibacter , and butyrate-producing taxa, thereby counteracting Salmonella -induced dysbiosis. Furthermore, AF restored the disrupted profile of short-chain fatty acids (SCFAs), strengthening the relationship between symbiotic microbiota and mucosal defense. Overall, AF exerted multifaced protection against Salmonella -induced colitis by alleviating oxidative stress, stabilizing intestinal homeostasis, and thus attenuating inflammation. These findings make AF a promising phytopharmaceutical for the prevention and treatment of inflammatory diseases.
研究领域:
药理学
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微生物学
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免疫学
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产品关联
DOI
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2023
·
IF 10.8
Deqing Lin,Xiaoning Xu,Lin Chen,Lei Chen,Mengyun Deng,Jinrun Chen,Zhibin Ren,Lei Lei,Jiaqing Wang,Jie Deng,Xingyi Li
Herein, we report a facile method for converting carboxylate-containing indomethacin (Idm) into a cyclooxygenase-2 (COX-2) selective inhibitor via the amidation of an unnatural peptide sequence (Nal-Nal-Asp). The resulting indomethacin amides ( i.e., Idm-Nal-Nal-Asp) have high selectivity for COX-2, and can self-assemble into a one-component supramolecular hydrogel that acts as a ‘self-delivery’ system for boosting anti-inflammatory efficacy. Self-assembled Idm-Nal-Nal-Asp hydrogel robustly inhibits COX-2 expression in lipopolysaccharide (LPS)-activated Raw 264.7 macrophages while also exhibits superior anti-inflammatory and antioxidant activities via reactive oxygen species (ROS)-related NF-κB and Nrf2/HO-1 pathways. Moreover, a rabbit model of endotoxin-induced uveitis (EIU) reveals that the Idm-Nal-Nal-Asp hydrogel outperforms clinically used 0.1 wt% diclofenac sodium eye drops in terms of in vivo anti-inflammatory efficacy via topical instillation route. As a rational approach to designing and applying COX-2 selective inhibitors, this work presents a simple method for converting non-selective nonsteriodal anti-inflammatory drugs (NSAIDs) into highly selective COX-2 inhibitors that can self-assemble into supramolecular hydrogel for anti-inflammation applications.
研究领域:
药物化学
·
材料科学
·
生物医学工程
·
药理学
✓ 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）