Natural Product Communications
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2024
·
IF 1.5
Yan Lei,Bing Wang,Guanglin Zhu,Guo Feng,Wei Li,Caiyao Han,Qian Qin,Xie-an Yu,Xueli Song,Zhengyan He,Ju Zhang,Hongmei Su,Wenjing Wang
Background: In the research of the pharmacological activity of modern Chinese medicine, a large number of traditional Chinese medicines show anti-inflammatory activity. Asparagi radix is one of the anti-inflammatory drugs. With the deepening of people's research on Asparagi radix, its anti-inflammatory pharmacological effects have been gradually explored, but its specific anti-inflammatory active ingredients are still unclear. Therefore, it is necessary to screen and identify its specific anti-inflammatory active ingredients from Asparagi radix. At present, COX-2 is an important target for the treatment of chronic inflammation, and many drugs targeting this target have been marketed. However, some drugs have serious side effects, so it is very meaningful to study new COX-2 inhibitors. Methods: In this experiment, the fractions of different time periods are separated by high performance liquid chromatography-separation-trapping system (HPLC-CAD-FC). Then, ultra-high performance liquid chromatography-quadrupole time-of-flight/mass spectrometry (UPLC-Q-TOF/MS) and biological activity analysis techniques are used to identify the chemical composition and in vitro anti-inflammatory activity of each fraction. Finally, the data is integrated to screen out the substances with potential anti-inflammatory activity in Asparagi radix. Results: The results showed that the method established in this experiment can successfully isolate the active components of Asparagi radix, and four saponins with potential anti-inflammatory activity are identified. Conclusion: In summary, the analysis method established in this study can quickly and effectively screen out its anti-inflammatory active substances, and its potential anti-inflammatory active ingredients are mainly steroidal saponins.
研究领域:
中药学
·
药理学
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产品关联
DOI
高影响因子
ChemMedChem
·
2025
·
IF 3.4
Xinlin Zhu,Qin Li,Junhui Wu,Zhiran Ju
Graphical In recent years, the development of COX-2 inhibitors has shifted from a focus on highly selective inhibition to emphasizes more moderate selectivity. This study presents a potent balanced COX-2 inhibitor, compound 21d, which effectively alleviates histological damage and provides protection against DSS-induced colitis. The severe adverse effects associated with imbalanced cyclooxygenase-2 (COX-2) inhibition continue to pose significant challenges in the development of contemporary anti-inflammatory drugs. In recent years, the approach to COX-2 inhibitor drug development has shifted from a focus on highly selective inhibition of COX-2 to a strategy that emphasizes more moderate selectivity. The amino acid sequence and structural similarities between inducible COX-2 and constitutive cyclooxygenase-1 (COX-1) isoforms present both substantial opportunities and challenges for the design of next generation of balanced COX-2 inhibitors. As part of our ongoing research into the discovering novel and safer COX-2 inhibitors, we reported herein a highly potent and balanced COX-2 inhibitor 21 d (IC 50 value=1.35 μM, selectivity profile (IC 50 (COX-1)/IC 50 (COX-2)=22.34)). In vivo assays demonstrated that 21 d significantly alleviated histological damage and provided robust protection against dextran sulfate sodium (DSS)-induced acute colitis.
研究领域:
药理学
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分子生物学
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药物开发
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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
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
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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
Biomed Research International
·
2020
·Vol. 2020
·期 1
·5084057
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IF 2.276
Li Yang,Yiwei Fang,Ronghua Liu,Junwei He
Dendropanax dentiger root is a traditional medicinal plant in China and used to treat inflammatory diseases for centuries, but its phytochemical profiling and biological functions are still unknown. Thus, a rapid, efficient, and precise method based on ultra high-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry (UHPLC-Q-TOF-MS/MS) was applied to rapidly analyse the phytochemical profiling of D. dentiger with anti-inflammatory and antioxidant activities in vitro . As a result, a total of 78 chemical compositions, including 15 phenylpropanoids, 15 alkaloids, 14 flavonoids, 14 fatty acids, 7 phenols, 4 steroids, 4 cyclic peptides, 3 terpenoids, and 2 others, were identified or tentatively characterized in the roots of D . dentiger . Moreover, alkaloid and cyclic peptide were reported from D . dentiger for the first time. In addition, the ethanol crude extract of D. dentiger roots exhibited remarkable anti-inflammatory activity against cyclooxygenase- (COX-) 2 inhibitory and antioxidant activities in vitro . This study is the first to explore the phytochemical analysis and COX-2 inhibitory activity of D. dentiger . This study can provide important phytochemical profiles and biological functions for the application of D. dentiger roots as a new source of natural COX-2 inhibitors and antioxidants in pharmaceutical industry.
研究领域:
天然药物化学
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药用植物学
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炎症生物学
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自由基生物学
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药物代谢
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DOI
高影响因子
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
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2025
·
IF 5.9
Zi-Jie Song,Xiao-Fei Wu,Zhi-Ya Zhou,Jing-Jing Zhang,Yan-Yan Pan,Xue Dong,Xuan Pang,Ya-Ping Xie,Juan Sun,Yu Zhang,Jie Qin
A library comprising twenty-four isosteric derivatives of celecoxib substituted with carboxylic acid (labeled as 5a - 5x ), was synthesized and characterized through 1 H NMR, 13 C NMR, HRMS, and elemental analysis. Molecular docking studies revealed that all compounds successfully docked into the binding pocket of COX-2, and the introduction of carboxyl group enhances the interaction between the derivatives and COX-2. The compounds were further evaluated for cell toxicity, and in vitro anti-inflammatory activity. Notably, compound 5l exhibited significant inhibition of both COX-2 and NO release in vitro in comparison to the standard compound, displaying the highest selectivity towards the COX-2 enzyme (SI = 295.9) in comparison to celecoxib (SI = 261.3). 5l also exhibited the most potent anti-inflammatory activity and safety (ulcer index = 5.2) in vivo comparable to celecoxib at the same concentration. Through the molecular modeling and dynamics analysis, it was observed that compound 5l effectively stabilized within the active binding site of COX-2 through strong hydrogen bond interactions, and through the ADMET studies investigated the physiochemical properties and drug-likeliness behavior of compound 5l . In conclusion, compound 5l demonstrated to be a potential selective COX-2 anti-inflammatory candidate with reduced gastrointestinal risks.
研究领域:
药理学
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药物化学
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炎症研究
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DOI
PubMed
高影响因子
MOLECULES
·
2019
·Vol. 24
·期 9
·1685
·
IF 3.06
Xiao-Qiang Yan,Zhong-Chang Wang,Bo Zhang,Peng-Fei Qi,Gui-Gen Li,Hai-Liang Zhu
Cyclooxygenase-2 (COX-2) as a rate-limiting metabolism enzyme of arachidonic acid has been found to be implicated in tumor occurrence, angiogenesis, metastasis as well as apoptosis inhibition, regarded as an attractive therapeutic target for cancer therapy. In our research, a series of dihydropyrazole derivatives containing benzo oxygen heterocycle and sulfonamide moieties were designed as highly potent and selective COX-2 inhibitors by computer-aided drug analysis of known COX-2 inhibitors. A total of 26 compounds were synthesized and evaluated COX-2 inhibition and pharmacological efficiency both in vitro and in vivo with multi-angle of view. Among them, compound4bexhibited most excellent anti-proliferation activities against SW620 cells with IC50of 0.86 ± 0.02 µM than Celecoxib (IC50= 1.29 ± 0.04 µM). The results favored our rational design intention and provides compound4bas an effective COX-2 inhibitor available for the development of colon tumor therapeutics.Keywords:dihydropyrazole derivatives;sulfonamide;COX-2 inhibitors;docking simulation;pharmacological efficiency;colon tumor therapeutics
研究领域:
药理学
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肿瘤学
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药物化学
✓ 已验证
DOI
PubMed
高影响因子
BIOORGANIC CHEMISTRY
·
2024
·
IF 4.5
Zhenwei Lan,Rui Yang,Hu Wang,Xingyang Xue,Yue Sun,Shumei Wang,Ying Zhang,Jiang Meng
Turmeric ( Curcuma longa ), a typical source with recognized anti-inflammatory activity, is one such medicine-food homology source, yet its anti-inflammatory mechanisms and specific component combinations remain unclear. In this study, a net fishing method combining bio-affinity ultrafiltration and ultra-high performance liquid chromatography-mass spectrometry (AUF-LC/MS) was employed and 13 potential COX-2 inhibitors were screened out from C. longa . 5 of them (C1, 17, 20, 22, 25) were accurately isolated and identified. Initially, their IC 50 values were measured (IC 50 of C1, 17, 20, 22 and 25 is 55.08, 48.26, 29.13, 111.28 and 150.48 μM, respectively), and their downregulation of COX-2 under safe concentrations (400, 40, 120, 50 and 400 μM for C1, 17, 20, 22 and 25, respectively) was confirmed on RAW 264.7 cells. Further, in transgenic zebrafish ( Danio rerio ), significant anti-inflammatory activity at safe concentrations (15, 3, 1.5, 1.5 and 3 μg/mL for C1, 17, 20, 22 and 25, respectively) were observed in a dose-dependent manner. More importantly, molecular docking analysis further revealed the mode of interaction between them and the key active site residues of COX-2. This study screened out and verified unreported COX-2 ligands, potentially accelerating the discovery of new bioactive compounds in other functional foods.
研究领域:
药理学
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分析化学
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分子生物学
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炎症研究
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2025
·
IF 8.5
Yongfang Sun,Jinmei Xie,Canzheng Wang,Shaoxue Qin,Kun Ren,Dongmei Wang,Yingni Pan,Shumeng Ren,Xiaoqiu Liu
Curcumae wenyujin Rhizoma (CWR) is extensively implemented in clinical practice for treating primary dysmenorrhea (PD) resulting from qi stagnation and blood stasis. However, the development of CWR-derived polysaccharides remains poorly investigated. In this study, the polysaccharide CWP-3 was isolated from CWR, and structurally characterized through FT-IR, HPLC, GC–MS, and NMR, which identified it as an RG-I-type pectin polysaccharide with a molecular weight of 423.6 kDa. CWP-3 consists of the monosaccharides Rha, GalA, Gal, and Ara (25.7: 28.6:42.8:2.9). The main backbone consisted of alternating 1,2-linked Rha p and 1,4-linked GalA p residues, with Gal and Ara forming the side chains, respectively. SEM revealed a porous, sheet-like morphology, while Congo Red staining and AFM analyses confirmed a triple helix structure with a height of 3.37 nm, and TG-DSC analysis indicated good thermal stability. In a mouse model of PD, 160 mg/kg CWP-3 reduced writhing by 70.3 %, prolonged coagulation time by 37.5 %, restored uterine and hepatic indices, and decreased AST, ALT, D2D, TXB2, IL-6, IL-1β, and TNF-α, while normalizing PGF₂α/PGE₂ levels. These results indicate that CWP-3 exerts blood-activating and analgesic effects through cytokine-mediated COX-2 suppression, suggesting its potential as a therapeutic candidate for PD with qi stagnation and blood stasis.
研究领域:
药理学
·
生物化学
·
药物化学
·
妇科学
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结构生物学
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多糖研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Pharmaceuticals
·
2025
·Vol. 18
·期 8
·1185
·
IF 4.8
Ya Li,Siyang Liu,Meng Zhou,Zihan Zhao,Dongfan Song,Hongqian Guo,Rong Yang
Background: Bladder cancer is a common and heterogeneous malignancy of the urinary tract. Traditional chemotherapy using bivalent platinum drugs such as cisplatin(CDDP) is often limited by severe side effects and acquired resistance. To overcome these limitations, we explored a novel Pt(IV) prodrug, DNP, designed to release both cytotoxic cisplatin and the anti-inflammatory cyclooxygenase-2 (COX-2) inhibitor naproxen(NPX).Methods: We evaluated the cytotoxic activity of DNP using both two-dimensional (2D) monolayer and three-dimensional (3D) spheroid models of bladder cancer cells. Transcriptomic analysis via RNA-seq identified apoptosis- and inflammation-related signaling pathways modulated by DNP. RNA-seq-based transcriptomic profiling revealed that DNP regulates signaling pathways associated with apoptosis and inflammation. The anti-inflammatory effects were evaluated using a lipopolysaccharide (LPS)-induced macrophage model, while the in vivo antitumor efficacy was assessed in an orthotopic MB49 bladder cancer model.Results: Compared with CDDP, DNP significantly increased intracellular platinum accumulation and exhibited superior cytotoxicity. It effectively inhibited tumor proliferation, induced apoptosis, and attenuated inflammation both in vitro and in vivo.Conclusions: These findings suggest that DNP exerts dual antitumor effects through enhanced delivery of cytotoxic and anti-inflammatory agents, offering a promising strategy for bladder cancer therapy.
研究领域:
肿瘤学
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药理学
·
分子医学
·
癌症治疗学
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炎症生物学
✓ 已验证
DOI
PubMed
高影响因子
BIOORGANIC CHEMISTRY
·
2020
·
IF 4.831
Bo Zhang,Xiu-Ting Hu,Kang-Min Zhou,Yu-Shun Yang,Hai-Liang Zhu
Cyclooxygenase is critical for maintaining physiological functions, whereas overexpression of COX-2 was closely implicated in various cancers. In this study, a series of novel aminophosphonate derivatives containing pyrazole moiety were synthesized with their anti-cancer activity evaluated. In vitro assays of the target compounds showed that Z21 displayed excellent COX-2 inhibitory activity against COX-2 (IC 50 = 0.22 ± 0.04 µM) and anti-proliferative activity against MCF-7 cell (IC 50 = 4.37 ± 0.49 µM). The apoptosis induction of compound Z21 was confirmed by flow cytometry and polymerase chain reaction. Further investigation demonstrated that compound Z21 induced apoptosis of MCF-7 cells through a mitochondrion-dependent pathway and involved cell-cycle arrest in G2 phase. Overall, these results provided some new insights into the design of therapeutic drugs for COX-2 inhibitors and indicated the connection between selective COX-2 inhibition and the anti-tumor activity.
研究领域:
药理学
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肿瘤学
·
药物化学
✓ 已验证
DOI
PubMed
高影响因子
BIOORGANIC CHEMISTRY
·
2020
·
IF 4.831
Li Yang,Shengzhang Liu,Ronghua Liu,Junwei He
The root of Dendropanax dentiger (Harms) Merr. is a traditional Chinese medicine that has been used to treat inflammation-related diseases with little scientific validation. In this study, a bioassay-guided phytochemical investigation of D. dentiger led to the isolation of 19 phenylpropanoid derivatives including one new compound ( 1 ) and 18 known ones ( 2 – 19 ). Their structures were elucidated by NMR and HRMS as well as comparison with literature data. The ability of cyclooxygenase-2 (COX-2) inhibition and antioxidant of all isolated compounds were measured in vitro . Chlorogenic acid derivatives ( 14 – 19 ) exhibited outstanding COX-2 inhibitory (IC 50 = 5.1–93.4 μM) and antioxidant (IC 50 = 13.2–31.9 μM) activities. Moreover, the tight structure-activities relationships were proposed. This is the first report on the COX-2 inhibitory activity of phenylpropanoids and D. dentiger .
研究领域:
药理学
·
天然产物化学
·
药用植物研究
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）