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
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分子医学
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癌症治疗学
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炎症生物学
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DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2024
·
IF 4.8
Li Guo,Sai Zhang,Cong Zhang,Shuang Ren,Zihan Zhou,Fengyuan Wang,Yuexuan Wang,Qiqi Chen,Yubing Wang,Wen-Hui Lee,Kui Zhu,Di Qin,Yuanyuan Gao,Tongyi Sun
Inflammatory pain is a chronic pain caused by peripheral tissue inflammation, seriously impacting the patient’s life quality. Cinobufacini injection, as a traditional Chinese medicine injection preparation, shows excellent efficacy in anti-inflammatory and analgesic treatment in patients with advanced tumors. In this study, a novel analgesic peptide CI5 with anti-inflammatory and analgesic bio-functions that naturally presents in Cinobufacini injection and its regulatory mechanism are reported. Our results showed that the administration of CI5 significantly relieved the pain of mice in the acetic acid twisting analgesic model and formalin inflammatory pain model. Furthermore, CI5 effectively reduced the inflammatory cytokines (IL-6, TNF-α and IL-1β) and inflammatory mediator (PGE2) expressions, and prevented the carrageenan-induced paw edema in mice. Further LC-MS/MS results showed the anti-inflammatory and analgesic bio-functions of CI5 depended on its interaction with the Rac-2 protein upstream of ERK1/2 and the inflammatory signaling pathway (ERK1/2/COX-2 axis). In summary, CI5, as a novel natural candidate identified from Cinobufacini injection, showed substantial clinical promise for inflammatory pain treatments.
研究领域:
药理学
·
疼痛管理
·
传统中药
·
分子生物学
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产品关联
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
·
肿瘤学
·
药物化学
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DOI
PubMed
高影响因子
Food & Function
·
2018
·Vol. 9
·期 12
·6155-6164
·
IF 3.289
Lang Zhang,Ya Fan,Hanwen Su,Li Wu,Yuying Huang,Lei Zhao,Bing Han,Guangwen Shu,Meixian Xiang,Jin-Ming Yang
The objective of this study was to investigate the anti-inflammatory effect of chlorogenic acid methyl ester (CME) and the molecular mechanism involved, through using non-infectious inflammation and infectious inflammation animal models as well as lipopolysaccharide (LPS)-stimulated mouse macrophage RAW264.7 cell models. Our results demonstrated that CME markedly inhibited ear swelling, paw swelling and granuloma swelling, and decreased intraperitoneal capillary permeability in non-infectious inflammation. Moreover, CME significantly alleviated the pathological damage of the lung tissue, reduced the levels of PGE2 and IL-1β in the serum and the protein expression levels of related-inflammatory factors in the lung tissue of LPS-induced mice with acute lung injury (ALI). In addition, CME affected the RAW264.7 cell cycle and inhibited the protein expressions of COX-2 and NLRP3 and prevented the phosphorylation of NF-κB p65 in RAW264.7 cells treated with LPS. These observations not only validated the anti-inflammatory effects of CME, but also revealed the underlying molecular basis, which involves the down-regulation of the expression of inflammatory factors and blockade of the COX-2/NLRP3/NF-κB signaling pathway.
研究领域:
药理学
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免疫学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
MICROCHEMICAL JOURNAL
·
2024
·
IF 4.9
Guanghou Wang,Xueqian Tang,Feixu Qin,Hongjin Wang,Hao Zhang,Hanyue Li,Lan Wei,Lixin Sun
Nauclea officinalis ( N. officinalis ), a medicinal plant of the genus Nauclea in the Rubiaceae family, is used to treat bronchitis, pneumonia and acute tonsillitis and enteritis in China. Extracts of N. officinalis include more than 60 alkaloids, which exert all kinds of pharmacological effects, such as antiproliferative, antiparasitic, antimicrobial, anticancer, and anti-inflammatory activities. In this study, an affinity ultrafiltration and high-performance liquid chromatography- tandem mass spectrometry (AUF-LC-MS/MS) approach was constructed and validated, and was applied to rapidly screen COX-2/5-LOX inhibitors in N. officinalis extracts (NOE). To gain a more comprehensive and profound understanding of the anti-inflammatory mechanism of N. officinalis . Central Composite Design (CCD) of Response Surface Method (RSM) was used to optimize extraction conditions for potential COX-2/5-LOX inhibitors from NOE. Next, COX-2/5-LOX dual targeted inhibitors were screened from NOE using AUF-LC-MS/MS, and the biological activity of the screened ligands was demonstrated by enzyme inhibition assay. Finally, the preferred binding modes for these COX-2/5-LOX inhibitors were then determined by molecular docking, and compared with active drugs celecoxib and zileuton, respectively, to further explore ligand active binding sites and intersections between ligands and target proteins. The optimum extraction conditions were follows: ethanol concentration of 79 %, liquid − solid ratio of 11.8 v / w and extraction time of 1.8 h. The results of COX-2 inhibition assay showed that angustine (AU) had the more stronger inhibition activity with an IC 50 of 20.49 μM, followed with IC 50 of angustidine (AD) and nauclefine (NF) were 35.89 and 60.45 μM, respectively. Among the three components, AU also exhibited the highest inhibition of 5-LOX with an IC 50 of 1.18 μM, followed by NF and AD at 2.75 and 4.35 μM, respectively. Owing to the synergistic effect of multiple components make NOE exhibit strong inhibitory activity, it is shown potent inhibitory activities with an IC 50 at 9.47 and 6.16 μg/mL for COX-2 and 5-LOX, respectively. This work has demonstrated that NF, AD, and AU are potential COX-2/5-LOX dual-target inhibitors, indicating that N. officinalis anti-inflammatory activities were partially based on these COX-2/5-LOX inhibitors. These research results can also be further used for developed or improved anti-inflammatory agents with more beneficial effects.
研究领域:
药理学
·
药物化学
·
植物科学
·
分析化学
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产品关联
DOI
高影响因子
International Journal of Pharmaceutics-X
·
2025
·
IF 6.4
Shiying Xu,Lina Wu,Boxin Chen,Xiaoliang Deng,Zhihui Zheng,Fei Wu,Lingjun Zeng,Changqing Zheng,Xiaomu Hu,Aiwen Huang,Xin Zhou,Xianquan Feng,Zhihong Liu
Photodynamic therapy (PDT) has emerged as a promising non-invasive cancer treatment due to its selective tumor ablation and excellent safety characteristics. However, its efficacy is limited by tumor hypoxia and excessive inflammation. In this study, we fabricated human serum albumin-based nanoparticles (CAI NPs) encapsulating celecoxib (CXB), atovaquone (ATO), and IR820 via sonication. The CAI NPs exhibited favorable physicochemical properties, including a uniform size distribution (<200 nm), high encapsulation efficiency and excellent colloidal stability. Initially, ATO acts as a mitochondrial complex III inhibitor, suppressing oxidative phosphorylation to ameliorate tumor hypoxia. This hypoxia alleviation potentiates PDT efficacy by enhancing tumor cell ROS generation. Furthermore, concomitant COX-2/PGE2 inhibition by CXB attenuates the excessive inflammatory cascade triggered during PDT, resulting in enhanced therapeutic outcomes through microenvironment modulation. Eventually, the dual-enhanced CAI NPs demonstrate potent antitumor activity in both in vivo and ex vivo models, while maintaining excellent biocompatibility under physiological conditions. In summary, the integrated three-drug regimen conclusively enhances photodynamic therapeutic outcomes through multimodal mechanisms, establishing a viable treatment approach for esophageal cancer.
研究领域:
肿瘤学
·
纳米医学
·
光动力治疗
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分子药理学
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肿瘤微环境
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转化医学
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药物递送系统
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产品关联
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
·
分析化学
·
分子生物学
·
炎症研究
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产品关联
DOI
PubMed
高影响因子
IUBMB LIFE
·
2024
·
IF 3.7
Yexuan Lin,Na Sun,Dengyuan Liu,Xinmeng Yang,Yixin Dong,Chengyu Jiang
In 2020, the number of deaths caused by lung cancer worldwide reached 1,796,144, making it the leading cause of cancer-related deaths. Cyclooxygenase-2/prostaglandin endoperoxide synthase 2 ( COX-2/PTGS2 ) is overexpressed in lung cancer, which promotes tumor proliferation, invasion, angiogenesis, and resistance to apoptosis. Here, we report that the oligonucleotide drug HQi-sRNA-2 from Traditional Chinese Medicine Huangqin targeting COX-2/PTGS2 significantly inhibited proliferation, migration, and invasion and induced apoptosis in the human lung cancer cell line NCI-H460. Oral delivery of HQi-sRNA-2 bencaosomes prolonged survival, reduced tumor burden, and maintained weight in a spontaneous mouse lung cancer model. Compared with paclitaxel, HQi-sRNA-2 may be less toxic and have approximately equal efficacy in reducing tumor burden. Our previous studies reported that herbal small RNAs (sRNAs) are functional medical components. Our data suggest that sphingosine (d18:1)-HQi-sRNA-2 bencaosomes, targeting COX-2/PTGS2 and downregulating the PI3K and AKT signaling pathways, may provide novel therapeutics for lung cancer.
研究领域:
肿瘤学
·
药理学
·
分子生物学
·
中医药
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产品关联
DOI
PubMed
高影响因子
Experimental and Therapeutic Medicine
·
2023
·Vol. 25
·期 5
·1-7
·
IF 2.7
Zhiguo Wu,Yuchan Wu,Weicheng Zhong,Qingmei Zhong,Shengfang Rao,Dongshan Yu,Xiaolu Luo,Fang Qiu,Zhiying Song,Di Jin,Maoxing Ai,Yu Lan,Gongchang Zhang,Shufeng Song,Baogang Xie,Shuilin Sun
Aspirin decreases liver fibrosis index and inflammation levels. However, the exact mechanism underlying the effects of aspirin are yet to be elucidated. The aim of the study was to investigate the potential protective effects of aspirin on carbon tetrachloride (CCl4)‑induced hepatic fibrosis in Sprague‑Dawley rats. Rats were divided into four groups, including healthy and CCl4 control and low‑(aspirin 10 mg/kg + CCl4) and high‑dose aspirin group (aspirin 300 mg/kg + CCl4). After 8 weeks treatment, the histopathological examinations of hepatocyte fibrosis in liver and serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), IL‑1β, transforming growth factor‑β1 (TGF‑β1), hyaluronic acid (HA), laminin (LN) and type IV collagen (IV.C) were determined. Histopathological examination suggested that aspirin decreased CCl4‑induced hepatic fibrosis and liver inflammation. The high‑dose aspirin group significantly decreased the serum levels of ALT, AST, HA and LN compared with the CCl4 control group. High‑dose aspirin group significantly decreased the levels of pro‑inflammatory cytokines IL‑1β compared with CCl4 group. The high‑dose aspirin group significantly inhibited the expression of TGFβ‑1 protein compared with CCl4 group. Overall, the present study indicated that aspirin exhibited potent protective effects against CCl4‑induced hepatic fibrosis via inhibition of the TGFβ‑1 pathway and pro‑inflammatory cytokine IL‑1β.
研究领域:
药理学
·
肝病学
·
炎症
·
纤维化
·
细胞因子
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Bioscience-Landmark
·
2023
·Vol. 28
·期 11
·311
·
IF 3.1
Qing Zhu,Yuanshan Han,Ying He,Yilan Fu,Hui Yang,Yun Chen,Yingrui Shi
Background: Breast cancer-related depression (BCRD) is strongly associated with BC and increases recurrence and mortality. This study investigated the role of kaempferol in the pathogenesis of BCRD and its underlying mechanism. Methods: 4T1 mouse BC cells were treated with corticosterone (Cort) in vitro to develop a neuronal injury model, and a BCRD mouse model was established by injecting 4T1 cells and Cort. The effects of kaempferol on 4T1 cells and BCRD models were measured by behavioral tests, Cell Counting Kit-8 assay, wound healing assay, colony formation assay, Western blot analysis, quantitative real-time PCR, hematoxylin and eosin staining, enzyme-linked immunosorbent assay, and immunofluorescence. BCRD cells were transfected with the cyclo-oxygenase-2 (COX-2) overexpression plasmid to study the role of the COX-2/prostaglandin E2 (PGE2) axis in the anti-BCRD activity of kaempferol. The connection between kaempferol and COX-2 was analyzed by molecular docking. Results: Kaempferol reduced the viability, migration, and clones of 4T1 cells and inhibited BC growth and depression-like behavior in mice. Kaempferol alleviated inflammation in BCRD, decreased interleukin 1 beta (IL-1β) and IL-6 levels, and increased transforming growth factor beta 1 (TGF-β1) and IL-10 levels. In addition, kaempferol elevated the levels of serotonin, dopamine, and norepinephrine and the amount of 5-Bromo-2′-deoxyuridine/neuronal nuclei-positive cells. Kaempferol downregulated COX-2 and PGE2, and kaempferol could dock with the protein structure of COX-2. Overexpression of COX-2 reduced BCRD viability, upregulated IL-1β and IL-6 levels, and downregulated TGF-β1 and IL-10 expression. Overexpression of COX-2 reversed the protective effects of kaempferol. Conclusion: Kaempferol exerted anti-BCRD effects, at least in part by inhibiting the COX-2/PGE2 pathway, which regulates neuroinflammation, neurotransmitter imbalance, and defective neurogenesis. Therefore, kaempferol may be a promising candidate active ingredient for treating BCRD.
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产品关联
DOI
PubMed
高影响因子
Natural Product Communications
·
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
Acta Crystallographica Section C-Structural Chemistry
·
2024
·Vol. 80
·期 8
·366-374
·
IF 0.7
Ma Y.H.,Yang K.,Qian Y.L.,Hong W.P.,Zhang K.Y.,Tao Z.W.,Meng H.,Ma W.J.
The structures of three 1:1 cocrystal forms of etoricoxib {ETR; systematic name: 5-chloro-2-(6-methylpyridin-3-yl)-3-[4-(methylsulfonyl)phenyl]pyridine, C18H15ClN2O2S} have been synthesized and characterized by single-crystal X-ray diffraction; these are etoricoxib–benzoic acid (1/1), C18H15ClN2O2S·C7H6O2 (ETR–Bz), etoricoxib–4-fluorobenzoic acid (1/1), C18H15ClN2O2S·C7H5FO2 (ETR–PFB), and etoricoxib–4-nitrobenzoic acid (1/1), C18H15ClN2O2S·C7H5NO4 (ETR–PNB). Powder X-ray diffraction and thermal differential scanning calorimetry–thermogravimetry (DSC–TG) techniques were also used to characterize these multicomponent systems. Due to the influence of the corresponding acids, ETR shows different conformations. Furthermore, the energetic contributions of the supramolecular motifs have been established by energy framework studies of the stabilizing interaction forces and are consistent with the thermal stability of the cocrystals.
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DOI
高影响因子
危险品化学品经营许可证（带存储）