MOLECULAR BIOLOGY REPORTS
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2025
·Vol. 52
·期 1
·1-14
·
IF 2.8
Liang Chen,Guo Liping,Tian Xinyan,Mu Zhidan,Chen Mingyang,Hu Yarong,Su Juan
Objective By establishing a mouse model of hepatic ischemia–reperfusion injury (HIRI), to investigate the effects of cyclooxygenase-2 (COX-2) and endoplasmic reticulum stress (ERS) on HIRI and their interaction in HIRI. Methods C57BL/6J male mice were divided into four groups: Sham operation group (Sham group), hepatic ischemia–reperfusion (HIR) group, hepatic ischemia–reperfusion + Salubrinal (ER stress inhibitor) pretreatment group (HIR + Sal group), hepatic ischemia–reperfusion + NS398 (inhibitor of COX-2) pretreatment group (HIR + NS398 group). The levels of Aspartate transaminase (AST) and Alanine transaminase (ALT) in serum, the activity of Super Oxide Dismutase (SOD) and the content of malondialdehyde (MDA) in liver tissue were detected. The mRNA and protein expression of Glucose-regulated protein 78 (GRP78), C/EBP homologous protein (CHOP), phosphorylated eukaryotic translation initiation factor 2α (p-eIF2α) and COX-2/PTGS (Prostaglandin-endoperoxide synthase) in liver tissue were detected. The morphological changes and apoptosis of liver tissue were observed. Results Compared with the Sham group, the serum ALT and AST levels of the HIR group were increased, the SOD activity in the liver tissue was decreased, the MDA content and the expression of COX-2, p-eIF2α, GRP78 and CHOP protein were increased, and the staining results showed that hepatic sinusoidal congestion, a large number of hepatocyte death, inflammatory cell infiltration and apoptotic cells were significantly increased. The levels of ALT and AST decreased after Sal or NS398 pretreatment. SOD activity was increased, MDA content, COX-2, GRP78, CHOP mRNA and protein were decreased in liver tissue, and staining showed that liver tissue injury was improved. Conclusion In mice with HIR, COX-2 interacts with ERS to cause liver injury by regulating oxidative stress and apoptosis.
研究领域:
分子生物学
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病理学
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药理学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2018
·
IF 3.118
Yuzhu Ye,Yuanlu Shan,Caiying Bao,Yi Hu,Liangrong Wang
Background/aims Ginsenoside Rg1 is regarded as the primary bioactive ingredient in Panax notoginseng that has been well recognized for its protective effects against ischemia/reperfusion (IR) injury. However, the mechanisms still remain elusive. Our study aims to investigate the effects of Rg1 against lung injury induced by hind-limb IR in rats. Methods Twenty-four Sprague Dawley rats were randomly submitted to sham operation (SM group), hind-limb IR (IR group), hind-limb IR + Rg1 (Rg1 group), and hind-limb IR + Pro-DTC group (PD group). All the rats except those in SM group were subjected to 3 h of ischemia followed by 6 h of reperfusion , and extra intravenous Rg1 and pyrrolidine dithiocarbamate (Pro-DTC), a selective inhibitor of nuclear factor kappa B (NF-κB), was administered intravenously before ischemia in the Rg1 and PD group, respectively. The activities of myeloperoxidase (MPO), superoxide dismutase (SOD) and catalase (CAT), as well as protein expressions of NF-κB p65 and cyclooxygenases-2 (COX-2) in lung tissue, and thromboxane B2 (TXB2) and 6-keto-ProstaglandinF 1α (6-keto-PGF 1α ) levels in bronchoalveolar lavage (BAL) fluid were detected. Morphological changes, index of quantitative assessment of histologic lung injury (IQA), apoptosis index (AI) and lung Wet/Dry ratio were also evaluated. Results The levels of Wet/Dry ratio, IQA, AI, activities of MPO and 6-keto-PGF 1α /TXB 2 ratio were increased, and NF-κB p65 and COX-2 protein expression were upregulated, while SOD and CAT levels were decreased in lung tissue in IR group as compared with SM group ( p < 0.05), all the alterations could be significantly reversed by Rg1 or Pro-DTC pretreatment ( p < 0.05). And Rg1 and Pro-DTC also significantly attenuated the pulmonary histological abnormalities induced by IR. Conclusion Ginsenoside Rg1 potentially attenuated lung injury induced by hind-limb IR by regulating NF-κB/COX-2 signaling pathway .
研究领域:
药理学
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免疫学
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病理学
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DOI
PubMed
高影响因子
FITOTERAPIA
·
2025
·
IF 2.6
Huan Liu,Yao Zhong,Rong Huang,Shian Meng,Guang Chen
Gentiana macrophylla Pall. (GMP), known as “Qinjiao” in the Chinese Pharmacopeia, has a long history of clinical application in treating rheumatoid arthritis, primarily due to its iridoid components. However, the transdermal anti-inflammatory efficacy, active ingredients, and underlying mechanisms of these components remain under-investigated. This study aimed to clarify the transdermal anti-inflammatory effects and mechanisms of seco-iridoids from GMP by establishing a hydrogel patch transdermal drug delivery system. Using crude and refined GMP iridoid extracts as active components, the hydrogel patch system was established based on physicochemical properties, skin irritation tests, in vitro drug release, and skin permeation. The anti-inflammatory efficacy of these iridoid hydrogel patches was assessed using a carrageenan-induced paw edema model in mice. Content analysis and skin permeation studies identified gentiopicroside (GPS) and swertiamarin (SWE) as the key bioactive constituents. The hydrogel patch system demonstrated superior skin permeation and sustained drug release profiles compared to oral administration, addressing issues of poor bioavailability and rapid metabolism. Mechanistic studies revealed that these seco-iridoids exert their anti-inflammatory effects primarily through modulation of the iNOS/COX-2/NF-κB signaling cascade. Pharmacokinetic evaluations showed significant improvements in bioavailability and prolonged drug release, highlighting the clinical advantages of the transdermal approach. This work lays a solid foundation for the further optimization and clinical translation of GMP-based transdermal formulations, providing a framework for the investigation of iridoid transdermal systems and their therapeutic applications in inflammatory conditions.
研究领域:
中药学
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药理学
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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
ANALYTICAL AND BIOANALYTICAL CHEMISTRY
·
2026
·
IF 4.1
Zhang Yonglin,Liu Jianxi,Song Shengfa,Hu Jiale,Chen Shulin,Zhu Lulu,Shen Li,Jiang Hao,Xia Yunqing,Yi Xuexue,Yue Ningning,Xue Ying,Liu Wanhui,Zhu Yanping,Xu Lixiao
Overexpression of cyclooxygenase-2 (COX-2) and associated reactive species, specifically hypochlorous acid (HClO) and peroxynitrite (ONOO⁻), in the tumor microenvironment are critical hallmarks for early cancer diagnosis. In this work, we designed and synthesized two fluorescent probes, S1 and S2 , for the targeted imaging of HClO and ONOO⁻, respectively. Both probes integrate a celecoxib ligand for COX-2 targeting with a naphthalimide fluorophore. The probes operate via a photoinduced electron transfer (PET) mechanism, producing a distinct fluorescence turn-on response with excellent linearity against analyte concentration ( R 2 = 0.9902 for S1 with HClO; R 2 = 0.9897 for S2 with ONOO⁻). This mechanism was theoretically validated through DFT calculations. In vitro cellular imaging demonstrated that both probes exhibit low cytotoxicity and achieve superior tumor cell selectivity, showing significantly higher fluorescence intensity in COX-2 overexpressing MCF-7 cancer cells than in normal HUVEC cells. The molecular basis for targeting was rigorously investigated using molecular docking and 100 ns molecular dynamics simulations. MM/PBSA calculations revealed favorable binding enthalpies for both S1 (−80.05 ± 7.19 kcal/mol) and S2 (−83.76 ± 3.88 kcal/mol) with COX-2, confirming stable and specific complex formation. This integrated experimental and computational strategy yields highly sensitive and selective probes, positioning S1 and S2 as promising tools for studying cancer-related biomarkers at the cellular level. Graphical
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PubMed
高影响因子
Frontiers in Pharmacology
·
2020
·
IF 4.225
Xie Jing,Luo Feng-xian,Shi Chong-ying,Jiang Wei-wei,Qian Ying-yan,Yang Ming-rong,Song Shuang,Dai Tian-yi,Peng Lei,Gao Xiao-yu,Tao Liang,Tian Yang,Sheng Jun
Moringa oleifera Lam. (M. oleifera) is valuable plant distributed in many tropical and subtropical countries. It has a number of medicinal uses and is highly nutritious. M. oleifera has been shown to inhibit tumor cell growth, but this effect has not been demonstrated on prostate cancer cells. In this study, we evaluated the inhibitory effect of M. oleifera alkaloids (MOA) on proliferation and migration of PC3 human prostate cancer cells in vitro and in vivo. Furthermore, we elucidated the mechanism of these effects. The results showed that MOA inhibited proliferation of PC3 cells and induced apoptosis and cell cycle arrest. Furthermore, MOA suppressed PC3 cell migration and inhibited the expression of matrix metalloproteinases (MMP)-9. In addition, MOA significantly downregulated the expression of cyclooxygenase 2 (COX-2), β-catenin, phosphorylated glycogen synthase 3β, and vascular endothelial growth factor, and suppressed production of prostaglandin E2 (PGE2). Furthermore, FH535 (β-catenin inhibitor) and MOA reversed PGE2-induced PC3 cell proliferation and migration, and the effects of MOA and FH535 were not additive. In vivo experiments showed that MOA (150 mg/kg) significantly inhibited growth of xenograft tumors in mice, and significantly reduced the protein expression levels of COX-2 and β-catenin in tumor tissues. These results indicate that MOA inhibits the proliferation and migration, and induces apoptosis and cell cycle arrest of PC3 cells. Additionally, MOA inhibits the proliferation and migration of PC3 cells through suppression of the COX-2 mediated Wnt/β-catenin signaling pathway.
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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分子生物学
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DOI
PubMed
高影响因子
TOXICOLOGY AND APPLIED PHARMACOLOGY
·
2018
·
IF 3.616
Yanzhuo Liu,Chenfan Duan,Honglei Chen,Chenlong Wang,Xiaoxiao Liu,Miao Qiu,Honglin Tang,Feng Zhang,Xiaoyang Zhou,Jing Yang
Cyclooxygenase-2 (COX-2), 5-lipoxygenase (5-LOX) and microsomal prostaglandin E synthase-1 (mPGES-1)-derived eicosanoids play an essential role in human inflammatory disorders. Here, we investigated whether inhibition of COX-2/mPGES-1 and 5-LOX in macrophages by leonurine ameliorates monosodium urate (MSU) crystal-induced inflammation. Virtual screening assay and in vitro enzyme inhibition assay showed that leonurine was a potential inhibitor of COX-2, mPGES-1 and 5-LOX. Compared with COX-2 inhibitor celecoxib , leonurine (30 mg/kg) significantly decreased ankle perimeter, gait score and neutrophil number in synovial fluid in MSU crystal-treated rats, accompanied with the decreased expression of COX-2, mPGES-1 and 5-LOX and production of prostaglandin E 2 (PGE 2 ) and leukotriene B 4 (LTB 4 ) in the synovial fluid macrophages. In addition, leonurine decreased representative M1 marker (iNOS and CD86) expression, NLRP3 inflammasome activation and M1 cytokine (TNF-α and IL-1β) production. In the in vitro cultured RAW264.7 and human monocyte-derived macrophages (MDMs), blockade of COX-2/mPGES-1 and 5-LOX by leonurine inhibited macrophage M1 polarization and NLRP3 inflammasome activation in response to MSU crystals, and thus down-regulated IL-1β and TNF-α with STAT1 and NF-κB inactivation. Conversely, these effects were partially abolished by overexpression of COX-2, mPGES-1, 5-LOX or STAT1. Furthermore, leonurine prevented a positive feedback loop between COX-2/mPGES-1/5-LOX and IL-1β/TNF-α in MSU crystal-induced inflammation. Together, simultaneous down-regulation of COX-2/mPGES-1 and 5-LOX by leonurine ameliorates MSU crystal-induced inflammation through decreasing IL-1β and TNF-α production. Our study may provide novel multi-target agents toward the arachidonic acid (AA) network for gouty arthritis therapy.
研究领域:
药理学
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免疫学
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风湿病学
·
炎症性疾病
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DOI
PubMed
高影响因子
JOURNAL OF MEDICINAL CHEMISTRY
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2022
·
IF 8.039
Wenxia Liu,Yating Liu,Haiyan Fan,Min Liu,Jun Han,Yunfei An,Yue Dong,Bin Sun
The design of novel dual-target (COX-2/CYP51) inhibitors was proposed in the study, and three series of compounds were constructed though the pathway of skeleton screening and combination; their molecular structures were synthesized and evaluated. Most of the compounds exhibited significant antifungal ability. Among them, potential compounds (10a-2, 16b-3) with excellent antifungal and anti-drug-resistant fungal ability (MIC50, 0.125–2.0 μg/mL) were selected for the subsequent mechanistic study. On the one hand, these compounds could block the ergosterol biosynthesis pathway by inhibiting CYP51 and influence the internal physiological function of fungal cells, which included the increase of the ROS level, the anomaly of ΔΨm, and the emergence of an apoptotic state. On the other hand, these compounds also effectively showed COX-2 inhibition ability, eliminated the inflammatory reaction of the infected region, and activated the body’s immune function. In summary, this study not only provided a novel antifungal drug design pathway but also discovered excellent target compounds.
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DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2021
·
IF 5.811
Zhou Yongfeng,Niu Ming,Zhang Dingkun,Liu Zhenxing,Wu Qinghua,Chen Jiang,Zhang Haizhu,Zhang Ping,Pei Jin
Influenza is a common respiratory infectious disease. In China, Lianhua Qingwen capsule (LHQWC), a drug with significant clinical efficacy and few side effects, is commonly used to treat influenza. However, the composition of LHQWC is complicated, and currently used quality control methods cannot ensure its consistency. In this study, combined with its clinical efficacy, the targets of LHQWC were screened using network pharmacology. Then, anti-inflammation quality markers of LHQWC were screened and judged by combined chemical with biological evaluation. Cyclooxygenase-2 (COX-2) was identified as one of the main targets of the anti-inflammatory activity of LHQWC. The rate of inhibition of COX-2 by different batches of LHQWC was determined. Furthermore, seven components of LHQWC were identified. The potential quality markers were screened by spectral-effect relationship. As a result, chlorogenic acid, isochlorogenic acid B, and isochlorogenic acid C were identified and confirmed as anti-inflammatory quality markers of LHQWC. We hope that these findings provide a scientific basis for the accurate quality control of LHQWC and serve as a reference for the quality control of other drugs.
研究领域:
中药学
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药理学
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分析化学
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DOI
高影响因子
Biomed Research International
·
2020
·Vol. 2020
·期 1
·5084057
·
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
BIOMEDICAL CHROMATOGRAPHY
·
2025
·Vol. 39
·期 2
·e6060
·
IF 1.7
Chen Wang,Xueying Qin,Ying Wang,Weiping Wang,Shuai Sun,Hongsen Wang,Shiyu Li,Xiao Dai,Xianhong Zhu,Xun Gao,Kunming Qin,Qing Zhang
Choerospondias axillaris is a medicinal plant used for treating coronary heart disease (CHD) due to its broad spectrum of anti-inflammatory activities. Cyclooxygenase 2 (COX-2) and lipoxygenase 5 (5-LOX) were immobilized on magnetic nanoparticles for selective ligand-extraction of these two enzymes present in C. axillaris . Sixteen extracted components were identified and analyzed using ultraperformance liquid chromatography plus Q-Exactive Orbitrap tandem mass spectrometry (UHPLC-Q-ExactiveOrbitrap-MS/MS), including flavonoids Curcumin and Epicatechin. The metabolization of the aforementioned 16 components in rats with acute blood stasis indicated a solid pharmacodynamic foundation. This method offers an effective approach for conducting basic research on the enrichment, analysis, and efficacy evaluation of active components in complex natural products.
研究领域:
药理学
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分析化学
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天然产物研究
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DOI
PubMed
高影响因子
INFLAMMATION
·
2021
·Vol. 44
·期 5
·2018-2032
·
IF 4.092
Zhou Changkai,Gao Jing,Ji Hongyan,Li Wenjing,Xing Xiaomin,Liu Donghua,Guo Qie,Zhou Lihua,Jing Fanbo
Previous studies have shown that benzoylaconine (BAC), a representative monoester alkaloid, has a potential anti-inflammatory effect. This study investigated the underlying molecular mechanisms using the mode of LPS-activated RAW264.7 macrophage cells. Our findings showed that BAC significantly suppressed the release of pro-inflammatory cytokines and mediators, including IL-6, TNF-α, IL-1β, ROS, NO, and PGE 2 . BAC treatment also effectively downregulated the elevated protein levels of iNOS and COX-2 induced by LPS in a dose-dependent manner. In this study, we found that BAC inhibited LPS-induced NF-κB activation by reducing the phosphorylation and degradation of IκBα by western blotting and blocking the nuclear translocation of p65 using an immunofluorescence assay. The elevated protein levels of JNK, p38, and ERK phosphorylation after LPS stimulation were restored effectively by BAC treatment. The protein expression of Toll-like receptor 4 (TLR4) and LPS-induced phosphorylation of TAK1, which is a crucial upstream regulatory factor of TLR-induced MAPK and NF-κB signaling, were inhibited by BAC in activated RAW264.7 macrophages. Moreover, BAC decreased the levels of TAK1 phosphorylation and pro-inflammatory cytokines and mediators associated with MAPK and NF-κB activation, similar to TLR4 inhibitor TAK-242. These findings demonstrated that BAC exhibited an anti-inflammatory effect by the inhibition of TLR-induced MAPK and NF-κB pathways, indicating that it could potentially be used for treating inflammatory diseases.
研究领域:
免疫学
·
药理学
·
细胞生物学
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炎症研究
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产品关联
DOI
PubMed
高影响因子
Frontiers in Immunology
·
2026
·
IF 7
Jiquan Shen,Changjian Zhou,Xinggao Wang,Yuxuan Chen,Run Liu,Liang Hong,Weiping Ji,Bo Wang
BackgroundRheumatoid arthritis (RA) is a chronic autoimmune disorder characterized by severe synovial inflammation, joint deformities, and progressive tissue destruction. Celastrol (Cel), a natural triterpenoid with anti-inflammatory and antioxidant activity, is a promising therapeutic candidate for RA; however, its application is limited by poor aqueous solubility, low bioavailability, and systemic toxicity.PurposeThis study aimed to develop folate-modified liposomes encapsulating Cel (FA-Cel-LPs) to improve its solubility, stability, and joint accumulation, and to evaluate their anti-inflammatory efficacy and associated molecular changes in LPS-activated RAW264.7 macrophages and collagen-induced arthritis (CIA) rats.MethodsFA-Cel-LPs were prepared by thin-film hydration followed by extrusion and characterized for particle size, morphology, polydispersity index (PDI), encapsulation efficiency (EE), and in vitro release behavior. In LPS-activated RAW264.7 cells, cellular uptake, intracellular ROS levels, NF-κB nuclear translocation, COX-2/iNOS expression, and cytokine secretion were evaluated. In CIA rats, therapeutic efficacy was assessed by paw swelling, arthritis scores, in vivo fluorescence imaging, MRI, histological analysis, and micro-CT-based bone parameters. Safety was evaluated using hemolysis, serum biochemical analysis, and organ histology.ResultsFA-Cel-LPs showed a mean particle size of 110.65 ± 1.24 nm, an EE of 84.67 ± 2.55%, a PDI of 0.230 ± 0.018, and a sustained release profile with pH-dependent differences in vitro. In RAW264.7 cells, folate-modified liposomes showed greater cellular uptake and were associated with reduced ROS levels, attenuated NF-κB activation, and decreased COX-2, iNOS, and pro-inflammatory cytokine expression, with low cytotoxicity. In CIA rats, in vivo imaging suggested greater accumulation of FA-Cel-LPs in inflamed joints. Compared with free Cel and Cel-LPs, FA-Cel-LPs more effectively reduced paw swelling and joint inflammation while attenuating bone erosion and preserving joint architecture. Serum ALT and AST levels in the FA-Cel-LPs group remained within physiological ranges and were significantly lower than those in the free Cel group. Organ histology showed no obvious treatment-related injury, suggesting acceptable preliminary safety.ConclusionFA-Cel-LPs improved the solubility, formulation stability, and apparent joint accumulation of Cel and enhanced its anti-inflammatory and bone-protective effects in experimental RA. These effects were associated with reduced ROS/NF-κB/COX-2-related inflammatory changes, suggesting FA-Cel-LPs may represent a promising liposomal strategy for RA.
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产品关联
DOI
高影响因子
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