Lipids in Health and Disease
·
2025
·Vol. 24
·期 1
·1-15
·
IF 4.2
An He,Cheng Dong-liang,Xia Xian-ru,Li Xian-dong,Ruan Zhi-hua,Peng Chun-yan
Background Dyslipidemia has been extensively documented as a key driver of cardiovascular pathology. Regulating lipid homeostasis holds promise for treating atherosclerosis (AS). Although the protein phosphatase 2 catalytic subunit beta (PPP2CB) is involved in post-transcriptional gene regulation, its role in AS-associated dyslipidemia is not well understood. Methods The study included both human participants and animal models. The following techniques were employed: cell culture, extraction of exosomes, preparation of pooled hyperlipidemic serum (HS), transfection, western blotting, immunofluorescence staining, quantitative reverse transcription polymerase chain reaction (qRT-PCR), co-immunoprecipitation, low-density lipoprotein cholesterol (LDL-C) uptake assay, biochemical assays, assessment of aortic atherosclerotic lesions, as well as statistical analysis. Results This study identified a marked upregulation of PPP2CB expression in peripheral blood leukocytes of AS patients, artery plaque of ApoE −/− mice given a high-fat diet, and hepatic cells exposed to hyperlipidemic stimuli. Overexpression of PPP2CB in hepatic cells exacerbated lipid accumulation and low-density lipoprotein uptake, whereas silencing PPP2CB mitigated this effect. Immunofluorescence co-localization and co-immunoprecipitation analysis confirmed a direct interaction between PPP2CB and lectin-like oxidized LDL receptor-1 (LOX-1). Notably, PPP2CB manipulation disrupted hyperlipidemia-induced LOX-1 expression. Additionally, PPP2CB-mediated lipid dysregulation was linked to the activation of the LOX-1/ mitogen-activated protein kinase (MAPK)/ extracellular signal-regulated kinase (ERK) signaling cascade. Conclusions These results unveil PPP2CB as a novel lipid regulator in the progression of pathological AS and highlight its involvement in signaling regulation during abnormal lipid metabolism. PPP2CB could be considered a promising candidate for biomarker development and therapeutic intervention in AS.
研究领域:
生物学
·
医学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Biomed Research International
·
2021
·
IF 3.411
Ruixi Luo,Lifeng Zhao,Shuaishuai Li,Peng Chen,La Wang,Honghong Yu,Kun Cai,Qi Yu,Weiyi Tian
Excessive free fatty acid- (FFA-) induced endothelial lipotoxicity is involved in the pathogenesis of atherosclerosis. Endoplasmic reticulum (ER) stress is mechanistically related to endothelial lipotoxicity. Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) is the major oxidatively modified low-density lipoprotein (OxLDL) receptor in endothelial cells and is highly abundant in atherosclerotic lesions. Curcumin reduces the LOX-1 expression; however, the mechanism underlying this effect remains unknown. In the current study, we explored whether curcumin ameliorates palmitic acid- (PA-) induced endothelial lipotoxicity and LOX-1 upregulation by reducing ER stress in human umbilical vein endothelial cells (HUVECs). We built endothelial lipotoxicity in vitro and found that LOX-1 was upregulated after PA stimulation, during which ER stress played an important role. Next, we observed that curcumin substantially alleviated PA-induced lipotoxicity by restoring cell viability, increasing angiogenesis, and decreasing lipid deposition. Furthermore, LOX-1 upregulation in HUVECs was blocked by curcumin, possibly via ER stress suppression. Overall, our findings demonstrated that curcumin alleviates endothelial lipotoxicity and LOX-1 upregulation, and ER stress inhibition may play a critical role in this effect.
研究领域:
心血管研究
·
分子生物学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Neuroinflammation
·
2025
·Vol. 22
·期 1
·1-16
·
IF 10.1
Ding Peng-Fei,Zhang Jia-Tong,Zhu Xiao-Long,Cui Yue,Chen Chun-Lei,Liu Xun-Zhi,Shen Jun-Da,Zou Le-Xuan,Lu Yue,Zhuang Zong,Hang Chun-Hua,Li Wei
Background
Subarachnoid hemorrhage (SAH) is a common acute condition in neurosurgery, with microglial function playing a crucial role in determining patient outcomes. However, the involved mechanisms are complex and demand thorough investigation. In our study, we combined transcriptomic and metabolomic approaches to identify key regulators of microglial function, offering novel insights for potential therapeutic strategies in SAH treatment.
Methods
The neurological function of SAH mice was evaluated using the open field test, rotarod test, and nissl staining. In an in vitro SAH model, key pathways and genes that regulate microglial function were identified through the integration of transcriptomics and metabolomics. Enzyme-Linked Immunosorbent Assay, Immunofluorescence, Western blot, Real-Time PCR, pHrodo, and Lyso-Tracker were employed to assess lysosomal and microglial function.
Results
In SAH mice, both neurological and microglial functions were significantly impaired on the first day but showed recovery over time. The combined results from transcriptomics and metabolomics identified 5-lipoxygenase (5-LOX) as a key target in regulating microglial function post-SAH. Administering resolvin D1 (RvD1) exogenously to inhibit 5-LOX nuclear translocation or directly supplementing lipoxin A4 (LXA4) to adjust the leukotriene B4 (LTB4)/LXA4 ratio, can improve lysosomal acidification, mitigate impaired lysosomal function, and enhance phagocytosis while reducing the inflammatory response. Protecting microglial function can also be achieved through JNJ or P2X purinoceptor 7 (P2X7) siRNA, which inhibit calcium/calmodulin-dependent protein kinase II (CaMKII) activation, prevent 5-LOX nuclear translocation, and improve lysosomal function. Furthermore, P2X7 siRNA also improved neurological function, lysosomal function and microglial function in SAH mice.
Conclusion
Activation of P2X7-CaMKII after SAH promotes 5-LOX nuclear translocation, increases the LTB4/LXA4 ratio, elevates intracellular Ca2+ concentration, and impairs lysosomal and microglial function.
研究领域:
神经科学
·
神经病学
·
分子生物学
·
免疫学
·
药理学
✓ 已验证
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
✓ 已验证
产品关联
DOI
高影响因子
EXPERIMENTAL CELL RESEARCH
·
2022
·
IF 4.145
Runze Zhao,Li Yang,Shuangjian He,Tingting Xia
Intervertebral disc degeneration (IVDD) is a main contributor to induce low back pain, and the pathogenic mechanism of IVDD remains unclear. The nucleus pulposus (NP) is a component of the intervertebral disc (IVD) that provides protection from mechanical stimuli. The matrix stiffness of NP tissue increases during the process of disc degeneration. Although several studies have found that pathological mechanical stimuli induce NP cell senescence, which is relevant for NP degeneration, however, the effect of matrix stiffness on NP cell senescence is not clear. Therefore, in the present study, we used polyvinyl alcohol (PVA) hydrogel with controllable stiffness to mimic the matrix stiffness of normal (4 kPa) and severely degenerated (20 kPa) NP tissue. Rat NP cells were isolated and cultured on substrates with different stiffness, and the cell proliferation , SA-β-gal activity, cell cycle, telomerase activity and the phenotype markers of NP cells were analyzed. Moreover, cytoskeleton staining and NP cellular Young's modulus on different substrates were also measured. To further investigate how substrate stiffness affects NP cell senescence, lysyl oxidase (LOX) was used to restore the extracellular matrix (ECM) synthesis of NP cells. The expression levels of integrin β1 and p38 MAPK were then measured. Our results showed that the 20 kPa substrate significantly induced NP cell senescence compared to the 4 kPa substrate. NP cells cultured on the 20 kPa substrate failed to maintain the expression of their phenotype markers. Furthermore, the 20 kPa substrate induced an increase of Young's modulus of NP cells, which possibly through up regulating the expressions of integrin β1 and p38 MAPK. These results indicated that the integrin β1-p38 MAPK signaling pathway may participated in substrate stiffness induced senescence of NP cells. LOX significantly increased ECM synthesis and inhibited substrate stiffness induced NP cell senescence, which indicated that matrix mechanics may be essential for maintaining the function of NP cell. Our results may provide a new perspective on the mechanism of IVDD by pathological matrix mechanics.
研究领域:
骨科
·
细胞生物学
·
生物力学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INFLAMMOPHARMACOLOGY
·
2024
·
IF 4.6
Iqbal Urooj,Malik Abdul,Sial Nabeela Tabassum,Mehmood Malik Hassan,Nawaz Shoaib,Papadakis Marios,Fouad Dalia,Ateyya Hayam,Welson Nermeen N.,Alexiou Athanasios,Batiha Gaber El-Saber
Background The current study aimed to evaluate the anti-inflammatory, anti-oxidant, and pronounced gastro-protective activities of β- Citronellol using in vitro , in vivo assays and in silico approaches. Methods In vitro assays, denaturation of bovine serum albumin, egg protein, and human Red Blood Cells (RBCs) membrane stabilization were performed, using Piroxicam as standard. For in vivo assessment, Histamine (0.1 ml from 1% w/v) and Formaldehyde (0.1 ml from 2% v/v) were used to mediate inflammation. In silico molecular docking and network pharmacology were employed to probe the possible target genes mediating gastroprotective effect of β-Citronellol at 25, 50, and 100 mg/kg, using indomethacin-induced (25 mg/kg i.p) gastric ulcer in rats. Moreover, Gastric tissues were evaluated for morphological, histopathological, and bio-chemical analysis of PGE 2, COX-I, COX-II, 5-LOX, eNOS, ICAM-1, oxygen-free radical scavengers (SOD, CAT), and oxidative stress marker (MDA). Results β - Citronellol prevented denaturation of proteins and RBCs membrane stabilization with maximum effect observed at 6,400 µg/mL. Citronellol decreased rat’s paw edema. Network pharmacology and docking studies revealed gastro-protective potential of Citronellol possibly mediated through arachidonic acid pathways by targeting COX-I, COX-II, PGE 2 , and 5-LOX. Citronellol reduced the ulcer indices, and histopathological changes. Further, β - Citronellol (50 and 100 mg/kg) increased gastric PGE 2, COX-1, and eNOS; while suppressing COX-2, 5-LOX and ICAM-1. Citronellol markedly enhanced the oxidative balance in isolated rat stomach tissues. Conclusions The anti-inflammatory, anti-oxidant, and gastro-protective effects of β - Citronellol against indomethacin-induced gastric ulcer model in rats through mediating COX-I, COX-II, PGE 2, 5-LOX, eNOS, and ICAM-1 inflammatory markers. Graphical abstract
研究领域:
药理学
·
炎症
·
胃肠病学
·
分子生物学
·
生物化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nano Today
·
2025
·
IF 10.9
Xueting Liu,Dingze Zhou,Yuxi Zhang,Zonghui Zhao,Wenhao Zhao,Xia Wang,Qigang Wang
Tumor cells, due to their reliance on aerobic glycolysis, contribute to the tumor microenvironment (TME), which is characterized by lactate accumulation and redox imbalances. Targeting lactate, a key metabolic substrate in the TME, a novel strategy combining gene therapy with enzyme dynamic therapy (EDT) has been proposed. This strategy utilizes a cascade oxidase-peroxidase system, which induces tumor DNA damage while simultaneously inhibiting repair mechanisms. By mimicking the construction of multienzyme complexes, a highly active and well-ordered oxidase-peroxidase and gene platform (ASO-miR21/DLC-NGs) has been developed. The platform is based on dextran-confined lactate oxidase (LOx) and chloroperoxidase (CPO) pairs, followed by small molecule monomer-induced diffusion-controlled self-terminating polymerization for efficient loading of Antisense Oligonucleotide targeting microRNA-21 (ASO-miR21). By precisely regulating the dimensions (nanoscale to microscale) and crosslinking density, this approach overcomes the limitations of traditional multi-enzyme systems, such as poor stability and inefficient substrate diffusion. The synergistic effects of DNA damage and anti-repair are achieved by catalytically regulating reactive oxygen species (ROS), which reverses the redox balance and downregulates miR21 expression, inhibiting tumor cell proliferation. The catalytic transformation research of metabolic substrates of abnormal tumor microenvironment and the multi-pathway design with the metabolic regulation can provide important insights for specialized or interdisciplinary researchers on the multipathway cancer therapy.
研究领域:
生物医学工程
·
肿瘤学
·
分子生物学
✓ 已验证
产品关联
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
·
分析化学
·
天然产物研究
✓ 已验证
DOI
PubMed
高影响因子
Chinese Journal of Integrative Medicine
·
2026
·
IF 3.1
Wang Ya-fen,Yue Shi-jun,Li Jia-yao,Meng Si-tong,Zheng Min,Zhang Yu-fang,Gu Ying,Hou Bin,Biao Ya-ning
Objective To explore the molecular mechanism of Xuefu Zhuyu Decoction (XFZYD) against myocardial fibrosis. Methods The active components of XFZYD were identified by high performance liquid chromatography (HPLC). Network pharmacology, molecular docking, and affinity dot-mass spectrometry (AD-MS) were used to predict and validate the binding interaction between XFZYD components and copper transporter 1 (CTR1). Sixty male Kunming mice were randomly divided into 6 groups using a random number table. Control, isoproterenol hydrochloride (ISO), captopril, low-, medium-, and high-dose XFZYD (5.69, 11.38, and 22.76 g/kg) groups, with 10 mice in each group. Except the control group, mice received daily subcutaneous injection of ISO (10 mg/kg) for 28 d to induce myocardial fibrosis, concurrently treated with respective drugs by gavage. Cardiac function was assessed by echocardiography (ECG) and electrocardiography (UCG). Serum myocardial injury markers and transforming growth factor beta 1 (TGF-β 1) were measured by a biochemical analyzer and enzyme-linked Immunosorbent assay (ELISA). Pathological changes and collagen deposition was observed using HE, Masson and sirius red staining methods. Copper content in cardiac tissue was determined by inductively coupled plasma mass spectrometry (ICP-MS), and protein expressions of collagen I, III, alpha-smooth muscle actin (α-SMA), lysyl oxidase (LOX), CTR1, copper chaperone for superoxide dismutase (CCS), and cytochrome c oxidase 17 (COX17) were detected by Western blot, immunohistochemistry, and immunofluorescence. In vitro , TGF-β 1 (5 ng/mL)-stimulated NIH-3T3 fibroblasts were treated with XFZYD (60 mg/L), with or without CuCl 2 (20 µ mol/L) or SLC31A1 overexpression for 24 h, and the same indicators were evaluated. Results HPLC identified 7 major components in XFZYD. Network pharmacology revealed that XFZYD targets copper metabolism related genes. Molecular docking showed strong binding affinities between the 7 compounds and CTR1, and AD-MS confirmed direct binding of paeoniflorin and amygdalin to CTR1. In vivo , XFZYD could ameliorate the collagen deposition, cardiac dysfunction, and elevated levels of collagen I/III, α-SMA, LOX, and copper content exhibited in ISO-induced myocardial fibrosis mice ( P <0.05 or P <0.01). In vitro , XFZYD had the effects of suppressing copper overload and the upregulation of LOX, collagen I/III, and α-SMA in TGF β 1 stimulated NIH-3T3 fibroblasts, whereas co-treatment with CuCl 2 exacerbates these fibrotic responses and attenuates the protective effect of XFZYD ( P <0.05 or P <0.01). XFZYD had the effect of partially reversing the enhanced copper accumulation, LOX activation, and collagen deposition induced by SLC31A1 (CTR1) overexpression in TGF β 1 stimulated fibroblasts, and SLC31A1 overexpression reduces its efficacy ( P <0.05 or P <0.01). Conclusions XFZYD exerted a protective effect against ISO-induced myocardial fibrosis. The mechanism may be related to regulating the CTR1–copper–LOX axis, thereby reducing excessive collagen deposition and cross-linking in cardiac fibroblasts.
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2023
·
IF 5.4
Amina Arken,Xinmin Zhao,Yanhua Gao,Adil Omar,Dan Tang,Ahmidin Waili,Zi Yang,Yahui Wang,Haji Akbar Aisa,Abulimiti Yili
Ethnopharmacological relevance Lamb abomasum is used as an edible medicinal source in traditional Chinese medicine for the treatment of gastrointestinal disorders . Lamb abomasum sourced biochemical drug Lamb's trip extract and Vitamin B12 capsule used for the clinical treatment of chronic gastritis , gastric ulcer , and reversal of intestinal metaplasia . Therefore, claimed to have prevention of gastric cancer activity. Aim of the study In this study, we aim to assess whether the glycoprotein has biological activity in the cure of gastric disorder and conduct a structure-activity relationship. Materials and methods Glycoproteins’ extraction conditions were optimized by the response surface method and purified with DEAE-cellulose and Sephadex G-50 chromatography. Two homogenous glycoproteins’ physiochemical structures were studied with electrophoresis , HPLC analysis, peroxide oxidation, and β-elimination, FT-IR, CD, LC-MS/MS, and EDS analysis. The antiinflammation activity of the glycoprotein was determined against COX-2 and LOX-15 enzyme inhibitory ability in vitro, and antitumor activity against HT-29 and HGC-25, and cytotoxicity on L-02 cells was determined in vivo with the MTT method. Results The abomasum was abundant in glycoprotein and the extraction yield of glycoprotein was up to 24.6 ± 2.1% under optimized conditions. Two homogeneous glycoproteins SAGP-I and SAGP-II determined to be ribose-conjugated and sulfated glycoproteins with a molecular weight of 15.6 kDa and 6.4 kDa. And according to the structural analysis, SAGP-I was a mucin-type ribose-conjugated glycoprotein with 14 O-glycosylation and one N- glycosylation site. SAGP-I and SAGP-II have remarkable anti-inflammatory activity against COX-2 enzyme with the IC 50 of 17.64 ± 1.25 μ g/mL and 16.14 ± 1.11 μ g/mL, respectively. Meanwhile, the two glycoproteins showed strong antitumor activity against HT-29 with the EC 50 of 19.19 ± 1.46 μ g/mL and 184.9 ± 5.6 μ g/mL, respectively. Conclusion The Highly purified glycoprotein SAGP-1 and SAGP-II showed anti-inflammatory activity against the COX-2 enzyme, and antitumor activity against HT-29 human colon cancer cells and noun-inhibitory activity against LOX-15 enzyme and HGC-25. Both glycoproteins are ribose conjugated and sulfated whose characters are related to their anti-inflammatory and anti-tumor activity. Such results suggest the possibility of anti-inflammatory and pre-cancer activity. And in some degree explains the pharmacy of abomasum's traditional use in gastric disorder and clinical use of lamb abomasum APIs drugs’ in gastric disorders and gastric cancer development. This study provides a preliminary basis for the further study of the per-cancer mechanism of lamb abomasum glycoprotein. And, would be the material basis of the clinical use of Lamb's trip extract and Vitamin B12 capsule.
研究领域:
药理学
·
生物化学
·
民族药理学
·
肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MICROCHEMICAL JOURNAL
·
2025
·
IF 5.1
Wei Wang,Yi Zheng,Ran Xia,uqiao Cheng,Shunan Lv,Nuo Xu,Xueyin Shi,Haiying Ji,Weiwei Li
Sepsis induces excessive inflammation and immune dysfunction via infection, often progressing to multiple organ dysfunction syndrome (MODS). Serum lactate is a key biomarker for evaluating tissue perfusion, oxygen metabolism, and prognosis in sepsis, making rapid, accurate, and portable lactate detection critical for sepsis management. To address this, we developed a portable screen-printed carbon electrode (SPCE) modified with a PB@PDA/LOX composite. PB nanoparticles enhance electrocatalysis to accelerate electron transfer and reduce oxidation overpotential, enabling the sensor to exhibit a linear response (2–1000 μmol/L, LOD = 1.195 μM) that matches lactate levels in pretreated sepsis serum; its low oxidation potential (~0.1 V vs. Ag/AgCl) also avoids interference from coexisting substances. Glutaraldehyde (via dual-terminal aldehyde bridging) immobilizes LOX, while PDA forms a stable “substrate-PB-PDA-LOX” structure-this provides a biomimetic microenvironment to prevent LOX inactivation, reduces non-specific protein adsorption, and extends detection lifetime. The mass-produced SPCE (1 cm × 2 cm, low cost) integrates with compact detectors for “drop-and-detect” functionality, with detection time < 5 min. Via multi-component synergy, this modified electrode overcomes limitations of existing sensors (stability, sensitivity, anti-interference, portability) and offers an efficient lactate detection tool for sepsis patient assessment and animal model mechanism studies.
研究领域:
生物医学工程
·
电分析化学
·
即时检测
·
生物传感器
·
重症医学
✓ 已验证
产品关联
DOI
高影响因子
PROSTAGLANDINS & OTHER LIPID MEDIATORS
·
2026
·
IF 2.6
Lili Liu,Lijuan Xue,Guiyue Hou,Jingxuan Zhang,Ling Tian,Xueqin Wang,Ronghua Dai
Inflammation initiates and progresses due to overexpression of the arachidonic acid cascade mediators. Cyclooxygenase (COX) and lipoxygenase (LOX) are considered to be the primary targets, and the aim of this study was to assess the anti- inflammatory activity of several herbal compounds as dual COX-LOX inhibitors on prostatic diseases. Compounds Timosaponin AⅡ, timosaponin AⅢ, berberine and demethyleneberberine were selected according to our previous studies. Human prostate cancer cells (PC-3) were cultured and the cell viability was detected by CCK-8 method at different concentrations. Ultra high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was applied to monitor the changes of AA metabolites after treatment. Western blot and qPCR were used to detect COX-2 and LOX-5 at protein and mRNA levels, respectively. Additionally, the levels of inflammatory factors (IL-6, IL-1β, TNF-α) in each group were detected by ELISA. After drug interference, 13 altered metabolites associated with the COX/LOX pathway, including PGE 2 , 5-HETE, LTB 4 , etc. were identified in cell medium. Quantitative metabolomics analysis showed that the candidate compounds could significantly decreased the concentrations of dual target related metabolites to varying degrees ( P < 0.01). These compounds could also suppressed COX-2 and LOX-5 expression at the protein and mRNA levels simultaneously. Moreover, the levels of cytokine IL-6, IL-1β and TNF-α were also significantly reduced in the treated group compared to controls ( P < 0.05 or P < 0.01). Our findings revealed the four active compounds were potential COX/LOX dual-target inhibitors, which inhibited a range of inflammatory responses by interfering with AA metabolism and down-regulating the levels of COX and LOX metabolites.
✓ 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）