TRANSPLANTATION
·
2024
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IF 5.3
Jia Degong,Wu Kun,Luo Jiefu,Xu Xuesong,Pan Wei,Zhao Minjie,Li Shengwei,Gong Jianping,Gong Junhua
Background. Donation after circulatory death livers are more susceptible to ischemia/reperfusion injury (IRI) because of a longer period of warm ischemia. Growing evidence now suggests that ferroptosis plays a key regulatory role in the development of IRI, so targeting ferroptosis may be an effective strategy to alleviate IRI in liver transplantation (LT). Methods. Using donation after circulatory death LT models in rats and oxygen-glucose deprivation/reoxygenation (OGD/R) models in BRL-3A cells, we tested the effect of the Chinese medicine monomer wogonin on liver IRI and explored the specific mechanism. Results. Wogonin attenuated liver IRI and increased the survival rate of rats by inhibiting lipid peroxidation and ferroptosis. Mechanistically, arachidonic acid 15-lipoxygenase-1 (ALOX15) and inducible nitric oxide synthase (iNOS) were identified as potential targets of baicalein through bioinformatics analysis combined with in vivo and in vitro experiments. This result was further confirmed by molecular docking and cellular thermal shift assays. Finally, we silenced ALOX15 and iNOS in the OGD/R cell model and found that silencing ALOX15 and iNOS could reproduce the regulatory effect of wogonin and abrogate the regulatory effect of wogonin. Conclusions. In brief, this study emphasizes that wogonin exerts a protective effect in liver IRI through the regulation of ALOX15- and iNOS-mediated ferroptosis. ALOX15 and iNOS are potential targets for intervention in IRI induced by LT, and wogonin is a drug candidate for LT patients. Export
研究领域:
移植医学
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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
LIFE SCIENCES
·
2024
·
IF 5.2
Qiuwen Fei,Jian Zhang,Liangqiong Chen,Manqi Shi,Qinglan Wang,Feifan Xu,Jiahai Shi,Yongwei Qin
Background Mycobacterium tuberculosis infection triggers various forms of host cell death, including ferroptosis in lung epithelial cells; YY1, a critical transcription factor, plays a pivotal role in regulating ferroptosis, however, the underlying mechanisms are not fully understood. Methods To investigate Mycobacterium marinum ( M.marinum )infection in lung epithelial cells A549 and H1299, we utilized flow cytometry to evaluate cell death and measure reactive oxygen species (ROS). Colony-forming unit (CFU) assays determined the intracellular bacterial load. Ferroptosis was analyzed using a specific detection kit to measure malondialdehyde (MDA) and glutathione (GSH) levels. The interaction between the transcription factor YY1 and the iNOS promoter was assessed through a dual-luciferase reporter assay. Results M.marinum induced ferroptosis in lung epithelial cells through invasion. This effect is most pronounced at 8 h of infection and decreases over time but increased with a higher multiplicity of infection (MOI). YY1 knockdown decreases the expression of SLC7A11 and GPX4, attenuates cellular ferroptosis, while YY1 overexpression has the opposite phenomenon, enhancing the expression of bactericidal molecules such as iNOS and MPEG1, thereby markedly reducing the intracellular bacterial load. We identified substantial binding of YY1 to the iNOS promoter region (−655 to −1018 bp), enhancing mycobactericidal activity in YY1-overexpressing cells. Conclusions Our study demonstrates that YY1 inhibits ferroptosis induced by Mycobacterium marinum infection and reduces intracellular bacterial proliferation in lung epithelial cells. These findings provide a crucial basis for developing anti-tuberculosis therapies that target YY1 modulation, potentially offering new clinical avenues for the treatment of tuberculosis.
研究领域:
微生物学
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细胞生物学
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传染病学
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药理学
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DOI
PubMed
高影响因子
BIOMEDICINE & PHARMACOTHERAPY
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2019
·
IF 3.743
Zhongchao Wang,Ying Yan,Yini Wang,Fei Tong
Introduction The purpose of the experiment was to survey the therapeutic function of resveratrol (RES)-loaded poly(ethylene glycol)-poly(phenylalanine) (PEG-PPhe) on intestinal ischemia/reperfusion injury (II/RI) via the interaction between CSE/H 2 S and iNOS/NO compared to free RES in diabetic rats. Methods Diabetic rats were pretreated with 20 mg/kg of RES or the RES/PEG-PPhe complex and then subjected to 1 h of ischemia and 3 h of reperfusion. Blood and intestines were collected, intestinal pathological injury was estimated, and the contents of body weight, weights of different tissues, blood glucose, serum insulin, HOMA index, serum nitric oxide (NO) and serum sulfureted hydrogen (H 2 S) were observed. The dry/wet intestine ratios, the activity of superoxide dismutase (SOD); the contents of methane dicarboxylic aldehyde (MDA), glutathione (GSH), H 2 S, and NO; and the concentrations of inducible nitric oxide synthase (iNOS) and cystathionine-γ-lyase (CSE) were observed in the intestinal tissues. Results A significant reduction of weights of different tissues, blood glucose, pathological damage, dry/wet ratios, MDA, NO, iNOS expression and a significant increasement of body weight, serum insulin, HOMA index, SOD, GSH, H 2 S, CSE expression were observed in both treatment groups. However, a greater reduction of weights of different tissues, blood glucose (7.49–13.49 mmol/L for 72 h vs. the control) and pathological damage, iNOS expression, dry/wet ratios (6.14 ± 0.29 vs. 8.51 ± 0.42), MDA (5.01 ± 0.71 nmol vs. 9.98 ± 0.67 nmol), NO (0.52 ± 0.09 μmol vs. 0.99 ± 0.08 μmol in intestinal tissue; 19.29 ± 0.89 μmol vs. 45.23 ± 1.17 μmol in serum) was observed in the RES/PEG-PPhe group relative to the I/R ( P < 0.01 for all); a greater increasement of body weight, serum insulin, HOMA index, SOD (39.79±1.78 U vs. 11.84 ± 1.02 U), GSH (31.25 ± 1.19 mg vs. 10.13 ± 0.64 mg), H 2 S (39.52 ± 1.32 nmol vs. 13.02 ± 1.03 nmol in intestinal tissue; 9.78 ± 0.79 μmol vs. 3.11 ± 0.85 μmol in serum), CSE expression was observed in the RES/PEG-PPhe group relative to the I/R ( P < 0.01 for all). In addition, aminoguanidine (AMI, iNOS inhibitor) reduced I/R injury, and dl -propargylglycine (PAG, CSE inhibitor) increased I/R injury. Conclusions The interaction between CSE/H2S and the iNOS/NO-mediated resveratrol/poly(ethylene glycol)-poly(phenylalanine) complex alleviates intestinal ischemia/reperfusion injuries in diabetic rats.
研究领域:
药理学
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医学
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分子生物学
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糖尿病研究
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产品关联
DOI
PubMed
高影响因子
Acta Biomaterialia
·
2025
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IF 9.6
Chunxia Liu,Mengjing Lin,Jing Dai,Binglin Chen,Jiali Wang,Jingyi Li,Xiaoyun Li,Ziyun Jiang,Miao Xiao,Mingliang Tang
Vascular calcification (VC) is a critical pathological hallmark of cardiovascular diseases but current therapeutic options remain inadequate. Nitric oxide (NO) homeostasis plays a vital role in endothelial function and phenotypic transformation of vascular smooth muscle cells (VSMCs), two key pathological processes in VC. In this study, Fe₃O₄@PDA@BNN6 (FPB) nanoparticles were prepared for directional and controllable NO therapy. Magnetic field enriched the nanoparticles to the site of VC and ultrasound triggered the controllable release of NO to regulate the homeostasis of endothelial nitric oxide synthase (eNOS) and inducible nitric oxide synthase (iNOS), further activated sGC-cGMP-PKG signaling pathway. Both in the rat and in vitro VC models, the innovative therapy inhibited osteogenic like transformation of VSMCs, alleviated endothelial inflammatory response, regulated eNOS/iNOS homeostasis, and effectively improved VC. By ensuring optimal NO bioavailability for vascular homeostasis, this magneto-ultrasonically controlled strategy overcomes limitations of conventional NO-based therapies and paves the way for precision NO-mediated interventions in cardiovascular diseases. Statement of Significance Engineering innovation: Dual-modality nanoparticle system for precision NO delivery: Magnetic guidance directs the FPB to calcified lesions, reducing systemic off-target effects. Ultrasound-triggered release of NO to ensure on-demand delivery at VC sites. Mechanistic innovation: Restoring eNOS/iNOS homeostasis as a therapeutic axis: Directional and controllable NO therapy uniquely modulates eNOS/iNOS homeostasis, further activating the sGC-cGMP-PKG signaling pathway.
研究领域:
心血管医学
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纳米医学
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分子治疗
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生物医学工程
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氧化还原生物学
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产品关联
DOI
PubMed
高影响因子
MOLECULAR CANCER THERAPEUTICS
·
2019
·Vol. 18
·期 1
·62-74
·
IF 4.856
Wang Hongzhi,Zhong Weilong,Zhao Jianmin,Zhang Heng,Zhang Qiang,Liang Yuan,Chen Shuang,Liu Huijuan,Zong Shumin,Tian Yixuan,Zhou Honggang,Sun Tao,Liu Yanrong,Yang Cheng
Oleanolic acid exhibits extensive pharmacologic activities and takes significant antitumor effects. Its pharmacologic mechanism, however, still remained to be further clarified. In this study, we demonstrated that oleanolic acid attenuated the migration and invasion abilities, resulting in the suppression of the epithelial–mesenchymal transition (EMT) process in liver cancer cells, and inhibited the tumor growth of the peritoneal lymphocytes–bearing mice. We further proved that inducible nitric oxide synthase (iNOS) may be the potential target of oleanolic acid. We confirmed that oleanolic acid could promote the dimerization of iNOS, activating it, and subsequently increasing the production of nitric oxide. Further experiments indicated that oleanolic acid promoted the nitration of specific proteins and consequently suppressed their EMT-related biological functions. Furthermore, it has been confirmed that oleanolic acid enhanced the antitumor effects of regorafenib in liver cancer treatment. These results deepened our understanding of the pharmacologic mechanism of the antitumor effect oleanolic acid, and the importance of nitric oxide synthetase as a therapeutic target for liver cancer treatment.
研究领域:
药理学
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肿瘤学
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分子生物学
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DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2019
·
IF 3.361
Runxiao Lv,Lili Du,Xueyong Liu,Fenghua Zhou,Zhiqiang Zhang,Lixin Zhang
Polydatin is a glucoside of resveratrol with lots of functional properties in the central nervous system , such as anti-edema, anti-oxidation and anti-inflammation. The purpose of this study was to evaluate the effects of polydatin on traumatic spinal cord injury (SCI) and explore the relative mechanisms. SCI models were established using the weight-drop method in rats, additionally, single polydatin administration (20, 40 mg/kg body weight) remarkably improved motor function of SCI rat, along with decreased nitric oxide (NO) generation and inflammatory factor (IL-1β, IL-6 and TNF-α) production in spinal cord tissues. Similar to the results of in vivo experiments, the inflammatory response was aggravated with the intervention of lipopolysaccharide (LPS) in BV2 microglia . However, polydatin treatment (1, 2 and 4 μM) inhibited iNOS expression, decreased NLRP3 inflammasome activation, which subsequently relieved microglial inflammation. Above all, our data indicated that polydatin possessed neuroprotective effects in SCI rats, possibly by suppressing iNOS expression and NLRP3 inflammasome activation in microglia.
研究领域:
神经科学
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药理学
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炎症
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2025
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IF 8.5
Kexin Liu,Yanling He,Shasha Li,Han Tao,Liang Wei,Jianqin Huang,Chenyu Jiang,Mohamed A. Farag,Lili Song,Fei Gao
Neuroinflammation, a critical innate immune response in the central nervous system (CNS), is closely associated with dysregulated inflammatory pathways. Targeting key mediators such as inducible nitric oxide synthase (iNOS) and the NF-κB/MAPK signaling axis offers a promising strategy for mitigating inflammatory cascades. In this study, three novel peptides derived from Carya cathayensis (DFR, GAR, NAK) were computationally screened via molecular docking and dynamics simulations for their iNOS inhibitory potential. DFR demonstrated superior binding affinity and stability, validated through in vitro assays where it significantly suppressed LPS-induced nitric oxide (NO) and pro-inflammatory cytokine (IL-1β, TNF-α, IL-6) production in BV2 microglia. To enhance therapeutic efficacy, DFR was engineered into a nanostructured delivery system (pADFR) through conjugation with a targeting ligand and PEGylation. In vivo evaluations revealed that pADFR alleviated LPS-induced behavioral deficits and reduced inflammatory mediators in mice, with mechanistic studies highlighting its suppression of NF-κB/MAPK pathway activation. This study underscores the potential of peptide-based nanostructures for targeted modulation of neuroinflammatory pathways, offering a platform for precision therapeutic development.
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产品关联
DOI
高影响因子
EUROPEAN JOURNAL OF PHARMACOLOGY
·
2026
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IF 5.7
Zhen-Min Zhang,Lian Zhu,Ru-Yue Zhang,Han-Xiu Deng,Shun-Li Xiao,Zi-Xuan Liu,Jia-Yu Zhang,Wei Cai
Background Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are severe respiratory diseases with high global incidence and mortality. Current therapeutic approaches remain limited, necessitating urgent development of novel treatments. Supramolecular complexes have gained attention in biomedicine due to their unique structural and functional properties. Purpose This study aimed to evaluate the therapeutic potential of neochlorogenic acid-copper supramolecular complexes (NA-Cu) against ALI/ARDS, building on prior evidence of its anti-inflammatory effects in vitro, and to elucidate its underlying metabolic mechanisms. Study design In vivo experimental investigation using an ALI model to assess NA-Cu's effects on lung pathology, inflammatory markers, and metabolic pathways. Mechanistic insights were validated through integrated metabolomics and molecular pathway analysis. Methods The therapeutic efficacy of neochlorogenic acid-copper supramolecular complexes (NA-Cu) was assessed by quantifying its effects on lung edema severity and pro-inflammatory cytokine expression levels (IL-1β, IL-6, TNF-α) in an ALI model. Mechanistic profiling was performed using an integrated analytical approach combining air flow-assisted desorption electrospray ionization mass spectrometry imaging (AFADESI-MSI) with untargeted metabolomics to map spatial metabolic alterations. Subsequently, we screened dysregulated metabolic pathways and signaling cascades, with emphasis on the PI3K/NF-κB/iNOS axis. Validation studies established correlations between NA-Cu-induced metabolic shifts and key therapeutic outcomes, including anti-inflammatory efficacy and histological protection of lung tissue. Results This study further found that neochlorogenic acid-copper supramolecular complexes can improve edema in lung tissue by inhibiting the expression of IL-1β, IL-6, and TNF-α. The anti-ALI metabolism mechanism of NA-Cu is revealed through AFADESI-MSI combined with metabolomics. It was found that supramolecular complexes mainly affects sphingolipid metabolism, linoleic acid metabolism, α linolenic acid metabolism, ether lipid metabolism, glycerol phospholipid metabolism, arachidonic acid metabolism and PI3K/NF-κB/iNOS pathway to improve protection of lung tissue. Conclusion NA-Cu demonstrates robust anti-ALI/ARDS efficacy by synergistically suppressing inflammation and reprogramming lipid metabolism. This study validates the therapeutic promise of supramolecular complexes for ALI treatment and provides novel mechanistic insights into their mode of action.
✓ 已验证
产品关联
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
·
药物递送系统
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产品关联
DOI
PubMed
高影响因子
CyTA-Journal of Food
·
2016
·
IF 0.769
Xu Si,Zhongkai Zhou,Dandan Bu,Jing Li,Padraig Strappe,Chris Blanchard
Polysaccharides were extracted from corn bran (CBPs) and then modified by a sulfating reaction to obtain sulfated corn bran polysaccharides (SCBPs). Synthesized sulfated polysaccharides were located in the equatorial bonds of monosaccharide residues. A more orderly and smooth surface of SCBPs was observed. Single factor experiment results showed 2.0 g of aminosulfonic acid, 60 mL of N-dimethylformamide and 2.5 h of reaction time were the optimum conditions for SCBPs preparation. Phenolic content of SCBPs significantly decreased with increasing concentration of aminosulfonic acid, while it increased with increasing DMF concentration and reaction time. SCBPs had higher DPPH, ABTS and iron chelating capacity under the optimum conditions. SCBPs significantly inhibited the proliferation of A549 and HepG2 cell lines, which was associated with the up-regulation at the mRNA expression level of pro-apoptotic genes CASP3, CASP8, CASP9 and reduced expression of p53, gene Bcl-2 and gene iNOS.
研究领域:
生物化学
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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
✓ 已验证
DOI
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
·
炎症研究
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产品关联
DOI
PubMed
高影响因子
CANCER SCIENCE
·
2020
·Vol. 111
·期 10
·3802-3812
·
IF 4.966
Xiaolong Zhang,Qinli Ruan,Yiqian Zhai,Dandan Lu,Chen Li,Yahan Fu,Zihui Zheng,Ying Song,Jun Guo
Baicalein, a flavonoid phytochemical, has been shown to be effective as an anti-metastatic agent for various cancers, especially for non-small-cell lung cancer (NSCLC). However, the underlying mechanism of how baicalein targets cellular processes during NSCLC cell invasion and metastasis remains elusive. In this study, we found that non-cytotoxic concentrations of baicalein still retained anti-dissemination activity both in vitro and in vivo. Using a genetic encoding tension probe based on Förster resonance energy transfer (FRET) theory, baicalein was shown to significantly decrease ezrin tension by downregulating cellular ezrin S -nitrosylation (SNO) levels in NSCLC cells in the inflammatory microenvironment. Decreased ezrin tension inhibited the formation of an aggressive phenotype of NSCLC cell and leader cell in collective migration, and subsequently suppressed NSCLC dissemination. Baicalein restrained SNO-mediated ezrin tension by decreasing iNOS expression levels. Overall this study demonstrates the novel mechanism used by baicalein to suppress NSCLC invasion and metastasis from a mechanopharmacology perspective and illustrates a new direction for drug development.
研究领域:
肿瘤学
·
药理学
·
细胞生物学
✓ 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）