INTERNATIONAL IMMUNOPHARMACOLOGY
·
2022
·
IF 5.714
Liping Wang,Tiantian Ji,Ye Yuan,Haoyu Fu,Yang Wang,Shaobo Tian,Jia Hu,Lin Wang,Zheng Wang
The dramatically increasing incidence and prevalence of inflammatory bowel disease (IBD) are reportedly related to a Western diet, which is characterized by high sugar consumption. Dietary simple sugars aggravate IBD in animal models. However, the mechanisms underlying this effect remain unclear. Given that high-fructose corn syrup (HFCS) is a major added sugar in food and beverages, we focus on HFCS and investigated the effects of HFCS on a dextran sulfate sodium (DSS)-induced murine colitis model and in RAW264.7 macrophages. Our data demonstrate that short-term consumption of HFCS aggravates colitis and upregulates the proportion of macrophages in IBD mice but not in healthy mice. We find that HFCS promotes proinflammatory cytokine production through reactive oxygen species (ROS)-mediated nuclear factor-κB (NF-κB) signaling in RAW264.7 macrophages. Furthermore, N-acetylcysteine (NAC), an ROS scavenger, alleviates HFCS-aggravated colitis in mice and inhibits the ROS-mediated NF-κB signaling pathway in RAW264.7 macrophages. Our work unveils the important role of macrophages in HFCS-induced exacerbation of colitis and reveals the mechanism of how HFCS immunologically aggravates IBD.
✓ 已验证
DOI
PubMed
高影响因子
Journal of Translational Medicine
·
2025
·Vol. 23
·期 1
·1385
·
IF 7.5
Gong Jiaxin,Wei Feng,Wu Tianyu,Zhang Ningzhi,Zhang Yongqiao,Cui Zhaoqiang,Ge Junbo
Background Obesity-related cardiac injury is a serious global condition associated with excessive fat intake, which is strongly linked to chronic low-degrade inflammation. Pyroptosis, a pro-inflammatory form of cell death, has been implicated in obesity recently. L-Fucose (Fuc), a sulfated polysaccharide with anti-inflammatory and antioxidant properties, remains unexplored in the area of pyroptosis and obesity-related cardiac injury. Methods Six-week-old wide type C57BL/6 mice were subjected to high-fat diet (HFD) feeding for 20 weeks to induce obesity with or without Fuc gavaging, followed by assessment of metabolic related indicators. Echocardiography, histopathological analysis and enzymatic assays were used to assess cardiac function. The level of pro-inflammatory cytokines was detected by ELISA, qRT-PCR and CD68 staining. Pyroptosis-related protein including NLRP3, GSDMD, pro-caspase-1, cleaved-caspase-1, IL-1β, and ASC were evaluated by western blot. Oxidative stress was detected by ROS level. Cardiac mitochondrial structure was assessed by electron microscopy and mitotracker staining. Mitochondrial function was measured by mitochondrial membrane potential (MMP) and oxygen consumption rate (OCR) assay. Molecular docking and molecular dynamics (MD) simulations were conducted to look for the potential target of Fuc. Cellular thermal shift assay (CETSA) and western blot were used to investigate the interaction between Fuc and its target. Palmitic acid (PA) induced lipotoxicity model in AC16 cells was used to further confirm the protective effects of Fuc and its downstream signaling pathway against inflammation, pyroptosis and mitochondrial injury in vitro. Results In vivo, Fuc treatment alleviated obesity-related weight gain, hyperlipidemia, elevated systolic blood pressure and cardiac diastolic dysfunction. It also reduced the expression of pro-inflammatory cytokines and pyroptosis-related proteins, the level of oxidative stress, and mitochondrial abnormalities in the myocardium. Moreover, the vitro lipotoxicity model further confirmed the protective effect of Fuc. The molecular docking analysis identified TLR4 as the key target of Fuc. Fuc reduced the level of TLR4 and its downstream proteins MyD88 and p-NF-κB, while activating TLR4/MyD88/NF-κB pathway by TLR4 agonist Neoseptin3 reversed the protective function of Fuc in vitro. Conclusions These findings demonstrated that Fuc mitigated cardiac inflammation, pyroptosis and mitochondrial injury by inhibiting the TLR4/MyD88/NF-κB pathway, highlighting its potential as a therapeutic agent for obesity-associated cardiac injury.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
·
2023
·
IF 6.7
Xiaoxiao Yang,Zhigang Liu,Mengyuan Fang,Tingfeng Zou,Zhen Zhang,Xianshe Meng,Tianxiang Wang,Huawen Meng,Yuanli Chen,Yajun Duan,Qingshan Li
Pterostilbene is a demethylated resveratrol derivative with attractive anti-inflammatory, anti-tumor and anti-oxidative stress activities. However, the clinical use of pterostilbene is limited by its poor selectivity and druggability. Heart failure is a leading cause of morbidity and mortality worldwide, which is closely related to enhanced oxidative stress and inflammation. There is an urgent need for new effective therapeutic drugs that can reduce oxidative stress and inflammatory responses. Therefore, we designed and synthesized a series of novel pterostilbene chalcone and dihydropyrazole derivatives with antioxidant and anti-inflammatory activities by the molecular hybridization strategy. The preliminary anti-inflammatory activities and structure-activity relationships of these compounds were evaluated by nitric oxide (NO) inhibitory activity in lipopolysaccharide (LPS)-treated RAW264.7 cells, and compound E1 exhibited the most potent anti-inflammatory activities. Furthermore, pretreatment with compound E1 decreased reactive oxygen species (ROS) generation both in RAW264.7 and H9C2 cells by increasing the expression of nuclear factor erythroid 2-related factor 2 (Nrf2), as well as downstream antioxidant enzymes superoxide dismutase 1 (SOD1), catalase (CAT) and glutathione peroxidase 1 (GPX1). In addition, compound E1 also significantly inhibited LPS or doxorubicin (DOX)-induced inflammation in both RAW264.7 and H9C2 cells through reducing the expression of inflammatory cytokines by inhibiting nuclear factor-κB (NF-κB) signaling pathway . Moreover, we found that compound E1 improved DOX-induced heart failure by inhibiting inflammation and oxidative stress in mouse model, which is mediated by the potential of antioxidant and anti-inflammatory activities. In conclusion, this study demonstrated the novel pterostilbene dihydropyrazole derivative E1 was identified as a promising agent for heart failure treatment.
✓ 已验证
DOI
PubMed
高影响因子
Analytical Cellular Pathology
·
2021
·
IF 2.916
Xinwei Liu,Yue Zhou
Background. Long noncoding RNAs (lncRNAs) are dysregulated in periodontitis development and involved in osteogenesis. The current study was aimed at investigating the function of lncRNA ANRIL in periodontal ligament cells (PDLCs) and potential molecular mechanisms. Methods. Firstly, the level of ANRIL was tested by qPCR. Then, PDLCs were treated with a mineralizing solution to induce osteogenic differentiation. ALP activity was measured, and protein levels of BMP2, Osterix, and OCN were measured by Western blot. A target of ANRIL was verified using dual-luciferase reporter assay. miR-7 level was measured by qPCR, and the signals of the NF-κB pathway were tested by Western blot. Results. ANRIL expression was downregulated in PDL tissues. Next, ALP activity and protein levels of BMP2, Osterix, and OCN were increased to show that PDLCs were differentiated. ANRIL level was increased in differential PDLCs, in which knockdown inhibited osteogenic differentiation. Then, miR-7 was found as a target of ANRIL. The miR-7 level was upregulated in PDL tissues and reduced in differential PDLCs. Inhibition of miR-7 suppressed ALP activity and BMP2, Osterix, and OCN expression. Moreover, inhibition of miR-7 reversed the effects on the osteogenic differentiation induced by knockdown of ANRIL. Besides, the levels of p-P65 and p-IκBα were elevated by ANRIL downregulation and were rescued by suppressing miR-7. Conclusions. Knockdown of ANRIL inhibited osteogenic differentiation via sponging miR-7 through the NF-κB pathway, suggesting that ANRIL might be a therapeutic target for periodontitis.
✓ 已验证
DOI
PubMed
高影响因子
Marine Drugs
·
2025
·Vol. 23
·期 11
·445
·
IF 5.4
Junming Zhang,Jiangming Zhong,Yi Li,Qi Zhou,Zhiyun Du,Li Lin,Peng Shu,Ling Jiang,Wei Zhou
Background: Ultraviolet B (UVB) radiation induces oxidative stress, inflammation, and collagen degradation in skin, leading to photodamage. Ergosterol (ERG)—a sterol widely distributed in fungi and algae, including numerous marine species—possesses antioxidant and anti-inflammatory activities, but its photoprotective mechanisms remain unclear. Methods: Using integratedin vitro(UVB-irradiated human keratinocytes) andin vivo(topical ERG in a murine UVB model) approaches, combined with transcriptomic and network pharmacology analyses, we evaluated ERG’s effects on oxidative stress, inflammation, and extracellular matrix integrity. Results: ERG treatment preserved keratinocyte viability, reduced reactive oxygen species, and suppressed pro-inflammatory mediators after UVB exposure. In mice, topical ERG significantly attenuated epidermal hyperplasia, maintained tight-junction integrity, and inhibited collagen matrix degradation. Mechanistically, ERG exerted dual inhibition of the nuclear factor kappa B (NF-κB) pathway, which mediates inflammation, and the mitogen-activated protein kinase (MAPK) pathway, which regulates collagen degradation. Conclusions: These findings identify ERG as a marine-derived sterol with potent photoprotective activity that simultaneously targets oxidative stress, inflammation, and extracellular matrix damage, highlighting its promise as a natural compound for dermatological applications and aligning with ongoing efforts to explore marine-derived agents against skin oxidative stress and inflammation.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
·
2025
·Vol. 26
·期 24
·12057
·
IF 4.9
Wenkai Li,Sifan Song,Wenyong Li,Jing Chen
Treating acute lung injury (ALI) presents significant challenges due to adverse drug reactions. This study systematically explored the protective effects and mechanisms of a flavonoid-rich extract fromBombyx batryticatus(FBB), a traditional Chinese medicine, in combating ALI. Through UPLC-MS/MS analysis, we identified 163 flavonoid components in FBB for the first time, including flavonoids, flavonols, and chalcones. Unlike single-component flavonoid therapies, FBB provides synergistic regulation across multiple targets and pathways. Network pharmacology predictions, supported by experimental validation, revealed that FBB primarily suppresses the expression of inflammatory factors (IL-1β, IL-6, TNF-α) and oxidative stress markers (iNOS, COX-2) by modulating the PI3K/Akt, MAPK, and NF-κB signaling pathways. FBB inhibits pro-inflammatory responses and upregulates chemokine receptors like Ccr1 and Ccr2, along with IL-2Rb, at the transcriptional level. This suggests its potential to promote inflammation resolution and tissue repair through immune microenvironment remodeling, rather than mere immunosuppression. Additionally, FBB demonstrated significant anti-apoptotic effects both in vitro and in vivo, effectively reducing pulmonary edema and vascular permeability. Its complex composition and multi-pathway synergistic mechanisms offer broader regulatory potential and unique therapeutic advantages in treating ALI compared to single flavonoid compounds or conventional hormone drugs like dexamethasone (DEX). This study reveals a novel mechanism by which FBB, a multi-component natural drug, exerts therapeutic effects in ALI, providing a theoretical and experimental foundation for developing flavonoid-based compound preparations from traditional Chinese medicine.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACTA PHARMACOLOGICA SINICA
·
2013
·Vol. 34
·期 7
·939-950
·
IF 2.354
Peng Yan-min,Zheng Jian-bin,Zhou Yu-bo,Li Jia
Aim: Curcumin has shown promising anticancer activity, which relies on its inhibition on NF-κB pathway. In this study, we characterized the pharmacological profile of a novel curcumin analog P1 and elucidate the related mechanisms. Methods: HEK293/NF-κB cells, stably transfected with an NF-κB-responsive luciferase reporter plasmid, were generated for high-throughput screen (HTS). Eight cancer cell lines, including PC3, COLO 205, HeLa cells etc . were tested. Cell viability was assessed using the sulforhodamine B (SRB) assays. Cell apoptosis was evaluated using FACS, immunocytochemistry, and Western blotting. H 2 -DCFDA and MitoSOX Red were used to detect cellular and mitochondrial reactive oxygen species (ROS). The mitochondrial function was evaluated using mitochondrial oxygen consumption assay. Results: P1, a tropinone curcumin, was found in HTS targeting the NF-κB pathway. Its IC 50 value in inhibition of TNF-α-induced NF-κB activation was 0.8 μmol/L, whereas its IC 50 values in inhibiting the growth of A549 and HeLa cells were 1.24 and 0.69 μmol/L, respectively, which was 20- to 30-fold more potent than curcumin. The inhibition of P1 on the NF-κB pathway was further addressed in HeLa cells. The compound up to 10 μmol/L did not affect the binding of NF-κB to DNA, but markedly inhibited NF-κB nuclear translocation, IκB degradation and IκB kinase phosphorylation. The compound (1 and 3 μmol/L) concentration-dependently induced ROS generation, whereas curcumin up to 20 μmol/L had no effect. P1-induced ROS generation was mainly localized in mitochondria, and reversed by NAC. Moreover, the compound significantly enhanced TNF-α-induced apoptosis. Conclusion: P1 is a novel curcumin analog with potent anticancer activities, which exerts a distinct inhibition on the NF-κB pathway.
✓ 已验证
DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2023
·
IF 5.6
Xin-Yu Shen,Jing-Mei Lu,Yu-Nan Lu,Guang-Nan Jin,Jing-Wen Ma,Jing-He Wang,Yu Wang,Xiang Xu,Lian-Xun Piao
Toxoplasma gondii ( T. gondii ) is an obligate intracellular protozoan parasite that causes pulmonary toxoplasmosis, although its pathogenesis is incompletely understood. There is no cure for toxoplasmosis. Coixol, a plant polyphenol extracted from coix seeds, has a variety of biological activities. However, the effects of coixol on T. gondii infection have not been clarified. In this study, we infected a mouse macrophage cell line (RAW 264.7) and BALB/c mice with the T. gondii RH strain to establish infection models in vitro and in vivo , respectively, to explore protective effects and potential mechanisms of coixol on lung injury caused by T. gondii infection. Anti- T. gondii effects and underlying anti-inflammatory mechanisms of coixol were investigated by real-time quantitative PCR, molecular docking, localized surface plasmon resonance, co-immunoprecipitation, enzyme-linked immunosorbent assay, western blotting, and immunofluorescence microscopy. The results show that coixol inhibits T. gondii loads and T. gondii -derived heat shock protein 70 ( T.g. HSP70) expression. Moreover, coixol reduced inflammatory cell recruitment and infiltration, and ameliorated pathological lung injury induced by T. gondii infection. Coixol can directly bind T.g. HSP70 or Toll-like receptor 4 (TLR4) to disrupt their interaction. Coixol prevented overexpression of inducible nitric oxide synthase, tumor necrosis factor-α, and high mobility group box 1 by inhibiting activation of the TLR4/nuclear factor (NF)-κB signaling pathway, consistent with effects of the TLR4 inhibitor CLI-095. These results indicate that coixol improves T. gondii infection-induced lung injury by interfering with T.g. HSP70-mediated TLR4/NF-κB signaling. Altogether, these findings suggest that coixol is a promising effective lead compound for the treatment of toxoplasmosis.
✓ 已验证
DOI
PubMed
高影响因子
Journal of Materials Chemistry A
·
2023
·Vol. 12
·期 5
·2994-3005
·
IF 11.9
Ting-Yu Shuai,Qi-Ni Zhan,Hui-Min Xu,Chen-Jin Huang,Zhi-Jie Zhang,Hong-Rui Zhu,Gao-Ren Li
The design of efficient, environment-friendly, stable, and low-cost oxygen evolution electrocatalysts is a technical difficulty in realizing the commercial application of water electrolysis. Herein, we developed a novel three-dimensional (3D) electrocatalyst to grow Ni3Se4/Fe(PO3)2 composites on nickel foam (NF) in a short time of 80 s by a simple electrodeposition method, which not only effectively prevents the agglomeration of Ni3Se4, but also reduces the size of Fe(PO3)2 particles from micron level to nanometer level, exposing more electroactive sites. Fe(PO3)2 with a low crystalline structure and crystalline Ni3Se4 can form a unique heterostructure to produce a strong electron coupling and synergistic effect for the oxygen evolution reaction (OER) in alkaline media, which effectively improves the intrinsic activity of Ni/FeOOH active sites. The Ni3Se4/Fe(PO3)2/NF composites as catalysts can achieve a low overpotential of 185 mV in alkaline media at a current density of 10 mA cm−2 and a small Tafel slope of 30.4 mV dec−1, exhibiting excellent OER catalytic activity and stability.
✓ 已验证
DOI
高影响因子
JOURNAL OF ELECTROANALYTICAL CHEMISTRY
·
2021
·
IF 4.464
Liyan Wu,Jianmei Cen,Asad Ali,Jiecai Li,Pei Kang Shen
Conducting polymers are commonly used as precursors for preparing carbon-based catalysts and have been used in electrocatalytic water splitting. However, so far, most of the catalytic materials synthesized with the assistance of high polymer conducting polymers are non-self-supporting and have only a single-function catalytic effect. Therefore, it is an inevitable trend to synthesize a bifunctional self-supported, highly efficient and long-stable water splitting catalyst. Herein, a self-supporting polypyrrole precursor PPy-PW 12 was prepared by electrodeposition with phosphotungstic acid as a dopant. In addition, the PPy-PW 12 precursor was then calcined. The as-prepared W/Ni 3 (PO 4 ) 2 @NC/NF electrocatalyst exhibits admirable HER and OER performances with overpotentials of 48 mV for HER and 236 mV for OER to reach a current density of 10 mA cm −2 in 1.0 M KOH solution. Additionally, when W/Ni 3 (PO 4 ) 2 @NC/NF is used in overall water splitting as a bifunctional catalyst, it needs only 1.53 V to deliver a current density of 10 mA cm −2 , which is superior to typically integrated Pt/C and RuO 2 counterparts. Our work offers a facile strategy to apply W/Ni 3 (PO 4 ) 2 @NC/NF as practical bifunctional electrocatalysts for large-scale water splitting.
✓ 已验证
DOI
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
·
IF 7.7
Hend Mohamed Anwar,Gad Elsayed Mohamed Salem,Hanan M. Abd El-Latief,Amany Abd Elhameid Osman,Sahar K. Ghanem,Haroon Khan,Suchana Chavanich,Alshaymaa Darwish
The COVID-19 pandemic has drawn attention to acute lung injury and respiratory distress syndrome as major causes of death, underscoring the urgent need for effective treatments. Protease enzymes possess a wide range of beneficial effects, including antioxidant, anti-inflammatory, antifibrotic, and fibrinolytic effects. This study aimed to evaluate the potential therapeutic effects of bacterial protease and chymotrypsin in rats in mitigating acute lung injury induced by lipopolysaccharide . Molecular docking was employed to investigate the inhibitory effect of bacterial protease and chymotrypsin on TLR-4, the receptor for lipopolysaccharide. Bacterial protease restored TLR-4, Nrf2 , p38 MAPK , NF-kB, and IKK-β levels to normal levels, while chymotrypsin normalized TLR-4, IKK-β, IL-6, and IL-17 levels. The expression of TGF-β, caspase-3, and VEGF in the bacterial protease- and chymotrypsin-treated groups was markedly reduced. Our results suggest that both therapies ameliorate LPS-induced acute lung injury and modulate the TLR4/Nrf2/NF-k signaling pathway. Each protease exhibited distinct mechanisms, with bacterial protease showing a better response to oxidative stress, edema, and fibrosis , whereas chymotrypsin provided a better response in the acute phase and innate immunity. These findings highlight the potential of each protease as a promising therapeutic option for acute lung injury and respiratory distress syndrome.
✓ 已验证
DOI
PubMed
高影响因子
Algal Research-Biomass Biofuels and Bioproducts
·
2026
·
IF 5
Yunmei Yin,Pei Wang,Zhen Zhang,Hongxiang Zhao,Meicong Xiao,Ran Chen,Kun Li,Shiqi Zhou,Rongqing Zhang
Astaxanthin's anti-atherosclerotic targets/pathways identified via network pharmacology and cellular assays. • Astaxanthin alleviates endothelial injury via dual anti-inflammatory and antioxidant effects. • Astaxanthin acts through PPARγ/NF-κB axis, with GW9662 reversing its regulatory effect. Astaxanthin, a lipophilic carotenoid predominantly derived from microalgae such as Haematococcus pluvialis , exhibits potent anti-inflammatory and antioxidant properties. Despite previous reports of its anti-atherosclerotic effects, the underlying molecular mechanisms of astaxanthin remain unclear. This study aimed to elucidate the pharmacological mechanisms of astaxanthin in alleviating atherosclerosis progression via an integrated approach of network pharmacology, molecular docking, and in vitro experimental validation. Molecular docking revealed strong binding affinities between astaxanthin and core targets including TNF, IL-6, and PPARγ. In vitro experiments demonstrated that astaxanthin attenuated oxidative stress and suppressed the secretion of pro-inflammatory cytokines in oxidized low-density lipoprotein (ox-LDL)-induced human umbilical vein endothelial cells (HUVECs). Mechanistically, astaxanthin upregulated PPARγ expression and reduced the phosphorylation of p65 and IκBα, two key components of the NF-κB pathway. Co-treatment with the specific PPARγ antagonist GW9662 abrogated these protective effects, confirming a PPARγ-dependent regulatory mechanism. These findings indicate that astaxanthin exerts anti-atherosclerotic effects by modulating the PPARγ/NF-κB signaling axis, highlighting its potential as a functional food ingredient for cardiovascular protection.
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）