Food & Function
·
2022
·Vol. 13
·期 22
·11676-11689
·
IF 6.317
Abel Wend-Soo Zongo,Daniel Zogona,Mahmoud Youssef,Shuxin Ye,Fuchao Zhan,Jing Li,Bin Li
The intestinal barrier dysfunction associated with chronic inflammation is a major health concern. This work aimed to investigate the protective effect and molecular mechanism of Senegalia macrostachya seed polysaccharide fraction (SMSP2) on inflammation-induced barrier dysfunction using Caco-2 cells and RAW264.7 macrophage co-culture model. The results showed that LPS stimulation of the basolateral RAW264.7 compromised the integrity of the apical differentiated Caco-2 cells monolayer, resulting in decreased transepithelial electrical resistance (TER) and increased inflammatory markers. SMSP2 apical treatment maintained a higher TER value and reduced the epithelial permeability to lucifer yellow (LY) dye. In addition, the SMSP2 group showed a significant decrease in the mRNA level of inflammatory factors such as inducible nitric oxide synthase (iNOS), cyclooxygenase 2 (COX-2), interleukin (IL)-8, and tumor necrosis factor-α (TNF-α) in the Caco-2 monolayer compared to the LPS group. Moreover, SMSP2 increased the expression of the tight junctions (TJ) zonula occludens (ZO-1), occludin, and claudin-1 at the mRNA and protein levels. Furthermore, the immunofluorescence assay showed that SMSP2 ameliorated the overall distribution of the TJ proteins in the Caco-2 monolayer. SMSP2 application also resulted in the downregulation of the nuclear factor kappa-B (NF-κB) phosphorylation and the myosin light chain kinase (MLCK) expression, which implies that SMSP2 preserved the monolayer integrity from the inflammation-induced barrier disruption through the inhibition of the NF-kB-mediated MLCK signaling pathway activation. Senegalia macrostachya seeds could therefore be a promising functional food that could be used to improve intestinal barrier function.
研究领域:
药理学
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免疫学
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细胞生物学
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分子生物学
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胃肠病学
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DOI
PubMed
高影响因子
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
·
2024
·
IF 4.5
Zhenghan Liu,Yadong Chen,Weimin Zeng,Yang Liu,Dandan Zhao,Yanlong Zhang,Xiangqian Jia
Materpaials-based drug delivery systems can enhance the effect of cancer treatment by improving chemotherapy and immunomodulation. Recent research revealed that Baicalin（BA）have good immunomodulatory activity and anti-tumor effect. Here, a pH-sensitive tumor-targeting delivery system for Baicalin (BA-LP-PEOz) was constructed using DSPE-PEOz for pH sensitization. This preparation method was conducted using three single-factor experiments. Response surface Box-Behnken (BBD) design was used to optimize the factor levels. Our results showed that BA-LP-PEOz had synergistic capacity of inhibiting tumor cell (HepG2，4T1 and A549) growth and activating macrophages (RAW264.7). Further mechanistic studies revealed that BA-LP-PEOz can activate RAW264.7 by affecting the NF-κB signaling pathway. We expect that the improved efficacy of the synergetic system provides a prospective strategy for cancer therapy.
研究领域:
药学
·
癌症研究
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纳米技术
·
免疫学
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产品关联
DOI
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2022
·
IF 5.895
Fanghua Guo,Rong Tsao,Chuyao Li,Xiaoya Wang,Hua Zhang,Li Jiang,Yong Sun,Hua Xiong
Green pea hulls are a byproduct of the processing of green pea and are rich in phenolic substances. In the present study, in vitro digestion, human colonic adenocarcinoma cell line (Caco-2) monolayer, and the Caco-2/macrophage cell lines of the murine origin (Raw264.7) coculture model were established to investigate the release of polyphenols, absorption, and transport of digestive products and their effects on inflammation and intestinal barrier. During the digestive process, polyphenols were constantly released from the pea hulls, reaching the maximum amount in the small intestine (total phenolic content (TPC): 5.41 ± 0.04 mg gallic acid (GAE)/g dry weight (DW)), and the digestive products (800 μg/mL) could reduce the secretion of NO (50.9%), IL-6 (50.6%), and TNF-α (24.6%) and inhibit the mRNA expression of cyclooxygenase-2 (COX-2) (37.2%) and inducible nitric oxide synthase (iNOS) (91.1%) compared with the lipopolysaccharide (LPS) group. A total of 12 phenolic components were quantified by ultraperformance liquid chromatography-linear ion trap orbitrap tandem mass spectrometry (UHPLC-LTQ-OrbiTrap-MS) technology. Kaempferol trihexoside in digestive products could be absorbed and transported (1.25 ± 0.13 ng quercetin/mL). The digestive products could promote the expression of claudin-1 (210.8%), occludin (64.9%), and zonulin occludin-1 (ZO-1) (52.0%) compared with the LPS group and exert anti-inflammatory effects after being absorbed. The results indicated that pea hull polyphenols could be continuously released and absorbed to play a positive role in protecting the intestinal barrier and anti-inflammatory activity.
研究领域:
食品科学
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营养学
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药理学
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细胞生物学
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炎症研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2019
·
IF 4.784
Yonglu Li,Xujing Li,Qiang Chu,Ruoyi Jia,Wen Chen,Yaxuan Wang,Xin Yu,Xiaodong Zheng
Russula alutacea Fr. (RaF) is a tasty mushroom with high nutritional value and have been regarded as food by local people for a long time. However, few researches have focused on the polysaccharide in RaF. In this study, a purified polysaccharide (Rap-1) was isolated with an average molecular weight of 1029.7 kDa. In vitro , Rap-1 significantly suppressed cell morphological changes and inhibited the production of nitric oxide (NO) in LPS-induced RAW 264.7 cells extracellularly and intracellularly. Besides, Rap-1 also down-regulated the expression of nuclear factor kappa-B (NF-κB), inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2) contents. Rap-1 ameliorated the oxidative stress and mitochondrial dysfunction caused by LPS via MAPKs signaling pathways in macrophages. In vivo , Rap-1 decreased the ROS and O 2 − levels and recovered the heart in zebrafish ( Danio rerio ) larvae induced by LPS, These results together suggested that Rap-1 could be a potential functional resource to protect against inflammatory and oxidative damage.
研究领域:
免疫学
·
药理学
·
分子生物学
·
细胞生物学
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DOI
PubMed
高影响因子
FOOD SCIENCE AND BIOTECHNOLOGY
·
2025
·
IF 3.1
Cao Jie,Zhang Jing,Yan Ling,Liu Changhong,Wang Yaqian,Cao Yaqi,Zheng Lei
Excessive inflammation and oxidative stress can accelerate inflammatory disease. Plant exosome-like nanoparticles demonstrate therapeutic capacity for anti-inflammatory and antioxidant effects. Here, the effects of red cabbage exosome-like nanoparticles (RELNs) on inflammation and oxidative stress triggered by LPS in macrophages were investigated. RELNs inhibited the expression of the TLR4/NF-κB pathway and blocked the entry of NF-κB p65 from the cytoplasm into the nucleus. Additionally, RELNs reduced the ROS level, alleviated oxidative damage in mitochondria, and increased antioxidant enzyme activity in macrophages. Importantly, RELNs promoted the expression of the Nrf2/Keap1 pathway-mediated antioxidant genes and increased the entry of Nrf2 from the cytoplasm into the nucleus. The research further demonstrated that RELNs might be dependent on Nrf2 expression to decrease the inflammatory response. In brief, RELNs could reduce LPS-induced macrophage inflammation and oxidative stress in vitro, suggesting the therapeutic potential of RELNs in clinical inflammatory diseases. Graphic abstract
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产品关联
DOI
PubMed
高影响因子
Evidence-based Complementary and Alternative Medicine
·
2014
·
IF 2.175
Chuan-li Lu,Wei Zhu,Min Wang,Xiao-jie Xu,Chuan-jian Lu
Smilax glabra Roxb. has been used for a long time as both food and folk medicine. In the present study, phenolic-enriched extract of S. glabra (PEESG) was extracted with 70% ethanol and purified by HP-20 column chromatography. Its antioxidant and anti-inflammatory activities were evaluated by radical scavenging assay, reducing power determination, and lipopolysaccharide (LPS)-induced RAW264.7 cells assays, respectively. PEESG exhibited obviously scavenging capacity for DPPH and ABTS radicals, as well as significant reducing power for ferric ion. Particularly, PEESG (12.5–50 μg/mL) showed a significantly higher efficiency for scavenging ABTS than that of ascorbic acid and no significant difference with ascorbic acid for DPPH scavenging. PEESG also possessed a significant suppression effect on proinflammatory mediators production, such as nitric oxide (NO), tumor necrosis factor- (TNF-), and interleukin-6 (IL-6), in LPS-induced RAW264.7 cells. In addition, the main ingredients of PEESG were identified using ultrahigh pressure liquid chromatography coupled to electrospray mass spectrometry (U-HPLC-ESI-MS). Seventeen components, including 5-O-caffeoylshikimic acid, neoastilbin, astilbin, neoisoastilbin, isoastilbin, engetin and isoengeletin were identified. These findings strongly suggest the potential of PEESG as a natural antioxidant and anti-inflammatory agent.
研究领域:
药理学
·
植物化学
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DOI
PubMed
高影响因子
FOOD SCIENCE AND BIOTECHNOLOGY
·
2015
·Vol. 24
·期 3
·1131-1138
·
IF 0.653
Wang Huaqian,Li Dongli,Du Zhiyun,Huang Mou-Tuan,Cui Xiaoxing,Lu Yujing,Li Chenyue,Woo Swee Lian,Conney Allan H.,Zheng Xi,Zhang Kun
Stems and leaves of Acanthopanax trifoliatus (L) Merr (AT) are commonly used as an edible vegetable in China. The scientific basis of antioxidant and antiinflammatory activities of AT was investigated. The polyphenol contents and free radical scavenging activities of AT ethanol extracts (EAT) were determined. Chlorogenic acid, isochlorogenic acid A, isochlorogenic acid C, and rutin were identified as major components in EAT. LPS-induced NO production in RAW264.7 cells was decreased significantly ( p <0.05) after EAT treatment, compared with controls. In vivo studies indicated that EAT had more activity than chlorogenic acid per mg of dry weight for inhibition of TPA-induced ear edema. TPA-induced increases in cytokine production (TNF-α, IL-6, MMP-9, and TIMP-1) were significantly ( p <0.05) reduced by EAT treatment, compared with controls. EAT exerts anti-inflammatory activities probably due, at least in part, to chlorogenic acid.
研究领域:
药理学
·
植物化学
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产品关联
DOI
高影响因子
GLYCOCONJUGATE JOURNAL
·
2020
·Vol. 37
·期 3
·361-371
·
IF 2.197
Zhang Wuxia,Hu Yihua,Zhao Jinzhong,Zhang Yongpo,Guo Dongdong,Gao Chunyan,Duan Jinyou,Li Peng
Radix Paeoniae Alba is widely used in Chinese traditional medicine to treat various diseases such as gastrointestinal disorders, immunomodulatory, cancer, and other diseases. In this paper, a novel acidic polysaccharide RPAPS purified from Radix Paeoniae Alba was evaluated for its structural features and potential of immunomodulatory and antioxidant activities. RPAPS (molecular weight: 1.0× 10 5 Da) was mainly composed of α-(1 → 4)-Glc p , α-Ara p , α-Gal p , α-Rha p , β-D-Glc p , α-(1 → 6)-linked Glc p and GalA. Immunological tests indicated that RPAPS could improve RAW264.7 phagocytic activity and LPS-induced splenocyte proliferation. For antioxidant activities, RPAPS showed reducing power and DPPH scavenging activity in dose dependent. Moreover, RPAPS could significantly protect the PC12 cells from H 2 O 2 damage. These data implied polysaccharides RPAPS had the potential to be novel natural antioxidative and immunopotentiating agents for using in functional foods or medicine.
研究领域:
中药学
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免疫学
·
药理学
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产品关联
DOI
PubMed
高影响因子
BIOORGANIC CHEMISTRY
·
2021
·
IF 5.275
Ziqing Wang,Wenwen Mu,Zhaotang Gong,Guoyun Liu,Jie Yang
Piperlongumine (PL) has been showed to have multiple pharmacological activities. In this study, we reported the synthesis of three series of PL derivatives, and evaluation of their anti-inflammatory effects in both lipopolysaccharide (LPS)-induced Raw264.7 macrophages and a dextran sulfate sodium (DSS)-induced mouse model of colitis. Our results presented that two meta -substituent containing derivatives 1 – 3 and 1 – 6 , in which γ-butyrolactam replaced α,β-unsaturated δ-valerolactam ring of PL, displayed low cytotoxicity and effective anti-inflammatory activity. Molecular docking also showed that the meta -substituted derivative, compared with the corresponding ortho - or para -substituted derivative, had significant interactions with the amino acid residues of CD14, which was the core receptors recognizing LPS. In vitro and in vivo studies, 1 – 3 and 1 – 6 could inhibit the expression of pro-inflammatory cytokines, and the excessive production of reactive nitrogen species and reactive oxygen species. Oral administration of 100 mg/kg/day of 1 – 3 or 1 – 6 alleviated the severity of clinical symptoms of colitis in mice, and significantly reduced the colonic tissue damage to protect the colonic tissue from the DSS-induced colitis. These results suggested that meta -substituted derivatives 1 – 3 and 1 – 6 were potential anti-inflammatory agents, which may lead to future pharmaceutical development.
研究领域:
药理学
·
炎症
·
药物开发
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DOI
PubMed
高影响因子
TOXICOLOGY AND APPLIED PHARMACOLOGY
·
2026
·
IF 3.6
Yangyi Huang,Jinfei Li,Yue Lu,Jie Cao,Xinzhi Wang,Hao Wu,Min Shen,Hongli Yu
A lectin from Pinellia ternata tubers (PTL, 12 kDa) with potent pro-inflammatory activity binds to the plasma membrane and translocates into the cytoplasm. However, its cellular entry route and inflammatory toxicity mechanisms remain unclear. Here, confocal microscopy showed that fluorescein isothiocyanate (FITC)-labeled PTL (50 μg/mL) accumulated on the cell surface and was endocytosed by RAW264.7 cells time-dependently. Pharmacological inhibition revealed that PTL uptake was mediated by the mannose receptor C-type 2 (MRC2) and predominantly via clathrin-mediated endocytosis. After endocytosis, PTL translocated to mitochondria with marked co-localization, inducing mitochondrial damage characterized by membrane potential dissipation, calcium overload, and excessive mitochondrial reactive oxygen species (mtROS) generation. These alterations promoted intracellular ROS accumulation and amplified inflammatory responses. Co-immunoprecipitation with mass spectrometry identified ATP synthase subunit beta (ATP5B) as a mitochondrial interacting protein of PTL. Their interaction was validated by molecular docking, co-localization, and microscale thermophoresis (MST). ATP5B knockdown markedly attenuated PTL (50 μg/mL)-induced ROS production, inflammatory cytokine expression, and mitochondrial injury, indicating ATP5B is a critical mediator of PTL's inflammatory toxicity. Collectively, these findings demonstrate that PTL induces mitochondrial damage and pro-inflammatory responses in RAW264.7 cells through MRC2-mediated, clathrin-dependent endocytosis and subsequent ATP5B interaction. This study establishes a mechanistic link between lectin endocytosis, mitochondrial targeting, and inflammatory toxicity, providing new insight into plant lectin-mediated immunotoxicity.
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
·
2023
·Vol. 24
·期 13
·10744
·
IF 5.6
Mingyue Hao,Minghui Wang,Danyu Zhao,Yong Shi,Ye Yuan,Junmei Li,Yunyi Zhai,Xiaofang Liu,Dong Zhou,Huatao Chen,Pengfei Lin,Keqiong Tang,Wei Liu,Yaping Jin,Aihua Wang
Brucella suis, the causative agent of brucellosis, poses a significant public health and animal husbandry threat. However, the role of the alanine racemase (alr) gene, which encodes alanine racemase inBrucella, remains unclear. Here, we analyzed analrdeletion mutant and a complemented strain ofBrucella suisS2. The knockout strain displayed an unaltered, smooth phenotype in acriflavine agglutination tests but lacked the core polysaccharide portion of lipopolysaccharide (LPS). Genes involved in the LPS synthesis were significantly upregulated in the deletion mutant. Thealrdeletion strain exhibited reduced intracellular viability in the macrophages, increased macrophage-mediated killing, and upregulation of the apoptosis markers. Bcl2, an anti-apoptotic protein, was downregulated, while the pro-apoptotic proteins, Bax, Caspase-9, and Caspase-3, were upregulated in the macrophages infected with the deletion strain. The infected macrophages showed increased mitochondrial membrane permeability, Cytochrome C release, and reactive oxygen species, activating the mitochondrial apoptosis pathway. These findings revealed that alanine racemase was dispensable inB. suisS2 but influenced the strain’s rough features and triggered the mitochondrial apoptosis pathway during macrophage invasion. The deletion of thealrgene reduced the intracellular survival and virulence. This study enhances our understanding of the molecular mechanism underlyingBrucella’s survival and virulence and, specifically, howalrgene affects host immune evasion by regulating bacterial LPS biosynthesis.Keywords:Brucella suisS2;alanine racemase;alr;lipopolysaccharide;apoptosis;mitochondrial membrane potential;intracellular survival
研究领域:
微生物学
·
分子生物学
·
传染病学
·
免疫学
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产品关联
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2022
·Vol. 10
·期 15
·2899-2911
·
IF 7.571
Zhi Li,Changning Xue,Lifen Zhang,Yuman Zhang,Yao Yu,Qianrui Liu,XinHong Guo,ZhenZhong Zhang
Oxidative stress can lead to a variety of diseases, and oxalate bonds can consume excess reactive oxygen species (ROS) in cells. In this study, a H2O2-responsive prodrug-nanosystem was synthesized using oxalate-bond-connecting water-soluble drugs (Tre) with a fluorescent indicator (PBI). The maximum fluorescence emission wavelength of PBI–Tre was at 548 nm, and the changes of nanoparticles could be directly observed in the cells. PBI–Tre was coated with hyaluronic acid (HA) to improve their intracellular uptake and ability to target macrophages. The particle size of HA–PBI–Tre was 200–300 nm, and the zeta potential was −36.9 mV. The results showed that the nano-drug loading system could easily decrease the ROS level, inhibit the production of inflammatory factors, remove the accumulation of lipids in foam cells. These nanoparticles could hinder foaming progress in the RAW264. 7 cell line.
研究领域:
纳米技术
·
药学
·
细胞生物学
·
炎症研究
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DOI
PubMed
高影响因子
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