Bioactive Carbohydrates and Dietary Fibre
·
2021
·
IF 0
Dongmei Wu,Xiaoliang Zheng,Weiwei Hu,Kai Zhu,Chengxiao Yu,Qiaojun He,Robert J. Linhardt,Xingqian Ye,Shiguo Chen
Pectic oligosaccharides are viewed as excellent immunomodulator, but the specific molecular weight (M w ) range required for anti-inflammatory effects remains unclear. In this study, citrus pectins was depolymerized by the ultrasound/H2O2/Vc system and the pectic mixtures was separated through the superdex 30 chromatography column . Three highly purified pectin fractions (USP1, USP2, USP3) were obtained, with the M w of 2713 g/mol, 3683 g/mol, and 7469 g/mol. All of them were RG-I pectins and USP3 contained more arabinan sidechains than USP1 and USP2. In vitro anti-inflammation assays based on LPS-induced RAW264.7 macrophages indicated that these pectins could suppress the NO release, ROS production and down-regulated the level of pro-inflammatory cytokines IL-1β, IL-6 and TNF-α in a M w -dependent manner. The inhibitory effects increased in the order of USP13KD should be effective as a prophylactic agent against inflammatory diseases in functional food.
研究领域:
食品科学
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生物化学
·
免疫学
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DOI
Frontiers in Pharmacology
·
2023
·
IF 5.6
Xu Liu,Qi Tao,Youming Shen,Xiwang Liu,Yajun Yang,Ning Ma,Jianyong Li
Introduction: Inflammation is a defensive response of the body and the pathological basis of many diseases. However, excessive inflammation and chronic inflammation impair the homeostasis of the organism. Arachidonic acid (AA) has a close relationship with inflammation and is the main mediator of the pro-inflammatory response. Based on the prodrug principle, the new pharmaceutical compound aspirin eugenol ester (AEE) was designed and synthesized. However, the effects of AEE on key enzymes, metabolites and inflammatory signaling pathways in the AA metabolic network have not been reported. Methods: In this study, the anti-inflammation effects of AEE were first investigated in mice and RAW264.7 cells in LPS induced inflammation model. Then, the changes of the key enzymes and AA metabolites were explored by RT-PCR and targeted metabolomics. Moreover, the regulatory effects on NF–kB and MAPKS signaling pathways were explored by Western Blotting. Results: Results indicated that AEE significantly reduced the number of leukocyte and increased the lymphocyte percentage. AEE decreased the expression levels of IL-1β, IL-6, IL-8 and TNF-α both in vivo and in vitro . In the liver of mice, AEE downregulated the levels of AA, prostaglandin D 2 (PGD 2 ) and upregulated 12- hydroxyeicosatetraenoic acid (12-HETE). However, the changes of PGE 2 , PGF 2α , 6-keto-prostaglandin F 1α (6-KETO-PGF 1α ), 9-hydroxy-octadecenoic acid (9- HODE), 13-HODE, 15-HETE, docosahexaenoic acid (DHA) and thromboxane B 2 (TXB 2 ) were not significant. Additionally, it was found that AEE decreased the relative mRNA expression levels of p65 and p38 and the ratio of p-p65/p65. Discussion: It was concluded that AEE might inhibit the LPS-induced inflammatory response through the regulation of AA metabolism. This study provides the theoretical foundation for the development of AEE as a medicinal anti-inflammatory drug.
研究领域:
药理学
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免疫学
·
细胞生物学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Food & Function
·
2024
·
IF 5.1
Yajie Ma,Fan Zhang,Yujun Xie,Luyao An,Bo-Li Zhang,Bo-Yang Yu,Renshi Li
Asparagi Radix is a healthy food type with medicinal and edible homology, which is now widely used for improving pulmonary inflammation in clinical. However, the lung-protective effect and the active constituents of Asparagi Radix have yet to be elucidated. Herein, the potential pulmonary protective effect of oligosaccharides was investigated. We firstly identified eighteen oligosaccharides with different degrees of polymerization from Asparagi Radix using HPLC-QTOF MS. Oligosaccharides were found to be simultaneously determined in 20 batches of Asparagi Radix collected from various regions in China by HILIC-ELSD, and oligosaccharides stably exist in this herb. In the present study, we found that AROS significantly reduced NO production, and effectively down-regulated the mRNA expression of IL-6, IL-1β and TNF-α in RAW 264.7 cells, thereby reducing the inflammatory response induced by LPS. AROS also inhibited LPS-stimulated intracellular ROS production. A murine model of lipopolysaccharide (LPS)-induced acute lung injury was used to evaluate the in vivo anti-inflammatory and lung protective efficacy of AROS. AROS could ameliorate the damage of the pulmonary cellular architecture pathological injury and lung edema. AROS significantly decreased the levels of cytokines IL-6, TNF-α and IL-1β, as well as the levels of MPO and MDA, and superoxide dismutase consumption in vivo. This effect of oligosaccharides could explain the traditional usage of Asparagus cochinchinensis as a tonic medicine for respiratory problems and oligosaccharides from Asparagi Radix used as a natural ingredient could play an important role in protecting from lung injury.
研究领域:
药理学
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免疫学
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肺科学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Food & Function
·
2024
·
IF 5.1
Yahui Wu,Mona Alrasheed Bashir,Changsheng Shao,Han Wang,Jianxia Zhu,Qing Huang
Numerous natural compounds are recognized for their anti-inflammatory properties attributed to antioxidant effects and modulation of key inflammatory factors. Among them, astaxanthin (AST), a potent carotenoid antioxidant, remains relatively underexplored regarding its anti-inflammatory mechanisms and specific molecular targets. In this study, human monocytic leukemia cell-derived macrophages (THP-1) were selected as experimental cells, and lipopolysaccharide (LPS) served as the inflammatory stimulus. Upon LPS treatment, the oxidative stress was significantly increased, accompanied by remarkable cellular damage. Moreover, LPS escalated the expression of inflammation-related molecules. Our results demonstrated that AST intervention could effectively allevate the LPS-induced oxidative stress, facilitate the cellular repair, and significantly attenuate the inflammation. Further exploration of anti-inflammatory mechanism revealed AST could substantially inhibit the NF-κB translocation and activation, and mitigate the inflammatory factor production by hindering NF-κB through the antioxidant mechanism. We further confirmed that AST exhibited protective effects against cell damage and reduced the injury from inflammatory cytokines by activating p53 and inhibiting STAT3. In addition, utilizing network pharmacology and in silico calculations based on molecular docking, molecular dynamics simulation, we identified interleukin-6 (IL-6) as a prominent core target of AST anti-inflammation, which was further validated by the RNA interference experiment. This IL-6 binding capacity actually enabled AST to curb the positive feedback loop of inflammatory factors, averting the onset of possible inflammatory storms. Therefore, this study offers a new possibility for the application and development of astaxanthin as an popular dietary supplement of anti-inflammatory or immunomodulatory function.
研究领域:
免疫学
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药理学
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分子生物学
·
细胞生物学
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产品关联
DOI
PubMed
高影响因子
Annals of Translational Medicine
·
2020
·
IF 3.297
Li Li,Xingfeng He,Xingtong Wang,Yu Sun,Guosheng Wu,He Fang,Chen Wang,Pengfei Luo,Zhaofan Xia
Background Ruxolitinib is an inhibitor of Janus kinases (JAK) 1/2. It was authorised recently by the U.S. Food and Drug Administration (FDA) as a new Myelofibrosis treatment. In this study, we identified ruxolitinib as a new inhibitor of nitric oxide (NO) production in response to lipopolysaccharide (LPS)stimulation of RAW 264.7 cells. Methods In vitro direct effects of ruxolitinib were determined through NO production on RAW 264.7 cells. Also the expression level of iNOS, TNF-α and IL-6 were detected by Western Blotting and qRT-PCR. In vivo therapeutic effects of ruxolitinib on sepsis were evaluated by an endotoxemia model with C57 mice. The survival was calculated and histopathological damage of organs was observed by HE. Cytokines in serum were detected by Mouse Cytokine Array Panel. Results Ruxolitinib was found to significantly reduce NO production, inducible nitric oxide synthase (iNOS), TNF-α, and IL-6 expression, suggesting that ruxolitinib blocks LPS signaling that leads to pro-inflammatory factor expression. Furthermore, the inhibitory effects of ruxolitinib contributed to the survival of septic mice by 70% and pro-inflammatory cytokines in serum declined apparently. The results taken together indicate that ruxolitinib can significantly suppress LPS-stimulated NO production and improve the survival of septic mice, perhaps by interfering with the NF-κB pathway. Conclusions These findings suggest ruxolitinib might be a possible therapeutic candidate for sepsis therapy.
研究领域:
药理学
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免疫学
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传染病学
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产品关联
DOI
PubMed
高影响因子
FOOD AND CHEMICAL TOXICOLOGY
·
2022
·
IF 5.572
Wenyue Qiu,Xinting Zhang,Xiaoyue Pang,Jianjia Huang,Shuilian Zhou,Rongmei Wang,Zhaoxin Tang,Rongsheng Su
Asiatic acid (AA), a triterpenoid compound isolated from Centella asiatica , has anti-inflammatory, antioxidant and anticancer biological characteristics . To explore the effect of AA on LPS-induced acute kidney injury (AKI) in broilers, a total of 60 one-day-old broilers were randomly divided into 6 groups, including the normal group, AKI model group, AKI + AA 15 mg/kg group, AKI + AA 30 mg/kg group, AKI + AA 60 mg/kg group and normal + AA 60 mg/kg group. Hematoxylin-eosin staining was used to observe the histopathology in kidney tissue, and the mRNA and protein expressions related to oxidative stress and ferroptosis were tested by qPCR and western blotting respectively. AA mitigated vacuolar degeneration and enlarged glomerular space caused by LPS in kidney tissue. Additionally, AA significantly increased the mRNA levels of Nrf2, HO-1, NQO1, GCLC, GCLM , GPX4 , SLC7A11 and FTH1 , and decreased the mRNA levels of Keap1 and PTGS2 in LPS-induced AKI. Likewise, AA significantly upregulated the protein expressions of Nrf2, HO-1, NQO1, GPX4, SLC7A11 and FTH1, and downregulated the protein expressions of Keap1 and PTGS2 in LPS-induced AKI. These results suggested that AA alleviated LPS-induced AKI by inhibiting oxidative stress and ferroptosis through targeting regulation of the Nrf2 pathway in broilers.
研究领域:
药理学
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兽医学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
NEUROSCIENCE
·
2019
·
IF 3.244
Lanqiu Zhang,Jinlu Zhang,Xiaolin Jiang,Lei Yang,Qi Zhang,Botao Wang,Lihua Cui,Ximo Wang
Neuroinflammation has been implicated in the mechanism underlying the progression of neurodegeneration and infectious neuropathology. Growing evidence suggest that hydroxytyrosol (3,4-dihydroxyphenil-ethanol, HT), one of the main polyphenols presented in extra virgin olive oil (EVOO), has shown potential anti-inflammatory and neuroprotective effects. However, the potential anti-neuroinflammation activity and underlying mechanism of HT remain poorly understood. The present study aimed to investigate the effects of HT on lipopolysaccharide (LPS)-induced inflammation in both in vitro and in vivo models and the associated molecular mechanism. Our results revealed that HT significantly reduced the production of pro-inflammatory mediators in BV2 microglia and primary microglia cells. Phenotypic analysis showed that HT significantly reduced M1 marker CD86 expression and increased M2 marker CD206 expression. In addition, HT significantly decreased the levels of phospho-NF-κB p65 and phospho-extracellular signal-regulated kinase (ERK) in a dose-dependent manner. Moreover, HT suppressed the LPS-induced Toll like receptor 4 (TLR4) in BV2 microglia. In vivo administration of HT following LPS injection significantly reduced some proinflammatory mediator levels and microglia/astrocyte activation in the brain. Together, these results suggest that HT suppressed the LPS-induced neuroinflammatory responses via modulation of microglia M1/M2 polarization and downregulation of TLR-4 mediated NF-κB activation and ERK signaling pathway.
研究领域:
神经科学
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药理学
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免疫学
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DOI
PubMed
高影响因子
FISH & SHELLFISH IMMUNOLOGY
·
2024
·
IF 4.1
Yuan-Xin Qian,Feng-Feng Zhou,Qiang Chen,Fen Dong,Han-Ying Xu,Yu-Long Sun,Ji-Teng Wang,Tao Han
Arginine plays a key role in regulating the immune function of fish. To evaluate the effect of arginine on the immune response of largemouth bass ( Micropterus salmoides ), the effects of arginine on cell viability, NADPH oxidase activity, respiratory burst activity, and NO production of leukocytes were analyzed both in vitro and in vivo . In this study, we found that arginine could promote the respiratory burst activity of leucocytes both in vivo and in vitro . By incubating leukocytes with the combination of LPS and arginine, we found that arginine supplementation inhibited the expression of inflammatory genes ( tumor necrosis factor-alpha , tnfα ; interleukin ( il ) 8 and il10 ) and apoptotic genes ( caspase 3 , caspase 8 , and caspase 9 ) induced by LPS, as well as promoted the arginine metabolism. Arginine supplementation significantly induced ( cd4-like ) cd4 gene expression after LPS challenge. Further studies showed that LPS could significantly increase nucleotide-binding oligomerization domain containing 1 ( nod1 ) gene expression, but decreased the nod2 gene. The arginine supplementation increased nuclear factor kappa-B (NF-κB) protein level. In conclusion, arginine can alleviate LPS-induced inflammatory response and apoptosis as well as induce cd4 gene expression against LPS challenge via adjusting the expression of NODs signaling.
研究领域:
免疫学
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水产养殖
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分子生物学
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产品关联
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
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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
JOURNAL OF FOOD SCIENCE
·
2020
·Vol. 85
·期 5
·1586-1595
·
IF 2.479
Yonglu Li,Yong Jiang,Qiang Chu,Xiaodong Zheng
Radix Tetrastigma (RT) is a medicinal plant and functional food in China, distributed in various places in the south of China. Radix Tetrastigma extract (RTE) from different origins were collected and analyzed for their anti-inflammatory effects. Different RTEs showed different abilities to suppress shape deformation, decrease the nitric oxide (NO) production, inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression in RAW 264.7 cells. Subsequently, their bioactive components were compared, and results showed RTEs are rich in flavonoid (85.25-436.70 mg RE/g DW), polysaccharides (100.45-349.26 mg glucose/g DW), phenolic (12.92-225.40 mg GAE/g DW) and protein contents (4.429-7.719 mg/g DW). Principal component analysis (PCA) and correlation studies indicated that anti-inflammatory capacity could be more associated with total flavonoid contents. High-performance liquid chromatography (HPLC) and Ultraperformance liquid chromatography-time-of flight mass spectrometry (UPLC-TOF/MS) analysis were conducted, and results showed that rutin, isoquercitrin, kaempferol-3-O-rutinoside and astragalin were main flavonoid compounds, among them astragalin exhibited a prior protective effect, suggesting it might be responsible for RTE's excellent anti-inflammatory capacity.
研究领域:
药理学
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免疫学
·
植物化学
✓ 已验证
DOI
PubMed
高影响因子
NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY
·
2023
·
IF 3.6
Zhu Xiaona,Bai Bin,Ge Xiangting,Zheng Bin,Xiao Zhongxiang,Tang Yue,Fang Letong,Tang Yelin,Dai Yuanrong,Zhang Bing,Zhang Yali
Inflammation is an important pathological process of many acute and chronic diseases, such as sepsis, arthritis, and cancer. Many factors can lead to an inflammatory state of the body, among which bacterial infection plays an important role. Bacterial infection often leads to sepsis, acute lung injury (ALI), or its more serious form of acute respiratory distress syndrome, which are the main fatal diseases in intensive care units. Costunolide has been reported to possess excellent anti-inflammatory activity; however, whether it can affect inflammation induced by gram-negative bacterial is still unclear. Lipopolysaccharide (LPS) stimulated mouse peritoneal macrophages (MPMs) to release proinflammatory cytokines was used as the cell model. The mouse model of sepsis and ALI was built through injecting intravenously and intratracheally of LPS. In the present study, costunolide inhibited LPS-induced inflammatory response through IKK/NF-κB signaling pathway in macrophages. In vivo, costunolide attenuated LPS-induced septic death in mice. Meanwhile, costunolide treatment alleviated LPS-induced lung injury and inflammation via inhibiting the infiltration of inflammatory cells and the expression of inflammatory cytokines. Taken together, these results demonstrated that costunolide could attenuate gram-negative bacterial induced inflammation and diseases and might be a potential candidate for the treatment of inflammatory diseases.
研究领域:
免疫学
·
药理学
·
炎症研究
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Functional Foods
·
2022
·
IF 5.223
Jinyuan Wang,Yinyan Yin,Nuo Xu,Bangyue Zhou,Tao Qin
In the bacterial infection of humans, sepsis is of great concern based on its high fatality rate. Correction of immune dysfunction by targeting dendritic cells (DCs) is a promising strategy for sepsis therapy. Royal jelly, a natural health product, is produced by worker bees for feeding queens. In the study, we evaluated whether royal jelly could attenuate LPS-induced immune dysfunction of DCs. We found that royal jelly reduced the expression levels of mature phenotype (MHCII, CD40, CD80, and CD86), activation marker (CD69), and inflammatory cytokines (TNF-α, IL-6, and IL-10) in LPS-induced DCs. In addition, royal jelly enhanced the endocytosis levels and abrogated allogeneic CD4 + T cell proliferation in LPS-induced DCs. Finally, we found that the Nrf2/HO-1 axis played a vital role in the inhibition of LPS-induced immune dysfunction of DCs by royal jelly. These results indicated that royal jelly had a potential application in sepsis therapy by regulating DC function.
研究领域:
免疫学
·
药理学
·
细胞生物学
·
传染病学
✓ 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）