MOLECULES
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2018
·Vol. 23
·期 7
·1788
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IF 3.098
Hong-Xin Cui,Ji-Hong Chen,Jing-Wan Li,Fang-Rong Cheng,Ke Yuan
Myrica rubra(MR) is rich in anthocyanins, and it has good anti-cancer, anti-aging, antioxidant, and antiviral effects. The proportion of disability and death caused by ischemic stroke gradually increased, becoming a major disease that is harmful to human health. However, research on effects of anthocyanin from MR on cerebral ischemia-reperfusion (I/R) injury is rare. In this study, we prepared eight purified anthocyanin extracts (PAEs) from different types of MR, and examined the amounts of total anthocyanin (TA) and cyanidin-3-O-glucoside (C-3-G). After one week of PAE treatment, the cerebral infarction volume, disease damage, and contents of nitric oxide and malondialdehyde were reduced, while the level of superoxide dismutase was increased in I/R mice. Altogether, our results show that Boqi1MR contained the most TA (22.07%) and C-3-G (21.28%), and that PAE isolated from Dongkui MR can protect the brain from I/R injury in mice, with the mechanism possibly related to the Toll-like receptor 4 (TLR4)/ nuclear factor-κB (NF-κB) and NOD-like receptor pyrin domain-containing 3 protein (NLRP3) pathways.Keywords:Myrica rubra;anthocyanins;cyanidin-3-O-glucoside;cerebral ischemia-reperfusion;TLR4/NF-κB;NLRP3
研究领域:
药理学
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神经科学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Oxidative Medicine and Cellular Longevity
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2022
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IF 7.31
Xinye Wang,Ran Huo,Zhongjie Liang,Congcong Xu,Tingting Chen,Jingjing Lin,Luyao Li,Wei Lin,Bingting Pan,Xiaoqin Fu,Shangqin Chen
Bronchopulmonary dysplasia (BPD) is a chronic lung disease commonly found in premature infants. Excessive inflammation and oxidative stress contribute to BPD occurrence and development. Simvastatin, as an inhibitor of HMG-CoA reductase, has been reported to have antioxidative and anti-inflammatory effects. However, its effect and possible mechanisms in hyperoxia-induced lung injury are rarely reported. In this study, in vivo and in vitro experiments were conducted to investigate whether simvastatin could ameliorate hyperoxia-induced lung injury and explore its potential mechanism. For the in vivo study, simvastatin could improve alveolar development after hyperoxic lung injury and reduce hyperoxic stress and inflammation. The in vitro study revealed that simvastatin can reduce inflammation in A549 cells after high-oxygen exposure. Simvastatin suppressed NLRP3 inflammasome activation and played anti-inflammatory and antioxidant roles by increasing KLF2 (Krüppel-like factor 2) expression. In vitro experiments also revealed that these effects of simvastatin were partially reversed by KLF2 shRNA, indicating that KLF2 was involved in simvastatin effects. In summary, our findings indicate that simvastatin could downregulate NLRP3 inflammasome activation and attenuate lung injury in hyperoxia-induced bronchopulmonary dysplasia via KLF2-mediated mechanism.
研究领域:
儿科
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肺科学
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药理学
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炎症
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氧化应激
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产品关联
DOI
PubMed
高影响因子
MEDIATORS OF INFLAMMATION
·
2018
·
IF 3.549
Dacheng Wu,Keyan Wu,Qingtian Zhu,Weiming Xiao,Qing Shan,Zhigang Yan,Jian Wu,Bin Deng,Yan Xue,Weijuan Gong,Guotao Lu,Yanbing Ding
Formononetin is a kind of isoflavone compound and has been reported to possess anti-inflammatory properties. In this present study, we aimed to explore the protective effects of formononetin on dextran sulfate sodium- (DSS-) induced acute colitis. By intraperitoneal injection of formononetin in mice, the disease severity of colitis was attenuated in a dose-dependent manner, mainly manifesting as relieved clinical symptoms of colitis, mitigated colonic epithelial cell injury, and upregulations of colonic tight junction proteins levels (ZO-1, claudin-1, and occludin). Meanwhile, our study found that formononetin significantly prevented acute injury of colonic cells induced by TNF-α in vitro, specifically manifesting as the increased expressions of colonic tight junction proteins (ZO-1, claudin-1, and occludin). In addition, the result showed that formononetin could reduce the NLRP3 pathway protein levels (NLRP3, ASC, IL-1β) in vivo and vitro, and MCC950, the NLRP3 specific inhibitor, could alleviate the DSS-induced mice acute colitis. Furthermore, in the foundation of administrating MCC950 to inhibit activation of NLRP3 inflammasome, we failed to observe the protective effects of formononetin on acute colitis in mice. Collectively, our study for the first time confirmed the protective effects of formononetin on DSS-induced acute colitis via inhibiting the NLRP3 inflammasome pathway activation.
研究领域:
药理学
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免疫学
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胃肠病学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
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2025
·
IF 5.4
Lei Yan,Qin Zeng,Wenru Wang,Ying Liang,Rui Lang,Jingyi Zhan,Jiayi Yang,Renhuan Yu,Xinhui Wang
Ethnopharmacological relevance Jianpi Qushi Heluo formula (JQHF) is an evidence-based herbal formula based on "Fangji Huangqi Decoction" in the classic of traditional Chinese medicine (TCM) synopsis of the Golden Chamber. Its effectiveness in reducing idiopathic membranous nephropathy (IMN) proteinuria, edema and other clinical symptoms and improving kidney injury has been confirmed by clinical trials and animal experiments. These results demonstrate the critical significance of reducing podocyte injury by regulating mitophagy through integrating ethnopharmacology. Aim of the study This study aimed to explore the protective effects of JQHF on podocyte injury in IMN, focusing on its role in promoting PINK1-dependent mitophagy to inhibit reactive oxygen species (ROS) mediated activation of the NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome. Materials and Methods The main components of JQHF were identified by ultra-performance liquid chromatography combined with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MSE). Passive Heymann nephritis (PHN) was induced in rats using anti-Fx1A antiserum, while podocyte injury in vitro was stimulated with sublytic complement C5b-9 (sC5b-9). The PHN rats were treated with JQHF, and autophagy inhibitor 3-methyladenine (3-MA) combined with JQHF was used for pathway verification, and Benazepril served as a positive control. In vitro, podocytes were exposed to palmitic acid (PA, a ROS inducer) and N-acetylcysteine (NAC, a ROS scavenger). Further, we silenced the expression of PINK1 in podocytes model and intervened with JQHF-containing serum. Renal function was assessed through biochemical analyses and histopathology. Mitochondrial function was measured by detecting mitochondrial membrane potential (MMP), ROS levels as well as mitochondrial ultrastructure. The expression of podocyte structural proteins (desmin, nephrin, podocin) and inflammasome-related markers (NLRP3, caspase-1, IL-1β, IL-6) was analyzed to assess podocyte injury and inflammasome activation. Results (1) In vitro, in contrast to the control group, PA intervention caused increased ROS accumulation, reduced MMP, upregulated NLRP3 and caspase-1 expression, as well as elevated expression of inflammatory factors IL-1β and IL-6. The expression of nephrin and podocin was notably reduced. By contrast, NAC reversed these effects. (2) In vivo, JQHF effectively ameliorated mitochondrial damage, reduced NLRP3 expression and mitigated podocyte injury in PHN rats. The protective effects of JQHF were diminished by 3-MA, confirming the involvement of autophagy. (3) In vitro, JQHF-containing serum attenuated C5b-9-induced podocyte injury, improved mitochondrial dysfunction, and inhibited ROS-mediated activation of NLRP3 inflammasome. Silencing PINK1 significantly reversed these protective effects. Conclusion JQHF can alleviate podocyte damage, that through inhibiting ROS-mediated NLRP3 inflammasome activation by improving PINK1-mediated mitophagy.
研究领域:
免疫学
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分子生物学
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药理学
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转化医学
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肾脏病学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2025
·
IF 4.7
Zhengyuan Huang,Guanghui Chen,Zhongyu Ren,Ling Xiao,Ziyue Chen,Yinping Xie,Gaohua Wang,Benhong Zhou
The management of cognitive impairments in schizophrenia presents a considerable challenge, with a strong association between neuroinflammation and its progression. Urolithin A (UA) demonstrates important anti-inflammatory properties in multiple neurological disease models, contributing to the enhancement of cognitive deficits. However, it remains uncertain if UA can produce comparable neuroregulatory effects in female rat models of schizophrenia. Eight-week-old female Sprague Dawley rats received either 0.1 mg/kg of MK801 or volume-matched saline via intraperitoneal injection for 5 consecutive days. Furthermore, they were administered 150 mg/kg of UA through oral gavage for 4 weeks. Behavioral assessments were performed to evaluate cognitive function and behavior after UA treatment. Immunofluorescence staining was employed to assess microglial activity in the hippocampus, while Western blot analysis was conducted to investigate the expression of neuroinflammation-associated proteins. Prolonged exposure to MK801 induces schizophrenia-like behaviors and cognitive deficits in female rats. It also elevates the expression of NLRP3, Caspase-1, IL-1β, and IL-18 proteins in the hippocampus, accompanied by the activation of microglial cells. However, UA treatment can reverse the expression of these inflammatory proteins and the activation of microglial cells induced by MK801. This is the first study to evaluate the effects of UA on behavior and cognition in a female rat model of schizophrenia. The findings indicate that UA mitigates MK-801-induced cognitive deficits in female rats by inhibiting neuroinflammation and microglial activation via modulation of the NLRP3 signaling pathway. These findings offer preclinical data endorsing the possible application of UA as a dietary supplement to prevent cognitive deficits in schizophrenia.
研究领域:
神经科学
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药理学
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行为科学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2023
·
IF 8.2
Qun Wang,Zhaomei Wang,Jun Song,Kangjie Xu,Wenni Tian,Xu Cai,Jiamei Mo,Yong Cao,Jie Xiao
A nanolipidcarrier (NLC) loaded homogalacturonan enriched pectin (citrus modified pectin, MCP4) hydrogel was designed as a novel colon inflammation site-specific oral delivery system for 6-gingerol (6G) (6G-NLC/MCP4 hydrogel) administration, and its colitis alleviation effect were investigated. 6G-NLC/MCP4 exhibited typical “cage-like” ultrastructure with 6G-NLC embedded in the hydrogel matrix as observed by cryoscanning electron microscope. And due to the homogalacturonan (HG) domain in MCP4 specifically combined with Galectin-3, which is overexpressed in the inflammatory region, the 6G-NLC/MCP4 hydrogel targeted to severe inflammatory region. Meanwhile, the prolonged-release characteristics of 6G-NLC provided sustained release of 6G in severe inflammatory regions. The matrix of hydrogel MCP4 and 6G achieved synergistic alleviation effects for colitis through NF-κB/NLRP3 axis. Specifically, 6G mainly regulated the NF-κB inflammatory pathway and inhibited the activity of NLRP3 protein, while MCP4 regulated the expression of Galectin-3 and peripheral clock gene Rev-Erbα/β to prevent the activation of inflammasome NLRP3.
研究领域:
药学
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生物医学工程
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炎症生物学
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药物递送系统
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产品关联
DOI
PubMed
高影响因子
ENVIRONMENTAL POLLUTION
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2024
·
IF 7.6
Xin-Ran Ge,Yi Zhao,Hao-Ran Ren,Fu-Wei Jiang,Shuo Liu,Ming Lou,Yi-Feng Huang,Ming-Shan Chen,Jia-Xin Wang,Jin-Long Li
As the most produced phthalate, di-(2-ethylhexyl) phthalate (DEHP) is a widely environmental pollutant primarily used as a plasticizer, which cause the harmful effects on human health. However, the impact of DEHP on spleen and its underlying mechanisms are still unclear. Pyroptosis is a novel form of cell death induced by activating NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasomes and implicated in pathogenesis of numerous inflammatory diseases. The current study aimed to explore the impact of DEHP on immune inflammatory response in mouse spleen. In this study, the male ICR mice were treated with DEHP (200 mg/kg) for 28 days. Here, DEHP exposure caused abnormal pathohistological and ultrastructural changes, accompanied by inflammatory cells infiltration in mouse spleen. DEHP exposure arouse heat shock response that involves increase of heat shock proteins 60 (HSP60) expression. DEHP also elevated the expressions of toll-like receptor 4 (TLR4) and myeloid differentiation protein 88 (MyD88) proteins, as well as the activation of NF-κB pathway. Moreover, DEHP promoted NLRP3 inflammasome activation and triggered NLRP3 inflammasome-induced pyroptosis. Mechanistically, DEHP drives splenic inflammatory response via activating HSP60/TLR4/NLRP3 signaling axis-dependent pyroptosis. Our findings reveal that targeting HSP60-mediated TLR4/NLRP3 signaling axis may be a promising strategy for inflammatory diseases treatment.
研究领域:
毒理学
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免疫学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
Molecular & Cellular Toxicology
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2025
·
IF 1.4
He Chaojie,Fan Hongyan,Zhu Chunyan,Huang Yueqing
Background Ischemia–reperfusion (I/R) injury is a severe disorder during revascularization therapy against acute myocardial infarction. Objective Our study aims to investigate the role and regulation mechanism of Annexin A1 (ANXA1) against I/R injury. Results Western blotting analysis showed that ANXA1 expression in rat cardiomyocytes (H9C2 cells) was notably decreased by oxygen–glucose deprivation/reperfusion (OGD/R) treatment. Meanwhile, the NLRP3 inflammasome activation accompanied by pyroptosis and inflammation was observed in H9c2 cells under OGD/R induction. Besides, overexpression or knockdown of ANXA1 dramatically inhibited or aggravated NLRP3-mediated pyroptosis and inflammation. Further investigations found that the m 6 A level of ANXA1 was upregulated by OGD/R, thus leading to decreased mRNA stability in H9C2 cells. FTO, a N6-methyladenosine (m 6 A) “eraser”, was downregulated in H9C2 cells by OGD/R and shown to increase the ANXA1 protein expression by demethylating mRNA in H9c2 cells under OGD/R induction. Moreover, knockdown FTO reversed the protection of ANXA1 against NLRP3-mediated pyroptosis and inflammation in OGD/R-induced H9C2 cells. Conclusion ANXA1 protects cardiomyocytes against I/R injury by alleviating NLRP3-mediated pyroptosis and inflammation via FTO-mediate demethylation. These findings innovatively suggest the therapeutic potential of ANXA1 for myocardial I/R injury.
研究领域:
分子生物学
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心脏病学
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表观遗传学
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产品关联
DOI
高影响因子
TOXICON
·
2025
·
IF 2.4
Jingyi Yang,Hao Xu,Ruiqi Ye,Yu Zhang,Jiale Wu,Erhui Jin,Xiaojin Li,Mixia Cao,Shenghe Li,Chang Liu,Lei Li
Ochratoxin A (OTA) is a prevalent contaminant in feed and poses a serious threat to the poultry industry and public health. The liver is the primary target of OTA, and oxidative stress alongside consequent inflammation, is considered the main contributor to OTA-induced liver damage. Astragaloside IV (AS-IV), a key constituent of the traditional Chinese medicinal herb Astragalus membranaceus, exhibits diverse pharmacological properties, including anti-inflammatory, antioxidant, immunoregulatory, and organ-protective effects. However, whether AS-IV can ameliorate OTA-induced liver damage remains uncertain. In the current investigation, we investigated the effect of AS-IV on OTA-induced liver damage in chicks and elucidated the underlying mechanisms. The results revealed that AS-IV inhibited OTA-induced increases in alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (AKP) activities. Additionally, AS-IV reversed the OTA-induced decrease in glutathione peroxidase (GSH-Px) and total superoxide dismutase (T-SOD) activities, as well as the increase in malondialdehyde (MDA) content (P < 0.05). The results demonstrated that AS-IV is capable of mitigating mitochondrial damage and reducing the elevation of reactive oxygen species (ROS) in the chicken liver cell line LMH induced by OTA. Moreover, AS-IV was discovered to reverse the OTA-induced decrease in nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase 1 (HO-1), NADPH quinone oxidoreductase 1 (NQO1) expression, and the increase in Kelch-like ECH-associated protein 1(Keap1) expression. Meanwhile, AS-IV also counteracted OTA-induced NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome expression. Taken together, our findings suggested that AS-IV ameliorated OTA-induced hepatotoxicity in chicks by regulating the Nrf2 and NLRP3 signaling pathways.
研究领域:
毒理学
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兽医学
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分子生物学
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药理学
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食品安全
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产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
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2019
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IF 3.845
Li Chen-Guang,Zeng Qiong-Zhen,Chen Ming-Ye,Xu Li-Hui,Zhang Cheng-Cheng,Mai Feng-Yi,Zeng Chen-Ying,He Xian-Hui,Ouyang Dong-Yun
Evodiamine is a major ingredient of the plant Evodia rutaecarpa, which has long been used for treating infection-related diseases including diarrhea, beriberi and oral ulcer, but the underlying mechanism is unclear. Here we aimed to explore whether evodiamine influenced NLRP3 (NLR family, pyrin containing domain 3) inflammasome activation in macrophages, which is a critical mechanism for defending the host against pathogenic infections. We uncovered that evodiamine dose-dependently enhanced NLRP3 inflammasome activation in lipopolysaccharide-primed macrophages, as indicated by increased interleukin (IL)-1β production and caspase-1 cleavage, accompanied by increased ASC speck formation and pyroptosis. Mechanistically, evodiamine induced acetylation of α-tubulin around the microtubule organization center (indicated by γ-tubulin) in lipopolysaccharide-primed macrophages. Such evodiamine-mediated increases in NLRP3 activation and pyroptosis were attenuated by activators of α-tubulin deacetylase, resveratrol and NAD+, or dynein-specific inhibitor ciliobrevin A. Small interfering RNA knockdown of αTAT1 (the gene encoding α-tubulin N-acetyltransferase) expression, which reduced α-tubulin acetylation, also diminished evodiamine-mediated augmentation of NLRP3 activation and pyroptosis. Evodiamine also enhanced NLRP3-mediated production of IL-1β and neutrophil recruitment in vivo. Moreover, evodiamine administration evidently improved survival of mice with lethal bacterial infection, accompanied by increased production of IL-1β and interferon-γ, decreased bacterial load, and dampened liver inflammation. Resveratrol treatment reversed evodiamine-induced increases of IL-1β and interferon-γ, and decreased bacterial clearance in mice. Collectively, our results indicated that evodiamine augmented the NLRP3 inflammasome activation through inducing α-tubulin acetylation, thereby conferring intensified innate immunity against bacterial infection.
研究领域:
免疫学
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药理学
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微生物学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
Heliyon
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2023
·
IF 4
Weichao Sun,Jiaji Yue,Tianhao Xu,Yinxing Cui,Dixi Huang,Houyin Shi,Jianyi Xiong,Wei Sun,Qian Yi
Osteoarthritis (OA) is a prevalent chronic degenerative joint disease worldwide. Obesity has been linked to OA, and increased free fatty acid levels (e.g., palmitate) contribute to inflammatory responses and cartilage degradation. Xanthohumol (Xn), a bioactive prenylated chalcone, was shown to exhibit antioxidative, anti-inflammatory, and anti-obesity capacities in multiple diseases. However, a clear description of the preventive effects of Xn on obesity-associated OA is unavailable. This study aimed to assess the chondroprotective function of Xn on obesity-related OA. The in vitro levels of inflammatory and ECM matrix markers in human chondrocytes were assessed after the chondrocytes were treated with PA and Xn. Additionally, in vivo cartilage degeneration was assessed following oral administration of HFD and Xn. This study found that Xn treatment completely reduces the inflammation and extracellular matrix degradation caused by PA. The proposed mechanism involves AMPK signaling pathway activation by Xn, which increases mitochondrial biogenesis, attenuates mitochondrial dysfunction, and inhibits NLRP3 inflammasome and the NF-κB signaling pathway induced by PA. In summary, this study highlights that Xn could decrease inflammation reactions and the degradation of the cartilage matrix induced by PA by inhibiting the NLRP3 inflammasome and attenuating mitochondria dysfunction in human chondrocytes.
研究领域:
风湿病学
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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
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DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2020
·
IF 3.943
Yu Li,Rong Wang,Lian Xue,Yilin Yang,Feng Zhi
Background Ischaemic stroke is a lethal cerebrovascular disease that occurs worldwide. Astilbin is a natural flavonoid compound with various physiological activities. The purpose of this study was to investigate the neuroprotective effects of Astilbin after cerebral ischaemia reperfusion (I/R) injury. Methods The oxygen and glucose deprivation (OGD) model was used to simulate cerebral I/R injury in vitro . Cell viability was measured via CCK-8 and LDH release assays. Cell apoptosis was measured via Hoechst 33258 staining and flow cytometry assays. ROS was detected via flow cytometry assay. The protein expression levels were determined by western blotting. The middle cerebral artery occlusion (MCAO) model was used to simulate cerebral I/R injury in vivo . Cerebral ischaemic volume was measured by TTC staining. The Zea-Longa score, rota-rod test, and foot-fault test were used to evaluate behavioural changes and neurological deficits in rats. Results Astilbin significantly enhanced cell viability and decreased LDH release after OGD treatment in vitro . Astilbin effectively curbed cell apoptosis induced by OGD via inhibiting the activation of caspase-3, decreasing the ratio of Bax/Bcl-2 and decreasing FADD. Astilbin also inhibited OGD-induced inflammation by suppressing ROS-NLRP3 inflammasome axis activation. Further results revealed that Astilbin could suppress the MAPK pathway and activate the PI3K/AKT pathway. Finally, Astilbin significantly reduced the cerebral infarction volume and relieved neurological deficits in rats in vivo . Conclusion Astilbin could defend against cerebral I/R injury by inhibiting apoptosis and inflammation via suppressing the MAPK pathway and activating the AKT pathway.
研究领域:
神经科学
·
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）