Frontiers in Nutrition
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2026
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IF 5.5
Bingye Xu,Xiaoxiao Li,Rong Liu,Ying Han,Pan Zhen,Hanyue Fu,Huan Lv,Fan Wei,Haoxin Cui,Bowei Zhang,Shuo Wang
IntroductionHyperuricemia (HUA) is a major risk factor for gout and renal injury, underscoring the need for safe and effective natural dietary interventions. This study investigated the chemical composition and antihyperuricemic effects of dealcoholized Zhuyeqing liquor extract (ZLE) using both cellular and animal models.MethodsThe nutritional composition and phytochemical profile of ZLE were characterized by quantitative analysis and ultra-performance liquid chromatography–tandem mass spectrometry (UPLC–MS/MS). The antihyperuricemic activity of ZLE was evaluated in adenosine-induced HepG2 cells and in a hypoxanthine/potassium oxonate-induced mouse model of HUA by assessing uric acid (UA) metabolism, hepatorenal function, urate transporter expression, and renal inflammatory signaling.ResultsQuantitative analysis showed that ZLE is rich in polysaccharides, terpenes, and flavonoids. UPLC–MS/MS identified 389 phytochemical constituents, predominantly iridoid glycosides, organic acids, and flavonoids. In adenosine-induced HepG2 cells, ZLE significantly reduced UA production and xanthine oxidase (XOD) activity. In HUA mice, ZLE dose-dependently decreased serum UA levels, improved renal and hepatic function by reducing serum creatinine, blood urea nitrogen, alanine aminotransferase, and aspartate aminotransferase levels, and inhibited hepatic XOD activity. Furthermore, ZLE restored renal urate homeostasis through coordinated regulation of key urate transporters and alleviated HUA-induced renal inflammation and histopathological injury by suppressing the lipopolysaccharide-mediated NLRP3/Caspase-1 signaling pathway.DiscussionThese findings demonstrate that ZLE exerts antihyperuricemic and renoprotective effects through coordinated modulation of uric acid production, renal urate transport, and inflammatory signaling. The results support the potential application of ZLE as a functional food ingredient for dietary management of HUA and provide a scientific basis for translating traditional dietary resources into modern nutritional interventions.
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Frontiers in Pharmacology
·
2022
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IF 5.988
Zhang Cong,Song Yingying,Chen Liang,Chen Peng,Yuan Ming,Meng Yan,Wang Qi,Zheng Guohua,Qiu Zhenpeng
Urolithin A (UroA) is one of the primary intestinal metabolites of ellagitannins, showing translational potential as a nutritional intervention in humans. Mounting evidence suggests that fructose consumption contributes to the progression of chronic kidney disease (CKD) that manifests in hyperuricemic nephropathy, renal inflammation, and tubulointerstitial injury. Here, we investigated the efficacy of UroA in alleviating fructose-induced hyperuricemic nephropathy in mice. Uric acid-exposed human kidney-2 (HK-2) cells were utilized for in vitro mechanism validation. Histopathological staining, immunoblotting, and transmission electron microscope were performed for the mechanistic investigations. Our results revealed that UroA ameliorated fructose-induced hyperuricemic nephropathy in mice. The histopathologic assessment showed that UroA attenuated tubular hypertrophy and dilation, glomerular basement membrane thickening, and collagen deposition in the kidney of fructose-fed mice. Mechanistically, UroA treatment impaired STING-NLRP3 activation, resulting in reduced production of proinflammatory cytokines IL-1β, IL-6, and TNF-α. Notably, UroA exhibited a scavenging effect against reactive oxygen species (ROS) and restored fructose-impaired PINK1/Parkin-mediated mitophagy in nephropathic mice. Furthermore, the inhibitory effect of UroA in STING-NLRP3 activation was impaired after Parkin gene silencing in HK-2 cells. Together, this study suggests that UroA alleviates fructose-induced hyperuricemic nephropathy by promoting Parkin-dependent mitophagy, thereby suppressing STING-NLRP3 axis-mediated inflammatory response. Thus, dietary supplementation with UroA or ellagitannins-rich foods may serve as a promising intervention to prevent CKD progression.
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Journal of Functional Foods
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2022
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IF 5.223
Yuzhe Huang,Kunfeng Zhang,Wenqiang Guo,Chan Zhang,Hao Chen,Tenglong Xu,Yongming Lu,Qingxi Wu,Yong Li,Yan Chen
Tartary buckwheat is a popular natural grain commonly used as a functional food in various countries. This study aimed to prepare buckwheat dietary fiber with improved biological activity using liquid fermentation of Aspergillus niger and to elucidate its physicochemical properties and related mechanisms. Compared with unfermented buckwheat dietary fiber, Aspergillus niger fermentation increased the soluble dietary fiber content, thereby improving dietary fiber's physical and chemical properties such as water, oil retention capacity, and swelling cholesterol-binding capacity. Fermented Tartary buckwheat dietary fiber treatment for 14 weeks significantly decreased the hepatic lipid profile, oxidative stress, and protein expression in mice. In addition, fermented Tartary buckwheat dietary fiber intervention could regulate high-fat diet-induced disorders of gut microbiota. These results suggested that fermented Tartary buckwheat dietary fiber has potential “prebiotic” effects in ameliorating obesity.
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BIOLOGICAL TRACE ELEMENT RESEARCH
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2023
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IF 3.9
Yan Nan,Wang Zhengdong,Li Zhou,Zheng Yang,Chang Nan,Xu Kangjie,Wang Qian,Duan Xiaoxu
This study aimed to examine the immuntoxic effects of arsenic in the nervous system. Our results showed that arsenic increased corticocerebral and hippocampal weights ( p < 0.05). Morris water maze tests revealed that arsenic significantly increased the time spent in latency to platform on the fourth day in 50 mg/L arsenic exposure and the fifth day in 25 and 50 mg/L arsenic exposure, as well as reduced the path length in target quadrant, time spent in target quadrant, and crossing times of the platform ( p < 0.05). Hematoxylin–eosin staining showed that the vacuolated degeneration and pyknosis was found in the cerebral cortex and hippocampus of arsenic-treated mice. The mRNA levels of corticocerebral and hippocampal brain-derived neurotrophic factor (BDNF) and vascular endothelial growth factor (VEGF) were decreased in the 50 mg/L arsenic-treated group ( p < 0.05). In addition, immunofluorescence staining showed that 25 and 50 mg/L arsenic all increased the expression of CD11b and glial fibrillary acidic protein (GFAP) in the cerebral cortex and hippocampus ( p < 0.05). Arsenic markedly raised antigen-presenting molecule MHCII and CD40 mRNA levels in the cerebral cortex and hippocampus and upregulated the cell chemokine receptor 5 (CCR5) and CCR7 mRNA levels in the cerebral cortex at the 50 mg/L arsenic group, and increased the CCR7 mRNA levels in the hippocampus at the 25 and 50 mg/L arsenic groups ( p < 0.05). Arsenic activated the nucleotide-binding domain-like receptor protein-3 (NLRP3) inflammasome, and enhanced its upstream promoter NF-κB protein level and downstream regulators IL-18 mRNA levels. Collectively, these results provide new evidences for the neuro-immune toxicity of arsenic. Graphical abstract
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JOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY
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2021
·Vol. 35
·期 9
·e22845
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IF 3.652
Hongsong Li,Rong Li,Lijun Wang,Dingying Liao,Wenyi Zhang,Jianming Wang
Diabetic retinopathy (DR) is a common diabetic complication known to cause vision impairment and blindness. Previous studies have demonstrated that proanthocyanidins (PACs), polyphenols that are naturally found in several plants and fruits, have powerful antioxidant and anti-inflammatory effects on various cells. However, the effects and underlying mechanism of PACs against DR pathogenesis remain unknown. Here, we investigated the proliferation, apoptosis, and mechanisms of ARPE-19 cells in response to oxidative stress and inflammation under high-glucose conditions with or without PACs treatment. The Cell-Counting Kit-8 assay and western blot analysis showed that treatment with 10 μl PACs significantly increased cell proliferation and the expression level of Bcl-2 in ARPE-19 cells under high-glucose conditions. Moreover, PACs attenuated the high glucose-induced apoptosis, and the increased expression levels of caspase-3 and Bax. Under high-glucose conditions, the generation of reactive oxygen species (ROS) and levels of malondialdehyde increased, whereas the superoxide dismutase content decreased. Moreover, the expression level of the NLRP3 inflammasome, and the release of interleukin 1β (IL-1β) and IL-18 increased. PACs reversed all of these high glucose-induced effects on ARPE-19 cells. Additionally, exposure to nigericin sodium salt, an agonist of the NLRP3 inflammasome, upregulated expression of the NLRP3 inflammasome accompanied by the release of IL-1β and IL-18. Again, treatment with PACs markedly downregulated these effects. Collectively, these results demonstrate that PACs can prevent retinal pigment epithelial cells from high glucose-induced injury via inhibiting the generation of ROS and activation of the NLRP3 inflammasome, suggesting PACs as a potential candidate for the management of DR.
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OBESITY SURGERY
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2020
·Vol. 30
·期 9
·3435-3443
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IF 3.412
Sun Kangyue,Wang Jing,Lan Zhixian,Li Ling,Wang Yadong,Li Aimin,Liu Side,Li Yue
Purpose Endoscopic sleeve gastroplasty (ESG) has been suggested to be effective for treating obesity and its related non-alcoholic fatty liver disease (NAFLD). A small molecule named CY-09 is the selective inhibitor of the NOD-like receptor pyrin domain-containing protein 3 (NLRP3) inflammasome. We aim to investigate whether a surgery imitating ESG combined with CY-09 is more effective for treatment of obesity and NAFLD in a mouse model. Material and Methods Forty mice were randomly divided into a control group ( n = 5) and an NAFLD group ( n = 35) fed by high-fat diet (HFD). The NAFLD mice were randomly assigned to the following groups at the timepoint of 19 weeks: (1) sham surgery; (2) surgery; (3) the combination of surgery with CY-09 injection. NAFLD activity score (NAS) was used for histological evaluation of steatosis. We also detected fasting glucose and insulin to measure the homeostasis model assessment of insulin resistance (HOMA-IR). Results HFD resulted in significant obesity and metabolic disorders, indicating successful modelling of obesity and NAFLD. The combination therapy resulted in significantly lower body weight than surgery alone at the end of the 8-week follow-up (40.4 ± 4.8 vs. 45.0 ± 2.2 g, P = 0.025). Furthermore, more dramatic improvements in HOMA-IR (5.8 ± 1.1 vs. 12.2 ± 2.1 mmol mIU L −2 , P = 0.036) and NAS (4.5 ± 1.3 vs. 8.0 ± 1.8, P = 0.006) were also observed in the combination group. Conclusions Surgery imitating ESG combined with CY-09 reduces body weight, improves insulin resistance and alleviates hepatic steatosis. The combination therapy may be a promising method for treating obesity and NAFLD.
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Biomed Research International
·
2019
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IF 2.197
Hao Lu,Hui Yao,Rong Zou,Xiwen Chen,Hanlin Xu
Renal inflammation can result in renal injury. Uric acid (UA) is the final product of purine metabolism in humans and because of the lack of urate oxidase, UA may accumulate in tissues, including kidney, causing inflammation. Galangin was isolated from a traditional Chinese medicine plant and possesses several beneficial effects, working as an anti-oxidant, anti-mutagenic, anti-tumor, anti-inflammatory, anti-microbial, and anti-viral agent. Therefore, this study aimed at investigating the molecular mechanism of galangin in the attenuation of UA induced renal inflammation in normal rat kidney epithelial cells NRK-52E. Our findings suggested that galangin treatment efficiently protected NRK-52E cells against UA induced renal inflammation by decreasing tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-18, prostaglandin E2 (PGE2), and nitric oxide (NO) release, and it inhibited nitric oxide synthase (iNOS), prostaglandin endoperoxide synthase 2 (PTGS2), TNF-α, IL-1β, and IL-18 mRNA expression. In addition, galangin was not exerting any cytotoxicity at the concentrations that were effective against inflammation as assessed by CCK8 assay. Moreover, western blotting showed that galangin treatment effectively inhibited nuclear factor-kappa B (NF-κB), phosphatidylinositol 3 kinase (PI3K)/protein kinase B (AKT) and nucleotide-binding domain- (NOD-) like receptor protein 3 (NLRP3) signaling pathway activation. Taken together, these findings suggested that galangin plays a pivotal role in renal inflammation by suppressing inflammatory responses, which might be closely associated with the inhibition of NLRP3 inflammasome, NF-κB and PI3K/AKT signaling pathway activation.
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CELLULAR SIGNALLING
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2024
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IF 4.4
Yun Zhou,Song Yue,Lihua Li,Jiahua Zhang,Lei Chen,Jun Chen
Abnormal inflammation of vascular endothelial cells occurs frequently in diabetic retinopathy (DR). Sphingomyelin phosphodiesterase acid-like 3B (SMPDL3B) is a lipid raft enzyme and plays an anti-inflammatory role in various diseases but its function in DR-related vascular endothelial dysfunction remains unknown. We first found that SMPDL3B expression was upregulated from week 10 to 18 in the retinal tissues of db/db mice. Particularly, the high expression of SMPDL3B was mainly observed in retinal vascular endothelium of DR mice. To interfere retinal SMPDL3B expression, adeno-associated viruses 2 (AAV-2) containing SMPDL3B specific shRNA (1233–1253 bp) were injected into the vitreous cavity of db/db mice. SMPDL3B silencing exacerbated the spontaneous DR by further activating the NF-κB/NLRP3 pro-inflammatory pathway. In vitro , human retinal microvascular endothelial cells (HRVECs) were infected with SMPDL3B-shRNA lentiviruses and then stimulated with 30 mM glucose (HG) for 24 h. SMPDL3B-silenced HRVECs secreted more interleukin-1β and had enhanced nuclear p65 translocation. Notably, HG treatment induced the palmitoylation of SMPDL3B. Zinc finger DHHC-type palmitoyltransferase 5 (ZDHHC5) is a palmitoyltransferase that catalyzes the palmitoylation of its substrates, HG exposure increased the interaction between ZDHHC5 and SMPDL3B in HRVECs. 2-BP, a palmitoylation inhibitor, accelerated the protein degradation of SMPDL3B, whereas palmostatin B, a depalmitoylation inhibitor, decreased its turnover rate in HRVECs. Collectively, the present study suggests a compensatory increase of SMPDL3B in HG-treated HRVECs and the retinal tissues of DR mice, indicating that SMPDL3B may be a potential target for DR treatment.
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INTERNATIONAL IMMUNOPHARMACOLOGY
·
2025
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IF 4.7
Wenyang Zhou,Zhenhao Liu,Xichuan Qiu,Minghao Tian,Baoqiang He,Chao Tang,Qiang Tang,Rupei Ye,Dejun Zhong,Yehui Liao
Following spinal cord injury (SCI), pyroptosis plays a significant role in regulating neuroinflammation during the secondary phase of injury. Although 1,8-cineole possesses anti-inflammatory effects, its role in SCI and underlying molecular mechanisms remains unclear. This study revealed that 1,8-cineole promoted motor function recovery in spinal cord-injured rats, reduced NLRP3 inflammasome-mediated microglial pyroptosis and activation, enhanced neuronal regeneration, and suppressed neuronal apoptosis and glial scar formation. Network pharmacology analysis showed that 1,8-cineole targets the PI3K/AKT and P38 MAPK pathways to inhibit microglial activation and pyroptosis. Finally, using a conditional co-culture system, we demonstrated that 1,8-cineole-treated microglia facilitated neuronal regeneration while inhibiting apoptosis. These findings indicate that 1,8-cineole promotes functional recovery post-SCI by protecting neurons by suppressing microglial pyroptosis and activation through the PI3K/AKT and P38 MAPK axes.
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Virulence
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2022
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IF 5.428
Qiankun Yang,Jianguo Zhang,Feixue Liu,Huizhen Chen,Wei Zhang,Haitao Yang,Nana He,Jingquan Dong,Panpan Zhao
Aeromonas caviae, an important food-borne pathogen, induces serious invasive infections and inflammation. The pro-inflammatory IL-1β functions against pathogenic infections and is elevated in various Aeromonas infection cases. However, the molecular mechanism of A. caviae-mediated IL-1β secretion remains unknown. In this study, mouse macrophages (PMs) were used to establish A. caviae infection model and multiple strategies were utilized to explore the mechanism of IL-1β secretion. IL-1β was elevated in A. caviae infected murine serum, PMs lysates or supernatants. This process triggered NLRP3 levels upregulation, ASC oligomerization, as well as dot gathering of NLRP3 and speck-like signals of ASC in the cytoplasm. MCC950 blocked A. caviae mediated IL-1β release. Meanwhile, NLRP3 inflammasome mediated the release of IL-1β in dose- and time-dependent manners, and the release of IL-1β was dependent on active caspase-1, as well as NLRP3 inflammasome was activated by potassium efflux and cathepsin B release ways. A. caviae also enhanced TLR2 levels, and deletion of TLR2 obviously decreased IL-1β secretion. What’s more, A. caviae resulted in NF-κB p65 nuclear translocation partly in a TLR2-dependent manner. Blocking NF-κB using BAY 11-7082 almost completely inhibited NLRP3 inflammasome first signal pro-IL-1β expression. Blocking TLR2, NF-κB, NLRP3 inflammasome significantly downregulated IL-1β release and TNF-α and IL-6 levels. These data illustrate that A. caviae caused IL-1β secretion in PMs is controlled by NLRP3 inflammasome, of which is mediated by NF-κB pathway and is partially dependent on TLR2, providing basis for drugs against A. caviae.
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MOLECULAR AND CELLULAR ENDOCRINOLOGY
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2016
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IF 3.859
Aiyun Li,Shuihong Zhang,Jia Li,Kang Liu,Fang Huang,Baolin Liu
Objective This study was designed to investigate the hypothesis that metformin and resveratrol exhibited the same effect on inhibition of NLRP3 inflammasome activation with regulation of AMPK in adipose tissue exposed to high glucose. Methods To induce adipose tissue dysfunction, we treated epididymal adipose tissue of mice or differentiated 3T3-L1 adipocytes with high glucose (33 mM) for 24 h. Meanwhile, mice were injected with streptozotocin STZ to induce diabetes and followed by oral administration of metformin (200 mg/kg), resveratrol (50 mg/kg) or ER stress inhibitor TUDCA (50 mg/kg) for 7 days. The effects of metformin and resveratrol on ROS production, mitochondrial fission , ER stress, TXNIP/NLRP3 inflammasome activation, inflammation and apoptosis were observed. Results Metformin and resveratrol inhibited ROS-associated mitochondrial fission by upregulating Drp1 phosphorylation (Ser 637) in an AMPK-dependent manner, and then suppressed ER stress indicated by dephosphorylation of IRE1α and eIF2α in the adipose tissue. As a result from suppressing TXNIP/NLRP3 inflammasome activation, metformin and resveratrol inhibited inflammation and reduced cell apoptosis in adipose tissue or adipocytes exposed to high glucose. Conclusion Metformin and resveratrol protected mitochondrial integrity by inhibiting Drp1 activity and prevented NLRP3 inflammasome activation by suppressing ER stress, and thereby protected adipose function from high glucose insult.
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FREE RADICAL BIOLOGY AND MEDICINE
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2021
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IF 7.376
Rana Dhar,Mohammad Nasiruddin Rana,Lejun Zhang,Yajun Li,Ning Li,Zhengqiang Hu,Chungunag Yan,Xuefeng Wang,Xuyang Zheng,Hongyun Liu,Huashun Cui,Zigang Li,Huifang Tang
Acute lung injury (ALI) is associated with overproduction of inflammatory mediators in lung tissue. Previous studies have revealed that inflammation induces activation of phosphodiesterase 4B (PDE4B) accompanied by the production of inflammatory mediators, but the detailed mechanism remains unclear. Here, we focused on the NOD-, LRR- and pyrin domain-containing protein 3(NLRP3) inflammasome complexes to study the crosstalk between PDE4B and NF-E2-related factor 2 (Nrf2). We used global knockout PDE4B or Nrf2 mice to prepare LPS induced acute lung injury model by intratracheally administration, and LPS primed bone marrow-derived macrophages (BMDMs), following overexpression of PDE4B or Nrf2, luciferase activity analysis, and chIP-qPCR analyses. We found that deficiency of PDE4B could potently attenuate the lung histopathological changes, suppress the secretion of pro-inflammatory mediators such as tumor necrosis factor α (TNF-α), interleukin (IL)-1β, IL-6, IL-18, and cleaved caspase-1, 8, and GSDMD accompanied with defective activation of the ROS/Nrf2/NLRP3. Meanwhile deficiency of Nrf2 showed the similar results. Furtherly, overexpression by PDE4B or Nrf2 plasmid transfection in MH-S cells could enhance the Nrf2 or PDE4B expression. Luciferase analysis suggested that Nrf2 activated PDE4B promoter activity, while PDE4B could increase Nrf2 substrate ARE activity in MH-S cells in dose dependent manners. ChIP-qPCR analyses showed that Nrf2 bound to the PDE4B promoter region at ̴ 1532 to ̴1199 position in macrophages. Altogether, deficiency of PDE4B inhibit the inflammasome activation and pyroptosis in LPS stimulated lung injury model and macrophages by regulating ROS/Nrf2/NLRP3 activation. The study provides new insight that PDE4B is required for NLRP3 inflammasome activation by positive feedback with Nrf2.
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