Nutrients
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2022
·Vol. 14
·期 13
·2765
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IF 6.706
Xuejiao Zhang,Bowei Zhang,Bo Peng,Jin Wang,Yaozhong Hu,Ruican Wang,Shuo Wang
Sugar reduction and sugar control are advocated and gaining popularity around the world. Sucrose, as the widely consumed ingredient in our daily diet, has been reported a relation to gastrointestinal diseases. However, the role of sucrose in inflammatory bowel disease remains controversial. Hence, our study aimed to elucidate the potential role of three doses of sucrose on DSS-induced colitis in C57BL/6 mice and the underlying mechanisms. The results showed that low-dose sucrose intervention alleviated colitis in mice, reducing the expression of inflammatory cytokines and repairing mucosal damages. In contrast, high-dose sucrose intervention exacerbated colitis. Furthermore, three doses of sucrose administration markedly altered gut microbiota composition. Notably, the low-dose sucrose restored microbial dysfunction and enhanced the production of short chain fatty acids (SCFAs). Specifically, the abundance of SCFAs-producing bacteriaFaecalibaculum,Bacteroides,andRomboutsiawere increased significantly in the LOW group. Consistently, PPAR-γ, activated by SCFAs, was elevated in the LOW group, thereby inhibiting the MAPK/NF-κB pathway. Together, our study demonstrates the differential effects of sucrose on colitis at different doses, providing a scientific basis for measuring and modifying the safe intake level of sugar and providing favorable evidence for implementing sugar reduction policies.Keywords:sucrose;gut microbiota;SCFAs;PPAR-γ;MAPK/NF-κB
研究领域:
胃肠病学
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免疫学
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微生物学
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营养学
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DOI
PubMed
高影响因子
BRAIN RESEARCH BULLETIN
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2024
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IF 3.5
Xu Ren,Yun-Fei Li,Tian-Wei Pei,Hao-Sheng Wang,Yu-Hai Wang,Tao Chen
Background Traumatic brain injury (TBI) is a leading cause of high mortality and disability worldwide. Overactivation of astrocytes and overexpression of inflammatory responses in the injured brain are characteristic pathological features of TBI. Rosiglitazone (ROS) is a peroxisome proliferator-activated receptor-γ (PPAR-γ) agonist known for its anti-inflammatory activity. However, the relationship between the inflammatory response involved in ROS treatment and astrocyte A1 polarization remains unclear. Objective This study aimed to investigate whether ROS treatment improves dysfunction and astrocyte A1 polarization induced after TBI and to elucidate the underlying mechanisms of these functions. Methods SD rats were randomly divided into sham operation group, TBI group, TBI+ROS group, and TBI+ PPAR-γ antagonist group (GW9662 + TBI). The rat TBI injury model was prepared by the CCI method; brain water content test and wire grip test scores suggested the prognosis; FJB staining showed the changes of ROS on the morphology and number of neurons in the peripheral area of cortical injury; ELISA, immunofluorescence staining, and western blotting analysis revealed the effects of ROS on inflammatory response and astrocyte activation with the degree of A1 polarization after TBI. Results Brain water content, inflammatory factor expression, and astrocyte activation in the TBI group were higher than those in the sham-operated group (P < 0.05); compared with the TBI group, the expression of the above indexes in the ROS group was significantly lower (P < 0.05). Compared with the TBI group, PPAR-γ content was significantly higher and C3 content was considerably lower in the ROS group (P < 0.05); compared with the TBI group, PPAR-γ content was significantly lower and C3 content was substantially higher in the inhibitor group (P < 0.05). Conclusion ROS can exert neuroprotective effects by inhibiting astrocyte A1 polarization through the PPAR-γ pathway based on the reduction of inflammatory factors and astrocyte activation in the brain after TBI.
研究领域:
神经科学
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药理学
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炎症
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创伤
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DOI
PubMed
高影响因子
BIOMEDICINE & PHARMACOTHERAPY
·
2023
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IF 7.5
Zhangnian Liu,Shiquan Gan,Lingyun Fu,Yini Xu,Shengquan Wang,Guangqiong Zhang,Di Pan,Ling Tao,Xiangchun Shen
1,8-Cineole, the main component of volatile oil in aromatic plants, has diverse pharmacological properties, including antioxidant, anti-inflammatory, and anti-cancer properties. Diabetic retinopathy (DR) is a common microvascular complication of diabetes mellitus (DM). Here, we investigated the protective effect of 1,8-cineole on DR and found that 1,8-cineole treatment could alter the expression of several genes in both high glucose (HG)-induced ARPE-19 cells and retinal tissues of DM mice, as well as inhibit ferroptosis. Subsequent investigations into the molecular mechanisms underlying this inhibition revealed that expression of thioredoxin-interacting protein (TXNIP) was significantly upregulated while that of peroxisome proliferator-activated receptor γ (PPAR-γ) was significantly downregulated in HG-induced ARPE-19 cells, and treatment with 1,8-cineole could effectively reverse these changes. Treatment with a PPAR-γ pharmacological agonist (rosiglitazone), alone or combined with 1,8-cineole, significantly inhibited the transcription of TXNIP and ferroptosis in HG-induced ARPE-19 cells. Conversely, pretreatment with GW9662, a PPAR-γ inhibitor, upregulated the transcription and expression of TXNIP in HG-induced ARPE-19 cells; 1,8-cineole failed to reverse this upregulated expression. To explore these relationships, we constructed a PPAR-γ adenovirus shRNA to elucidate the effect of 1,8-cineole on the negative regulation of TXNIP by PPAR-γ. Taken together, the present findings indicate that HG-induced ferroptosis in retinal tissue plays an essential role in the pathogenesis of DR, which can be ameliorated by 1,8-cineole.
研究领域:
药理学
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眼科学
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分子生物学
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糖尿病研究
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DOI
PubMed
高影响因子
Food Bioscience
·
2025
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IF 5.9
Li Xin,Ma Yuntian,Wang Xin,Lü Xin
Macronutrients participate in vital biological processes and are critical in regulating organismal health. DL-norvaline, a nonproteinogenic amino acid, is an important pharmaceutical intermediate and a functional food ingredient for obesity control. This study aimed to explore the ameliorative effect and underlying mechanisms of DL-norvaline on lipid metabolism in high-fat diet-induced obese mice. The results showed that DL-norvaline inhibited adipogenesis and lipid accumulation in 3T3-L1 adipocytes, ameliorated tissue weight, food efficiency ratio and serum biochemical markers in obese mice. The combined transcriptomics and lipidomics analysis showed that lipid metabolism of adipose tissue such as sphingolipid and glycerophospholipid metabolism was ameliorated in obese mice after DL-norvaline treatment, particularly ceramides, via regulating peroxisome proliferators-activated receptor signaling pathway. This study offered a complementary perspective for exploring the effects of amino acids on lipid metabolism and speculated the possible mechanisms of ameliorating lipid-metabolism disorders by DL-norvaline in obese mice.
研究领域:
生物化学
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分子生物学
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营养学
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药理学
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产品关联
DOI
高影响因子
Foods
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2025
·Vol. 14
·期 24
·4267
·
IF 5.1
Jing Xu,Wen-Zhao Wen,Jun-Hui Zhao,Jun-Rong Guo,Zhuo-Ya Zhang,Ping Xiong
Citri grandis exocarpium ( Citri grandis ) has been consumed by human beings for fifteen hundred years. It is commonly consumed as a health drink and dietary supplement in China. However, its nutritional and healthcare functions are still not fully understood. Objective: Our previous study found that oral administration of Citri grandis extract can significantly decrease the blood lipid levels of hyperlipidemic mice fed a high-fat diet. The aim of this study was to confirm the preventative effects of Citri grandis extract against atherosclerosis. Methods: Atherosclerotic lesion models were induced in HUVECs and apoE −/− C57BL/6J mice. ApoE −/− mice fed a high-fat diet were orally administered Citri grandis extract (0.4, 0.8, and 1.6 g/kg/d BW) and Simvastatin (1 mg/kg/d BW) on the first day of model establishment. After a 16-week treatment, serum samples and aorta and liver tissues were collected. Observation of pathological changes in aortic and liver tissues was performed using a light microscope with oil red O, H&E, Masson’s trichrome staining, and TEM. Biochemical detection was employed to determine the serum levels of TC, TG, LDL-C, and HDL-C as well as the activities of AST and ALT. In addition, expression studies of TGF-β, PI3K, AKT1, PPAR-γ, LXR-α, and ABCA1 were performed via qPCR and Western blot analysis. Results: Compared with cholesterol-induced HUVECs, Citri grandis extract significantly enhanced cell viability, attenuated the morphological changes in HUVECs, and reduced LDH release. Furthermore, after treatment with Citri grandis extract, the levels of TC, TG, and LDL-C significantly decreased in the atherosclerosis model apoE −/− mice after 16 weeks, and aortic plaque, lipid deposition, and endothelial injury were obviously ameliorated. The mRNA and protein expression of TGF-β, PPAR-γ, LXR-α, and ABCA1 in aortic and liver of atherosclerosis apoE −/− mice were upregulated ( p < 0.05, p < 0.01), while those of PI3K and Akt1 were suppressed ( p < 0.05, p < 0.01). Conclusions: Citri grandis extract can significantly decrease the high circulating lipid levels and the liver lipid deposition of high-fat-diet-fed apoE −/− mice and reduce aorta lipid accumulation and atherosclerotic plaques by regulating the expression of TGF-β1, PI3K, AKT1, PPAR-γ, LXR-α, and ABCA1. Citri grandis extract can be used as a healthcare dietary supplement for the prevention of abnormal lipid metabolism and atherosclerosis.
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PubMed
高影响因子
FISH & SHELLFISH IMMUNOLOGY
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2022
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IF 4.622
Xiaojing Li,Ruichen Bai,Yichen Bai,Xu Shi,Yuhong Yang,Shiwen Xu
Acetochlor is a high-volume herbicide whose widespread use threatens ecosystems and affects aquaculture. Apoptosis and autophagy are important causes of hepatotoxicity caused by toxicants, which can be mediated by oxidative stress and the inhibition of PPAR/RXR pathway. However, the mechanism of acetochlor on fish hepatocyte damage still needs to be further investigated. Therefore, we treated the Ctenopharyngodon idella hepatic cell line (L8824 cells) with different concentrations (10, 20, and 40 μM) of acetochlor and/or ROS scavenger NAC (1 mM) for 24 h. The results showed that acetochlor decreased the cell viability in a dose-dependent manner. AO/EB staining and flow cytometry verified the increased apoptotic rates . Quantitative analysis of gene expression levels or protein expression levels displayed that the expression levels of Beclin1, P62, LC3B, BAX, and cleaved Casp3 were increased, and the expression of BCL2 was reduced. Besides, we detected the increased ROS contents and decreased PPAR/RXR pathway expressions after acetochlor treatment. The clearance of ROS alleviated the inhibition of the PPAR/RXR pathway and lightened apoptosis and autophagy under acetochlor stress. Overall, these results revealed that acetochlor exposure triggered BCL2/BAX/Casp3-cascaded apoptosis and Beclin1-dependent autophagy through ROS-mediated PPAR/RXR inhibition. The results partially explain the toxicological mechanism of acetochlor and provide targets for the development of its antidote.
研究领域:
毒理学
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细胞生物学
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环境科学
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水产养殖
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DOI
PubMed
高影响因子
JOURNAL OF NUTRITIONAL BIOCHEMISTRY
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2024
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IF 4.8
Yanqing Wang,Huanying Zhang,Feng Ding,Jianhua Li,Lianyu Li,Zhong Xu,Yan Zhao
Alzheimer's disease (AD) is a common neurodegenerative disease that causes progressive cognitive decline. A major pathological characteristic of AD brain is the presence of senile plaques composed of β-amyloid (Aβ), the accumulation of which induces toxic cascades leading to synaptic dysfunction, neuronal apoptosis, and eventually cognitive decline. Dietary n-3 polyunsaturated fatty acids (PUFAs), such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are beneficial for patients with early-stage AD; however, the mechanisms are not completely understood. In this study, we investigated the effects of n-3 PUFAs on Aβ-induced toxicity in a transgenic AD Caenorhabditis elegans (C. elegans) model. The results showed that EPA and DHA significantly inhibited Aβ-induced paralytic phenotype and decreased the production of reactive oxygen species while reducing the levels of Aβ in the AD worms. Further studies revealed that EPA and DHA might reduce the accumulation of Aβ by restoring the activity of proteasome. Moreover, treating worms with peroxisome proliferator-activated receptor (PPAR)-γ inhibitor GW9662 prevented the inhibitory effects of n-3 PUFAs on Aβ-induced paralytic phenotype and diminished the elevation of proteasomal activity by n-3 PUFAs, suggesting that PPARγ-mediated signals play important role in the protective effects of n-3 PUFAs against Aβ-induced toxicity.
研究领域:
神经生物学
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分子生物学
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营养学
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DOI
PubMed
高影响因子
Translational Research
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2024
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IF 6.4
Shan-Shan Li,Qiao-Juan Liu,Jia-Xin Bao,Meng-ting Lu,Bing-Quan Deng,Wen-Wen Li,Chang-Chun Cao
Peptide drug discovery for the treatment of chronic kidney disease (CKD) has attracted much attention in recent years due to the urge to find novel drugs and mechanisms to delay the progression of the disease. In this study, we identified a novel short peptide (named YR-7, primary sequence ‘YEVEDYR’) from the natural Fibroin protein, and demonstrated that it significantly alleviated pathological renal changes in ADR-induced nephropathy. PANX1 was identified as the most notably upregulated component by RNA-sequencing. Further analysis showed that YR-7 alleviated the accumulation of lipid droplets via regulation of the lipid metabolism-related proteins PPAR α and PANK1. Using chemical proteomics, fluorescence polarization, microscale thermophoresis, surface plasmon resonance, and molecular docking, YR-7 was proven to directly bind to β-barrel domains of TGM2 protein to inhibit lipid accumulation. TGM2 knockdown in vivo increased the protein levels of PPAR α and PANK1 while decreased the levels of fibrotic-related proteins to alleviate nephropathy. In vitro , overexpression TGM2 reversed the protective effects of YR-7. Co-immunoprecipitation indicated that TGM2 interacted with PANX1 to promote lipid deposition, and pharmacological inhibition or knockdown of PANX1 decreased the levels of PPAR α and PANK1 induced by ADR. Taken together, our findings revealed that TGM2-PANX1 interaction in promoting lipid deposition may be a new signaling in promoting ADR-induced nephropathy. And a novel natural peptide could ameliorate renal fibrosis through TGM2-PANX1-PPAR α/PANK1 pathway, which highlight the potential of it in the treatment of CKD.
研究领域:
药理学
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肾病学
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分子生物学
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药物发现
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DOI
PubMed
高影响因子
Frontiers in Pharmacology
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2019
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IF 3.845
Linghu Ke-Gang,Wu Guo-Ping,Fu Ling-Yun,Yang Hong,Li Hai-Zhi,Chen Yan,Yu Hua,Tao Ling,Shen Xiang-Chun
1,8-Cineole (eucalyptol), a monoterpene, has been widely reported for the anti-inflammatory effects. Our previous data confirmed that 1,8-cineole ameliorated the inflammatory phenotype of human umbilical vein endothelial cells (HUVECs) by mediating NF-κB expression in vitro. At present, we investigated the protection effects of 1,8-cineole on vascular endothelium in lipopolysaccharide (LPS)-induced acute inflammatory injury mice and the potential mechanisms involved in the protection in HUVECs. Results from enzyme linked immunosorbent assays revealed that 1,8-cineole suppressed the secretion of interleukin (IL)-6 and IL-8 and increased the expression of IL-10 in the serum of LPS-induced mice. 1,8-Cineole reduced the inflammatory infiltration and the expression of vascular cell adhesion molecular 1 (VCAM-1) in the sections of thoracic aorta in LPS-induced acute inflammatory mice. Western blotting indicated that 1,8-cineole significantly decreased the phosphorylation of NF-κB p65 and increased the expression of PPAR-γ in the thoracic aorta tissue. 1,8-Cineole increased the expression of PPAR-γ in LPS-induced HUVECs. 1,8-Cineole and rosiglitazone reduced the protein and mRNA levels of VCAM-1, E-selectin, IL-6, and IL-8 in LPS-induced HUVECs, which could be reversed by the action of GW9662 (inhibitor of PPAR-γ). 1,8-Cineole and rosiglitazone blocked the LPS-induced IκBα degradation and NF-κB p65 nucleus translocation, which could be reversed by the pretreatment of GW9662 or silence of PPAR-γ gene. In conclusion, 1,8-cineole attenuated LPS-induced vascular endothelial cells injury via PPAR-γ dependent modulation of NF-κB.
研究领域:
药理学
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免疫学
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分子生物学
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心血管科学
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产品关联
DOI
PubMed
高影响因子
TOXICOLOGY
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2025
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IF 4.6
Zhisen Zhuang,Lijuan You,Jianbo Kong,Yaru Tian,Yongning Li,Yuan Zhi,Bo Zhang,Yi Wan,Xudong Jia,Hui Yang
Phthalate esters (PAEs) and per- and polyfluoroalkyl substances (PFAS) are ubiquitous pollutants tied to metabolic and immune disorders. The peroxisome proliferator-activated receptor (PPAR) pathway has been indicated to mediate their toxic effects, but the specific functions of PPAR subtypes and their mediating roles remain unclear. In this study, we generated PPARα-, δ-, and γ-specific knockout THP-1 cell lines by using CRISPR/Cas9 system and then differentiated them into interleukin-4 (IL-4) and interleukin-13 (IL-13)-polarized macrophages (alternative activation). During the induction process, the cells were exposed to 0, 6.25, 12.5, 25, 50, 100 μM of five PAE metabolites: Mono-(2-ethylhexyl) phthalate (MEHP), Monocyclohexyl phthalate (MCHP), Monoisonyl phthalate (MINP), Monoisobutyl phthalate (MIBP), and Monobenzyl phthalate (MBzP); and five PFAS: Perfluoroundecanoic acid (PFUnDA), Perfluorodecanoic acid (PFDA), Perfluorooctanoic acid (PFOA), Potassium perfluorooctanesulfonate (PFOS-K), and Potassium 9-chlorohexadecafluoro-3-oxanonane-1-sulfonate (F53B) for 48 h. The results showed that PPARδ deletion abolished CD209 expression, confirming its essential role, whereas PPARα deletion reduced and PPARγ deletion enhanced CD209, indicating PPARα promotes and PPARγ restrains alternative activation. Compounds displayed subtype-selective actions: MEHP activated PPARα/γ; MBzP/MCHP inhibited PPARδ yet activated PPARγ; MINP activated PPARγ only. Among PFAS, PFOS-K activated PPARδ/γ; F53B inhibited PPARα; PFOA activated PPARγ; PFDA inhibited PPARα/δ. Transcriptomics revealed compound-specific enrichments—cholesterol (MEHP), fatty-acid (MCHP), glycolysis (PFOS-K), TCA cycle (PFOA)—despite common PPAR pathway engagement. In conclusion, PAEs and PFAS disrupt macrophage plasticity through distinct PPAR-subtype signatures, providing molecular landmarks for future hazard assessment of environmental pollutants.
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PubMed
高影响因子
LIFE SCIENCES
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2023
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IF 6.1
Kang Du,Qun Zhou,Ziwen Wang,Chou Mo,Wanwen Dong,Ning Wei,Wenshen Zhong,Yuejiao You,Yifei Wang,Zhiping Wang
Aims Polygonum cuspidatum Sieb. et Zucc is one of the commonly used herbs for the treatment of gouty arthritis, and polydatin is one of its main effective components. This study evaluated the therapeutic potential of polydatin for the treatment of gout. Main methods The ankle joint of C57BL/6 mice were injected with MSU suspensions to simulate human gouty arthritis, and oral treatment with polydatin (25, 50, and 100 mg/kg body weight) was performed at 1 h after MSU crystal injection. The effect of polydatin on model mice was evaluated by measuring ankle swelling, gait, histopathological analysis, proinflammatory cytokine expression, as well as the contents of NO, MDA and GSH. The targets of polydatin were explored by Real-Time PCR and IHC. Key findings Treatment with polydatin inhibited ankle swelling, improved abnormal gait, and reduced ankle lesions dose-dependently. Moreover, polydatin decreased pro-inflammatory cytokine expression, and promoted expression of anti-inflammatory cytokine. In addition, polydatin inhibited MSU-induced oxidative stress by decreasing oxidative product (NO, MDA) generation and promote the antioxidant (GSH). Further, we found that polydatin reduced inflammation by decreasing the expression of NLRP3 inflammasome component via activating PPAR-γ. Moreover, polydatin can protect against iron overload and attenuate oxidative stress by promoting the activation of ferritin. Significance Our findings indicates that polydatin ameliorates MSU-induced inflammation and oxidative stress by regulating PPAR-γ and ferritin activation in gouty arthritis model mice, and this research result suggests that polydatin has therapeutic potential for the treatment of gout in humans through multiple targets.
研究领域:
药理学
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免疫学
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风湿病学
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产品关联
DOI
PubMed
高影响因子
Food & Function
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2023
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IF 6.1
Zhongcai Wu,Xuezhi Zuo,Xiuru Wang,Mengxia Shi,Han Zhu,Chujin Cao,Xiaoqin Liu,Wangqun Liang,Ying Yao,Le Wang
Peritoneal fibrosis is a complication of long-term peritoneal dialysis (PD) that restricts its clinical application for the treatment of end-stage renal disease. Lactobacillus casei Zhang (LCZ), a probiotic strain isolated from traditional fermented koumiss, exhibits health benefits such as anti-inflammatory and antioxidative effects, improvement of insulin resistance and mitigation of renal injury. However, whether LCZ can prevent peritoneal fibrosis remains unknown. Here, we assessed the effects of LCZ in a mouse model of PD-induced peritoneal fibrosis. Our results showed that the administration of LCZ significantly ameliorated peritoneal fibrosis in experimental mice. Macrophage infiltration, inflammatory M1 polarization and inflammatory cytokines in peritoneal dialysis effluents were effectively reduced by LCZ. Meanwhile, LCZ corrected gut dysbiosis and enriched beneficial bacteria that produce short-chain fatty acids, specifically Dubosiella, Lachnospiraceae, Parvibacter, and Butyricicoccus. Correspondingly, the local butyrate level in peritoneal dialysis effluents was significantly elevated by LCZ. Mechanistically, we found activation of PPARγ and inhibition of the NF-κB pathway in LCZ-treated mice, an observation that was replicated in a butyrate-treated macrophage cell line. In conclusion, our study suggests that LCZ is beneficial for preventing PD-induced peritoneal fibrosis through modulating the gut microbiota, enhancing butyrate production, activating PPARγ, and suppressing NF-κB-mediated inflammation.
研究领域:
微生物学
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免疫学
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肾病学
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药理学
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产品关联
DOI
PubMed
高影响因子
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