Food Science & Nutrition
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2024
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IF 3.5
Guangjie Zhang,Huiying Zhang,Ruiyi Dong,Hongmei Zhao,Junfeng Li,Weiming Yue,Zheng Ma
As a natural pentacyclic triterpenoid, oleanolic acid has hepatoprotective, anti-inflammatory, and antioxidant activities. This work performed the in vitro experiments and animal assay to explore whether oleanolic acid alleviates lipid accumulation induced by high-fat diet by mediating PPARγ. Oil red O staining showed that oleanolic acid can reduce lipid accumulation in HepG2 cells, which were treated with oleic acid and palmitic acid. Immunofluorescence, western blot analysis, and RT-qPCR showed that oleanolic acid could promote nuclear translocation of PPARγ and reduce the expression level of PPARγ, C/EBP-β, and SREBP-1c. The results of in vivo experiments indicated that dietary intervention with oleanolic acid can effectively improve the fat accumulation in liver tissue and attenuate the level of IL-6 and TNF-α in serum caused by high-fat diet. Meanwhile, oleanolic acid did not cause lesions in vital organs at the experimental concentrations. In addition, the computer simulation indicated that oleanolic acid could directly bind to PPARγ with a reasonable and stable docking conformation. The above research results can provide new evidence for oleanolic acid to prevent nonalcoholic fatty liver disease.
研究领域:
药理学
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营养学
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分子生物学
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生物化学
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PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
·
IF 7.7
Mingjing Zheng,Huan Ouyang,Zhipeng Li,Tao Hong,Yanbing Zhu,Yuanfan Yang,Xiaoming Guo,Hui Ni,Zedong Jiang
The structure and in vitro hypolipidemic activity of Bangia fusco-purpurea polysaccharide (BFP) assisted extracted with ultra-high pressure (UHP) at 100–600 MPa were studied. Compared to native BFP, UHP assisted extracted BFP had a more loose network structure with higher total sugar and uronic acid contents while less molecular weight ( p < 0.05). Moreover, UHP assisted extraction significantly improved the in vitro hypolipidemic and antioxidant activity of BFP. Especially at 400 MPa UHP, the cholesterol adsorption and antioxidant capacities of BFP were increased by approximately 38.02 % and 11.69 %–32.29 %, respectively. BFP with UHP assisted extraction could alleviate oleic acid-induced lipid accumulation and lipid oxidation in HepG2 cells more effectively by activating the AMPK signaling pathway as well as inhibiting PPARγ expression, which was much related with its reduced molecular weight and loose network structure. The findings indicated that UHP assisted extracted BFP has better potential to develop natural hypolipidemic agent.
研究领域:
食品科学
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生物化学
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药理学
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PubMed
高影响因子
ENVIRONMENT INTERNATIONAL
·
2022
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IF 13.352
Qiyu Wang,Jing Huang,Shuai Liu,Caiyun Wang,Yuanxiang Jin,Hong Lai,Wenqing Tu
Perfluorooctane sulfonate (PFOS) has been reported to induce hepatotoxicity in wildlife and humans. Novel PFOS alternatives have been widely used following restrictions on PFOS, but little is known about their potential toxicity. Here, the first comprehensive investigation on the chronic hepatotoxicity and underlying molecular mechanisms of PFOS, 6:2Cl-PFESA (F-53B), and sodium p -perfluorous nonenoxybenzene sulfonate (OBS) was carried out on adult zebrafish through a histopathological examination, biochemical measurement, and multi-omics analysis. PFOS and its alternatives caused changes in liver histopathology and liver function indices in the order of F-53B > PFOS > OBS, which was consistent with their concentration in the liver. In silico modeling and transcriptional profiles suggested that the aberrant hepatic lipid metabolism induced by F-53B and PFOS was initiated by the action on peroxisome proliferator-activated receptor γ (PPARγ), which triggered changes in downstream genes transcription and led to an imbalance between lipid synthesis and expenditure. Gut microbiome analysis provided another novel mechanistic perspective that changes in the abundance of Legionella , Ralstonia , Brevundimonas , Alphaproteobacteria , Plesiomonas , and Hyphomicrobium might link to alterations in the PPAR pathway based on their significant correlation. This study provides insight into the molecular mechanisms of hepatotoxicity induced by PFOS and its novel alternatives and highlights the need for concern about their environmental exposure risks.
研究领域:
环境毒理学
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分子生物学
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微生物学
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水生毒理学
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PubMed
高影响因子
BMC CANCER
·
2018
·Vol. 18
·期 1
·1-10
·
IF 3.288
Ai Xinghao,Mao Feng,Shen Shengping,Shentu Yang,Wang Jiejun,Lu Shun
Background Thirty to 40 % of non-small cell lung cancer (NSCLC) patients developed higher hypertriglyceridemia in the process of treatment with bexarotene. And bioinformatics studies discovered that the expression of slc10a2 was increased in high-grade hypertriglyceridemia patients. So, we will explore the mechanism which may involve in this process.Methods We constructed slc10a2 overexpressed A549 cells and H1299 cells as cell models, normal A549 cells and H1299 cells as control. Then we explored the effects of slc10a2 on A549 cells and H1299 cells behaviors, including proliferation, invasion and apoptosis. The expression of apoptotic related genes and anti-cancer genes also been detected.Results We found that the proliferation and migration were inhibited and the apoptosis of NSCLC cells was accelerated by bexarotene. In addition, overexpressed slc10a2 in NSCLC cells can further suppress the proliferation and migration, and promote apoptosis under the treatment of bexarotene. On the contrary, the opposite results were obtained after slc10a2 gene was silenced in NSCLC cells treated with bexarotene. Moreover, the expression of caspase 3, caspase 7, PTEN, P21, P53, LKB1, TSC2 were increased and the expression of Bcl-2, cyclin D1, c-FLIP were declined in NSCLC cells and slc10a2 overexpressed NSCLC cells with the treatment of bexarotene, and the opposite situations were seen after slc10a2 gene was silenced in NSCLC cells. The further studies revealed the increased expression of slc10a2 activated the expression of peroxisome proliferator-activated receptor γ (PPARγ), then up-regulated PTEN expression and down-regulated mTOR expression.Conclusion These results suggest that bexarotene inhibits the viability of lung cancer cells via slc10a2/PPARγ/PTEN/mTOR signaling pathway.
研究领域:
肿瘤学
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分子生物学
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药理学
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DOI
PubMed
高影响因子
FITOTERAPIA
·
2026
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IF 2.9
Xia Zhang,Yuying Li,Chengfu Zhang,Huali Zhang,Jing Zhao,Dong Pei,Tingfu Jiang,Lichun Zhao,Qingli Qu
The therapeutic potential of Olea europaea L. leaf in hepatitis is recognized, yet its active constituents against metabolic dysfunction-associated steatohepatitis (MASH), a specific form of hepatitis driven by metabolic disturbances, remain poorly defined. This study integrated HPLC fingerprinting of Olea europaea L. leaf extracts (OLE) with chemometrics and bioactivity profiling to identify anti-MASH components. Bioactivity was assessed using a palmitic acid-induced steatohepatitis model in L02 cells. Spectrum–effect relationships derived from pearson correlation and partial least squares regression highlighted four putative active compounds, designated P7, P8, P10, and P11. HPLC-MS identified these as cynaroside (P7), apigenin-7-O-glucoside (P8), oleuroside (P10), and ligustroside (P11). Subsequent in vitro and in vivo evaluations in a zebrafish MASH model confirmed that P7, P8, and P10 exhibited significant anti-MASH activity. Notably, a robust synergism was observed between cynaroside and oleuroside, which their 1:1 M combination yielded a ZIP synergy score of 11.965 and a combination index (CI) of 0.3151, indicating strong synergy at lower doses. These results identify key anti-MASH constituents in OLE and provide a mechanistic basis for using multi-component OLE, highlighting a synergistic approach for MASH management.
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ENVIRONMENTAL SCIENCE & TECHNOLOGY
·
2026
·
IF 12.2
Qiang Li,Kaisheng Hong,Chenke Xu,Linwan Li,Geng Yue,Cheng Xu,Min Yang,Jianying Hu
Abstract While exposure to PPAR active compounds can lead to various adverse health effects, studies on the environmental contaminants and their transformation products with PPAR activity remain limited. This study employed PPARγ protein affinity selection-mass spectrometry (AS-MS) to comprehensively identify and prioritize PPARγ-active contaminants in the Yangtze and Yellow Rivers, key drinking water sources in China. From wastewater treatment plant effluents, river, and source water samples, 61 PPARγ ligands were identified, including 18 antagonists not reported previously. Notably, a novel biodegradation product of di-2-ethylhexyl phthalate (DEHP), phthalic acid 1-(2-ethylhexyl) 2-(2-ethyl-5-carboxypentyl) ester (5CX-DEHP), was discovered and characterized as a potent PPARγ antagonist (IC50 = 8.5 μM). Semi-quantification revealed total concentrations of 61 chemicals ranging from 965.2 to 5748 ng/L in source waters, with priority agonistic chemicals such as 4-dodecylbenzenesulfonic acid and priority antagonistic chemicals such as 2-amino-6-methylmercaptopurine and 5CX-DEHP posing high ranking. This study comprehensively revealed the widespread occurrence of PPARγ agonistic and antagonistic chemicals in the water samples and identified a previously overlooked transformation product of DEHP as a relatively strong PPARγ antagonist.
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高影响因子
Nutrients
·
2026
·Vol. 18
·期 17
·2750
·
IF 5.8
Jiang Li,Jiaojiao Tan,Junjie Liu,Minghui Wang,Xiaoqian Gu,Zhiyan Wang,Jican Han,Chaofan Pan,Ting Fu,Shirong Xue,Long Chen,Xinning Pan
Background: Marine algal oligosaccharide (MAO) molecular structural characteristics are closely related to their bioactivity. However, an understanding of the specific relationships between MAO molecular structure (including polymerization degree [DP] and sulfate groups) and bioactivity is lacking. Methods: In this work, laboratory-prepared DP4 and DP8 MAOs, including agar- (AOs) and κ-, ι-, and λ-carrageenan-oligosaccharides (COs), were examined for their anti-inflammatory activity in RAW264.7 macrophages and therapeutic effect on colitis in mice; additionally, the potential mechanisms involved were explored. Results: The results showed that CO (ι- and λ-COs) anti-inflammatory activity was higher than that of AOs and was positively correlated with sulfate group content. MAOs with different structures all alleviated colitis symptoms; those with higher sulfate group content and DP showed excellent therapeutic efficacy. MAOs modulated gut microbiota and promoted the enrichment of microbiota-derived short-chain fatty acid production (butyrate), which potentially induced PPARγ signaling and contributed to the impacts of MAOs on mucosal homeostasis restoration. Conclusions: Therefore, MAOs with higher sulfate content and DP showed improved therapeutic efficacy compared with those with lower contents, which involved higher SCFA production.
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高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2021
·
IF 5.279
Jing Zhou,Ji Zhang,Jiayi Li,Yiqiu Guan,Ting Shen,Fu Li,Xueqin Li,Xiaojun Yang,Weicheng Hu
Ginsenoside F2 (GF2) is a protopanaxdiol saponin from Panax ginseng leaves and possesses many potential pharmacological properties. GF2 may prevent obesity by directly binding to the peroxisome proliferator-activated receptor-γ (PPARγ) and inhibiting adipocyte differentiation. However, the mechanism by which GF2 alleviates obesity is unknown. We therefore explored the anti-adipogenesis and anti-obesity effects of GF2 in vitro and in vivo. GF2 inhibited differentiation and reduced the triglyceride (TG) content of 3T3-L1 preadipocytes in the early stage of adipogenesis. Administration of GF2 (50 and 100 mg/kg) to obese mice for 4 weeks reduced the body weight gain, weight of adipose tissues, adipocyte size, and total cholesterol, TG, and AST levels in serum. RNA sequencing and real-time quantitative PCR indicated that GF2 decreased the expression levels of adipokines, including PPARγ, fatty acid synthase, and adiponectin. KEGG enrichment and western blot analyses demonstrated that GF2 accelerated the phosphorylation of AMPK and ACC in vitro and in vivo. Moreover, GF2 promoted the biosynthesis of mitochondria in 3T3-L1 adipocytes and increased the expression of antioxidant enzymes such as SOD and GSH-Px in the liver of obese mice. Therefore, GF2 suppressed adipogenesis and obesity by regulating the expression of adipokines and activating the AMPK pathway. Hence, the findings suggest that GF2 may have potential therapeutic implications to treat obesity.
研究领域:
药理学
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分子生物学
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细胞生物学
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代谢
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PubMed
高影响因子
FOOD CHEMISTRY
·
2021
·
IF 7.514
Zhuqing Dai,Jiangfeng Song,Ye Chen,Lei Feng,Yayuan Xu,Dajing Li,Caie Wu,Zhongyuan Zhang,Jun Liu
This study aims to develop novel lutein nanoparticles encapsulized by stevioside (LUT-STE, 165 ± 2 nm average particles size) and systematically evaluate its bioavailability. Multiple spectroscopy and NMR analyses showed lutein and stevioside could interact through hydrogen bonds, C H π interaction and van der Waals forces. Molecular docking simulation showed lutein was well distributed in the hydrophobic cavity of stevioside. Analyzed by Caco-2 cellular models, the transported amount of LUT-STE was 2.39 times that of lutein in 120 min with a P app (B → A)/ P app (A → B) value of 0.63 ± 0.04. Nystatin and dynasore significantly reduced the cellular uptake of LUT-STE by 41.3% and 57.7%, respectively. Compared with free lutein, LUT-STE increased the C max in mice plasma by 5.01-fold and promoted the accumulation in multiple organs. LUT-STE promoted the protein expressions of CD36, NPC1L1 and PPARγ in both cell and animal models. In conclusion, stevioside entrapment significantly promote the bioavailability of lutein through multiple transmembrane pathways.
研究领域:
药学
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营养学
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分子生物学
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药理学
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DOI
PubMed
高影响因子
FASEB JOURNAL
·
2021
·Vol. 35
·期 2
·e21316
·
IF 5.192
Qianhong Ye,Xiangfang Zeng,Shuai Wang,Xiangzhou Zeng,Guangxin Yang,Changchuan Ye,Shuang Cai,Meixia Chen,Siyu Li,Shiyan Qiao
Maintaining ovarian steroidogenesis is of critical importance, considering that steroid hormones are required for successful establishment and maintenance of pregnancy and proper development of embryos and fetuses. Investigating the mechanism that butyrate modulates the ovarian steroidogenesis is beneficial for understanding the impact of lipid nutrition on steroidogenesis. Herein, we identified that butyrate improved estradiol and progesterone synthesis in rat primary ovarian granulosa cells and human granulosa KGN cells and discovered the related mechanism. Our data indicated that butyrate was sensed by GPR41 and GPR43 in ovarian granulosa cells. Butyrate primarily upregulated the acetylation of histone H3K9 (H3K9ac). Chromatin immune-precipitation and sequencing (ChIP-seq) data of H3K9ac revealed the influenced pathways involving in the mitochondrial function (including cellular metabolism and steroidogenesis) and cellular antioxidant capacity. Additionally, increasing H3K9ac by butyrate further stimulated the PPARγ/CD36/StAR pathways to increase ovarian steroidogenesis and activated PGC1α to enhance mitochondrial dynamics and alleviate oxidative damage. The improvement in antioxidant capacity and mitochondrial dynamics by butyrate enhanced ovarian steroidogenesis. Collectively, butyrate triggers histone H3K9ac to activate steroidogenesis through PPARγ and PGC1α pathways in ovarian granulosa cells.
研究领域:
生殖生物学
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内分泌学
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分子生物学
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DOI
PubMed
高影响因子
Advanced Science
·
2025
·
IF 14.1
Miao Wei,Yujia Huo,Jingchang Yuan,Xiao Fan,Xiaochen Wang,Sisi Tan,Xi Gao,Ruotong Ouyang,Hong Li
Glaucoma is a leading cause of irreversible blindness, characterized by progressive retinal ganglion cells (RGCs) loss. Increasing evidence links microglial activation and lipid metabolism dysregulation to neurodegeneration. However, the role of microglial lipid metabolic reprogramming in disease pathogenesis remains unclear. This study finds that microglia in an acute ocular hypertension (AOH) model exhibit abnormal lipid droplet accumulation, downregulation of low-density lipoprotein receptor-related protein 1 (LRP1), and a shift toward a pro-inflammatory M1 phenotype. Importantly, serum samples from glaucoma patients reveal significantly reduced LRP1 levels compared to controls. To restore lipid homeostasis, this study develops alpinetin-loaded PLGA nanoparticles (AlpNPs), which demonstrate efficient microglial uptake and sustained release. AlpNPs reduced intracellular lipid accumulation, promoted M2 polarization, and suppressed microglial proliferation and migration. Mechanistically, AlpNPs directly bind to LRP1 and enhance its interaction with PPARγ, thereby activating the downstream LXRα-ABCA1 pathway, which is pivotal for cholesterol efflux and anti-inflammatory responses. Knockdown of LRP1 abolished the protective effects of AlpNPs, confirming its essential role in mediating metabolic reprogramming. In vivo, intravitreal injection of AlpNPs significantly attenuates retinal inflammation and preserves RGCs in AOH. These findings identify microglial lipid metabolic dysfunction as a key driver in glaucoma and highlight LRP1-targeted nanotherapy as a promising strategy for neuroprotection.
研究领域:
眼科学
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神经科学
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纳米医学
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免疫代谢
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分子生物学
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高影响因子
CHEMICAL & PHARMACEUTICAL BULLETIN
·
2019
·Vol. 67
·期 9
·1006-1014
·
IF 1.405
Pan Yu,Chao-Jie Xia,Dong-Dong Li,Zhenzhong Wang,Wei Xiao,Lin-Guo Zhao
Chlorogenic acid (CGA) has been considered as one of important active components in a number of medicinal herbs. Recently our group demonstrated that caffeoyl salicylate scaffold derived from CGA can be employed for the development of novel anti-inflammatory agents. The most active compound D104 can be a very promising starting point for the further structural optimization. A series of novel caffeoyl salicylate analogs were designed, synthesized, and evaluated by preliminary biological evaluation. The obtained results showed that the two compounds B12 and B13 can not only inhibit production of nitric oxide (NO) in RAW264.7 cells induced by lipopolysaccharides (LPS) effectively, but also have high safety in in vitro cytotoxic test, which could be comparable with D104. Molecular docking study on the peroxisome proliferator-activated receptor γ (PPARγ) protein revealed that compounds B12 and B13 can follow the same binding mode with D104, and the carboxyl group of caffeoyl salicylate scaffold might play a key role in the interaction with protein target, which implied the carboxyl group should be retained in the further optimization.
研究领域:
药理学
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药物化学
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药物研发
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DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）