BIOMEDICINE & PHARMACOTHERAPY
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2020
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IF 4.545
Zhishen Xie,Gai Gao,Hui Wang,Erwen Li,Yong Yuan,Jiangyan Xu,Zhenqiang Zhang,Pan Wang,Yu Fu,Huahui Zeng,Junying Song,Christian Hölscher,Hui Chen
Dual-PPAR-α/γ agonist has the dual potentials to improve insulin resistance (IR) and hepatic steatosis associated with obesity. This study aimed to investigate whether dehydroabietic acid (DA), a naturally occurred compound, can bind to and activate both PPAR-γ and PPAR-α to ameliorate IR and hepatic steatosis in high-fat diet (HFD)-fed mice.. We found that DA formed stable hydrogen bonds with the ligand-binding domains of PPAR-γ and PPAR-α. DA treatment also promoted 3T3-L1 differentiation via PPAR-γ activation, and mitochondrial oxygen consumption in HL7702 cells via PPAR-α activation. In HFD-fed mice, DA treatment alleviated glucose intolerance and IR, and reduced hepatic steatosis, liver injury markers (ALT, AST), and lipid accumulation, and promoted mRNA expression of PPAR-γ and PPAR-α signaling elements involved in IR and lipid metabolism in vivo and in vitro , and inhibited mRNA expression of pro-inflammatory factors. Therefore, DA is a dual-PPAR-α/γ and PPAR-γ partial agonist, which can attenuate IR and hepatic steatosis induced by HFD-consumption in mice.
研究领域:
药理学
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代谢性疾病
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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
EUROPEAN JOURNAL OF PHARMACOLOGY
·
2025
·
IF 4.7
Qing-qing Fang,Yang-jun Gu,Yong Wang,Zheng-cai Wang,Xiao-ying Lin,Kai Guo,Ze-ming Zhuang,Xin-cao Zhong,Li-yun Zhang,Jian Chen,Wei-qiang Tan
The prevention and treatment of scars has always posed a challenge in the medical field. Researchers have reached the consensus that safe, effective and affordable treatments are needed. Here, by conducting non-targeted metabolomics and RNA sequencing experiments, we revealed that a significant number of metabolites and genes related to glucose and lipid metabolism underwent changes during scar formation, with peroxisome proliferator-activated receptor-γ (PPAR-γ) exerting a profound influence. Considering that rosiglitazone is a selective orally active PPAR-γ receptor agonist, scar models were induced in rats, and rosiglitazone was administered at different dosages. We characterized rosiglitazone as a crucial mediator in a rat scar model in vivo and in vitro in two models of transforming growth factor β1(TGF-β1) stimulated fibroblasts (NIH 3T3 and 3T3 L1). Functionally, activation of PPAR-γ with rosiglitazone effectively impedes fibrosis and mitigates scar formation. Rosiglitazone also inhibits some inflammatory factors, and downregulates triglyceride, lactic acid, glycogen and lactic dehydrogenase levels in rat scars. Conversely, rosiglitazone increases adenosine triphosphate (ATP) production and increases free fatty acid levels and the activity of acetyl-CoA carboxylase, fatty acid synthetase, succinate dehydrogenase. Collectively, these findings shed light on the underlying mechanisms and suggest that the use of rosiglitazone could be a promising therapeutic approach to alleviate fibrosis and reduce scar formation.
研究领域:
医学
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药理学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Frontiers in Immunology
·
2019
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IF 4.716
Zong Xin,Cao Xiaoxuan,Wang Hong,Xiao Xiao,Wang Yizhen,Lu Zeqing
The molecular mechanisms underlying the cellular uptake of long-chain fatty acids and the regulation of this process have been debated in recent decades. Here, we established an intestinal barrier dysfunction model in mice and Caco2 cell line by Lipopolysaccharide (LPS), and evaluated the fatty acid uptake capacity of the intestine. We found that LPS stimulation restricted the absorption of long chain fatty acid (LCFA), while Cathelicidin-WA (CWA) pretreatment facilitated this physiological process. At the molecular level, our results demonstrated that the stimulatory effects of CWA on intestinal lipid absorption were dependent on cluster determinant 36 and fatty acid transport protein 4, but not fatty acid–binding protein. Further, an enhanced intestinal barrier was observed in vivo and in vitro when CWA alleviated the fatty acid absorption disorder induced by LPS stimulation. Mechanistically, peroxisome proliferator-activated receptor (PPAR-γ) signaling was considered as a key pathway for CWA to enhance LCFA absorption and barrier function. Treatment with a PPAR-γ inhibitor led to impaired intestinal barrier function and suppressed LCFA uptake. Moreover, once PPAR-γ signaling was blocked, CWA pretreatment could not maintain the stability of the intestinal epithelial cell barrier or LCFA uptake after LPS stimulation. Collectively, these findings suggested that PPAR-γ may serve as a target for specific therapies aimed at alleviating fatty acid uptake disorder, and CWA showed considerable potential as a new PPAR-γ agonist to strengthen intestinal barrier function against fatty acid malabsorption.
研究领域:
胃肠病学
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分子生物学
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免疫学
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产品关联
DOI
PubMed
高影响因子
EXPERIMENTAL BIOLOGY AND MEDICINE
·
2024
·
IF 2.8
Run Ma,Na Xie,Yuanhui Shu,Yafeng Wu,Ping He,Yining Xiang,Yan Zhou,Yuping Wang
Liver fibrosis has become a serious public health problem that can develop into liver cirrhosis and hepatocellular carcinoma and even lead to death. Cannabidiol (CBD), which is an abundant nonpsychoactive component in the cannabis plant, exerts cytoprotective effects in many diseases and under pathological conditions. In our previous studies, CBD significantly attenuated liver injury induced by chronic and binge alcohol in a mouse model and oxidative bursts in human neutrophils. However, the effects of CBD on liver fibrosis and the underlying mechanisms still need to be further explored. A mouse liver fibrosis model was induced by carbon tetrachloride (CCl 4 ) for 10 weeks and used to explore the protective properties of CBD and related molecular mechanisms. After the injection protocol, serum samples and livers were used for molecular biology, biochemical and pathological analyses. The results showed that CBD could effectively improve liver function and reduce liver damage and liver fibrosis progression in mice; the expression levels of transaminase and fibrotic markers were reduced, and histopathological characteristics were improved. Moreover, CBD inhibited the levels of inflammatory cytokines and reduced the protein expression levels of p-NF-κB, NF-κB, p-IκBα, p-p38 MAPK, and COX-2 but increased the expression level of PPAR-α. We found that CBD-mediated protection involves inhibiting NF-κB and activating PPAR-α. In conclusion, these results suggest that the hepatoprotective effects of CBD may be due to suppressing the inflammatory response in CCl 4 -induced mice and that the NF-κB and PPAR-α signaling pathways might be involved in this process.
研究领域:
药理学
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肝病学
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分子生物学
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DOI
PubMed
高影响因子
JOURNAL OF FOOD BIOCHEMISTRY
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2021
·Vol. 45
·期 11
·e13976
·
IF 2.72
Longkai Shi,Emad Karrar,Xingguo Wang
Non-alcoholic fatty liver disease (NAFLD) is a chronic hepatopathy caused by disordered lipid metabolism in the liver. Sesamol, a phenolic compound derived from sesame oil, has been shown to inhibit obesity, hyperlipidemia, and atherosclerosis in previous investigations. However, the preventive effect of sesamol against hepatic steatosis and oxidative stress in NAFLD has not been well-studied. In this work, sesamol was observed to alleviate lipid accumulation and oxidative stress in high oleic acid (300 μM)/cholesterol (25 μM) induced HepG2 cells, thus indicating that sesamol was involved in regulating hepatic lipid metabolism and oxidative injury. Mechanism studies found that the activated peroxisome proliferator-activated receptors (PPAR) signaling pathway by sesamol intervention up-regulated gene and protein expressions related to fatty acid oxidation and cholesterol efflux and catabolism, thus accelerating lipid consumption and reducing intracellular lipid accumulation in the process of NAFLD. These data suggested that sesamol can effectively ameliorate hepatic steatosis and sesamol riched sesamol oil may be a potential agent for finding therapeutic strategies to treat the NAFLD. Practical applications Sesamol and sesamol-rich sesame oil have received much attention due to their performance on hepatic lipid regulation. The results of this study indicate that sesamol treatment could ameliorate hepatic steatosis by inhibiting lipid accumulation and oxidative stress, thus demonstrating that sesamol and sesame oil can be used for functional foods and nutraceutical applications in the future. In addition, the present work provides knowledge of the effects of sesamol on NAFLD and involved mechanisms, and further supplies nutritional guidelines for sesame oil consumption.
研究领域:
营养学
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分子生物学
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医学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
·
2025
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IF 3.1
Xiang Li,Kevin Shyong Wei Tan,Li Wang
This study was aimed to explore the alleviating effect of black rice (BR), black peeled rice (BPR), and black rice bran (BRB) on lipid metabolism disorders in hyperlipidemia mice caused by high fat and cholesterol diet (HFCD). Combined untargeted metabolomics and RNA-seq transcriptomics analysis was used to demonstrate the potential mechanism regulated by BR, BPR and BRB. The untargeted metabolomics analysis indicated that BR especially BRB significantly increased Deoxycholic acid, 5-Dehydroavenasterol, scyllo-Inositol, Phloretin, 5-KETE, Lipoxin B4, 3,4-Dihydroxybenzeneacetic acid levels, while BRB significantly regulated PPAR signaling pathway, Arachidonic acid metabolism, Regulation of lipolysis in adipocytes, Steroid biosynthesis, and Sphingolipid signaling pathway, which closely linked to lipid metabolism. Furthermore, RNA-seq transcriptomics analysis showed that BRB obviously regulated Steroid hormone biosynthesis ( Cyp2b9 , Cyp2b13 and Cyp2c38 ) and PPAR signaling pathway ( Pparg , Fabp4 , Cd36 and Plin4 ), which were closely associated with inflammation and lipid metabolism. Moreover, quantitative Real-Time Polymerase Chain Reaction (qRT-PCR) analysis validated this. The obtaining results were hoping to reveal the detailed mechanism of BRB in alleviating hyperlipidemia and provide some insights for developing a new kind of natural anti-hyperlipidemia drug.
研究领域:
营养学
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分子生物学
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代谢组学
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产品关联
DOI
PubMed
高影响因子
Journal of Pharmaceutical Analysis
·
2025
·
IF 8.9
Lingyun Fu,Shidie Tai,Jiajia Liao,Youqi Du,Guangqiong Zhang,Die Guo,Xingmei Chen,Tian Zheng,Xiaoxia Hu,Wenbing Yao,Ling Tao,Xueting Wang,Yini Xu,Xiangchun Shen
Vascular endothelial senescence is an important pathophysiological factor in the development and exacerbation of cardiovascular health problems linked to diabetes mellitusn (DM). Accumulating evidence confirms that 1,8-cineole has multiple pharmacological properties, including anti-inflammatory, anti-microbial, and antioxidant activities. We investigated whether 1,8-cineole could ameliorate cardiovascular diseases and endothelial dysfunction, as the pharmacological properties and mechanism of diabetic vascular ageing remain unknown. Our results revealed notable senescence biomarkers in both in vivo and in vitro models. Treatment with 1,8-cineole alleviated lipid profiles and vascular senescence in mice with DM. Additionally, bioinformatics analysis suggested that peroxisome proliferator-activated receptor-γ (PPAR-γ) plays a crucial role in DM and ageing. We confirmed the binding capacity PPAR-γ with 1,8-cineole. Accordingly, experiments with the PPAR-γ agonist rosiglitazone, the PPAR-γ inhibitor GW9662, and PPAR-γ siRNA were performed to validate the pharmacological characteristics of 1,8-cineole. Finally, we clarified that 1,8-cineole can directly target PPAR-γ protein, as verified by cellular thermal shift assay, drug affinity responsive target stability, and surface plasmon resonance analyses. Taken together, these results provide the first evidence that 1,8-cineole ameliorates DM-induced vascular endothelial ageing via stabilising PPAR-γ protein by promoting deubiquitination at the Lys-466 site.
研究领域:
药理学
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心血管疾病
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Nutrients
·
2025
·Vol. 17
·期 10
·1693
·
IF 5
Binsong Han,Yuhui Ye,Cunzheng Zhang,Lina Zhang,Peng Zhou
Background: Camel milk is considered to be an important source of bioactive peptides with potential anti-diabetic effects. However, the mechanism by which these active peptides exert their anti-diabetic effects is not clear. The aim of this study was to systematically evaluate the in vivo anti-diabetic effects of Leucine-Leucine-Proline-Lysine (LLPK), a novel dipeptidyl peptidase-4 (DPP-4) inhibitory peptide identified from the in vitro gastrointestinal digestion product of camel milk.Methods: Adb/dbdiabetic mouse model was used, and LLPK was administered to mice at doses of 50 mg/kg BW and 100 mg/kg BW as a daily oral gavage for 30 days. The effects of LLPK on fasting blood glucose (FBG), oral glucose tolerance test (OGTT), insulin tolerance test (ITT), and serum lipid levels were monitored, and possible mechanisms of action were elucidated using proteomics.Results: The results demonstrated that LLPK significantly improved diabetic symptoms, including FBG, OGTT, ITT, and serum lipid levels indb/dbdiabetic mice. Furthermore, significantly increased levels of serum glucagon-like peptide 1 (GLP-1) and reduced serum DPP-4 activity were observed in the LLPK-treated group compared to the control group. Hepatic proteomics indicated that LLPK improved glucose and lipid metabolism via the PPAR signaling pathway, where the key targets were Scd1, Acox1, Acaa1b, Slc27a1, Acsl1, and Ehhadh.Conclusions: In summary, this study provided new insights into the anti-diabetic mechanisms of camel milk and supported the development of camel milk-based anti-diabetic functional foods or nutraceuticals.
研究领域:
营养学
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分子生物学
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代谢研究
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DOI
PubMed
高影响因子
PHYTOTHERAPY RESEARCH
·
2025
·
IF 6.3
Jingyi Hu,Feng Xu,Lei Zhu,Yuan Cui,Ryan Au,Yanan Li,Yiheng Tong,Hong Shen
Angelica dahurica radix (ADR), the root of the botanical family Apiaceae (genus Angelica , species Angelica dahurica ( Hoffm .)), has been used to treat colitis in clinical practice. The immunomodulatory effects of ADR are attributed to its polysaccharides (RP). However, its mechanism of action has not been elucidated. In this study, RP's structure was determined through nuclear magnetic resonance analysis. Dextran sulfate sodium-induced colitis in mice was utilized to assess the therapeutic efficacy of RP, while experiments involving fecal microbiota transplantation (FMT) and antibiotic treatment were performed to investigate the contribution of gut microbiota to RP's protective function. Non-targeted metabolomics was utilized to identify potential targets for elucidating the underlying mechanisms. RP is likely composed of (→4)-α-D-Glcp-(1→ and →4)-α-D-Galp-(1→). It effectively alleviated DSS-induced colitis by restoring the balance of the gut microbial community, a finding validated through FMT and antibiotic intervention experiments. Imidazole propionate (ImP) emerged as a potential target for RP's efficacy in treating colitis, which inhibits the activation of peroxisome proliferator-activated receptor gamma (PPAR-γ). Our findings suggest that RP may confer protection against colitis by activating the PPAR-γ signaling pathway through alleviating the constraint imposed by ImP.
研究领域:
药理学
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微生物学
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免疫学
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产品关联
DOI
PubMed
高影响因子
AQUATIC TOXICOLOGY
·
2024
·
IF 4.1
Afrasyab Khan,Bibimaryam Khan,Shakeel Hussain,Yuhan Wang,Weijun Mai,Yongzhong Hou
Permethrin (Per) is a widely used and frequently detected pyrethroid pesticide in agricultural products and the environment. It may pose potential toxicity to non-target organisms. Per has been reported to affect lipid homeostasis, although the mechanism is undefined. This study aims to explore the characteristic transcriptomic profiles and clarify the underlying signaling pathways of Per-induced lipid metabolism disorder in zebrafish liver. The results showed that environmental exposure to Per caused changes in the liver index, histopathology, and oxidative stress in zebrafish. Moreover, transcriptome results showed that Per heavily altered the pathways involved in metabolism, the immune system, and the endocrine system. We conducted a more in-depth analysis of the genes associated with lipid metabolism. Our findings revealed that exposure to Per led to a disruption in lipid metabolism by activating the KRAS-PPAR-GLUT signaling pathways through oxidative stress. The disruption of lipid homeostasis caused by exposure to Per may also contribute to obesity, hepatitis, and other diseases. The results may provide new insights for the risk of Permethrin to aquatic organisms and new horizons for the pathogenesis of hepatotoxicity.
研究领域:
毒理学
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分子生物学
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环境科学
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产品关联
DOI
PubMed
高影响因子
BIOMEDICINE & PHARMACOTHERAPY
·
2022
·
IF 7.419
Jingyi Hu,Yiheng Tong,Zhaofeng Shen,Yanan Li,Cheng Cheng,Ryan Au,Feng Xu,Yajun Liu,Lei Zhu,Hong Shen
Ulcerative colitis (UC) is a chronic and relapsing inflammatory disease of the intestine. Dysbiosis, especially the expansion of facultative anaerobic Enterobacteriaceae , maybe the main pathogenesis of UC. Gegen Qinlian decoction (GD), a traditional Chinese medicinal formula chronicled in the Shang Han Lun , is commonly used to treat UC and has shown an excellent effect on inducing disease remission. However, the role of GD in regulating gut microbiota has not been fully clarified. Herein, we investigated the potential effect of GD on inhibiting the expansion of Enterobacteriaceae and further explored the potential mechanism of this action. Our study demonstrated that GD remarkably reduced body weight loss of colitis mice, shortening of colon length, and inflammation of the colon. Peroxisome proliferator-activated receptor-γ (PPAR-γ) signaling was inactivated in colitis colon tissue, and the abundance of Escherichia coli ( E. coli, family of Enterobacteriaceae ) in colonic contents and the concentration of lipopolysaccharide (LPS) in colonic tissue were significantly upregulated after DSS-treatment. Notably, GD administration can result in the activation of PPAR-γ and inactivation of iNOS, which lead to the reduction of nitrate, the inhibition of E. coli, and less production of LPS. Combined GD with PPAR-γ antagonist, the effect of GD on the treatment of UC was weakened, and effectless in inhibiting the expansion of Enterobacteriaceae . Therefore, GD ameliorates UC by preventing a dysbiotic expansion of potentially pathogenic E. coli by reducing nitrate levels in the lumen through activating PPAR-γ signaling.
研究领域:
药理学
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微生物学
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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
MOLECULAR NUTRITION & FOOD RESEARCH
·
2023
·Vol. 67
·期 22
·2300258
·
IF 5.2
Yiju Li,Zhi Feng,Tianliang Wu,Haixi You,Wei Wang,Xuebo Liu,Long Ding
Scope The obesity epidemic continues to be a major global public health threat with limited effective treatments. Peptides are a group of promising bioactive molecules. Both in vivo and in vitro studies have demonstrated that quinoa has potential prebiotic benefits. Thus, the present study aims to investigate the influence of quinoa peptides (QP) consumption on obesity and its underlying mechanisms in high-fat diet (HFD)-induced mice. Methods and results QP (1000 mg kg −1 day −1 ) is administered to HFD mice for 8 weeks, and is found to significantly reduce the body weight, and plasma levels of triacylglycerol (TG) and total cholesterol (TC) compare to the HFD group. In addition, QP significantly decreases lipid accumulation in the liver caused by HFD. The liver transcriptome analysis shows that the alleviation of QP on obesity is related to the PPAR signaling pathway. QP upregulates the expressions of PPAR-α and its related genes and downregulates the expressions of PPAR-γ and its downstream genes. Furthermore, QP remodels the community composition of gut microbiota by lowering the ratio of Firmicutes c Bacteroidetes (F/B). Conclusion These findings suggest that QP consumption alleviates HFD-induced obesity by regulating the PPAR-α/γ signaling pathway in the liver and community structure of gut microbiota.
研究领域:
营养学
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分子生物学
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微生物学
✓ 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）