EXPERIMENTAL BIOLOGY AND MEDICINE
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2024
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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
Translational Research
·
2024
·
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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产品关联
DOI
PubMed
高影响因子
SCIENCE OF THE TOTAL ENVIRONMENT
·
2024
·
IF 8.2
Xiaoping Liang,Jiehua Liang,Shengqi Zhang,Haowei Yan,Tiangang Luan
Di-2-ethylhexyl phthalate (DEHP), a widely utilized plasticizer , has been described as a potential obesogen based on in vivo disruption of hepatic lipid homeostasis and in vitro promotion of lipid accumulation. However, limited literature exists regarding the specific ramifications of DEHP exposure on obese individuals, and the precise mechanisms underlying the adverse effects of DEHP exposure remain unclear. This study aimed to assess the impact of DEHP on hepatic lipid metabolism in obese mice by comparing them to normal mice. Following a 10-week DEHP exposure period, the obese mice exhibited higher blood lipid levels, more severe hepatic steatosis, and more infiltrations of inflammatory cells in liver tissue than normal mice. Interestingly, the body weight of the mice exhibited no significant alteration. In addition, transcriptomic analyses revealed that both lipogenesis and fatty acid oxidation contributed to hepatic lipid metabolism dysregulation following DEHP exposure. More specifically, alterations in the transcription of genes associated with hepatic lipid metabolism were linked to the different responses to DEHP exposure observed in normal and obese mice. Additionally, the outcomes of in vitro experiments validated the in vivo findings and demonstrated that DEHP exposure could modify hepatic lipid metabolism in normal mice by activating the LXR/SREBP-1c signaling pathway to promote lipogenesis. At the same time, DEHP exposure led to inhibition of the Camkkβ/AMPK pathway to suppress β -fatty acid oxidation. Conversely, in obese mice, DEHP exposure was found to be associated with the stimulation of both lipogenesis and fatty acid oxidation via activation of the LXR/SREBP-1c and PPAR-α signaling pathways, respectively. The findings presented in this study first elucidate the contrasting mechanisms underlying DEHP-induced liver damage in obese and normal mice, thereby offering valuable insights into the pathogenesis of DEHP-induced liver damage in individuals with obesity.
研究领域:
毒理学
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肝病学
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分子生物学
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肥胖研究
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产品关联
DOI
PubMed
高影响因子
BIOMEDICINE & PHARMACOTHERAPY
·
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
MEDICINAL CHEMISTRY RESEARCH
·
2024
·Vol. 33
·期 5
·796-810
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IF 2.6
Quan Lina,Guo Ying,Wang Siyao,Sun Mengfei,Pang Yan,Cui Chunli,Wang Jinrui,Wei Jinlian,Wei Peifeng,Xie Yundong
Molecular hybridization method was applied to design and synthesize a series of target compounds paeonol-based fibrate derivatives. The target compound was screened using a Triton WR-1339 induced hyperlipidemia mouse model, and compound T9 was found to have good lipid-lowering activity. The dose-dependent study of its lipid-lowering activity was also conducted. To further evaluate the lipid-lowering activity of compound T9, a hyperlipidemic mouse model induced by high fat emulsion can be used. The findings of the research illustrate that T9 is capable of significantly decreasing blood lipid levels, including TG, TC, LDL-C, and increasing HDL-C. The results of liver tissue oil red O staining and HE staining demonstrated that T9 improved the hepatic lipid accumulation, thus decreasing AST and ALT levels and protecting against hyperlipidemic liver injury. Studies into the lipid-lowering effect of T9 have indicated that it can upregulate PPAR-α protein expression in liver tissue, while simultaneously decreasing the expression of HMG-CoA protein. T9 was further demonstrated to possess antioxidant properties, as evidenced by an increase in SOD and a decrease in MDA, as well as anti-inflammatory effects, demonstrated by a decrease in TNF-α, IL-1β, and IL-6, thus confirming its potential as a hypolipidemia and hepatoprotective agent. Graphical Abstract
研究领域:
药理学
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分子生物学
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产品关联
DOI
高影响因子
Food Chemistry: Molecular Sciences
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2025
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IF 4.7
Rabia Durrani,Sun Yutian,Hou Bowen,Hammad Ullah,Erwann Durand,Yang Meiyun,Long Yiyang,André Delavault,Muhammad Yasir,Huan Weiwei,Gao Fei,Song Lili
Plant-derived bioactive peptides have drawn increasing attention in the field of nutrition and food science due to their biological activities, low cost, safety, and ease of industrial production. Functional peptides from Torreya grandis are being investigated due to their potential as dietary supplements. This study focuses on T. grandis nut peptides that regulate LIPID-II inhibitor in mice fed a high-fat diet. Proteome analysis identified a Vicilin -like antimicrobial peptide involved in host defense. 16S rRNA Sequencing revealed alteration in gut microbiota with T. grandis administration as manifested by increased Akkermansia and Parabacteroides concurrently by decreased Firmicutes . Beneficial bacteria i.e., Akkermansia improved intestinal functions and increased levels of short chain fatty acids (SCFAs). T. grandis supplementation in HFD mice reduced body weight, TC, TG, LDL, and decreased inflammation, while reducing oxidative stress and increasing HDL in the model group fed a high-fat diet. Lipid droplets in liver, muscles, and blood vessels were highly reduced, evoked by the high peptide group. Transcriptome analysis highlighted lipid regulation via the PPAR-α pathway, with molecular docking revealing 4 potential lipid II inhibitory peptides. These findings suggested T. grandis as a promising supplement in food and a key nut for nutraceutical purposes.
研究领域:
营养与食品科学
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微生物学
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生物化学与分子生物学
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产品关联
DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF PHARMACOLOGY
·
2026
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IF 5.7
Lan Luo,Wei Liu,Shenglan Qi,Jiamei Chen,Hua Zhang,Yongping Mu,Gaofeng Chen,Wei'an Yuan,Ping Liu,Linzhang Zhang
DDC-induced cholestatic liver injury in mice was significantly ameliorated by IAS II through the suppression of ductular reaction, hepatic fibrosis, and inflammatory responses. • Gut microbiota integrity is essential for IAS II efficacy, as its protective effects are lost upon antibiotic depletion. • IAS II activates PPAR-α and FXR signaling in a receptor-dependent manner to restore BA homeostasis, a mechanism validated by in vitro inhibitor studies. Cholestatic liver disease (CLD) is a severe hepatobiliary disorder with limited treatment options. Although the natural compound Isoastragaloside II (IAS II) has been suggested to possess general hepatoprotective properties, its therapeutic efficacy against CLD has not been reported. In this study, the therapeutic potential and underlying mechanisms of IAS II for CLD were investigated using a murine model established by 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) feeding. It was demonstrated that DDC-induced cholestatic liver injury was significantly alleviated by IAS II treatment, as indicated by the normalization of key serum biochemical parameters. An integrated analysis of histopathological, protein, and gene expression data demonstrated that IAS II treatment effectively suppressed the ductular reaction, inhibited hepatic fibrosis, and attenuated inflammation. Analysis of 16S rRNA sequencing data revealed that IAS II treatment was accompanied by alterations in gut microbiota composition, including an enrichment of Bacteroides and a reduction in Lachnospiraceae_NK4A136_group . Antibiotic depletion experiments demonstrated that the hepatoprotective effects of IAS II were abrogated by gut microbiota depletion, confirming the essential role of the gut microbiota in its pharmacological action. At the molecular level, IAS II activated both the PPAR-α pathway (as indicated by transcriptomic analysis) and the FXR pathway (as confirmed by subsequent validation), which collectively resulted in a significant reduction in the hepatic accumulation of toxic bile acids (BAs). In vitro studies in LCA-induced HepG2 cells further revealed that the restoration of PPAR-α, ACOX2, FXR, and BSEP protein expression by IAS II required receptor activation, as these effects were blocked by specific inhibitors. In summary, to our knowledge, this study provides the first demonstration that a protective effect against DDC-induced cholestatic liver injury is conferred by IAS II through coordinated regulation of PPAR-α and FXR signaling, restoration of BA homeostasis, and in a gut microbiota-dependent manner, with these effects requiring the activation of both PPAR-α and FXR pathways, thereby identifying IAS II as a novel and promising therapeutic candidate for CLD. Download: Download high-res image (191KB) Download: Download full-size image
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DOI
PubMed
高影响因子
Food & Function
·
2026
·
IF 6.3
Ziyuan Zhou,Xiaxia Pan,Jiali Ni,Zhuoqi Lou,Yangfan Shen,Shiman Jiang,Xiangmin Dong,Fengjiao Wang,Yanfei Chen,Lanjuan Li
Existing evidence indicates that pre-existing metabolic dysfunction-associated steatotic liver disease (MASLD) confers susceptibility to acute liver injury (ALI). Nevertheless, the underlying mechanism prompting ALI risk in such condition is not fully uncovered yet. Gut dysbiosis has been well-documented in MASLD patients which prompts us to hypothesize that gut dysbiosis may serve as a contributing factor and regulating target to ALI susceptibility. A case-control study was performed and verified the increased risk of ALI in MASLD patients. Mice pretreated with MASLD mice/patients-derived fecal microbiota transplantation (FMT), demonstrated worsened ALI after D-GalN/LPS injection. We identified significant gut dysbiosis with decreased microbial α-diversity, beneficial genus lactobacillus, increased potential harmful bacteria Campylobacter and helicobacter. Probiotic Akkermansia muciniphila (A. muciniphila) was reported to improve gut dysbiosis. Thus, we tested the effect of A. muciniphila on ALI mice pretreated with MASLD mice-derived FMT. A. muciniphila significantly ameliorated the worsened ALI and improved gut dysbiosis. Transcriptomic analysis reveled that A. muciniphila restored the impaired liver PPAR-α signaling, alleviating the aggravated NF-κB signaling and downstream inflammation response in liver. Specifically, A. muciniphila restored the decreased abundance of PPAR-α agonist daidzein in colon, thereby restoring PPAR-α activation and inhibiting NF-κB signaling in liver. Daidzein is also capable to ameliorate ALI aggravated by MASLD-associated dysbiosis, accompanied by PPAR-α activation and NF-κB inhibition. Our findings revealed that gut dysbiosis in MASLD increased the risk of ALI. A. muciniphila exhibited preventive potential for MASLD patients to reduce ALI risk. Daidzein/PPAR-α/NF-κB signaling is important to maintain host resistance to hepatoxic challenge.
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DOI
PubMed
高影响因子
Journal of Cosmetic Dermatology
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2024
·
IF 2.3
Lu Hu,Jiyu Weng,Ziqin Wang,Chujie Huang,Lanyue Zhang
Background Aging is a physiological phenomenon in the process of life, and skin aging has a significant impact on human appearance. Therefore, the search for methods to delay skin aging is of great significance for improving the quality of human life. Materials and Methods This study investigated the anti-photoaging effect of Tricholoma matsutake (T) extract composition combined with bakuchiol (B) and ergothioneine (E), and explored its potential mechanism through transcriptome, metabolomics, and network pharmacology. Results 57 main chemical components are identified from the ethanol extract of T. matsutake (T), including D-carnitine (24.55%), α,α-trehalose (15.56%), DL malic acid (8.99%), D-(−)-quinic acid (7.46%), erucamide (7.04%) and so on. After TBE treatment, inflammation of the mice dorsal skin is significantly minimized. Hematoxylin and eosin (H&E) staining and toluidine blue staining reveal that TBE has an anti-inflammatory effect on the back skin tissue of mice. Masson staining shows that TBE has a repair effect on mice dorsal skin tissue. In addition, the inflammatory factors (IL-1β, IL-6, TNF-α) in the mice dorsal skin tissues are significantly reduced but collagen (COL-1) is significantly increased. By cellular immunofluorescence assay, TBE is shown to promote PPAR-α expression in cells. Transcriptomics, metabolomics, and network pharmacology have revealed that TBE can regulate exogenous stimuli and cancer-related signaling pathways to prevent skin aging. Conclusion The results suggest that TBE can be a beneficial supplement to natural anti-aging.
研究领域:
药理学
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皮肤科学
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分子生物学
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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
·
分子生物学
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微生物学
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产品关联
DOI
PubMed
高影响因子
CHEMOSPHERE
·
2020
·
IF 5.778
Jiafeng Zhou,Ruonan Shu,Chunan Yu,Ze Xiong,Qingfeng Xiao,Zezhi Li,Xiaoxian Xie,Zhengwei Fu
Trifluoromethanesulfonic acid (TFMS) is the shortest chain perfluorinated compound . Recently, it has been identified as a persistent and mobile organic chemical with a maximum concentration of 1 μg/L in the environment. However, its toxicological mechanism remains unclear. In this study, to evaluate the liver and intestinal toxicity of TFMS in mammals, male mice were orally exposed to 0, 1, 10 and 100 μg/kg for 12 weeks. Our results showed that TFMS exposure reduced the epididymal fat weight in mice, caused the decrease of serum and liver triglyceride (TG) level and the increase of serum low density lipoprotein (LDL) level. Also, we observed the inflammatory cell infiltration in the liver of mice exposed to 10 μg/kg and 100 μg/kg TFMS, which was coupled with the increased mRNA expression levels of inflammatory factors such as COX2 , TNF-α , IL-1β in the liver. In addition, the mRNA expression levels of lipid metabolism-related genes ( PPAR-α , ACOX , SCD1 , PPAR-γ , etc.) were significantly decreased in the liver of mice after exposure to both doses of TFMS. We also found TFMS exposure caused the imbalance of cecal gut microbiota and change of cecal microbiota diversity. KEGG pathway predictions showed that the exposure of 100 μg/kg TFMS changed the synthesis and degradation of ketone bodies, benzoate degradation and several other metabolic pathways. Our findings indicated that TFMS exposure disturbed the liver lipid metabolism possibly via altering the gut microbiota.
研究领域:
毒理学
·
分子生物学
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微生物学
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环境科学
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产品关联
DOI
PubMed
高影响因子
SCIENCE OF THE TOTAL ENVIRONMENT
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2024
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IF 8.2
Xin Wang,Bo Peng,Cheng Zhang,Mengqi Wu,Wenping Xu,Jiagao Cheng,Liming Tao,Zhong Li,Yang Zhang
The pesticide acetochlor (ACT) is a chiral isomer commonly detected in the global environment, yet its specific impacts on liver function remain poorly understood. We utilized zebrafish and L02 cells as research models to comprehensively investigate how ACT and its chiral isomers affect the liver. Our investigations unveiled that the R , Rac , and S isomers of ACT disrupt hepatic lipid transport, catabolism, and synthesis, leading to delayed yolk sac absorption and the accumulation of lipids in zebrafish embryos. These isomers induce oxidative stress in the liver of zebrafish embryos, reducing antioxidant levels and enzyme activity . The accumulated lipids in the liver render it susceptible to oxidative stress, further exacerbating hepatocyte damage. Hepatocyte damage manifests as extensive vacuolization of liver cells and alterations in liver morphology, which are induced by R , Rac , and S . Furthermore, we elucidated the molecular mechanisms underpinning the disturbance of hepatic lipid metabolism by R , Rac , and S in L02 cells. These compounds stimulate lipid synthesis through the upregulation of the AMPK/SREBP-1c/FAS pathway while inhibiting lipolysis via downregulation of the PPAR-α/CPT-1a pathway. Remarkably, our results highlight that S exhibits significantly higher hepatotoxicity in comparison to R . This study provides valuable insights into the hepatic effects of ACT chiral isomers.
研究领域:
环境毒理学
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分子生物学
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细胞生物学
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药理学
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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）