CELL PROLIFERATION
·
2020
·Vol. 53
·期 8
·e12871
·
IF 5.753
Hongping Yu,Pei Liu,Daoyu Zhu,Junhui Yin,Qianhao Yang,Yigang Huang,Yixuan Chen,Changqing Zhang,Youshui Gao
Objectives Osteonecrosis of the femoral head (ONFH), largely caused by alcohol abuse, is a refractory bone disease characterized by the impaired capacity of osteogenic differentiation of bone mesenchymal stem cells (BMSCs), as well as the disordered adipocyte accumulation. Chrysophanic acid (CPA) is a natural anthraquinone which has lipid regulation and bone protection capacity. The aim of this study was to reveal the potential function of CPA and the underlying mechanisms for the alcohol-induced ONFH. Materials and Methods The effects of alcohol and CPA on BMSCs were investigated by cell proliferation, induced differentiation assays and immunofluorescent staining. Meanwhile, the function of PI3K/AKT and AMPK pathway was investigated in the process of osteogenic and adipogenic differentiation, respectively. Furthermore, we established the rat model of alcohol-induced ONFH to reveal the pharmacotherapeutic effect of CPA in vivo using radiographical and histopathological methods. Results In vitro, alcohol significantly inhibited the proliferation and osteogenic differentiation of BMSCs but stimulated the adipogenic differentiation. However, CPA could counteract the anti-osteogenesis of alcohol partly via PI3K/AKT pathway and retard the promotion of alcohol-induced adipogenesis via AMPK pathway. In vivo, radiographical and histopathological findings showed that CPA could alleviate alcohol-induced ONFH and substantially restore the bone volume. Conclusions We demonstrated that CPA ameliorated alcohol-induced ONFH possibly via regulating the differentiation tendency of BMSCs. Hence, CPA may become a beneficial herb extract to alleviate alcohol-induced ONFH.
研究领域:
药理学
·
骨科
·
干细胞研究
✓ 已验证
DOI
PubMed
高影响因子
MOLECULAR NUTRITION & FOOD RESEARCH
·
2025
·
IF 4.2
Guoli Chang,Siyi Tian,Xinyu Luo,Yannan Xiang,Chenggang Cai,Ruiyu Zhu,Haiying Cai,Hailong Yang,Haiyan Gao
The Myrica rubra pomace polyphenols (MRPP) were used to study their hypoglycemic effects and mechanisms using Type 2 diabetes (T2D) (db/db) mice as the model. The results showed that the oral administration of MRPP (low-dose myricitrin, 50 mg/kg BW by gavage; high-dose myricitrin, 250 mg/kg BW by gavage; and Myrica rubra pomace, 500 mg/kg BW by gavage) for 4 weeks significantly reduced fasting blood glucose, glycated serum protein, serum insulin, and insulin resistance index in mice, as well as the dyslipidemia in mice was improved. MRPP was able to improve the structural morphology of hepatocytes and pancreatic β-cells in diabetic mice. Its hypoglycemic mechanism may involve the upregulation of GLUT-4 and IRS-1 genes expression in the PI3K and AMPK signaling pathways, downregulation of GSK-3β, AMPK, PI3K, and AKT genes expression, and enhancement of the activity of enzymes related to glycogen synthesis and glucose metabolism. Research findings on 16S rRNA suggest that MRPP has the ability to alter the composition of the gut microbiota, impede the growth of harmful bacteria, and foster the growth of beneficial bacteria. Therefore, MRPP was capable of reshaping the specific gut microbial community and supporting its application as a novel supplement in functional foods for the treatment of T2D.
研究领域:
营养学
·
代谢生物学
·
药理学
·
微生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Biology-Basel
·
2026
·Vol. 15
·期 13
·999
·
IF 4.3
Xiang Li,Bo Tian,Yuxin Chen,Huili Tong,Xiaoming Chen,Zhifeng Cheng
Simple SummaryType 2 diabetes (T2DM) often leads to skeletal muscle loss and weakness, a condition called sarcopenia, which worsens human health. This study explored whether carnosine, a natural dipeptide found in meat and present in human muscle, can help protect against muscle wasting. Using a T2DM sarcopenia mouse model and a high-glucose-treated C2C12 myotube in vitro model, the researchers found that carnosine levels were reduced in T2DM sarcopenia muscles. Oral carnosine supplementation in the mice helped alleviate skeletal muscle atrophy. Carnosine works by activating a cellular signaling pathway that boosts the number of mitochondria (the energy powerhouses of cells) and shifts muscle fibers toward a more oxidative type, leading to stronger and healthier muscles in T2DM sarcopenia mice. These findings suggest that carnosine supplementation could be a simple and promising nutritional strategy to help manage skeletal muscle loss in people with type 2 diabetes, though further studies in humans are needed to confirm its effectiveness.Type 2 diabetes mellitus (T2DM) accounts for over 90% of diabetes cases, and T2DM-related sarcopenia is a growing concern. Carnosine, abundant in human skeletal muscle, helps maintain muscle quality and function. This study investigated whether carnosine deficiency contributes to T2DM-related sarcopenia and whether exogenous carnosine supplementation alleviates muscle atrophy. A mouse model of T2DM sarcopenia was established using streptozotocin combined with a high-fat diet. LC-MS metabolomics revealed a significant reduction in carnosine content in the gastrocnemius muscle of model mice. A C2C12 myotube atrophy model was induced by high-glucose (HG), and qRT-PCR showed altered expression of carnosine metabolism-related enzymes, suggesting disrupted carnosine homeostasis under T2DM conditions. Mechanistic investigations using immunofluorescence, Western blotting, transcriptome sequencing, mitochondrial staining, and molecular docking indicated that carnosine may alleviate high-glucose-induced myotube atrophy through the PI3K/AMPK/PGC-1α signaling pathway. In vivo, carnosine supplementation increased the number of mitochondria and the proportion of slow muscle fibers in gastrocnemius muscle, ameliorating the atrophic phenotype. These findings suggest that carnosine has potential as a candidate for intervention in T2DM-related sarcopenia, though further validation of its direct molecular targets is required.
✓ 已验证
DOI
PubMed
高影响因子
LIFE SCIENCES
·
2026
·
IF 6.4
Gaoxuan Shao,Chenceng Sun,Chenhao Ye,Ying Liu,Jiashu Pan,Yujing Liu,Lu Lu,Lei Wang,Zemin Lin,Fan Yang,Guang Ji,Hanchen Xu
Luteolin significantly reduces tumor burden and fibrosis in a MASH-HCC mouse model. • Luteolin attenuates hepatic lipid accumulation by inhibiting de novo lipogenesis. • The protective effects of luteolin are mediated via the AMPK/ACC signaling pathway. • Inhibition of AMPK abolishes the lipid-lowering benefits of luteolin in hepatocytes. Aims Metabolic dysfunction-associated steatohepatitis (MASH) is a primary driver of hepatocellular carcinoma (HCC), yet effective therapeutic interventions remain limited. While luteolin is known for its anti-inflammatory properties, its efficacy and underlying mechanism in the MASH-HCC transition are not fully understood. This study investigated the protective effects of luteolin against MASH-HCC and the role of the AMPK/ACC signaling pathway in this process. Materials and methods In vivo , a MASH-HCC mouse model was established using diethylnitrosamine (DEN) combined with a high-fat, high-cholesterol (HFHC) diet. Mice were treated with vehicle or luteolin (50 or 100 mg/kg) for 26 weeks. Progression was monitored via serum alpha-fetoprotein (AFP), histological analysis, and Western blotting. In vitro , HepG2 and Huh-7 cells were challenged with cholesterol and treated with luteolin. The AMPK inhibitor BAY-3827 was employed to verify whether the metabolic benefits of luteolin were pathway-dependent. Key findings Luteolin treatment significantly reduced tumor burden, lowered serum AFP levels, and attenuated hepatic lipid accumulation and fibrosis in MASH-HCC mice. In vitro results mirrored these findings, showing that luteolin reduced cholesterol-induced lipid loading. Mechanistically, luteolin increased the phosphorylation of AMPK and its downstream target, ACC. Furthermore, pharmacological inhibition of AMPK with BAY-3827 abolished the lipid-lowering effects of luteolin in hepatic cells, confirming that its therapeutic benefits are mediated through AMPK activation. Significance Luteolin suppresses the progression of MASH to HCC by activating the AMPK/ACC signaling pathway and subsequently inhibiting de novo lipogenesis. These findings highlight luteolin as a promising potential therapeutic candidate for the prevention and treatment of MASH-related liver cancer. Download: Download high-res image (314KB) Download: Download full-size image
✓ 已验证
DOI
PubMed
高影响因子
CELLULAR SIGNALLING
·
2025
·
IF 3.7
YaoNan Han,XingTong Wang,DeShui Yu
Spinal cord injury (SCI) is a serious central nervous system disease. Ferroptosis is one of the major causes of spinal cord neurological loss, and targeting ferroptosis is a promising therapeutic strategy. Roflumilast has shown promising applications in the treatment of neurological diseases due to its potent anti-inflammatory and anti-oxidative stress effects. This study aimed to investigate whether roflumilast could inhibit neuronal ferroptosis to improve motor function after SCI in rats. In vitro experiments, we found that roflumilast significantly increased cell survival in an in vitro ferroptosis model, improved mitochondrial function, reduced intracellular iron, reactive oxygen species (ROS), and lipid peroxides accumulation as well as the expression of the pro-ferroptosis proteins, long-chain acyl-coenzyme A synthase 4 (ACSL4), and prostaglandin-endoperoxide synthase 2 (PTGS2), and increased the expression of ferroptosis-inhibitory protein glutathione peroxidase 4 (GPX4), and ferritin heavy chain 1 (FTH1) expression. Mechanistically, these protective effects were achieved by activating AMP-dependent protein kinase (AMPK)/nuclear factor E2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling and were attenuated when AMPK signaling was blocked. In vivo experiments, roflumilast attenuated spinal cord tissue damage, increased the number of motor neuron survivors, and improved motor function after SCI in rats. Overall, activation of AMPK/Nrf2/HO-1 signaling by roflumilast attenuated neuronal ferroptosis and improved motor function after SCI in rats.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MEDICAL SCIENCE MONITOR
·
2018
·
IF 1.894
Lingling Wang,Yan Yin,Gang Hou,Jian Kang,Qiuyue Wang
Background Cigarette smoking is a well-known risk factor in multiple chronic pulmonary diseases. This study aims to investigate the role of peroxisome proliferator-activated receptor (PPAR) γ in cigarette smoking-induced inflammation. Material/Methods Cigarette smoking extract (CSE) was employed to induce inflammation in bronchial epithelial cells (BECs). After CSE administration, several autophagy-related proteins (Beclin1, autophagy-related gene (ATG)5, ATG7, p62, and LC3) and PPARγ levels were examined by western blot. Subsequently, PPARγ agonists and antagonist were used to treat CSE-induced BECs, several inflammatory factors (interleukin (IL)-6, IL-8, inducible nitric oxide synthase (iNOS), and cyclooxygenase (COX)-2) and autophagy-related proteins were detected to measure the inflammatory and autophagy levels. Then LC3 knockdown was performed to verify the role of autophagy in CSE-induced inflammation. Finally, the AMP-activated protein kinase (AMPK) and its downstream S6 kinase (S6K) were detected in CSE-stimulated BECs. Results CSE administration caused insufficient autophagy and the decrease of PPARγ in BECs. The PPARγ agonists ameliorate the CSE-induced inflammation and promote the autophagy development, evidenced by the changes of inflammatory factors and autophagy-related proteins. Loss-of-function experiments demonstrated that the PPARg played an anti-inflammatory role in an autophagy-dependent manner. In addition, CSE administration inactivated the AMPK signaling, which was restored by PPARγ agonists. The effects of PPARγ agonists on inflammation and autophagy could be abolished by AMPK inhibitor. Conclusions We demonstrated that PPARγ played a protective role in CSE-induced inflammation and autophagy by activating AMPK signaling in BECs, which may provide investigation basis for clinical therapy of chronic pulmonary diseases.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
·
2017
·
IF 5.476
Xihong Zhou,Liuqin He,Shengnan Zuo,Yumei Zhang,Dan Wan,Ciming Long,Pan Huang,Xin Wu,Canrong Wu,Gang Liu,Yulong Yin
Serine deficiency has been observed in patients with nonalcoholic fatty liver disease (NAFLD). Whether serine supplementation has any beneficial effects on the prevention of NAFLD remains unknown. The present study was conducted to investigate the effects of serine supplementation on hepatic oxidative stress and steatosis and its related mechanisms. Forty male C57BL/6J mice (9 week-old) were randomly assigned into four groups ( n = 10) and fed: i) a low-fat diet; ii) a low-fat diet supplemented with 1% (wt:vol) serine; iii) a high-fat (HF) diet; and iv) a HF diet supplemented with 1% serine, respectively. Palmitic acid (PA)-treated primary hepatocytes separated from adult mice were also used to study the effects of serine on oxidative stress. The results showed that serine supplementation increased glucose tolerance and insulin sensitivity, and protected mice from hepatic lipid accumulation, but did not significantly decreased HF diet-induced weight gain. In addition, serine supplementation protected glutathione (GSH) antioxidant system and prevented hypermethylation in the promoters of glutathione synthesis-related genes, while decreasing reactive oxygen species (ROS) in mice fed a HF diet. Moreover, we found that serine supplementation increased phosphorylation and S -glutathionylation of AMP-activated protein kinase α subunit (AMPKα), and decreased ROS, malondialdehyde and triglyceride contents in PA-treated primary hepatocytes. However, while AMPK activity or GSH synthesis was inhibited, the abovementioned effects of serine on PA-treated primary hepatocytes were not observed. Our results suggest that serine supplementation could prevent HF diet-induced oxidative stress and steatosis by epigenetically modulating the expression of glutathione synthesis-related genes and through AMPK activation.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Scientific Reports
·
2017
·Vol. 7
·期 1
·1-13
·
IF 4.259
Chen Xubo,Zhao Xueyan,Lan Fazhang,Zhou Tao,Cai Hua,Sun Haiying,Kong Weijia,Kong Wen
Studies have reported attenuation of insulin resistance (IR) by improving phosphorylation of the insulin signalling pathway. However, the upstream molecular signalling pathway is still elusive. In this study, Western blot was used to evaluate the phosphorylation level of the insulin signalling pathway and the AMPK pathway. 2-NBDG was used to evaluate glucose uptake. Ca 2+ imaging was used to assess change of intracellular Ca 2+ concentration. We found that NaHS enhanced the intracellular Ca 2+ concentration and glucose uptake and activated the insulin signalling cascade in a palmitic acid (PA)-induced IR model in C2C12 cells. Furthermore, activation of the IRS1/PI3K/AKT pathway and glucose uptake were decreased when AMPK or CaMKKβ was inhibited. Our study also showed that the mitochondrial electron transport chain, ATP production, and intramitochondrial cAMP declined in the IR model but that this effect was reversed by NaHS, an effect that may be mediated by the Ca 2+ /CaMKK2/AMPK and PI3K/AKT pathways. Our data indicate that H 2 S improves activation of the insulin signalling cascade and glucose uptake via activation of the Ca 2+ /CaMKK2/AMPK pathway and mitochondrial metabolism in C2C12 cells. Furthermore, NaHS protects mitochondrial function and maintains normal ATP production by activating the cAMP system and the Ca 2+ /CaMKK2/AMPK and PI3K/ATK pathways.
✓ 已验证
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
·
IF 7.7
Pin Gong,Xufeng Wang,Yewen Han,Hui Long,Wenjuan Yang,Fuxin Chen,Mengjiao Cui,Wenjun Zhai,Benzhong Zheng,Xuefeng Chen
This study devised optimal conditions to extract Eucommia ulmoides leaf (EUL) polysaccharides using a cellulase and pectinase composite enzyme system based on one-way experiments and response surface methodology. Crude EUL polysaccharides (EULPs) were extracted and purified using a DEAE chromatography column. The polysaccharides EUL-w, EUL1, EUL2, and EUL3 were obtained by elution with water, 0.1 mol/L NaCl, 0.2 mol/L NaCl, and 0.3 mol/L NaCl, respectively. The EUL-w fraction had the highest hypoglycemic activity based on its α-amylase and α-glucosidase activities. The preliminary structure of purified EUL-w1 was elucidated. In vitro hypoglycemic activity studies and metabolomics analyses suggested that EUL-w1 modulated glucose metabolism by mediating the AMPK/PI3K/Akt signaling pathway. Our findings provide novel insights and data support for the utilization of EULPs as an emerging food resource in functional foods.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOCHEMICAL PHARMACOLOGY
·
2024
·
IF 5.3
Shan Meng,Xin Chen,Jikai Zhao,Xinyi Huang,Yuting Huang,Tao Huang,Zijun Zhou,Wenpu Ren,Tao Hong,Jinfeng Duan,Liming Yu,Huishan Wang
Fibronectin type III domain-containing protein 5 (FNDC5) exerts potential anti-arrhythmic effects. However, the function and mechanism of FNDC5 in diabetes-associated atrial fibrillation (AF) remain unknown. In this study, bioinformatics analysis, in vivo and in vitro experiments were conducted to explore the alteration and role of FNDC5 in diabetes-related atrial remodeling and AF susceptibility. RNA sequencing data from atrial samples of permanent AF patients and diabetic mice exhibited significantly decreased FNDC5 at the transcriptional level, which was in line with the protein expression in diabetic mice as well as high glucose and palmitic acid (HG+PA) injured atrial myocytes. Diabetic mice exhibited adverse atrial remodeling and increased AF inducibility. Moreover, reduced atrial FNDC5 was accompanied with exacerbated NOD-like receptor pyrin domain containing 3 (NLRP3) activation and disturbed mitochondrial fission and fusion processes, as evidenced by decreased expressions of optic atrophy 1 (OPA-1), mitofusin (MFN-1, MFN-2) and increased phosphorylation of dynamin-related protein 1 (Ser616). These effects were validated in HG+PA-treated atrial myocytes. Critically, FNDC5 overexpression remarkably enhanced cellular antioxidant capacity by upregulating the expressions of superoxide dismutase (SOD1, SOD2) level. In addition, HG+PA-induced mitochondrial dysfunction was ameliorated by FNDC5 overexpression as evidenced by improved mitochondrial dynamics and membrane potential. Moreover, NLRP3 inflammasome-mediated inflammation was reduced by FNDC5 overexpression, and AMPK signaling might serve as the key down-stream effector. The present study demonstrated that reduced atrial FNDC5-AMPK signaling contributed to the pathogenesis of diabetes- associated AF by impairing mitochondrial dynamics and activating the NLRP3 inflammasome. These findings provide promising therapeutic avenues for diabetes-associated AF.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
GENE
·
2024
·
IF 2.6
Wen Zhong,Huanan Jia,Haiyan Zhu,Yuan Tian,Wei Huang,Qiyue Yang
Sarcopenia has become a prominent health problem among the elderly because of its adverse consequence, including physical disabilities and death. Fibro-adipogenic progenitors (FAPs) exhibit adipogenic and fibrogenic potencies and regulate skeletal muscle development, which plays important role in sarcopenia. Mairin, as an ingredient of Astragalus membranaceus, has the effect of anti-fibrosis. Therefore, we predicted that mairin targeted the fibrosis of FAPs and then affected sarcopenia. To verify our ideas, mairin (30 mg/kg/day or 60 mg/kg/day) was given to senescence accelerated mouse-prone 8 (SAMP8) mice by oral administration. Aging led to loss of weight, skeletal muscle mass, strength, and function, and an increase in muscle atrophy and fibrosis, while mairin administration inhibited physiological decline caused by aging. Similarly, mairin (20 μM or 40 μM) treatment enhanced FAP proliferation but blocked the differentiation into fibroblasts. Mechanically, mairin played an anti-fibrotic role via AMP-activated protein kinase-transforming growth factor beta-drosophila mothers against decapentaplegic protein (AMPK-TGF-β-SMAD) axis, as evidenced by increased phosphorylation of AMPKα and decreased TGF-β and phosphorylated-SMAD2/3. In addition, the potential target genes of mairin were explored by mRNA sequencing in our study. In conclusion, mairin may interfere with the AMPK/TGF-β/SMAD pathway to repress the fibrosis of FAPs and eventually ameliorate sarcopenia.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY C-TOXICOLOGY & PHARMACOLOGY
·
2025
·
IF 4.3
Yimin Li,Chunnuan Zhang,Zihao Meng,Mengkang You,Huajuan Shi
TBBPA, a ubiquitously distributed brominated flame retardant, poses significant ecological risks due to its bioaccumulative potential and toxicity. Previous investigations have predominantly focused on untargeted metabolomics and lipidomics to characterize the effects of TBBPA on metabolic end products. However, limited data are available regarding the mechanisms underlying TBBPA-induced disruption of lipid metabolism in aquatic organisms. This study systematically investigated the dose-dependent effects of TBBPA on lipid metabolism in common carp through integrated biochemical, histochemical evaluations, and transcriptomic profiling. Fish were exposed to environmentally relevant TBBPA concentrations (0, 0.005, 0.05, and 0.5 mg/L) for a 14-day duration. Serum biochemical analyses revealed dose-dependent hyperlipidemia, manifested by elevated TG and T-CHO levels, suppressed SOD and CAT activities, and increased MDA levels. Oil Red O staining demonstrated hepatic lipid droplet accumulation despite no significant ( P > 0.05) alterations in intrahepatic TG/T-CHO content, with the 0.5 mg/L group exhibited the most severe histopathological phenotype. Transcriptomic profiling identified the AMPK and PPAR signaling pathways as pivotal regulators of TBBPA-induced metabolic dysregulation. Under low-dose TBBPA exposure (0.05 mg/L), lipid accumulation triggered compensatory activation of the AMPK / PPAR-α / CPT1 axis, enhancing fatty acid β-oxidation to partially counteract lipid deposition. Conversely, high-dose TBBPA (0.5 mg/L) disrupted lipid metabolism through coordinated upregulation of genes associated with lipid synthesis, transport, and storage, culminating in pathological lipid deposition. This study provides critical insights into the molecular cascades underlying TBBPA-induced metabolic dysregulation in aquatic species, highlights the dose-dependent disruption of lipid homeostasis.
研究领域:
环境毒理学
·
水生毒理学
·
分子生物学
·
生物化学
·
转录组学
✓ 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）