Oxidative Medicine and Cellular Longevity
·
2017
·
IF 4.593
Hui Zhou,Baocai Fu,Bo Xu,Xiangquan Mi,Gang Li,Chengjun Ma,Jianxin Xie,Ji Li,Zhenhua Wang
Endothelial dysfunction is the key player in the development and progression of vascular events. Oxidative stress is involved in endothelial injury. Rosmarinic acid (RA) is a natural polyphenol with antioxidative, antiapoptotic, and anti-inflammatory properties. The present study investigates the protective effect of RA on endothelial dysfunction induced by hydrogen peroxide (H2O2). Compared with endothelium-denuded aortic rings, the endothelium significantly alleviated the decrease of vasoconstrictive reactivity to PE and KCl induced by H2O2. H2O2 pretreatment significantly injured the vasodilative reactivity to ACh in endothelium-intact aortic rings in a concentration-dependent manner. RA individual pretreatment had no obvious effect on the vasoconstrictive reaction to PE and KCl, while its cotreatment obviously mitigated the endothelium-dependent relaxation impairments and the oxidative stress induced by H2O2. The RA cotreatment reversed the downregulation of AMPK and eNOS phosphorylation induced by H2O2 in HAEC cells. The pretreatment with the inhibitors of AMPK (compound C) and eNOS (L-NAME) wiped off RA’s beneficial effects. All these results demonstrated that RA attenuated the endothelial dysfunction induced by oxidative stress by activating the AMPK/eNOS pathway.
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2024
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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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CyTA-Journal of Food
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2024
·
IF 2
Fang Luo,WenLuer Meng,Ruo-Shi Hao,Xiangxuan Yang,Jinbo Yang,Ye-Wei Huang,Jun Sheng,Xuanjun Wang
This study investigated the impact of Oleanolic Acid (OA) on cholesterol metabolism and. MTT assays demonstrated that OA had no cytotoxic effects on HepG2 cells at concentrations below 20 μM. Subsequent experiments focused on 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMGCR), a key enzyme in cholesterol biosynthesis. OA significantly reduced HMGCR protein expression without affecting other enzymes. Further investigations revealed that OA reduced the protein and mRNA expression of HMGCR and its upstream regulator Sterol regulatory element binding protein-2 (SREBP-2) in HepG2 cells. OA activated Adenosine 5’-monophosphate (AMP)-activated protein kinase (AMPK), enhancing HMGCR phosphorylation and inhibiting its activity. Molecular docking experiments suggested that OA could suppress HMGCR enzymatic activity through hydrophobic interactions, reducing catalytic efficiency. Overall, OA downregulated HMGCR expression and activity, leading to decreased cholesterol synthesis. These findings highlight OA’s regulatory role in cholesterol metabolism and its potential for improving atherosclerosis (AS), supporting its application in functional food development.
研究领域:
药理学
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生物化学
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分子生物学
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细胞生物学
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营养学
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Journal of Functional Foods
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2026
·
IF 3.9
Wei Wei,Shuai Wang,Qiming Wu,Xinyong Zheng,Fuguo Liu
Walnut is a nutrient-rich food resource, yet the utilization of its high-quality plant proteins remains inefficient. Advanced processing strategies are therefore needed to develop walnut-based functional foods. In this study, walnut peptides were prepared by sequential hydrolysis with alcalase and papain, leading to the identification of a novel antioxidant peptide, IRALPEEVL. In vitro , IRALPEEVL increased the viability of PC12 cells under H 2 O 2 -induced oxidative stress. In vivo , it ameliorated cognitive and memory dysfunctions in zebrafish exposed to the environmental toxicant bisphenol AF. Proteomic analysis indicated that the neuroprotective effects of IRALPEEVL were associated with caveolin-1 (Cav1)-dependent penetration of the blood-brain barrier, regulating the AMPK-PI3K/Akt signaling, and inhibiting neuronal apoptosis. These findings highlight the potential of value-added walnut processing and support the application of walnut-derived peptides as functional food ingredients for health promotion.
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JOURNAL OF ETHNOPHARMACOLOGY
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2026
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IF 6.8
Yangdi Chen,Fanggang Bi,Zhong Hua,Jianshe Chen,Chenxi Li,Mingsan Miao,Zixue Sun
Ethnopharmacological relevance Yishen Tongluo Formula (YSTLF) is a modern compound formula derived from the traditional Chinese medicine (TCM) theory of “kidney deficiency and collateral obstruction”, and consists of seven Chinese medicinal herbs. It has been used clinically to treat oligoasthenozoospermia (OAS) for more than two decades, with proven efficacy and a favorable safety profile. However, its precise molecular mechanism has yet to be fully elucidated. Aim of the study The aim was to investigate the therapeutic efficacy and the underlying mechanism of YSTLF in treating OAS associated with the kidney deficiency and collateral obstruction pattern. Materials and methods The chemical constituents of YSTLF were identified by UHPLC-Q-Orbitrap HRMS, and molecular docking was performed between the ten most abundant compounds and AMPK/mTOR. Rat OAS models were established by combined GTW, adrenaline, and ice-water immersion. Pharmacodynamic effects were evaluated through general status, reproductive organ weights, sperm quality, coagulation parameters, and serum sex hormones. Testicular histopathology, ultrastructure, and autolysosomes were examined by HE staining and TEM. Apoptosis was detected by TUNEL staining, and autophagy/apoptosis-related protein expression by IHC. Integrated metabolomics and proteomics with KEGG enrichment were conducted. In GTW-injured GC-1spg cells treated with Compound C or rapamycin, CCK-8 assay assessed viability, flow cytometry evaluated apoptosis, immunofluorescence examined LC3B/cleaved caspase-3 expression and colocalization, and Western blotting/RT-qPCR validated AMPK/mTOR pathway key molecules. Results Among 307 identified compounds (mostly flavonoids), YSTLF improved general status, organ weights, and sperm quality in model rats. The ten most abundant compounds showed binding energies < −7.0 kcal/mol for AMPK/mTOR. Sperm concentration and motility increased dose-dependently. PT and TT were prolonged, FIB decreased, and FSH, LH, T, PRL, and Inh-B were restored. H&E, TEM, and TUNEL revealed alleviated testicular pathology, improved ultrastructure, reduced autolysosomes, and decreased apoptosis. IHC showed downregulated Beclin1 and Bax, and upregulated p62 and Bcl-2. Multi-omics revealed co-enrichment of differential proteins/metabolites in autophagy and mTOR pathways. Western blot/RT-qPCR validated downregulated p-AMPK/AMPK, AMPK mRNA, LC3II, Beclin1, Bax, cleaved caspase-3, and cleaved caspase-3/caspase-3 ratio, alongside upregulated p-mTOR/mTOR, mTOR mRNA, p62, and Bcl-2. In vitro , GTW reduced viability concentration-/time-dependently (stable model: 10%/24 h); YSTLF reversed this (optimal: 15%/24 h), restored viability, reduced apoptosis, and decreased LC3B/cleaved caspase-3 fluorescence/colocalization, while downregulating p-AMPK, LC3II, Bax and upregulating p-mTOR, p62, Bcl-2. Compound C alone mimicked YSTLF's effects without additivity, whereas rapamycin aggravated GTW-induced viability loss, apoptosis, and autophagy/apoptosis co-activation. Conclusion YSTLF improved spermatogenic function in rats with OAS (kidney deficiency and collateral obstruction pattern). Its mechanism of action involves regulation of the AMPK/mTOR signaling pathway and restoration of the balance between autophagy and apoptosis.
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JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
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2026
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IF 6.7
Wang Haijing,Gao Jie,Bai Xuefei,Liu Xiaofeng,Qu Shurong,Gao Yugang,Zhao Yan,Teng Hongbo
Age-related hearing loss (ARHL) is a pervasive sensorineural
deficit
lacking effective pharmacological interventions. Although Eleutherococcus senticosus fruit extracts exhibit
otoprotective potential, their precise bioactive constituents and
underlying molecular mechanisms remain elusive. Using network pharmacology
and transcriptomic analysis as hypothesis-generating tools, followed
by experimental validation, this study identifies chiisanoside (CSS)
as a key bioactive compound mitigating d -galactose-induced
cellular senescence and auditory impairment, with an optimal effective
dose of 25 μM in vitro (HEI-OC1 cells) and 50 mg/kg/day in vivo
(oral gavage in C57BL/6 mice). Mechanistically, the in vitro and in
vivo models demonstrate that CSS suppresses age-related auditory decline
primarily by targeting the SESN2/AMPK signaling axis. Specifically,
CSS upregulates SESN2 to activate AMPK, which not only enhances autophagy
via the mTOR/ULK1 pathway but also concurrently inhibits the HIF-1α/TFRC/FTH1
cascade. These findings provide mechanistic insights supporting the
potential of CSS as a therapeutic candidate in ARHL.
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BIOLOGICAL & PHARMACEUTICAL BULLETIN
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2015
·Vol. 38
·期 8
·1142-1149
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IF 1.828
Kexin Wang,Yu Sun,Peng Lin,Jun Song,Ruxing Zhao,Wenjuan Li,Xinguo Hou,Chuan Wang,Lingshu Wang,Ping Zhu,Li Chen
β-Cell insufficiency plays an important role in the development of diabetes. Environmental factors, including lifestyle, play a critical role in β-cell dysfunction. Modern lifestyles affect the inherent circadian clock in central and peripheral organs. Recent studies have demonstrated that the normal intrinsic circadian clock in islets was essential for the viability of β cells and their insulin secretory function. Overall, however, the data are inconclusive. Our study demonstrated that the disrupted circadian rhythm of islets in streptozotocin induced type1 diabetic mice may be associated with impaired β-cell function and glucose intolerance. Liraglutide, a glucagon-like peptide-1 (GLP-1) analogue, could partially restore the normal circadian rhythm and activate the 5′ AMP-activated protein kinase (AMPK) signaling pathway. Our study provided evidence demonstrating that Liraglutide might restore β-cell function and protect against the development of diabetes in a mouse model by attenuating the disruption of the intrinsic circadian rhythm in islets and by activating AMPK signaling.
研究领域:
内分泌学
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糖尿病
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药理学
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分子生物学
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DRUG AND CHEMICAL TOXICOLOGY
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2026
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IF 1.9
Wenxin Wang,Shuhua Xi,Yue Wang
N-nitrosodimethylamine (NDMA), as a disinfection by-product of drinking water, has been detected in various water. Epidemiological investigations have found that exposure to NDMA can exacerbate the development of diseases related to insulin resistance. In this study, male C57BL/6 mice were exposed to 0.5 and 12.5 mg/L NDMA by drinking water for 12 weeks. The mice in 12.5 mg/L NDMA group appeared fasting blood glucose elevation, and glucose tolerance and insulin sensitivity decreased. NDMA exposure enhanced hepatic gluconeogenesis and suppressed glycolysis of mice, but not affecting glycogen synthesis. In addition, NDMA exposure inhibited the phosphorylation of AMPK and FoxO1 as well as GLUT2 protein expression, and increased PGC-1α protein levels. GLUT2 protein decreasing could reduce glucose uptake of hepatocyte and enhance blood glucose concentration. Dephosphorylated FoxO1 might translocate to the nucleus, binding promoters of gluconeogenesis key enzymes PEPCK and G6Pase to upregulate their expression and promote gluconeogenesis. PGC-1α could also stimulate the expression of PEPCK and G6Pase. Furthermore, human normal liver cells (MIHA) were treated with NDMA for 24 hours. AMPK as a central energy sensor, regulates hepatic glucose production, uptake, and the process of glycolmetabolism. Therefore, AMPK agonist AICAR was used to explore the mechanism of NDMA causing hyperglycemia. AICAR reversed p-FoxO1, PGC-1α, GLUT2, PEPCK and G6Pase proteins expression and improved the glycolysis and glucose uptake capacity in NDMA treated MIHA cells. In conclusion, NDMA in drinking water led to fasting blood glucose enhancing, impairment of glucose tolerance and insulin sensitivity, increasing hepatic gluconeogenesis via AMPK signaling.
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ENVIRONMENTAL TOXICOLOGY
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2023
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IF 4.5
Weipu Mao,Lei Zhang,Yiduo Wang,Si Sun,Jianping Wu,Jie Sun,Xiangyu Zou,Ming Chen,Guangyuan Zhang
Cisplatin nephrotoxicity is an etiological factor for acute kidney injury (AKI). MicroRNA (miRNA) expression is dysregulated in cisplatin-induced AKI (cAKI) although the underlying mechanisms are unclear. A cAKI model was established by intraperitoneally injecting cisplatin, and key miRNAs were screened using high-throughput miRNA sequencing. The functions of key miRNAs were determined using the cell viability, live/dead, reactive oxygen species (ROS), and 5-ethynyl-2′-deoxyuridine (EdU) proliferation assays. Additionally, the macrophage membrane was wrapped around a metal–organic framework (MOF) loaded with miRNA agomir to develop a novel composite material, macrophage/MOF/miRNA agomir nanoparticles (MMA NPs). High-throughput miRNA sequencing revealed that miR-30e-5p is a key miRNA that is downregulated in cAKI. The results of in vitro experiments demonstrated that miR-30e-5p overexpression partially suppressed the cisplatin-induced or lipopolysaccharide (LPS)-induced downregulation of cell viability, proliferation, upregulation of ROS production, and cell death. Meanwhile, the results of in vivo and in vitro experiments demonstrated that MMA NPs alleviated cAKI by exerting anti-inflammatory effects. Mechanistically, cisplatin downregulates the expression of miR-30e-5p, and the downregulated miR-30e-5p can target Galnt3 to activate the adenosine 5‘-monophosphate activated protein kinase (AMPK) signaling pathway, which promotes the progression of AKI. Our study found that miR-30e-5p is a key downregulated miRNA in cAKI. The downregulated miR-30e-5p promotes AKI progression by targeting Galnt3 to activate the AMPK signaling pathway. The newly developed MMA NPs were found to have protective effects on cAKI, suggesting a potential novel strategy for preventing cAKI.
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Drug Design Development and Therapy
·
2023
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IF 4.8
Ning Zhang,Tong Liu,Jianan Wang,Yingying Xiao,Ying Zhang,Jun Dai,Zhihong Ma,Donglai Ma
Background Metabolic associated fatty liver disease (MAFLD) is a chronic disease characterized by excessive lipid deposition in the liver without alcohol or other clear liver-damaging factors. AMP-activated protein kinase (AMPK)/silencing information regulator (SIRT)1 signaling pathway plays an important role in MAFLD development. Si-Ni-San (SNS), a traditional Chinese medicine, has shown reducing hepatic lipid deposition in MAFLD rats, however, the underlying mechanisms of SNS are barely understood.Purpose The aim of this research was to investigate the mechanisms of SNS in reducing hepatic lipid deposition in MAFLD rats by regulating AMPK/SIRT1 signaling pathways.Methods The components of SNS were determined by high performance liquid chromatography with mass spectrometry (HPLC-MS) analysis. MAFLD rats were induced by high-fat and high-cholesterol diet (HFHCD), and treated by SNS. SNS-containing serum and Compound C (AMPK inhibitor) were used to treat palmitic acid (PA)-induced HepG2 cells. To elucidate the potential mechanism, lipid synthesis-related proteins (SREBP-1c and FAS), fatty acid oxidation (PPARα and CPT-1), and AMPK/SIRT1 signaling pathway (p-AMPK and SIRT1) were assessed by Western blot.Results SNS improved serum lipid levels, liver function and reduced hepatic lipid deposition in MAFLD rats. SNS-containing serum reduced lipid deposition in PA-induced HepG2 cells. SNS could up-regulate protein expressions of PPARα, CPT-1, p-AMPK and SIRT1, and down-regulate protein expressions of SREBP-1c and FAS. Similar effects of SNS-containing serum were observed in PA-induced HepG2 cells. Meanwhile, Compound C weakened the therapeutic effects of SNS-containing serum on lipid deposition.Conclusion SNS could reduce hepatic lipid deposition by inhibiting lipid synthesis and promoting fatty acid oxidation, which might be related with activating the AMPK/SIRT1 signaling pathway. This study could provide a theoretical basis for the clinical use of SNS to treat MAFLD.
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EUROPEAN JOURNAL OF PHARMACOLOGY
·
2023
·
IF 5
Ling Yang,Linzi Li,Qian Lu,Lingfeng Li,Chun Xie,Fakun Jiang,Hongbing Li,Ai Zhao,Qian Wang,Wenyong Xiong
As a global epidemic disease, obesity causes dysfunction of glucose and lipid metabolism leading to persistently high morbidity and mortality. Given the difficulty to achieve and maintain weight loss through controlling diet and physical exercise, pharmacotherapy is considered an effective treatment for obesity. This investigation revealed that alisol B, a triterpene monomer isolated from the classical Chinese medicine Alisma orientale (Sam.) Juzep, functioned in suppressing adipogenesis and reducing the mass of subcutaneous adipose tissue, resulting in the reduction of weight gain, and improvements of hyperglycemia, hyperlipidemia, and insulin resistance in HFD-induced obese mice. In consistent to the results, alisol B also significantly inhibited adipocyte differentiation and maturation in vitro . Furthermore, our data revealed that the effects of alisol B on adipogenesis were mediated by LKB1-AMPK signaling pathway. In total, alisol B could be a potential lead compound which contributes to the improvement of obesity-related metabolic disorders.
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CHEMICO-BIOLOGICAL INTERACTIONS
·
2023
·
IF 5.1
Hongzhou Lin,Huihui Chen,Rengcheng Qian,Guoqi Tang,Yinjuan Ding,Yalan Jiang,Congde Chen,Dexuan Wang,Maoping Chu,Xiaoling Guo
Background Nephrotic syndrome (NS) is a chronic kidney disease mainly caused by impaired podocytes, ultimately resulting in massive proteinuria or even end-stage renal disease (ESRD). Methods The objective of this study was to explore the potential pathogenesis of NS caused by podocyte injury, and further explore the underlying mechanism through data mining , bioinformatics analysis, and experimental verification. The integrated analyses including Seurat, CellChat, gene ontology (GO), and molecular docking were performed based on the single-cell RNA-seq data (scRNA-seq). The adriamycin (ADR)-induced podocyte injury model in vitro was established to conduct the experimental verification for bioinformatics analysis results through western blot and real-time quantitative PCR (RT-qPCR). Results The results of bioinformatics analysis revealed that the bone morphogenetic protein (BMP) signaling pathway was involved in the podocyte-to-podocyte communication, which plays a crucial role in podocyte injury. The expression of BMP7 was significantly increased in ADR-induced podocytes through activating the Adenosine-monophosphate activated-protein kinase/Mammalian target of rapamycin (AMPK/mTOR) mediated autophagy pathway, and these findings were confirmed by in vitro experiments. Conclusion This study first demonstrated that BMP7 participated in ADR-induced podocyte injury. The BMP7/AMPK/mTOR mediated autophagy pathway may play a crucial role in podocyte injury, which may be the potential therapeutic target for NS patients.
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