Food Chemistry-X
·
2024
·
IF 6.5
Kangkang Liu,Junxiang Li,Wenting Hao,Jingjing Li,Israr Khan,Yibo Liang,Haijuan Wang,Xiaofeng Li,Chunjiang Zhang
Microbial fermentation is an effective method to enhance the bioavailability of herbs. This study utilized Lactiplantibacillus plantarum LZU-J-Q21 to ferment Cistanche deserticola and evaluated its metabolic properties and biological activity. Results showed that the contents of total acid and flavone, and the clearance rates of DPPH, ABTS and OH − in fermented Cistanche deserticola (FCD) were increased by 142.74 %, 56.45 %, 58.1 %, 62.3 %，51.2 %, compared with non-fermented Cistanche deserticola (NFCD). The metabolic profile of FCD had remarkable changes, especially elevated glucose and adenosine (97.31 % and 59.18 %). Further, FCD increased the weight-bearing swimming time of mice by 88.57 %, reduced fatigue markers BUN, BLA, and MDA (18.47 %, 12.92 %, and 15.16 %), and enhanced liver/muscle glycogen and SOD (28.99 %, 28.57 %, and 14.47 %). The investigation into its anti-fatigue mechanism suggested that FCD enhanced GS protein expression by activating PI3K/AKT/GSK3β signaling. These findings suggest that FCD enhances anti-fatigue effects by modifying its metabolic properties and biological activity.
研究领域:
微生物学
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药理学
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功能食品科学
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DOI
PubMed
高影响因子
Frontiers in Bioscience-Landmark
·
2025
·Vol. 30
·期 6
·36615
·
IF 3.1
Shanli Wu,Gun Yang,Xiaosha Wen,Yi Lin,Shenglong Wang,Jing Wang,Quan Liu,Dixian Luo
Background:Aldo-keto reductase 1B10 (AKR1B10) is expressed in various malignant tissues. Several studies have highlighted the essential function of AKR1B10 in lipid metabolism and in the detoxification of lipid peroxides. The aim of this research was to explore the role of AKR1B10 in the susceptibility of MDA-MB-231 cells to ferroptosis. These cells serve as a model for triple-negative breast cancer (TNBC).Methods:Lentiviral transfection was used to establish stable cell lines with high or low expression of AKR1B10. Our model of ferroptosis used the ferroptosis activator RSL3, and the specific ferroptosis inhibitor ferrostatin-1 (Fer-1) to rescue cell death. Stable cell lines were treated with the specific inhibitor OSU-T315 directed against phosphorylation of Ser473 in protein kinase B (AKT) and Ser9 in glycogen synthase kinase 3 beta (GSK3β), either alone or in combination with RSL3. A fatty acid stress model was established using palmitic acid (PA) or arachidonic acid (AA), either in the presence or absence of serum starvation and with or without co-treatment with RSL3. Cell viability was evaluated with the cell counting kit-8 (CCK8) assay and lipid peroxidation levels by flow cytometry after staining with C11 BODIPY 581/591. Exploration of the underlying mechanisms was conducted through RNA sequencing and bioinformatics analysis. Western blotting was performed to evaluate protein levels, and quantitative real-time polymerase chain reaction (qPCR) was used to evaluate transcript levels.Results:Western blot and qPCR analyses validated the successful establishment of stable MDA-MB-231 cell lines with and without AKR1B10 overexpression. Cell viability and lipid reactive oxygen species (ROS) assays showed that AKR1B10 suppressed ferroptosis in the RSL3-induced cell death model. Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Set Enrichment Analysis (GSEA) analyses indicated the phosphatidylinositol 3-kinase (PI3K)-AKT pathway was likely to play a role in the underlying mechanisms. AKR1B10 increased the expression of glutathione peroxidase 4 (GPX4), thus potentially implicating the AKT/GSK3β/nuclear factor erythroid 2-related factor 2 (NRF2)/GPX4 pathway in the mechanism. These changes in protein levels were also observed by Western blot analysis after 6 h of RSL3 treatment. Under the influence of RSL3, the transcript levels of NRF2-related genes including GPX4, ferritin heavy chain 1 (FTH1), heme oxygenase 1 (HO-1), and NAD(P)H quinone dehydrogenase 1 (NQO-1) were significantly elevated in the AKR1B10 overexpression cell line, whereas that of prostaglandin-endoperoxide synthase 2 (PTGS2) was significantly reduced. Similar changes were observed after treatment with OSU-T315. AKR1B10 was found to suppress the sensitivity to ferroptosis induced by treatment with OSU-T315, PA, or AA. These phenomena were rescued by the ferroptosis inhibitor Fer-1.Conclusions:AKR1B10 appears to be an important mechanism protecting MDA-MB-231 cells from ferroptosis, possibly through the AKT Ser473/GSK3β Ser9/NRF2/GPX4 pathway. AKR1B10 may be a key factor underlying the therapeutic effect of RSL3 under different exogenous fatty acid microenvironments.
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PubMed
高影响因子
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
·
2025
·Vol. 29
·期 16
·e70800
·
IF 4.2
Xiangling Yi,Liming Wang,Xiao-yue Wang,Yu Fang,Jiarui Liu,Kehong Chen,Ya-ni He,Jia Chen
Renal recovery following acute kidney injury (AKI) is a key determinant of long-term prognosis, while non-recovery significantly increases the risk of chronic kidney disease and progression to end-stage renal disease. Although cell cycle arrest is implicated in renal non-recovery and fibrosis, its association with decoy receptor 2 (DcR2) remains unclear. In this study, we evaluated 139 patients with biopsy-confirmed AKI, defining renal non-recovery as a ≥ 50% increase in baseline serum creatinine (Cr) or the initiation of dialysis. Patients were divided into recovery ( n = 79) and non-recovery ( n = 60) groups. Urinary DcR2/creatinine (uDcR2/Cr) levels were significantly higher in non-recovery cases, with an area under the curve of 0.733 and a diagnostic cut-off of 378 ng/gCr. Elevated uDcR2/Cr predicted poor renal survival and was independently correlated with non-recovery. In mouse models of ischemia–reperfusion-induced AKI, increased urinary and tubular DcR2 levels were also associated with impaired recovery. Proteomics analysis revealed GSK3b enrichment in cell cycle pathways. Functional studies showed that DcR2 mediated cell cycle arrest through GSK3b/cyclin D1 signalling. In conclusion, DcR2 functions as a biomarker of cell cycle arrest and renal recovery, offering both diagnostic and mechanistic insights, and may serve as a potential therapeutic target in AKI.
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PubMed
高影响因子
CHEMISTRY & BIODIVERSITY
·
2026
·Vol. 23
·期 9
·e71695
·
IF 2.9
Li Yang,Junhui He,Dongmei Li,Yi Li,Qibiao Su,Hongning Liang,Jiantong Yuan,Kedao lai,Guining Wei
Water extract of Semiliquidambar cathayensis (WESC) exhibits favorable therapeutic effects against depression, yet its pharmacodynamic material basis and mechanism of action remain unclear. In this study, ultra‐high‐performance liquid chromatography coupled with quadrupole time‐of‐flight mass spectrometry (UPLC‐Q‐TOF‐MS) was employed to analyze the chemical constituents of WESC. Network pharmacology and molecular docking were further applied to screen the antidepressant mechanism basis and potential targets of WESC. Lipopolysaccharide (LPS)‐induced mouse and PC12 cell models were established as in vivo depressive animal model and in vitro cellular injury model, respectively. Combined with pathological examination and molecular biological techniques, the antidepressant mechanism of WESC was systematically investigated. Results showed that a total of 14 chemical components were identified from WESC. Network pharmacology and molecular docking analyses indicated that GSK3β was one of the key targets, and the active components in WESC possessed strong binding affinities with GSK3β, Axin1, and NF‐κB. Pathological studies demonstrated that WESC significantly alleviated inflammatory infiltration in the mouse prefrontal cortex and hippocampal neuronal damage. Molecular biological analyses revealed that WESC markedly downregulated the expression of proteins related to the GSK3β/NF‐κB signaling pathway in LPS‐stimulated mice and PC12 cells, thereby attenuating neuroinflammation, promoting neural plasticity, and exerting antidepressant effects. Ultra‐high‐performance liquid chromatography coupled with quadrupole time‐of‐flight mass spectrometry (UPLC‐Q‐TOF‐MS) was used to characterize the chemical constituents of the water extract of Semiliquidambar cathayensis (WESC). Network pharmacology and molecular docking were applied to screen core active components and potential targets. An LPS‐induced mouse depression model and PC12 cell injury model were established. Combined with HE staining, Western blot, and qRT‐PCR, in vivo and in vitro experiments were carried out to explore the antidepressant mechanism of WESC via regulating signaling pathways and alleviating neuroinflammation.
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PubMed
高影响因子
LIFE SCIENCES
·
2021
·
IF 5.037
Yue Xiong,Yan Chen,Xinping Huang,Zhen Yang,Jiaye Zhang,Xiaorui Yu,Ji Fang,Jiawang Tao,Kai You,Ziqi Cheng,Shenglin Tan,Yingying Xu,Fang Yuan,Ying Liu,Yuanqi Zhuang,Fan Yang,Yinxiong Li
Aim This study aimed to reveal the effects of icaritin (ICT) on lipotoxicity induced by palmitate (PA) in hepatic cells and steatosis in high-fat diet (HFD)-fed mice as well as exploring the potential mechanisms. Main methods Primary mouse hepatocytes and human hepatoma Huh7 cells were used to evaluate ICT effect in vitro. HFD-fed mice were used to evaluate the ICT effect in vivo. Results In vitro study indicated that ICT significantly rescued PA-induced steatosis, mainly through a combination of robust increased mitochondrial respiration, fatty acid oxidation and mildly decreased synthesis of fatty acid. An HFD-fed mouse model with 8 weeks HFD-fed showed metabolic disorders, while ICT application significantly reduced the weight, serum glucose levels, insulin resistance, hepatic steatosis level and adipose contents. In consistent with the observations in cell lines, ICT rescued the HFD-impaired functions and contents of key factors related to fatty acid β-oxidation through elevated expression of peroxisome proliferator-activated receptor α (PPARα). Meanwhile, it also reversed the decreased phosphoryl levels of AKT and glucogen synthase kinase 3 (GSK3β), leading to the improvement of insulin resistance. Significance ICT administration had a therapeutic effect on PA- or HFD-induced hepatic steatosis and metabolic disorders. It may provide a novel strategy to construct preventive and therapeutic means for hepatic steatosis.
研究领域:
药理学
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代谢学
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肝病学
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DOI
PubMed
高影响因子
MOLECULAR NUTRITION & FOOD RESEARCH
·
2024
·
IF 4.5
Qiuming Liu,Qingyu Ma,Jiao Li,Liping Sun,Yongliang Zhuang
Scope Type 2 diabetes mellitus (T2DM) is a metabolic disease with a major global public health effect. Rambutan peel polyphenols (RPPs) have been reported to exert hypoglycemic activity. However, few studies have been explored from the viewpoint of gut microbiota and its metabolites. Methods and results RPPs are administered by gavage to a mice model of T2DM established by using a high-fat diet combined with streptozotocin. It finds that RPPs treatment alleviates hyperglycemia symptoms by improving glucolipid metabolism and liver function. Immunohistochemistry indicates that the antihyperglycemic effect of RPPs is regulated by the IRS-1/PI3K/AKT/GSK3β signaling pathway. RPPs treatment remodels the structure of gut microbiota ( Odoribacter , Lachnospiraceae_NK4A136_group , Lactobacillus , Turicibacter , Erysipelatoclostridium , and Tuzzerella ) and enriches the metabolites (RPPs-derived urolithins, short-chain fatty acids, dehydrocholic acid, (+)-catechin, dihydroberberine, pterostilbene, and artesunate) associated with diabetes regulation in T2DM mice. The effects of RPPs in ameliorating glycolipid metabolism disorders are correlated with differential gut microbiota and metabolites. Conclusion The gut microbiota and its metabolites are key targets for the hypoglycemic effects of RPPs.
研究领域:
药理学
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营养学
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微生物学
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内分泌学
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分子生物学
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PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2025
·
IF 8.2
Junpeng Liu,Wei Liu,Yefan Zhang,Junwen Ouyang,Boxiao Zhao,Changyu Wu,Boda Li,Jiaxuan Jiang,Kai Hu
Pterygium is a common ocular surface lesion, and postoperative recurrence remains a major challenge due to insufficient therapeutic strategies targeting fibroblast proliferation and inflammation. Fibrinogen hydrogel (Fibrin glue, FG), a bioadhesive hydrogel, is widely used in pterygium surgery to secure conjunctival autografts. However, its low adhesion often leads to graft detachment, hindering effective repair. To overcome this limitation, we developed an injectable high-adhesion fibrin-silk glue (FG-GP-SF-Cur) by genipin-cross-linking silk fibroin (SF) into FG, enabling sustained release of the anti-inflammatory/antiproliferative drug curcumin (Cur). The material exhibited enhanced shear/tensile adhesion and prolonged Cur release (>10 days) in vitro, supported by FTIR and SEM analyses of its cross-linked structure. In primary pterygium fibroblasts, FG-GP-SF-Cur suppressed migration and proliferation by downregulating α-SMA, FN1, and COL3A1 while reducing VEGF/MMP2 via GSK3β/β-catenin pathway inhibition. Flow cytometry revealed its ability to promote anti-inflammatory M2 macrophage polarization, elevating IL-4/IL-10 and suppressing IL-1β/TNFα. In a corneal alkali burn model, FG-GP-SF-Cur effectively inhibited neovascularization and sustained M2 polarization, correlating with reduced inflammation and fibrosis. This study demonstrates FG-GP-SF-Cur as a dual-functional, high-adhesion biomaterial combining mechanical stability with controlled anti-inflammatory and antiproliferative drug delivery, offering a promising strategy to minimize pterygium recurrence and enhance surgical outcomes.
研究领域:
生物材料
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眼科学
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组织工程
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药物递送
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炎症研究
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细胞生物学
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DOI
PubMed
高影响因子
Pharmaceuticals
·
2025
·Vol. 18
·期 6
·817
·
IF 4.8
Luqi Qin,Yixia Zhou,Bei Fan,Jiahuan Zheng,Rao Diao,Jiameng Liu,Fengzhong Wang
Background/Objectives: Endophytes can produce bioactive metabolites similar to their host plants. CM-YJ44 ( Pseudomonas protegens CHA0, 99.24% similarity), an endophyte from Dendrobium officinale , has not yet validated hypoglycemic potential. This study aimed to evaluate its anti-insulin resistance (IR) activity and metabolite profile. Methods: The fermentation broth of CM-YJ44 was separated into three fractions (CM-YJ44-1, -2, and -3) using semi-preparative high-performance liquid chromatography (pre-HPLC). An IR HepG2 cell model was constructed to evaluate their glucose uptake capacity. CM-YJ44-3 was further tested for oxidative stress, inflammatory, and insulin signaling pathway activation. Metabolites in CM-YJ44-3 were preliminarily identified using the Q Exactive Focus LC-MS system (QE), and the dendrobine content was quantified by ultra-performance liquid chromatography–tandem mass spectrometry (UPLC-MS/MS). Molecular docking was performed to predict the binding affinities between dendrobine and target proteins. Results: Among the three fractions, CM-YJ44-3 significantly reduced nitric oxide (NO) and reactive oxygen species (ROS) levels in IR cells, enhanced glycogen synthesis, upregulated the activities of pyruvate kinase (PK) and hexokinase (HK), and suppressed the expression of inflammatory factors. Its mechanism of action was mainly through activation of the IRS1/PI3K/Akt/GSK3β/GLUT4 signaling pathway. QE analysis preliminarily identified 24 metabolites in CM-YJ44-3. Quantitative analysis by UPLC-MS/MS showed that the dendrobine content was 78.73 ± 4.29 ng/mL. Molecular docking results indicated that dendrobine exhibited binding energies below −5 kcal/mol with multiple target proteins involved in this signaling pathway, suggesting it may be a key bioactive component responsible for the anti-IR effect. Conclusions: This study provides the first evidence of hypoglycemic bioactive metabolite production by strain CM-YJ44, indicating its potential as a novel microbial candidate for alleviating IR.
研究领域:
微生物学
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药理学
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植物学
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生物化学
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DOI
PubMed
高影响因子
Neuroscience Bulletin
·
2025
·
IF 5.8
He Junqiu,Sun Shan,Wang Hongfeng,Ying Zheng,Tam Kin Yip
Alzheimer’s disease (AD) poses one of the most urgent medical challenges in the 21st century as it affects millions of people. Unfortunately, the etiopathogenesis of AD is not yet fully understood and the current pharmacotherapy options are somewhat limited. Here, we report a novel inhibitor, Compound 44, for targeting cholinesterases, amyloid-β (Aβ) aggregation, and glycogen synthase kinase 3β (GSK-3β) simultaneously with the aim of achieving symptomatic relief and disease modification in AD therapy. We found that Compound 44 had good inhibitory effects on all intended targets with IC 50 s of submicromolar or better, significant neuroprotective effects in cell models, and beneficial improvement of cognitive deficits in the triple transgenic AD (3 × Tg AD) mouse model. Moreover, we showed that Compound 44 acts as an autophagy regulator by inducing nuclear translocation of transcription factor EB through GSK-3β inhibition, enhancing the biogenesis of lysosomes and elevating autophagic flux, thus ameliorating the amyloid burden and tauopathy, as well as mitigating the disease phenotype. Our results suggest that triple-target inhibition via Compound 44 could be a promising strategy that may lead to the development of effective therapeutic approaches for AD.
研究领域:
神经科学
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药理学
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分子生物学
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DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2026
·
IF 5.6
Zhidan Shi,Xinyi Cheng,Chu Zhang,Jiayi Hu,Xinqi He,Shuting Chen,Hao Wu,Meng Tian,Chuang Yan,Ling He
Alzheimer's disease (AD) is a neurodegenerative disorder with significant sex-related differences, exhibiting a higher incidence rate in elderly women. Tau pathology has been implicated in sex-associated differences in AD susceptibility and disease progression, contributing to differential pathological burden between males and females. Vorinostat (SAHA), a histone deacetylase inhibitor (HDACi) used in cancer treatment, has shown potential therapeutic effects in various neurological and psychiatric disorders; however, the mechanisms underlying its regulation of tau-associated pathology remain poorly understood, with limited evidence regarding its effects in tau-related neurodegenerative conditions. In this study, we investigated the effects of SAHA treatment on an AAV-P301L-Tau-induced tauopathy model. In vivo, we observed that SAHA administration significantly improved p-Tau levels in the hippocampus and cortex of mice, reduced microglial activation and neuronal damage, and alleviated tauopathy-associated cognitive impairments. Our findings revealed sex-associated differences in Tau-related pathological alterations, with female mice exhibiting greater pathological changes and differential responses to SAHA treatment in several molecular and histological indicators. Further combined in vivo and in vitro experiments revealed that SAHA was associated with modulation of the PI3K/AKT/GSK3β signaling pathway, suppression of NF-κB activation, and attenuation of neuroinflammatory responses, including reductions in experimentally measured inflammatory markers such as interleukin-6 (IL-6) and tumour necrosis factor alpha (TNF-α). These molecular alterations may represent important regulatory components contributing to the neuroprotective effects of SAHA, rather than acting as the sole determinants of its therapeutic efficacy. In summary, these results indicate that SAHA can improve Tau-associated pathological alterations in an AAV-P301L-Tau-induced tauopathy model. The potential mechanisms may involve coordinated regulation of multiple pathological processes, including modulation of Tau phosphorylation, neuroinflammatory responses, and aging-associated signaling pathways. The observed sex-dependent responses to SAHA provide additional insights into the potential influence of biological sex on HDACi-based therapeutic strategies, although the molecular mechanisms underlying these differences require further investigation.
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高影响因子
PHYTOTHERAPY RESEARCH
·
2019
·Vol. 34
·期 4
·817-824
·
IF 3.766
Mingming Zhu,Xi Yu,Zongmei Zheng,Jiaming Huang,Xuepan Yang,Hongfei Shi
Cancer stem cells (CSCs) are considered as the origin and driving cells of cancer, and play a key role in the progress of cancer. Studies have shown that capsaicin exerted inhibitory effect on prostate cancer cells, however, the effects of capsaicin on prostate CSCs remain undefined. In the present study, we showed that capsaicin could downregulate prostate CSCs markers and inhibit the growth of PC-3 and DU145 prostate cancer stem cells. Further, we found capsaicin suppressed the expression of Wnt-2, p-GSK3β and β-catenin, along with downregulation of Wnt/β-catenin pathway target genes c-myc and cyclinD1. Using LiCl, a activator of Wnt/β-catenin pathway, we found activation of Wnt/β-catenin pathway could ameliorate the downregulation of prostate CSCs markers and the growth inhibition induced by capsaicin in prostate cancer stem cells. Those data suggested that the inhibition effect of capsaicin on prostate cancer stem cells and the anti-cancer effect of capsaicin on prostate cancer stem cell may be mediated by Wnt/β-catenin pathway. Findings from this study reveals for the first time the potential role and mechanisms of capsaicin on prostate cancer stem cells.
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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PubMed
高影响因子
Frontiers in Pharmacology
·
2018
·
IF 3.831
Huang Xianfeng,Wang Jing,Chen Xiao,Liu Pan,Wang Shujin,Song Fangchen,Zhang Zaijun,Zhu Feiqi,Huang Xinfeng,Liu Jianjun,Song Guoqiang,Spencer Peter S.,Yang Xifei
Alzheimer’s disease (AD) is a progressive neurodegenerative disorder that has proved refractory to drug treatment. Given evidence of neuroprotection in animal models of ischemic stroke, we assessed the prenylflavonoid xanthohumol from the Common Hop (Humulus lupulus L.) for therapeutic potential in murine neuroblastoma N2a cells stably expressing human Swedish mutant amyloid precursor protein (N2a/APP), a well-characterized cellular model of AD. The ELISA and Western-blot analysis revealed that xanthohumol (Xn) inhibited Aβ accumulation and APP processing, and that Xn ameliorated tau hyperphosphorylation via PP2A, GSK3β pathways in N2a/APP cells. The amelioration of tau hyperphosphorylation by Xn was also validated on HEK293/Tau cells, another cell line with tau hyperphosphorylation. Proteomic analysis (2D-DIGE-coupled MS) revealed a total of 30 differentially expressed lysate proteins in N2a/APP vs. wild-type (WT) N2a cells (N2a/WT), and a total of 21 differentially expressed proteins in lysates of N2a/APP cells in the presence or absence of Xn. Generally, these 51 differential proteins could be classified into seven main categories according to their functions, including: endoplasmic reticulum (ER) stress-associated proteins; oxidative stress-associated proteins; proteasome-associated proteins; ATPase and metabolism-associated proteins; cytoskeleton-associated proteins; molecular chaperones-associated proteins, and others. We used Western-blot analysis to validate Xn-associated changes of some key proteins in several biological/pathogenic processes. Taken together, we show that Xn reduces AD-related changes in stably transfected N2a/APP cells. The underlying mechanisms involve modulation of multiple pathogenic pathways, including those involved in ER stress, oxidative stress, proteasome molecular systems, and the neuronal cytoskeleton. These results suggest Xn may have potential for the treatment of AD and/or neuropathologically related neurodegenerative diseases.
研究领域:
神经科学
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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
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