Food Bioscience
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2025
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IF 5.9
Jingwen Yu,Shilian Zheng,Abdul Mueed,Zeyuan Deng,Hongyan Li
The objectives of this study were to evaluate the antioxidant interactions and underlying mechanisms of the combinations of purple carrot anthocyanins extracts (PCAE) and red papaya carotenoids extracts (RPCE) using tert-butyl hydrogen peroxide (TBHP)-induced human umbilical vein endothelial cells (HUVEC). The results revealed that cyanidin-3-xylosyl (feruloyl glucosyl) galactoside (731.65±2.66 μg/mg) and lycopene (787.50±5.73 μg/mg) were the dominant anthocyanins and carotenoids in purple carrot and papaya, respectively. Cellular antioxidant assays, including cellular antioxidant activity (CAA) and antioxidant enzymes expression, reactive oxygen species (ROS) and malondialdehyde (MDA) levels, showed that in the combinations which contained more hydrophilic PCAE, the combinations would tend to show synergistic effects. When RPCE were in the majority, the combinations would tend to show antagonistic effects. Reverse transcriptase-PCR and western blot analysis revealed the underlying mechanisms of synergistic/antagonistic antioxidant interactions were that they significantly inhibited intracellular ROS generation, exhibiting either synergistic/antagonistic effects on reducing mitochondrial ROS levels, restoring the mitochondrial membrane potential, and inhibiting the activity of the nicotinamide adenine dinucleotide phosphate oxidase 4. Meanwhile, they also reduced cellular ROS level via inhibition of the nuclear factor kappa-light-chain-enhancer of activated B (NF-κB) signaling pathway, to elevate the activities of antioxidant enzymes based on HUVEC cell model. The synergistic/antagonistic antioxidant effects of phytochemical combinations supported their potential as functional food ingredients for cardiovascular diseases prevention.
研究领域:
营养生物化学
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分子生物学
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食品科学与技术
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氧化应激与抗氧化
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心血管药理学
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细胞生物学
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DOI
高影响因子
Food Science & Nutrition
·
2025
·Vol. 13
·期 12
·e71310
·
IF 3.8
Fan Cao,Hua Wu,Zhen He,Mengxin Di,Bin Liu,Zhenwei Chen,Jieming Xie,Yonghong Zhang,Xinhua Ma
Melia azedarach L., also known as the chinaberry tree, has long been used in traditional medicine to treat inflammatory conditions. In this study, we preliminarily investigated the anti-inflammatory effect of 21 α -methylmelianol (MMN), a tirucallane-type triterpenoid isolated from M. azedarach , in lipopolysaccharide (LPS)-mediated RAW264.7 macrophages in vitro and in a dextran sodium sulfate (DSS)-stimulated ulcerative murine colitis model in vivo. MMN reduced LPS-stimulated nitric oxide production without inducing cytotoxicity. It significantly attenuated LPS-induced protein expression of reactive oxygen species and effectively suppressed the production of pro-inflammatory factors, including tumor necrosis factor-alpha (TNF- α ), interleukin (IL)-6, and IL-1 β . In addition, mechanistic investigations showed that MMN inhibited signal transduction and activator of STAT3 phosphorylation and activation of nuclear factor κ B (NF- κ B). In mice with DSS-induced colitis, MMN attenuated DSS-mediated pathological manifestations, including colon shortening, body weight loss, and histopathological alterations. Its in vivo effects were associated with the regulation of pro- and anti-inflammatory cytokine levels through suppression of the NF- κ B signaling cascade and downstream inflammatory pathways. Collectively, these findings provide compelling evidence of the anti-inflammatory properties of MMN and highlight its therapeutic potential for the management of inflammatory disorders.
研究领域:
药理学
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免疫学
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天然产物化学
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分子生物学
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炎症性疾病
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DOI
PubMed
高影响因子
Frontiers in Immunology
·
2025
·
IF 5.9
Jikai He,Jiaqi Jia,Wenhao Qu,Shuyu Zhang,Keyu Fan,Runze Lin,Wei Zhao,Yan Niu,Yanqiang Huang,Lizhou Jia
Objective To analyze differences in gut microbiota composition, metabolites, and metabolic pathways between healthy individuals and colorectal cancer (CRC) patients, and to investigate the inhibitory effects of N-methylserotonin (NMS) produced by Bacteroides ovatus (B.o) from orange fiber on CRC progression and its underlying mechanisms. Methods (1) Fecal samples from CRC patients (n=26) and healthy controls (n=20) were collected for metagenomic sequencing and untargeted metabolomics analysis; (2) The ability of B.o to produce NMS from orange fiber was validated in vitro ; (3) A CRC mouse model was established using azoxymethane (AOM)/dextran sulfate sodium (DSS) induction, followed by evaluation of body weight, rectal bleeding, colorectal length, tumor number, and intestinal barrier function; (4) Network pharmacology, molecular docking, and western blot analysis were combined to verify the mechanism of action; (5) 16S rRNA sequencing was performed to analyze gut microbiota changes. Results (1) CRC patients showed significantly increased metabolic pathways including glycolysis, methane metabolism, beneficial amino acid degradation, and linoleic acid degradation, along with significantly decreased B.o abundance and NMS levels, which were positively correlated; (2) NMS significantly inhibited CRC cell proliferation, migration, and invasion, while promoting apoptosis; (3) Combined treatment with B.o and orange fiber or NMS alone reduced tumorigenesis and improved intestinal barrier function; (4) Mechanistic studies revealed that these effects could be mediated through downregulation of 5-hydroxytryptamine receptor 1D (HTR1D) expression and inhibition of the cAMP/PKA/IκBα/NF-κB pathway; (5) The treatments optimized gut microbiota structure and metabolite composition. Conclusion B.o and its metabolite NMS possibly inhibit CRC progression by modulating the HTR1D-mediated cAMP/PKA/NF-κB signaling pathway, while improving gut microbiota structure, providing a novel therapeutic target for CRC prevention and treatment.
研究领域:
肿瘤学
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微生物组研究
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分子生物学
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代谢组学
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胃肠病学
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药理学
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产品关联
DOI
PubMed
高影响因子
ONCOLOGY REPORTS
·
2016
·Vol. 36
·期 1
·315-323
·
IF 2.486
Qiang Liu,Lei Dong,Hong Li,Jia Yuan,Yuping Peng,Shejiao Dai
Bone marrow (BM) suppression (also known as myelosuppression) is the most common and most severe side-effect of therarubicin (THP) and thereby limits the clinical application of this anticancer agent. Lentinan (LNT), a glucan extracted from dried shiitake mushrooms (Lentinula edodes), exhibits a variety of pharmacological activities. The objectives of the present study were to determine the effect of LNT on the myelosuppression of THP-treated mice and to examine the pharmacological mechanism of these effects. In vivo experiments indicated that non-cytotoxic levels of LNT strongly increased blood myeloperoxidase (MPO) activity; improved BM structural injuries; increased the numbers of leukocytes and neutrophils in the blood and BM; elevated the blood levels of granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF) and macrophage colony-stimulating factor (M-CSF); and reduced the self-healing period in THP-treated mice. In vitro experiments indicated that LNT increased the viability of BM-derived macrophages (BMDMs) in a time- and dose-dependent manner without toxic side-effects and markedly increased the release of G-CSF, GM-CSF and M-CSF by BMDMs. Further analyses revealed that LNT activated the NF-κB and MAPK signalling pathways and promoted the nuclear import of p65 and that BAY 11-7082 (a specific inhibitor of NF-κB) suppressed the release of G-CSF, GM-CSF and M-CSF. Furthermore, we found that U0126, SB203580 and SP600125 (specific inhibitors of ERK, p38 and JNK, respectively) markedly inhibited the IKK/IκB/NF-κB-dependent release of G-CSF, GM-CSF and M-CSF. In conclusion, LNT induces the production of G-CSF, GM-CSF and M-CSF by activating the MAPK/NF-κB signalling pathway in BM cells, thereby mitigating THP-induced myelosuppression.
研究领域:
肿瘤学
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药理学
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免疫学
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细胞生物学
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DOI
PubMed
高影响因子
FASEB JOURNAL
·
2025
·Vol. 39
·期 24
·e71339
·
IF 4.2
Weina Gao,Pingping Li,Kexin Liu,Yanfang Zheng,Xiaoli Zhang,Xiufang Li
Preeclampsia (PE) is a pregnancy complication that requires urgent attention, with early recognition and timely management being crucial to ensure the safety of both mother and child. Cryptotanshinone (CTS), a fat-soluble diterpenoid quinone compound derived from Salvia miltiorrhiza Bunge, exhibits various pharmacological activities, including anti-inflammatory, antioxidative stress, and immunomodulatory effects. This study investigates the preventive role of CTS in PE. In this research, an in vivo rat model of PE was established through intraperitoneal injection of N(ω)-nitro-L-arginine methyl esters (L-NAME). CTS was administered at dosages of 30 and 60 mg/kg/day to evaluate its impact on symptoms resembling those of PE. The results indicated that CTS ameliorates the maternal and fetal outcomes associated with PE and mitigates placental injury. Treatment with CTS restored inflammatory markers as well as oxidative stress and vascular molecular indicators. Additionally, we developed an in vitro model induced by hypoxia/reoxygenation (H/R) in HTR-8/SVneo cells and treated the cells with 20 and 40 μM of CTS. Our findings demonstrated that CTS reduces H/R-induced damage in HTR-8/SVneo cells while alleviating oxidative stress and promoting angiogenesis in human umbilical vein endothelial cells. Mechanistically, we identified NF-κB as a target for CTS through network pharmacology analysis combined with molecular docking. Subsequent experiments confirmed that CTS mitigates trophoblast cell damage via inhibiting the NF-κB signaling pathway. In conclusion, our study reveals that CTS prevents the development of PE-like symptoms by reducing oxidative damage within trophoblastic cells and enhancing angiogenesis through inhibiting the NF-κB pathway. These findings provide a novel strategy for the treatment of PE. Graphical CTS prevents the development of PE-like symptoms by reducing oxidative damage within trophoblastic cells and enhancing angiogenesis through inhibiting the NF-κB pathway.
研究领域:
药理学
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生殖医学
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分子生物学
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细胞生物学
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信号转导
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产品关联
DOI
PubMed
高影响因子
ENVIRONMENTAL POLLUTION
·
2021
·
IF 8.071
Jiaqi Xu,Qiuhui Qian,Min Xia,Xuedong Wang,Huili Wang
Trichlorocarban (TCC) is ubiquitously detected in environmental matrices, while there is a paucity of information regarding its systemic toxicity. In the present study, we observed that TCC exposure led to high embryo mortality, delayed hatching and yolk absorption, as well as increased malformations, such as closure of swim sac and yolk sac edema. Meanwhile, TCC affected the formation and branch of subintestinal veins (SIVs), intersegmental vessels and posterior cardinal veins. Especially, the SIVs were shrunk, and their branches were reduced or even broken along with reduced coverage area. TCC-induced oxidative stress and excessive apoptosis resulted from abnormal expression of the anti/pro-apoptotic genes. Significant reduction in the number and aggregation function of immune cells proved that TCC had prominent immunotoxicity to zebrafish. TCC-targeted TLR4 signaling pathway was demonstrated by abnormal expression of the marker genes ( tlr4 , MyD88 and nf-κb ) and release of the downstream inflammatory factors (TNF-α, IL-6, etc.). Inhibition of TLR4/MyD88/NF-κB pathway by an inhibitor (CA-4948) rescued the decreasing trend of the immune cells induced by TCC. Molecular docking results demonstrated that TCC could stably bind to TLR4 receptor to form hydrogen bonds and hydrophobic interactions with amino acids. Overall, these findings reveal the underlying molecular mechanisms on TCC-induced developmental and immune toxicity to zebrafish.
研究领域:
毒理学
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环境科学
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分子生物学
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免疫学
·
发育生物学
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DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2018
·
IF 3.831
Yang Junfa,Liu Qingxue,Cao Shiyang,Xu Tao,Li Xiaofeng,Zhou Dandan,Pan Linxin,Li Changyao,Huang Cheng,Meng Xiaoming,Zhang Lei,Wang Xiao
During the liver fibrosis recovery stage tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) can effectively induce apoptosis of activated hepatic stellate cells (HSCs). Normal hepatic stellate cells are resistant to TRAIL cytotoxicity. Therefore, enhancing the sensitivity of TRAIL-induced apoptosis of HSCs may be useful to treat hepatic fibrogenesis. Here, we demonstrated that miR-145 and TRAIL were down-regulated in both liver fibrosis tissue samples and transforming growth factor-β1 induced HSCs, concomitant with increased the expression of ZEB2. In addition, we found that mimics-mediated over-expression of miR-145 led to resistance to the ZEB2 expression and up-regulation of the TRAIL-induced apoptosis after treatment of LX-2 cells with TRAIL. Furthermore, ZEB2-siRNA transfected LX-2 cells showed the increased sensitivity to TRAIL-induced apoptosis. Whereas, opposite results were obtained in miR-145-inhibitor group or ZEB2 plasmid group. Moreover, miR-145 regulated ZEB2 gene expression by specifically interacting with the 3′-UTR of ZEB2 mRNA to inhibit the expression of ZEB2. Further studies showed that the over-expression of ZEB2 could inhibit TRAIL-induced apoptosis via inhibiting nuclear factor-κB (NF-κB) signaling pathway in LX-2 cells. Collectively, our data suggest that up-regulation of miR-145 can down-regulate ZEB2 expression, consequently promoting TRAIL-induced apoptosis in LX-2 cells through NF-κB signaling pathway, which facilitates the resolution of liver fibrosis.
研究领域:
分子生物学
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细胞生物学
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肝病学
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DOI
PubMed
高影响因子
INFLAMMATION
·
2026
·Vol. 49
·期 1
·41
·
IF 5
Zheng-qing Hu,Ruijie Ma,Hang Zhang,Jiahao Miao,Jia-qing Sun,Jinlong Yuan,Jiaqiang Liu,Zihuan Zhang,Dayong Xia
This study aims to elucidate the mechanism by which Heat Shock Protein 60 (HSP60) mediates microglial pyroptosis in the context of early brain injury (EBI) following subarachnoid hemorrhage (SAH), and to investigate the effects of HSP60 inhibition on EBI after SAH. A mouse subarachnoid hemorrhage (SAH) model was established using prechiasmatic cistern blood injection. In vitro, microglia were stimulated with 25 µmol/L oxyhemoglobin (OxyHB) to simulate the SAH pathological environment. In vivo, mice received 100 mg/kg Mizoribine, while in vitro, 80 µmol/L Mizoribine was used to suppress SAH-induced HSP60 upregulation. Techniques including Western blotting, immunofluorescence, immunohistochemistry, transmission electron microscopy, ELISA, modified Garcia neurological scoring, beam walking, brain water content measurement, Morris water maze, TUNEL staining, and Nissl staining were employed to systematically investigate the role of HSP60 inhibition in neuroinflammation and microglial pyroptosis after SAH. Compared to the sham group, both in vivo and in vitro studies with blinded, random sampling of six groups demonstrated a significant increase in HSP60 expression post-SAH. In vivo, 100 mg/kg Mizoribine alleviated blood-brain barrier disruption, cerebral edema, neuronal apoptosis/necrosis, and improved neurological deficits and cognitive impairment. In vitro, 80 µmol/L Mizoribine markedly attenuated microglial activation and pyroptosis, downregulated pro-inflammatory cytokines, and mitigated neuroinflammation. The upregulation of HSP60 after SAH promotes NLRP3 inflammasome assembly by activating the TLR4/MyD88/NF-κB signaling pathway, thereby inducing microglial pyroptosis and exacerbating the progression of early brain injury. Inhibition of HSP60 represents a potential therapeutic strategy for ameliorating EBI after SAH.
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PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2026
·
IF 5.4
Aoyu Zhang,Shuying Li,Jie Qiao,Chuanqi Zhong,Zhiwen Zhang,Xiguang Ye,Jun Jin,Shiyan Shang,Song Wu,Qing Zhang,Gongxu Yang
Ethnopharmacological relevance The therapeutic effect of Psoralea corylifolia L. on knee joint pain was recorded as early as the Ming Dynasty in the Compendium of Materia Medica, which notes its actions of tonifying the kidney, strengthening tendons, and bones. Isopsoralen (ISO), derived from the Psoralea corylifolia L., has shown efficacy in improving osteoarthritis (OA) in both traditional use and our previous screening, demonstrating effects in alleviating joint inflammation and protecting cartilage. Aim of the study OA is a common disabling disease. Its progression connects local joint pathology to systemic metabolic and inflammatory states, extending to gut microbiota and metabolites. This study examines the therapeutic mechanism of isopsoralen against OA using a DMM-induced model. Materials and methods ISO's targets were predicted by network pharmacology approaches. Therapeutic effects were evaluated through behavioral tests, micro-CT, histology, Western blot, and PCR, while safety was assessed via liver/kidney staining. 16S rDNA sequencing and targeted metabolomics were employed to analyze gut microbiota structure and short-chain fatty acids (SCFAs). Pseudo germ-free mice and fecal microbiota transplantation (FMT) were used to validate the role of gut microbiota. Results Network pharmacology indicated ISO's multi-target action against OA. ISO downregulated the MAPK/NF-κB pathway, attenuated subchondral bone abnormalities, and alleviated joint degeneration in DMM mice. It also modulated gut microbiota composition and SCFA levels. FMT confirmed the essential role of gut microbiota in ISO's efficacy. Furthermore, no hepatorenal toxicity was observed. Conclusion ISO alleviates OA by modulating gut microbiota/SCFAs and inhibiting the MAPK/NF-κB pathway, thereby reducing inflammation and improving bone abnormalities, without hepatorenal toxicity.
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DOI
PubMed
高影响因子
Frontiers in Molecular Biosciences
·
2026
·
IF 4
Xingwei Yu,Hongao Tan,Yunqiu Gao,Dandan Qiu,Yan Zhu,Haixin Qi
Background: Given the lack of effective treatment for chronic nonbacterial prostatitis (CNP) and the anti-inflammatory property of natural bioactive compound forsythiaside A (FTA), the therapeutic potential of FTA on CNP is worthy of investigation.Methods: CNP rat models were established using complete Freundʼs adjuvant, followed by a 4-week administration of FTA at different concentrations (40 and 80 mg/kg/d). The body and prostate of rats were weighed to calculate the prostatic index. Prostate damage and inflammatory infiltration were assessed using histological analysis and immunohistochemistry staining. Levels of inflammation-related cytokines, autophagic markers as well as the protein kinase C alpha (PKCα)/NF-κB pathway in prostate tissues were detected using enzyme-linked immunosorbent assay and western blot.Results: No significant change was observed in the body weight of CNP rat models administered with or without FTA. FTA treatment reduced the prostatic index and mitigated prostate damage and inflammatory infiltration of CNP rat models. FTA treatment decreased the number of CD3-positive cells and CD45-positive cells, while downregulating interleukin 1 beta (IL-1β), IL-2, IL-6, IL-17A, monocyte chemoattractant protein-1, and tumor necrosis factor alpha in prostate tissues of CNP rat models. FTA treatment promoted Beclin-1 and LC3B II/LC3B I expressions, and inhibited PKCα and p-p65/p65 expressions in prostate tissues of CNP rat models.Conclusion: FTA alleviates inflammation and facilitates autophagy in CNP rat models by blocking the PKCα/NF-κB pathway.
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产品关联
DOI
PubMed
高影响因子
POULTRY SCIENCE
·
2026
·
IF 4.5
Jie Qi,Haotian Yang,Yang Yang,Xinyi Dou,Xin Chen,Qiuyue An,Tingyang Wu,Xiuzhi Liu,Yu Boyuan,Hao Wang,Siqi Wang,Yinkang Song,Chenjia Shi,Chao Ma,Jia Chen,Yuan Zhao,Honggang Fan
This study evaluated the effects of esculetin on heat stress-induced splenic immunosuppression in broilers. Esculetin significantly reduced rectal temperature and respiratory rate in heat-stressed broilers ( P < 0.05), improved growth performance, serum biochemical parameters, and the spleen index, and attenuated heat stress-induced splenic histopathological damage and HSP70 expression. Concurrently, esculetin elevated serum levels of immunoglobulins (IgA, IgM, and IgG) and upregulated the gene expression of anti-inflammatory cytokines, while downregulating pro-inflammatory cytokine genes (IL-1β, IL-6, and TNF-α). Network pharmacology analysis, molecular docking, and in vivo validation demonstrated that the immunomodulatory effects of esculetin were primarily mediated through targeting NF-κB, TNF-α, and IL-6, thereby modulating the NF-κB/MAPK signaling pathway. These findings provide a scientific basis for the application of esculetin as a functional feed additive to alleviate heat stress-induced immune dysfunction in poultry.
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DOI
高影响因子
POULTRY SCIENCE
·
2026
·Vol. 105
·期 12
·107847
·
IF 4.5
Shunxing Liu,Yanling Xiong,Zhentao Cheng,Anchun Cheng,Rutao Lin,Hui Li,Yao Huang,Binlan Zhou,Ting Yang,Chunlan Shan
Mycoplasma gallisepticum ( MG ), a significant pathogen, causes chronic respiratory disease (CRD) in poultry, characterized by coughing, wheezing, and dyspnea. This widespread disease severely impedes the healthy development of the poultry industry. Hydroxytyrosol (HT), a plant-derived monomeric compound, possesses diverse bioactivities, including antibacterial, antioxidant, and cardiovascular protective properties. This study aimed to investigate HT's protective effect against MG -induced inflammatory damage in HD11 cells. The findings revealed that MG infection activated the TLR4/NF-κB signaling pathway and the NLRP3 inflammasome, resulting in macrophage accumulation and inflammatory damage in the lung tissue of chicks. HT mitigated MG -induced inflammatory damage in HD11 cells, inhibited the M1 phenotype shift, and reduced the secretion of pro-inflammatory factors. Molecular docking and molecular dynamics simulations demonstrated HT's stable, spontaneous binding to NLRP3. Further investigations showed that HT alleviates oxidative stress-induced cellular damage, diminishes pathological apoptosis and pore formation, and concurrently reduces NLRP3 activation by regulating the TLR4/NF-κB pathway, thereby downregulating the expression of key pyroptosis factors. In summary, HT reduces NLRP3 inflammasome activation by specifically inhibiting the TLR4/NF-κB signaling axis, consequently alleviating inflammation-induced damage, oxidative stress, and pyroptosis in HD11 cells caused by MG infection.
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DOI
高影响因子
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