Food & Function
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2026
·Vol. 17
·期 11
·5152-5169
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IF 6.3
Xin Cao,Hongjuan Liu,Miao Yang,Zhixian Chen,Qian Cheng,Jialin Sun,Xudong Wu,Yan Zhang,Liping Hao
Yeast protein (YP) is a sustainable alternative protein, offering a favorable amino acid profile. However, its digestion kinetics and potential as a source of bioactive peptides (BAPs) remain neglected. This study applied the INFOGEST digestion model to compare in vitro digestion kinetics of YP, whey and soy protein. YP exhibited delayed amino acid release and distinct proteomic features. Analysis of the final intestinal chyme of YP identified 312 unique peptides. In silico screening identified several low-molecular-weight peptides (<1000 Da) with high bioactivity potential and favorable pharmacokinetics. Crucially, cell-based assays revealed that two high-abundance peptides, GDWPLPT and PLPPAPAPK, significantly alleviated lipopolysaccharide (LPS)-induced injury in C2C12 myotubes. These peptides reduced reactive oxygen species (ROS) levels and interleukin-6 (IL-6) secretion, while restoring mitochondrial membrane potential and adenosine triphosphate (ATP) synthesis. Overall, this study provides a comprehensive characterization of the digestion kinetics and peptide profiles of YP. Beyond these findings, the cytoprotective potential of the identified peptides was validated in a muscle injury model, thereby proving YP as a promising source of functional food ingredients for future applications.
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FITOTERAPIA
·
2026
·
IF 2.9
Hengxing Ran,Yan Wen,Yiebi Qin,Kaiwen Kang,Zhengrong Wu,Yifan Li,Yu Wang,Rihui Wu,Dongli Li,Song Ang,Lishe Gan,Jingwei Jin
This study aims to identify the most primary hepatoprotective compound from Hypericum japonicum and elucidate its underlying mechanisms of liver protection. This study screened 15 compounds from Hypericum japonicum against D-GalN-induced AML12 cell injury, identifying TAX ( Compound 8 , taxifolin 7-rhamnoside) as the most hepatoprotective. This study indicates that TAX reduced AST, ALT, and MDA levels, while enhancing SOD and GSH levels in D-GalN-induced AML12 and LPS/D-GalN -induced liver. In addition, TAX attenuated LPS/D-GalN-induced hepatic injury by lowering inflammatory infiltration and pro-inflammatory cytokines (TNF-α, IL-6 and NO) levels. Network pharmacology analysis revealed common targets between TAX and drug-induced liver injury, forming a protein-protein interaction (PPI) network. Functional enrichment (GO/KEGG) and molecular docking indicated strong binding affinity between TAX and AKT1, confirmed by molecular dynamics simulations. Western blot analyses that TAX ameliorated inflammation and oxidative stress through down-regulating the AKT/NF-κB pathways and up-regulating Nrf2/HO-1 pathways in vivo, TAX inhibited apoptosis via up-regulating Bcl-2 and down-regulating Bax in vitro. Collectively, this study demonstrates that TAX ameliorates LPS/D-GalN-induced ALI by attenuating hepatocyte apoptosis, inflammatory responses, and oxidative stress.
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EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
·
2025
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IF 5.9
Wanyang Xiao,Ruize Sun,Jietao Lou,Yanyan Xu,Xiaokun Li,Kaiyun Xin,Weijie Lu,Chenhui Sun,Tianbao Chen,Yitian Gao,Di Wu
The increasing prevalence of antibiotic-resistant Gram-negative bacteria necessitates the development of novel antimicrobial agents with targeted specificity. In this study, we designed and optimized derivatives of the antimicrobial peptide AA16, which truncated from CD14 protein α-helical region, to selectively target Gram-negative bacteria by enhancing lipopolysaccharide (LPS)-enriched interactions, thereby achieving antibacterial spectrum conversion. Starting from the parent peptide AA16 (Ac-AARIPSRILFGALRVL-Amide), we performed strategic amino acid substitutions based on structure–activity relationship analysis. This led to the identification of AA16-10R, a derivative with a specific substitution at position 10, which demonstrated significantly enhanced antibacterial activity against Gram-negative strains such as Escherichia coli and Pseudomonas aeruginosa , while maintaining low hemolytic activity. Mechanistic studies revealed that AA16-10R exhibited a strong binding affinity to LPS ( K d = 0.15 μM), and its interaction with LPS induced the formation of an α-helical structure. This conformational change facilitated its accumulation on the bacterial outer membrane and disrupted membrane integrity. Our innovative approach of exploiting LPS-enriched interactions successfully converted the antimicrobial spectrum of AA16 derivatives from broad-spectrum to Gram-negative-specific. This study highlights a novel strategy for the rational design of antimicrobial peptides based on specific protein–protein interactions, offering a promising avenue for targeted antimicrobial therapy against Gram-negative pathogens.
研究领域:
微生物学
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药物化学
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分子生物学
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INTERNATIONAL IMMUNOPHARMACOLOGY
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2020
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IF 3.943
Haihua Zhang,Wuying Lang,Shiyong Wang,Binru Li,Guangyu Li,Qiumei Shi
Lung injury is a common critical life-threatening syndrome. Inflammation is a key factor in the pathogenesis of lung injury. It is reported that Echinacea Polysaccharides (EP) has anti-inflammatory activity. However, the effect of EP on lung injury remains unclear. In our study, murine model of lung injury was induced with 2.5 mg/kg LPS before administration of 5 mg/kg or 10 mg/kg EP. EP ameliorated LPS-induced lung pathological damage, along with reduction in lung wet/dry weight ratio and myeloperoxidase activity. EP decreased the number of leukocytes, eosinophils, neutrophils, lymphocytes and macrophages in bronchoalveolar lavage fluid, and the release of tumour necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1β (IL-1β) in LPS-treated lung. EP suppressed LPS-induced apoptosis along with down-regulation of Bcl2-associated X (Bax) and cleaved caspase-3 (CC3), and elevated B-cell lymphoma-2 (Bcl-2). Besides, RAW 264.7 cells were treated with EP 100 μg/ml for 1 h and then incubated with 1 μg/ml LPS for 24 h. TNF-α, IL-6 and IL-1β levels were lowered by treatment of EP in LPS-treated RAW 264.7 cells. Moreover, EP down-regulated the expression of toll-like receptor 4 (TLR4), myeloid differentiating factor 88 (MyD88), p-IκBα, nuclear factor kappa-B (NF-κB), p-NF-κB, and up-regulated the inhibitor of NF-κB (IκBα) in vivo and in vitro following LPS induction, which is consistent with the effect of TAK-242. In conclusion, EP may alleviate LPS-induced lung injury via inhibiting inflammation, apoptosis and activation of TLR4/NF-κB signal pathway.
研究领域:
药理学
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免疫学
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肺科学
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Marine Drugs
·
2020
·Vol. 18
·期 6
·328
·
IF 4.073
Jing Ye,Donghui Chen,Zhicheng Ye,Yayan Huang,Na Zhang,Edmund M. K. Lui,Changhu Xue,Meitian Xiao
Fucoidan has been reported to have a variety of biological activities. However, different algae species, extraction methods, harvesting seasons, and growth regions lead to the structural variation of fucoidan, which would affect the bioactivities of fucoidan. To date, the anti-inflammatory properties and the underlying mechanism of fucoidan from brown algaSaccharina japonica(S. japonica) remain limited. The aims of the present study were to investigate the structure, the anti-inflammatory properties, and the potential molecular mechanisms of fucoidan isolated fromS. japonica(SF6) against lipopolysaccharide (LPS)-activated RAW 264.7 macrophages. SF6 was characterized using high performance liquid gel permeation chromatography (HPGPC), Fourier transform infrared spectroscopy (FTIR), and nuclear magnetic resonance spectroscopy (NMR), and observed to be rich in fucose, galactose, and sulfate. Additionally, results showed that SF6 remarkably inhibited LPS-induced production of various inflammatory mediators and pro-inflammation cytokines, including nitric oxide (NO), NO synthase (iNOS), cyclooxygenase-2 (COX-2), tumor necrosis factor-α (TNF-α), interleukin-β (IL-β), and interleukin-6 (IL-6). A mechanism study showed that SF6 could effectively inhibit inflammatory responses through blocking LPS-induced inflammation pathways, including nuclear factor-κB (NF-κB), mitogen-activated protein kinase (MAPK), and Janus kinase (JAK)-2 and signal transducer and activator of transcription (STAT)-1/3 pathways. These results suggested that SF6 has the potential to be developed as an anti-inflammatory agent applied in functional food.Keywords:fucoidan;Saccharina japonica;anti-inflammation;mechanism
研究领域:
药理学
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免疫学
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分子生物学
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BRITISH JOURNAL OF PHARMACOLOGY
·
2022
·Vol. 180
·期 8
·1114-1131
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IF 9.473
Weiwei Zhu,Minxiu Wang,Leiming Jin,Bin Yang,Bin Bai,Rumbidzai Natasha Mutsinze,Wei Zuo,Nipon Chattipakorn,Joo Young Huh,Guang Liang,Yi Wang
Background and Purpose Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) is a challenging clinical syndrome that leads to various respiratory sequelae and even high mortality in patients with severe disease. The novel pharmacological strategies and therapeutic drugs are urgently needed. Natural products have played a fundamental role and provided an abundant pool in drug discovery. Experimental Approach A compound library containing 160 natural products was used to screen potential anti-inflammatory compounds. Mice with LPS-induced ALI was then used to verify the preventive and therapeutic effects of the selected compounds. Key Results Licochalcone A was discovered from the anti-inflammatory screening of natural products in macrophages. A qPCR array validated the inflammation-regulatory effects of licochalcone A and indicated that the potential targets of licochalcone A may be the upstream proteins in LPS pro-inflammatory signalling. Further studies showed that licochalcone A directly binds to myeloid differentiation factor 2 (MD2), an assistant protein of toll-like receptor 4 (TLR4), to block both LPS-induced TRIF- and MYD88-dependent pathways. LEU61 and PHE151 in MD2 protein are the two key residues that contribute to the binding of MD2 to licochalcone A. In vivo , licochalcone A treatment alleviated ALI in LPS-challenged mice through significantly reducing immunocyte infiltration, suppressing activation of TLR4 pathway and inflammatory cytokine induction. Conclusion and Implications In summary, our study identified MD2 as a direct target of licochalcone A for its anti-inflammatory activity and suggested that licochalcone A might serve as a novel MD2 inhibitor and a potential drug for developing ALI/ARDS therapy. Graphical Licochalcone A directly binds with MD2 whereas LEU61 and PHE151 are two key residues for conformational stabilization. This interaction blocks the biological function of MD2 in transducing the signalling from the LPS-induced TLR4 pathway, subsequently restrains both TBK1/IRF3 and TAK1/MAPKs/NF-κB activation and inflammatory cytokines, chemokines, interferons, and so on overexpression, thus decreasing the immune cell infiltration in lung tissue and improving the acute lung injury.
研究领域:
药理学
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免疫学
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分子生物学
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药物发现
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Oxidative Medicine and Cellular Longevity
·
2022
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IF 7.31
Pingjun Zhu,Junyan Wang,Wenjuan Du,Jun Ren,Ying Zhang,Fei Xie,Guogang Xu
Mitochondrial dysfunction and necroptosis have been perceived as the primary molecular mechanisms underscoring acute lung injury. Meanwhile, nuclear receptor subfamily 4 group A member 1 (NR4A1) is considered a regulator of inflammation-related endothelial injury in lung tissue although the downstream molecular events remain elusive. In this study, we employed NR4A1-/- mice to decipher the role of NR4A1 in the onset and progression of acute lung injury with a focus on mitochondrial damage and necroptosis. Our results demonstrated that NR4A1 was significantly upregulated in lipopolysaccharide- (LPS-) treated lung tissues. Knockout of NR4A1 overtly improved lung tissue morphology, inhibited inflammation, and reduced oxidative stress in LPS-treated lung tissue. A cell signaling study suggested that NR4A1 deletion repressed levels of PGAM5 and attenuated LPS-mediated necroptosis in primary murine alveolar epithelial type II (ATII) cells, the effects of which were mitigated by PGAM5 overexpression. Moreover, LPS-mediated mitochondrial injury including mitochondrial membrane potential collapse and mitochondrial oxidative stress was drastically improved by NR4A1 deletion. Furthermore, NR4A1 deletion preserved mitochondrial homeostasis through activation of Opa1-related mitochondrial fusion. Silencing of Opa1 triggered mitochondrial dysfunction in NR4A1-deleted ATII cells. Taken together, our data identified NR4A1 as a novel regulator of LPS-related acute lung injury through regulation of mitochondrial fusion and necroptosis, indicating therapeutic promises of targeting NR4A1 in the treatment of acute lung injury in clinical practice.
研究领域:
分子生物学
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免疫学
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呼吸病学
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Frontiers in Microbiology
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2023
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IF 5.2
Zhou Ziyuan,Wang Baohong,Pan Xiaxia,Lv Jiawen,Lou Zhuoqi,Han Yuqiu,Yao Yuanyuan,Chen Jun,Wang Qiangqiang,Li Lanjuan
Introduction: Acute liver failure (ALF) is a clinical condition with many causes, fast progression, and a poor prognosis. Previous research has indicated that microbial factors have a role in ALF, but a clear picture has yet to emerge.Methods: To investigate the specific involvement of microbial metabolites in ALF development, we pretreated D-GalN/LPS-induced ALF mice with indole derivatives, an influential class of gut microbial metabolites.Results: Contrary to their typical role as anti-inflammatory agents in the host, indole-3-acetic acid (IAA), indole-3-lactic acid (ILA), and indolepropionic acid (IPA) gavage sensitize mice to D-GalN/LPS-induced-ALF with a rapid rise in serum transaminases and histologic lesion. For a clearer picture, we performed comprehensive analysis for the IAA therapy. IAA markedly amplified inflammatory response and cellular damage. The transcriptome analysis indicated the participation of the TNF-α/NF-κB signaling pathway. The structure of gut microbiota in ileum and the expression of Toll-like receptor 2 (Tlr2) in the liver were also significantly changed.Discussion: In conclusion, IAA pretreatment can exacerbate D-GalN/LPS-induced ALF via probable Tlr2/NF-κB pathway involvement and ileac dysbiosis characterized by enriched gram-positive genus with potential pathogenesis. Microbial metabolites IAA may aggravate individual susceptibility to D-GalN/LPS-induced ALF. Further investigation of the underlying mechanism is needed, and intervention with indole derivatives and related commensal species should be undertaken with caution.
研究领域:
肝病学
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免疫学
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微生物学
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PESTICIDE BIOCHEMISTRY AND PHYSIOLOGY
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2023
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IF 4.7
Tongtong Li,Hao Chen,Baohua Xu,Mengwei Yu,Jun Li,Ying Shi,Shaohui Xia,Shijin Wu
The improper use of deltamethrin (DM) can result in its accumulation in soil, water, food, and even the human body, which is associated with an elevated risk of neurotoxicity and behavioral abnormalities; however, the underlying mechanisms remain insufficiently investigated. Emerging evidence underscores the significance of the gut-brain axis in central nervous system (CNS) dysfunctions. Accordingly, this study investigates the role of the gut-brain axis in DM-induced behavioral anomalies in mice. The results showed that DM exposure induced depressive-like behavior, and the hippocampus, the region that is responsible for the modulation of emotional behavior, showed structural integrity disrupted (neuronal nuclear shrinkage and decreased tight junction protein expression). In addition, DM exposure led to compromised gut barrier integrity (disruptions on crypt surfaces and decreased tight junction protein expression), which might contribute to the gut bacterial-derived lipopolysaccharide (LPS) leakage into the bloodstream and reaching the brain, triggering LPS/toll-like receptor (TLR) 4 -mediated increases in brain pro-inflammatory cytokines. Subsequently, we observed a disturbance in neurotransmitter metabolic pathways following DM exposure, which inhibited the production of 5-hydroxytryptamine (5-HT). Additionally, DM exposure resulted in gut microbiota dysbiosis. Characteristic bacteria, such as Alistipes , Bifidobacterium , Gram-negative bacterium cTPY-13 , and Odoribacter exhibited significant correlations with behavior, tight junction proteins, inflammatory response, and neurotransmitters. Further fecal microbiota transplantation (FMT) experiments suggested that DM-induced gut microbiota dysbiosis might contribute to depressive-like behavior. These results provide a new perspective on the toxicity mechanism of DM, indicating that its neurotoxicity may be partially regulated by the microbiota-gut-brain axis.
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CELL AND TISSUE RESEARCH
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2023
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IF 3.6
Yuan Haojie,Yu Junbo,Liu Chun,Zhao Heyan,Xue Jianhua,Liu Jiajia,Yang Yang
This study aims to discuss the role of exosomes KCNQ10T1 derived from bone marrow mesenchymal stem cells (BMMSCs) in sepsis and to further investigate its potential molecular mechanisms. Exosomes extracted from BMMSCs are identified by transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA), and western blot. Fluorescence labeling is applied to detect the internalization of exosomes in receptors. The proliferation ability, migration ability, and invasion ability of HUVECs are determined by CCK-8, EdU, wound healing, and Transwell. The levels of inflammatory cytokines in sepsis cells are quantitatively detected by ELISA. Kaplan–Meier survival curve is used to describe the overall survival. RT-qPCR is used to detect mRNA expression of related genes. Bioinformatics analysis is performed to search the downstream target of KCNQ1OT1 and miR-154-3p and the interaction is verified by luciferase reporter assay. Exosomes derived from BMMSCs alleviated the toxicity in sepsis cell models and animal models. In mice with septic cell models, exosomal KCNQ10T1 was down-regulated and associated with lower survival. Overexpression of KCNQ10T1 inhibited the proliferation and metastasis of LPS-induced HUVECs. Further research illustrated that miR-154-3p was the downstream target gene of KCNQ1OT1 and RNF19A was the downstream target gene of miR-154-3p. Importantly, functional research findings indicated that KCNQ1OT1 regulated sepsis progression by targeting miR-154-3p/RNF19A axis. Our study demonstrates that the exosomal KCNQ1OT1 suppresses sepsis via mediating miR-154-3p/RNF19A, which provides a latent target for sepsis treatment.
研究领域:
分子生物学
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干细胞研究
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免疫学
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细胞生物学
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医学遗传学
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BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
·
2021
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IF 3.575
Wei Wei,Yuanyuan Yao,Hongyuan Bi,Wenxin Xu,Yan Gao
Our previous findings revealed that hsa_circ_0068,888 was markedly down-regulated in the plasma of patients with sepsis-associated acute kidney injury (AKI). However, its molecular mechanism in AKI remains unclear. Herein, we explored the role of hsa_circ_0068,888 in AKI. Human renal proximal tubular cell line HK-2 was stimulated with lipopolysaccharide (LPS) to mimic AKI in vitro . Decreased hsa_circ_0068,888 expression was observed in AKI cell model. The overexpression of hsa_circ_0068,888 significantly increased the viability of LPS-stimulated HK-2 cells, whereas hsa_circ_0068,888 downregulation showed the opposite effect. Furthermore, LPS triggered inflammatory response and oxidative stress , which was inhibited by hsa_circ_0068,888 overexpression and enhanced by hsa_circ_0068,888 down-regulation. Hsa_circ_0068,888 overexpression suppressed the activation of nuclear factor-κB (NF-κB) pathway triggered by LPS as evidenced by decreased p-p65 protein level and nuclear translocation of p65 in hsa_circ_0068,888 overexpressed cells. Additionally, we proved that hsa_circ_0068,888 targeted microRNA-21–5p (miR-21–5p). The expression of miR-21–5p was markedly increased and was negatively regulated by hsa_circ_0068,888 in LPS-stimulated HK-2 cells. Furthermore, we demonstrated that miR-21–5p overexpression reversed the effects on cell viability , inflammatory response, oxidative stress, and NF-κB pathway induced by hsa_circ_0068,888 overexpression in LPS-stimulated HK-2 cells. Overall, these results implied that hsa_circ_0068,888 shows a protective effect on AKI by sponging miR-21–5p. Hence, up-regulation of hsa_circ_0068,888 might be a potential strategy in treatment for AKI.
研究领域:
分子生物学
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细胞生物学
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肾脏病学
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Annals of Hepatology
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2020
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IF 2.125
Shuxia Tian,Min Chen,Bing Wang,Yonglong Han,Haonan Shang,Junming Chen
Introduction and objectives The activation of hepatic stellate cells (HSCs) is the main cause of liver fibrosis. The beneficial effects of fibroblast growth factor (FGF) 19 on liver fibrosis were recently reported. The S. miltiorrhiza as well as S. miltiorrhiza derived bioactive chemical components has shown prominent antifibrotic effects in liver fibrosis but the mechanism is still not fully understood. We aimed to investigate the bioactive compounds derived from S. miltiorrhiza which exerts antifibrotic effects in HSCs via regulating FGF19. Materials and methods FGF19 level in culture media was determined by enzyme-linked immunosorbent assay. Cell proliferation was measured by Cell Counting Kit-8 assay. Further, mRNA and protein expressions were assessed by quantitative polymerase chain reaction and western blotting, respectively. Knocking down of FGF receptor 4 (FGFR4) by transfection with siRNA was used to confirm the role of FGF19/FGFR4 signaling. Results Using the human HSC cell line LX-2, we screened several natural products and found that bioactive compounds isolated from Salvia miltiorrhiza , particularly salvianolic acid B, strongly upregulated FGF19 secretion by LX-2 cells. We further showed that salvianolic acid B inhibited lipopolysaccharide (LPS)-induced HSC proliferation and activation. LPS treatment may also reduce the mRNA and protein levels of FGF19 and its receptor FGFR4. Salvianolic acid B treatment restored the impaired expressions of FGF19 and FGFR4. Finally, FGFR4 knockdown abolished the antifibrotic effects of salvianolic acid B in the LPS-induced HSC activation model. Conclusions Salvianolic acid B prevented LPS-induced HSC proliferation and activation by enhancing antifibrotic FGF19/FGFR4 signaling.
研究领域:
药理学
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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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危险品化学品经营许可证（带存储）