Journal of Functional Foods
·
2024
·
IF 3.8
Deying Men,Jiahe Dai,Yuxue Yuan,Haifen Jiang,Xinyu Wang,Yifan Wang,Liang Tao,Jun Sheng,Yang Tian
Moringa oleifera leaf peptide, which is a plant-derived bioactive peptide, exhibits several advantages, including safety, high efficiency and nontoxic side effects. The goal of this study was to identify representative antiosteoporotic peptides from Moringa oleifera leaf proteins and determine their regulatory mechanisms using network pharmacology, molecular docking and molecular dynamics. The following core targets of Moringa oleifera leaf antiosteoporotic peptides were screened by network pharmacology: SRC, MAPK1, JUN and STAT3. Through molecular docking, DPYLGK was identified as a representative active peptide from the Moringa oleifera leaf protein, and SRC was determined to be a potential primary target. Molecular dynamics revealed the intermolecular mechanism of DPYLGK and SRC. Cellular assays showed that DPYLGK promotes bone formation and inhibits bone resorption. These findings demonstrated that DPYLGK is an anti-osteoporotic peptide with dual regulatory effects and will aid in the development of functional foods to prevent osteoporosis.
研究领域:
药理学
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分子生物学
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生物信息学
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营养科学
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高影响因子
RSC Advances
·
2017
·Vol. 7
·期 66
·41779-41786
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IF 3.108
Zhou Yang,Fan Wu,Hongjie Yang,Ping Zhou
A novel protein tyrosine phosphatase 1B (PTP1B) inhibitor, FYGL, extracted from Ganoderma lucidum, was first reported to have an efficient hypoglycemic effect and high safety in vivo in our previous study. However, the underlying mechanism of the anti-diabetes activity was still unclear. The dominant effective component of FYGL was demonstrated to be a neutral hyperbranched proteoglycan macromolecule. Therefore, it is necessary to first elucidate how the biomacromolecule works at the cellular level, in order to understand its possible functional mechanism in vivo. Herein, we focused on demonstrating the cell internalization and endocytosis mechanism of FYGL in HepG2 cells. A series of cellular uptake pathways was explored, including clathrin-mediated endocytosis, caveolae/lipid-mediated endocytosis, and macropinocytosis. Confocal laser scanning microscopy and flow cytometry were used to demonstrate the absorption of FYGL by HepG2 cells. Furthermore, pharmacologically selective inhibitors and Western blot methods were used to demonstrate that macropinocytosis mediated by c-Src/PI3K cascades was the preferred route for the uptake of FYGL in cells. Our study provided the basis of uptake of FYGL for an efficient hypoglycemic effect. The functional mechanism of the signaling pathway in vivo will be reported in the future.
研究领域:
药理学
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细胞生物学
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分子生物学
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高影响因子
BIOMEDICAL CHROMATOGRAPHY
·
2026
·Vol. 40
·期 9
·e70570
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IF 1.7
Yi Han,Renbin Li,Baobao Yao,Xuefeng Hou,Shixia Xu,Lizhen Yu,Jun Han,Huidan Huang,Di Cao
Inflammation is a defensive immune response to tissue damage or infection. Polygonatum cyrtonema Hua ( P . cyrtonema Hua, PCH) is bioactive on immune homeostasis due to its rich components and reportedly plays a therapeutic role in the treatment and prevention of diabetes. Flavonoids of PCH possess anti‐inflammatory properties, but their molecular mechanisms remain elusive. Here, chemical profiling of key flavonoids was conducted using UPLC‐QTOF‐MS/MS and the Global Natural Products Social Molecular Networking (GNPS) platform. Network pharmacology predicted potential targets and pathways, validated by molecular docking, surface plasmon resonance (SPR), and western blotting. Totally, 67 compounds were identified, with methylophiopogonanone B (MOB) as the key bioactive flavonoid. Although MOB's anti‐inflammatory activity has been previously noted, the present study provides the first evidence that this effect may be mediated through targeting SRC and modulating the PI3K/AKT signaling axis. Core therapeutic targets were identified as SRC, TNF, and AKT1 by topological analysis of network pharmacology. Molecular docking and SPR confirmed strong MOB‐SRC binding affinity. Western blotting revealed MOB dose‐dependently inhibited LPS‐induced phosphorylation of SRC, PI3K, and AKT1, without altering total protein levels. Furthermore, MOB significantly suppressed the phosphorylation of NF‐κB pathway proteins IκB and p65, confirming the involvement of NF‐κB as a downstream effector. In conclusion, this study integrates chemical profiling and network pharmacology with experimental validation to define the flavonoid composition of PCH, and is the first to implicate the SRC‐PI3K‐Akt pathway in MOB's anti‐inflammatory action and providing novel evidence supporting the mechanism and use of PCH in contemporary diabetes treatment.
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PubMed
高影响因子
Nanoscale
·
2021
·Vol. 13
·期 29
·12577-12586
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IF 7.79
Yuan Huang,Suxiao Wang,Jinzhi Zhang,Hangxing Wang,Qichao Zou,Limin Wu
Nanomaterial induced endothelial cell leakiness (NanoEL) is caused because nanomaterials enter the interstitial space of the endothelial cells and disrupt the endothelial cell–cell interactions by interacting with vascular endothelial cadherin (VE-cad). Whereas the NanoEL effect could cause controllable leakiness in cancer therapy, the gaps created by the NanoEL effect can make the cancer cells cross the endothelial barrier and produce side effects induced by using nanomedicine. In this paper, a series of ultralow protein corona nanoparticle is reported that can penetrate the endothelial cell junction without obviously interacting with the VE-cad and phosphorylating the tyrosine 658 (Y658) and tyrosine 731 (Y731) residues on VE-cad, thus preventing the VE-cad from being activated by Src kinase, and this avoids inducing of the NanoEL effect and cancer cell migration, regardless of particle material, density and surface charge. These findings provide a new idea for the design of novel nanoparticles without side effects and can maximize their cancer-killing effect.
研究领域:
纳米技术
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生物医学工程
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癌症研究
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药理学
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DOI
PubMed
高影响因子
Heliyon
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2024
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IF 3.4
Min Cai,Yangchen Mao,Wenjing Gao,Zhenzhen Wang,Jianwei Mao,Ruyi Sha
Inflammatory bowel disease (IBD) is a growing global health problem. IBD is commonly prevalent in Europe and America and the incidence rate in Asia is on the rise due to altered dietary structure. Diosgenin is a natural steroidal saponin derived from Dioscorea plants. Diosgenin is the main active ingredient of some Chinese medicines which are mainly used to treat coronary heart disease, angina and hyperlipidemia. Recently, growing evidence has exhibited a crucial role of diosgenin and dioscin in alleviating IBD in multiple ways. However, the precise mechanism of diosgenin against IBD needs further exploration. In this study, network pharmacological and systematic bioinformatic analyses were performed to investigate the diosgenin's targets against IBD. 71 targets such as SRC, TNF and STAT3 were identified as overlapped genes between diosgenin and IBD. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis exhibited their involvement in the tyrosine kinase signaling pathway and its membrane receptors. Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor resistance and its downstream Ras-MAPK pathway and PI3K-Akt pathway might become the mechanism of diosgenin against IBD. In addition, molecular docking analysis showed that diosgenin has the massive potential of direct binding to tyrosine kinase and its receptors such as SRC, EGFR, FGFR1 and VEGFR. The results above collectively provided evidence that diosgenin is a promising nutraceutical food against IBD.
研究领域:
药理学
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分子生物学
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生物信息学
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功能性食品
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DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2025
·
IF 5.4
Chengcheng Xiao,Peng Wang,Yayun Wang,Jiaxi Zhu,Hai Zhu,Xin Li,Renhe Wang
Ethnopharmacological relevance Acute kidney injury (AKI) is a growing worldwide health concern. Danggui Shaoyao San (DGSYS) was an frequently-used representative prescription to "promote blood and water and harmonize the body" in traditional Chinese medicine, and its underlying mechanism against AKI remains to be elucidated. Aim of the study To investigate the protective effect and potential molecular mechanism of DGSYS in alleviating AKI by network pharmacology and experiment validation. Materials and methods DGSYS was analyzed and separated by UHPLC. Network pharmacology, molecular docking and molecular dynamics simulation were used to screen the active ingredient-target pathway of DGSYS for AKI treatment. Meanwhile, the predictions were experimentally validated both in vivo and in vitro . Results 30 bioactive compounds and 821 non-repetitive targets were screened for DGSYS, and 292 potential DGSYS-AKI intersection targets were identified. According to the protein–protein interaction results and GO and KEGG analyses, we found that apoptosis mediated by SRC pathway exerted a vital role in DGSYS against AKI. In vivo experiments indicated that DGSYS mitigated I/R-induced kidney injury by suppressing SRC signaling pathway. Molecular docking and molecular dynamics simulation revealed that paeoniflorin (PF) have good binding affinity to SRC. Subsequently, in vitro experiments suggested that PF was the key bioactive compound against AKI from DGSYS by inhibiting SRC/ERK1/2 signaling pathway. Conclusion We exhibited the promising anti-AKI mechanism of DGSYS, and our findings also opened up an avenue for future basic experimental validation, indicating a novel research direction.
研究领域:
药理学
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网络生物学
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计算生物学
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中医药学
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分子生物学
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细胞生物学
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PubMed
高影响因子
JOURNAL OF MOLECULAR STRUCTURE
·
2025
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IF 4.7
Yingqi Qiu,Chenhao Zhao,Jiahao Lu,Pin Cheng,Aiqun Wu,Haiou Jiang,Liqun Shen
The Vilsmeier reagent was prepared from N, N-dimethylformamide and POCl₃. Cyclization with 2-hydroxyacetophenone derivatives followed by Pinnick oxidation afforded 3-carboxychromone intermediates. Subsequent condensation with dehydroabietylamine yielded eight target dehydroabietylamine-chromone derivatives 1-8 . In vitro antitumor assays demonstrated that compound 3 exhibited potent inhibitory activity against HeLa, B16F10, and HepG2 cell lines with IC₅₀ values of 2.07 ± 0.18, 4.46 ± 0.23, and 3.04 ± 0.12 μM, respectively. DAPI staining and fluorescence microscopy confirmed that compound 3 induces early apoptosis and causes cell cycle arrest at the G2/M phase. Molecular electrostatic potential (MEP) and frontier molecular orbital (FMO) analyses revealed electronic distributions and reactive sites, while docking studies indicated strong binding affinities of compound 3 toward AKT1 and SRC proteins (-9.20 and -7.76 kcal/mol). Network pharmacology and molecular dynamics simulations further validated the stability of protein complexes, profiling to evaluate pharmacokinetic properties. These findings establish a foundation for developing dehydroabietylamine-chromone hybrids as promising antitumor agents.
研究领域:
药物化学
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药理学
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肿瘤学
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计算生物学
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有机合成
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生物信息学
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DOI
高影响因子
Scientific Reports
·
2016
·Vol. 6
·期 1
·1-13
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IF 5.228
Wu Xunxun,Chen Xiaofei,Jia Dan,Cao Yan,Gao Shouhong,Guo Zhiying,Zerbe Philipp,Chai Yifeng,Diao Yong,Zhang Lei
Traditional Chinese Medicine (TCM) has been developed for thousands of years and has formed an integrated theoretical system based on a large amount of clinical practice. However, essential ingredients in TCM herbs have not been fully identified, and their precise mechanisms and targets are not elucidated. In this study, a new strategy combining comprehensive two-dimensional K562/cell membrane chromatographic system and in silico target identification was established to characterize active components from Indigo naturalis , a famous TCM herb that has been widely used for the treatment of leukemia in China, and their targets. Three active components, indirubin, tryptanthrin and isorhamnetin, were successfully characterized and their anti-leukemia effects were validated by cell viability and cell apoptosis assays. Isorhamnetin, with undefined cancer related targets, was selected for in silico target identification. Proto-oncogene tyrosine-protein kinase (Src) was identified as its membrane target and the dissociation constant (Kd) between Src and isorhamnetin was 3.81 μM. Furthermore, anti-leukemia effects of isorhamnetin were mediated by Src through inducing G2/M cell cycle arrest. The results demonstrated that the integrated strategy could efficiently characterize active components in TCM and their targets, which may bring a new light for a better understanding of the complex mechanism of herbal medicines.
研究领域:
药理学
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肿瘤学
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中医
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色谱学
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生物信息学
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF MASS SPECTROMETRY
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2022
·
IF 1.934
Xiaoyan Liu,He Zhu,Yanan Li,Hongqiang Qin,Mingliang Ye
In this study, we presented a MALDI-TOF MS based approach for the screening of recombinant protein high-yield strains. It relies on the MALDI MS analysis of the affinity tag containing peptide that released from the targe t recombinant proteins expressed in host strains. This approach was illustrated by quantifying the His-tag containing target peptide which was removed from the recombinant protein of Src Homology 2 superbinder by tobacco etch virus protease . After the specific enrichment and detection of target peptide with the theoretical molecular weight of 1895.09 Da, we could achieve the identification of strains with different expression levels of Src Homology 2 superbinder. Furthermore, the screening of strains at the absolute quantitative level was realized by adding the synthesized heavy labeled peptide as internal standards, and the quantitative results have a good linear correlation. In general, based on the virtue of high speed, accuracy and sensitivity of MALDI-TOF MS, this approach has the potential to achieve high throughput detection, and then provide powerful technical support for the screening of recombinant protein high-yield strains.
研究领域:
生物化学
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分子生物学
·
蛋白质组学
·
微生物学
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DOI
高影响因子
Reproductive and Developmental Medicine
·
2022
·
IF 0
Wang Xian-Li,Tang Jing
Objective: Hydrogen sulfide (H 2 S) has been elucidated that it promotes migration and invasion in human placenta trophoblasts. However, the signaling pathway underlying H 2 S-based regulation of trophoblasts remains unknown. Hence, we investigated the potential effect of sodium hydrosulfide (NaHS), an exogenous H 2 S donor, on extravillous trophoblasts. Methods: The Cell Counting Kit-8 was used to detect the proliferative activity of trophoblasts and to screen the optimal concentration of NaHS. The migration and invasion of HTR8/SVneo cells were measured by Transwell assays. Gene expression was determined by quantitative real-time PCR analysis. Protein expression was determined by western blot. Results: We found that NaHS could promote the proliferation , migration , and invasion of HTR8/SVneo cells. The phosphorylation of focal adhesion kinase (FAK), Src, and extracellular signal-regulated kinase (ERK) were activated by NaHS. Moreover, NaHS also upregulated the expression of matrix metalloproteinase-2(MMP-2) and MMP-9, downregulated the expression of E-cadherin in HTR8/SVneo cells. The application of NaHS could increase the expression of cystathionine-β-synthase. Conclusion: Both FAK–Src signaling and the upstream signaling cascade of ERK activation play a significant important role in NaHS-induced proliferation , migration , and invasion via upregulating activity of MMP-2, MMP-9, and downregulating E-cadherin in HTR8/SVneo cells. These novel findings may provide a strong foundation for the clinical application of H 2 S donor drugs.
研究领域:
细胞生物学
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分子生物学
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生殖生物学
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药理学
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DOI
Bio-Design and Manufacturing
·
2021
·Vol. 4
·期 4
·776-789
·
IF 6.302
Fei Panyu,Ding Haibo,Duan Yu,Wang Xinyi,Hu Wei,Wu Peng,Wei Mengxiao,Peng Zhengchun,Gu Zhongze,Chen Wei
Biophysical restrictions regulate protein diffusion, nucleus deformation, and cell migration, which are all universal and important processes for cells to perform their biological functions. However, current technologies addressing these multiscale questions are extremely limited. Herein, through two-photon polymerization (TPP), we present the precise, low-cost, and multiscale microstructures (micro-fences) as a versatile investigating platform. With nanometer-scale printing resolution and multiscale scanning capacity, TPP is capable of generating micro-fences with sizes of 0.5–1000 μm. These micro-fences are utilized as biophysical restrictions to determine the fluidity of supported lipid bilayers (SLB), to investigate the restricted diffusion of Src family kinase protein Lck on SLB, and also to reveal the mechanical bending of cell nucleus and T cell climbing ability. Taken together, the proposed versatile and low-cost micro-fences have great potential in probing the restricted dynamics of molecules, organelles, and cells to understand the basics of physical biology. Graphic abstract
研究领域:
细胞生物学
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生物物理学
·
微制造
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高影响因子
Cell Stem Cell
·
2022
·
IF 25.269
Changzheng Li,Binghuo Wu,Yishan Li,Jie Chen,Zhitao Ye,Xiaobin Tian,Jin Wang,Xi Xu,Shuai Pan,Yucan Zheng,Xiongwei Cai,Linjia Jiang,Meng Zhao
Summary Hematopoietic stem cells (HSCs) adapt their metabolism to maintenance and proliferation; however, the mechanism remains incompletely understood. Here, we demonstrated that homeostatic HSCs exhibited high amino acid (AA) catabolism to reduce cellular AA levels, which activated the GCN2-eIF2α axis, a protein synthesis inhibitory checkpoint to restrain protein synthesis for maintenance. Furthermore, upon proliferation conditions, HSCs enhanced mitochondrial oxidative phosphorylation (OXPHOS) for higher energy production but decreased AA catabolism to accumulate cellular AAs, which inactivated the GCN2-eIF2α axis to increase protein synthesis and coupled with proteotoxic stress. Importantly, GCN2 deletion impaired HSC function in repopulation and regeneration. Mechanistically, GCN2 maintained proteostasis and inhibited Src-mediated AKT activation to repress mitochondrial OXPHOS in HSCs. Moreover, the glycolytic metabolite, NAD + precursor nicotinamide riboside (NR), accelerated AA catabolism to activate GCN2 and sustain the long-term function of HSCs. Overall, our study uncovered direct links between metabolic alterations and translation control in HSCs during homeostasis and proliferation.
研究领域:
血液学
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干细胞生物学
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代谢
·
蛋白质合成调控
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DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）