INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
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2023
·Vol. 24
·期 3
·2126
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IF 5.6
Shouchao Xu,Jiehong Yang,Haitong Wan,Li Yu,Yu He
Promotion of angiogenesis and restoration of the blood flow in the ischemic penumbra is an effective treatment for patients with ischemic stroke (IS). Radix astragali-safflower (AS), a classic herbal pair for accelerating blood circulation and dispersing blood stasis, has been used for thousands of years to treat patients with IS in China. Even so, the mechanism of the treatment of IS by AS is still undecipherable. In the current study, network pharmacology was firstly employed to unveil the mechanism of AS in treating IS, which showed that AS might promote angiogenesis associated with PTGS2 silence. Middle cerebral artery occlusion/reperfusion (MCAO/R) model rats were then used as the experimental animals to verify the prediction result. The experimental results revealed that treatment with AS improved the cerebral infarct volume, neurological damage, and cerebral histopathological damage; inhibited cell apoptosis; increased the contents of PDGF-BB, EPO, and TGF-β1; and reduced the levels of PF4, Ang-2, and TIMP-1 in serum. Immunohistochemical staining demonstrated that the expression of PTGS2 was dramatically increased in the hippocampus and cerebral cortex of rats with MCAO/R, and this trend was reversed by the treatment of AS. Immunofluorescent staining expressed that AS reversed the down-regulation of VEGF and further promoted the expression of CD31, which indicated that AS promoted angiogenesis in MCAO/R rats. The abnormal protein or mRNA expression of PTGS2, PGI2, bFGF, TSP-1, and VEGF in the penumbra were transposed by AS or Celecoxib (an inhibitor of PTGS2). In conclusion, the protective mechanism of AS for IS promoted angiogenesis and was involved with PTGS2 silence.Keywords:Radix astragali and safflower;angiogenesis;ischemic stroke;ischemic penumbra;PTGS2
研究领域:
药理学
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神经科学
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中医药学
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DOI
PubMed
高影响因子
PHYTOMEDICINE
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2024
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IF 6.7
Qing Zhu,Yuanshan Han,Ying He,Pan Meng,Yilan Fu,Hui Yang,Gefei He,Minghui Long,Yingrui Shi
Background Quercetin, the key ingredient in Xiaoyao Kangai Jieyu Formula, has been previously found to relieve breast cancer-related depression (BCRD). Purpose We want to explore the potential mechanisms and therapeutic targets of quercetin alleviating BCRD. Methods BALB/c mice were injected subcutaneously with 4T1 cells and corticosterone (CORT) to create a BCRD mice model. The primary hippocampal neurons were co-induced with 10 μg/mL lipopolysaccharide (LPS) and 200 μM CORT for 6 h to establish an in vitro model of BCRD. Quercetin was applied to explore its effect on disease symptoms, gut microbiota, and lipid metabolism of BCRD mice. Lipid metabolism-related genes were screened based on network pharmacology. Molecular docking was employed to prove whether quercetin bound to prostaglandin-endoperoxide synthase 2 (PTGS2). PTGS2 overexpression was carried out to explore the underlying mechanism of quercetin treatment on BCRD. Results Quercetin treatment not only altered the composition and abundance of gut microbiota but also alleviated abnormal lipid metabolism in BCRD mice. In particular, quercetin down-regulated BCRD and lipid metabolism-related genes screened by network pharmacology, especially PTGS2. Further, molecular docking verified the stable binding between quercetin and PTGS2. In hippocampal neurons, quercetin promoted proliferation but reduced ferroptosis-related markers (total Fe, Fe2+, MDA, and ROS) levels by targeting PTGS2. In BCRD mice, quercetin reduced the high immobility time and increased the sucrose preference rate and serotonin (5-HT), dopamine (DA), and noradrenaline (NE) levels. Meanwhile, quercetin increased CD4+/CD8+ T cells ratio and IL-2 and IFN-γ levels but reduced CA153 and IL-10 levels to alleviate BCRD development. However, PTGS2 overexpression reversed these effects of quercetin on BCRD. Conclusion Quercetin inhibited neuronal ferroptosis and promoted immune responses in BCRD mice by targeting the lipid metabolism-related gene PTGS2. This provided a reference for quercetin in the treatment of BCRD.
研究领域:
药理学
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神经科学
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肿瘤学
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免疫学
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代谢组学
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DOI
PubMed
高影响因子
IUBMB LIFE
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2024
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IF 3.7
Yexuan Lin,Na Sun,Dengyuan Liu,Xinmeng Yang,Yixin Dong,Chengyu Jiang
In 2020, the number of deaths caused by lung cancer worldwide reached 1,796,144, making it the leading cause of cancer-related deaths. Cyclooxygenase-2/prostaglandin endoperoxide synthase 2 ( COX-2/PTGS2 ) is overexpressed in lung cancer, which promotes tumor proliferation, invasion, angiogenesis, and resistance to apoptosis. Here, we report that the oligonucleotide drug HQi-sRNA-2 from Traditional Chinese Medicine Huangqin targeting COX-2/PTGS2 significantly inhibited proliferation, migration, and invasion and induced apoptosis in the human lung cancer cell line NCI-H460. Oral delivery of HQi-sRNA-2 bencaosomes prolonged survival, reduced tumor burden, and maintained weight in a spontaneous mouse lung cancer model. Compared with paclitaxel, HQi-sRNA-2 may be less toxic and have approximately equal efficacy in reducing tumor burden. Our previous studies reported that herbal small RNAs (sRNAs) are functional medical components. Our data suggest that sphingosine (d18:1)-HQi-sRNA-2 bencaosomes, targeting COX-2/PTGS2 and downregulating the PI3K and AKT signaling pathways, may provide novel therapeutics for lung cancer.
研究领域:
肿瘤学
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药理学
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分子生物学
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中医药
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
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2025
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IF 5.2
Dazhen Zhang,Xinzhe Qu,Fuchao Chu,Zhenxin Wang,Jie Mou,Feng Yuan
Background Heterotopic ossification (HO) is characterized by abnormal bone formation outside the skeleton following injury or inherited disease, leading to limb dysfunction and neurological deficits. Current treatment options for HO are largely ineffective. Methods A network pharmacological analysis was conducted to identify the active ingredients and protein targets in Astragalus and Cinnamon Twig Five-Substance Decoction (ACTFSD) on HO. Protein-protein interaction analysis and Gene Ontology Enrichment Analysis were used to investigate the key genes associated with the target proteins. Molecular docking was employed to validate the interactions between the core components and targets of ACTFSD. Kaempferol was encapsulated in liposomes synthesized via the thin-film dispersion method. In vitro and in vivo experiments were conducted to evaluate the therapeutic effects of kaempferol liposomes. Results Kaempferol, an active ingredient in ACTFSD, effectively inhibits the PTGS2\ NF-κB pathway, regulates macrophage immune responses, and reduces cytokine released by macrophages induce abnormal osteogenesis in tendon stem cells (TDSCs), thereby slowing the formation of HO. Kaempferol liposomes demonstrate better therapeutic effect than kaempferol alone. Conclusion This study indicates that targeting macrophages may represent an effective therapeutic strategy for HO. Furthermore, kaempferol liposomes appear to be a promising treatment for trauma-induced HO. These findings provide potential new directions for future HO treatment strategies.
研究领域:
医学
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药理学
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DOI
PubMed
高影响因子
MICROCHEMICAL JOURNAL
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2025
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IF 5.1
Xinyue Lin,Luxi Zhou,Lingfang Chen,Qiyue Chen,Zhuming Jin,Peixi Zhu,Ni Yang
Houttuynia cordata Thunb. is a perennial herb with a distinct “fishy” flavour, commonly used in Asian cuisine and traditional medicine. To overcome the compound identification challenges in the composite formula of its mixture, a comprehensive two-dimensional ultra-high-performance liquid chromatography quadrupole time-of-flight mass spectrometry (2D UHPLC-QTOF-MS) method was developed and identified 293 chemical compounds. Given the herb’s strong anti-inflammatory properties, network pharmacology was employed to predict potential targets, revealing TNF, AKT1, MMP9, and PTGS2 as key theoretical targets for its anti-inflammatory effects. Molecular docking showed strong binding energies between these targets and the top 10 compounds (8,13-dihydroxy-9,11-octadecadienoic acid, neobaicalein, chrysin, apigenin, genistein, chrysoeriol, norwogonin, cirsiliol, luteolin and deoxyandrographolide), with genistein exhibiting the highest affinity for AKT1 (−10.4 kcal/mol). This innovative approach, combining advanced 2D UHPLC-QTOF-MS with network pharmacology, offers great potential for screening active components in herbs and their complex mixtures.
研究领域:
中药学
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分析化学
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药理学
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DOI
高影响因子
BIOMEDICAL CHROMATOGRAPHY
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2024
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IF 1.8
Xiaomin Xu,Donghua Yu,Yu Wang,Peng Xu,Xin Jiang,Fang Lu,Shumin Liu
Resveratrol (Res) has been demonstrated to have beneficial effects on gouty nephropathy (GN). However, the mechanisms of Res on GN remain unclear. This study aimed to investigate the mechanisms of Res on GN. In this study, network pharmacology technology was used to predict the Res targets in the prevention and treatment of GN. Renal metabonomics was used to identify differential metabolites in kidney tissue of GN model rats. Finally, molecular docking technology was used to verify the binding ability of Res to key targets. Metabonomics analysis showed that 24 potentially important metabolites were involved in the prevention and treatment of GN with Res. After exposure to Res, metabolite levels normalized. The network pharmacology analysis showed that 24 key targets were involved in the prevention and treatment of GN disease. According to the metabolite–gene network diagram, we identified two core genes, PTGS1 and PTGS2, and found that both were involved in the arachidonic acid metabolism pathway. Molecular docking further verified the affinity of Res binding to PTGS1 and PTGS2. In conclusion, the mechanism of Res against GN may be the regulation of arachidonic acid metabolism through the regulation of PTGS 1 and PTGS 2.
研究领域:
药理学
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代谢组学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Materials Today Bio
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2026
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IF 11
Zhipeng Li,Yaoyao Wu,Jialin Wu,Cheng Zhang,Xinsheng Cheng,Hongzhen Zhang,Shikai Wang
Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized clinically by recurrent abdominal pain and bloody diarrhea, for which there is currently a lack of curative therapeutic strategies. In recent years, neutrophil extracellular traps (NETs) have been identified as playing a key role in the pathogenesis of UC, emerging as a potential therapeutic target. Although deoxyribonuclease I (DNase I) can exert therapeutic effects by degrading the DNA backbone of NETs, its clinical application is limited by inherent drawbacks, including poor in vivo stability, low bioavailability, and inefficient penetration of biological barriers. Herein, this study constructed a biomimetic membrane-based nanodelivery system. Initially, zeolitic imidazolate framework-8 (ZIF-8) was used to encapsulate DNase I, forming ZD nanoparticles to enhance enzymatic stability. Subsequently, these nanoparticles were coated with bacterial outer membrane vesicles (BOMVs), yielding the final BVZD composite system, designed to improve targeting to inflammatory sites. The BVZD system exhibited suitable particle size, good biocompatibility, and a demonstrated ability to specifically accumulate in the inflamed intestinal regions of a UC model. Both in vitro and in vivo experiments confirmed that BVZD effectively degraded NETs, suppressed endoplasmic reticulum stress (ERS) by downregulating the expression of prostaglandin-endoperoxide synthase 2 (PTGS2), and promoted the repair of the intestinal epithelial barrier. These findings highlight the promising therapeutic potential of BVZD for the treatment of UC.
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DOI
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
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2026
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IF 6.7
Donglei Zheng,Xiaojuan Xin,Hui Ouyang,Lulu Ma,Hao Wang,Xin Liu,Xiangxin Liao,Xinzi Chu,Ying Gao,Jiaying Huo,Shugang Li
Ovotransferrin (OVT) is a functionally active protein demonstrated to alleviate ulcerative colitis (UC), although its mechanism remains incompletely understood. Notably, UC is closely associated with dysbiosis of the gut microbiota. This study investigates the potential of OVT to alleviate colitis by reshaped gut microbiota composition in a DSS-induced UC mouse model. Specifically, Ligilactobacillus murinus (L. murinus) was isolated from the gut microbiota of OVT-treated UC mice and stimulated by OVT in vitro. Integrated whole-genome sequencing and targeted metabolomics revealed that L. murinus encodes bile salt hydrolase, thereby driving secondary bile acid biosynthesis. Mechanistically, fermentation products (FP) derived from coculture of L. murinus with bile exerts potent anti-inflammatory in both Caco-2 cells and a colitis model by Ptgs2 (COX-2) downregulation and the JAK-STAT signaling pathway inhibition. These results established the “OVT-L. murinus-bile acids-Ptgs2/JAK-STAT” axis as a novel mechanism for UC treatment, providing a foundation for high-value applications of OVT in functional foods.
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DOI
PubMed
高影响因子
TOXICOLOGY AND APPLIED PHARMACOLOGY
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2025
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IF 3.4
Jingjing Chen,Lu Zhou,Mengxin Li,Jun Wang,Yaru Chen,Jing Xia,Yue Lin,Huizhen Chen,Zibo Dong
Chronic Intermittent Hypoxia (CIH) is a central pathological feature of diseases such as obstructive sleep apnea hypopnea syndrome (OSAHS), which induces oxidative stress in lung tissues and leads to lung injury. Atraric acid (AA), a lichen-derived compound, has been reported to possess anti-inflammatory and antioxidant activities. In this study, we investigated the functions and mechanisms of AA in CIH-induced lung injury by constructing a CIH mouse model and an in vitro hypoxia/reoxygenation model in MLE-12 cells. Various methods were employed, including hematoxylin and eosin (H&E) staining, biochemical assay kits, quantitative polymerase chain reaction (qPCR) analysis, protein blotting, immunofluorescence, and flow cytometry. The results showed that AA pretreatment significantly attenuated pathological injury of mouse lung tissue, reduced pulmonary edema, reactive oxygen species (ROS) and malondialdehyde production, as well as the depletion of total antioxidant capacity, catalase and glutathione, and lowered the expression levels of inflammatory factors. Mechanistic studies showed that AA up-regulated solute transport family 7 member 11 (SLC7A11) and glutathione peroxidase 4 (GPX4) expression and down-regulated prostaglandin-endoperoxide synthase 2 (PTGS2) through activation of the Nrf2 signaling pathway, whereas the Nrf2 inhibitor ML385 completely blocked this protective effect. In conclusion, the present study demonstrates that AA targets the Nrf2 axis, attenuated CIH-induced inflammation, alleviates ROS accumulation, and blocks the vicious cycle of oxidative stress, ferroptosis, and inflammation, making it a promising therapeutic strategy for the treatment of CIH-induced lung injury.
研究领域:
药理学
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分子生物学
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呼吸病学
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生物化学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
Iranian Journal of Basic Medical Sciences
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2022
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IF 2.532
Hongxia Wang,Zhiyu Shao,Zhiwen Xu,Binghao Ye,Ming Li,Qiaoqiao Zheng,Xingyuan Ma,Ping Shi
Objective(s): Gemcitabine is a first-line drug for the treatment of bladder cancer. One of the most important mechanisms of gemcitabine resistance is the low expression of cellular membrane transporter hENT1. Various derivatives containing fatty acid side chains have been developed in order to facilitate gemcitabine uptake and prolong its retention in cells, such as CP-4126. In this study, the anti-tumor effect and mechanism of a new derivative of gemcitabine named SZY-200 on bladder cancer cells were investigated. SZY-200 was assembled from the gemcitabine-lauric acid conjugate. Materials and Methods: Antiproliferative activities of SZY-200 and lauric acid were evaluated using CCK-8 assay and clonogenic survival assay. The hENT1 inhibitor NBMPR was employed to determine the role of hENT1 in the apoptotic activity of GEM, CP-4126, and SZY-200. RT-qPCR, flow cytometry, fluorescence microscope, western blotting, and wound healing assay were used to study the mechanisms of SZY-200. The target genes were predicted using the BATMAN-TCM database. Results: Our data showed that SZY-200 could inhibit the proliferation of bladder cancer cells by inducing cell cycle arrest and apoptosis. The inhibitory effects were comparable to gemcitabine and CP-4126. SZY-200 does not rely on hENT1 to help it enter bladder cancer cells. Also, we found that lauric acid could inhibit the proliferation of bladder cancer cells. SZY-200 could down-regulate the expressions of PPARG and PTGS2 which were related to the occurrence and development of bladder cancer. Conclusion: SZY-200 has the same or more advantages as CP-4126 and could be an ideal candidate drug for further in vivo investigation.
研究领域:
肿瘤学
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药理学
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分子生物学
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癌症研究
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产品关联
DOI
PubMed
高影响因子
Journal of Natural Medicines
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2024
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IF 2.5
Cao Yongyi,Wang Yu,Li Yueyang,Liu Sihan,Wang Lizhe,Zhou Li,Zhu Ting
Ferroptosis is a unique programmed cell death driven by iron-dependent phospholipid peroxidation. Tumor cells that escape from the conventional therapies appear more sensitive to ferroptosis. Therefore, it is extremely urgent to find safe and efficient active ingredients that induce ferroptosis in tumor cells. Herein, we identified that angelic acid, as a potent anti-tumor active ingredient in Angelica sinensis , profoundly sensitizes CRC cells to ferroptosis via a natural compound library screen. We revealed that angelic acid treatment is sufficient to predispose CRC cells to ferroptosis phenotype, evidenced by malondialdehyde (MDA) accumulation, lipid peroxidation, and upregulation of ferroptosis-associated markers CHAC1 and PTGS2, which is abolished by ferroptosis inhibitor Fer-1. Moreover, the results of network pharmacology showed that NRF2 is critical for angelic acid-mediated CRC cell ferroptosis. Mechanistically, angelic acid exerted its ferroptosis induction via directly binding and facilitating the degradation of NRF2. In addition, the syngeneic mouse models revealed that angelic acid boosts CRC cell sensitivity to ferroptosis inducer sulfasalazine with essentially no toxicity in vivo. Collectively, our findings highlighted a previously unrecognized anti-tumor mechanism of angelic acid and represented an appealing therapeutic strategy for CRC treatment. Graphical abstract
研究领域:
肿瘤学
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药理学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
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2022
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IF 3.322
Ting Zhou,Bao Yang
Prenylated resveratrols are drug candidates presented in many natural sources. They possess multiple pharmacological activities. Due to the limited abundance in nature and disadvantage of chemical synthesis, it is required to produce prenylated resveratrols by biological strategy. In this work, a prenyltransferase iacE from Pestalotiopsis fici was prepared by heterologous overexpression. It could catalyze 2- C -prenylation of resveratrol efficiently. Dimethylallyl diphosphate (DMAPP) and geranyl diphosphate (GPP) could serve as prenyl donor. Glu97, Thr114 and Tyr413 were proved to be important residues in the active site by site-directed mutagenesis. The product was purified and identified to be 2- C -prenyl resveratrol by NMR . 2- C -prenyl resveratrol exerted neuroprotective activity through inhibiting ROS overproduction and improving the activities of antioxidant enzymes in HT22 cell. The genes involved in antioxidant defense were regulated, including upregulated CAT , SOD2 , NFE2L2 , GPx4 , and downregulated PTGS2 and ACSL4 . These results supplied a novel technique for prenylated resveratrols production.
研究领域:
生物技术
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药理学
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神经科学
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产品关联
DOI
PubMed
高影响因子
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