Nature Communications
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2023
·Vol. 14
·期 1
·1-15
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IF 16.6
Lu Xiangyu,Kuai Le,Huang Fang,Jiang Jingsi,Song Jiankun,Liu Yiqiong,Chen Si,Mao Lijie,Peng Wei,Luo Ying,Li Yongyong,Dong Haiqing,Li Bin,Shi Jianlin
Psoriasis is a common inflammatory disease of especially high recurrence rate (90%) which is suffered by approximately 3% of the world population. The overexpression of reactive oxygen species (ROS) plays a critical role in psoriasis progress. Here we show that biomimetic iron single-atom catalysts (FeN 4 O 2 -SACs) with broad-spectrum ROS scavenging capability can be used for psoriasis treatment and relapse prevention via related gene restoration. FeN 4 O 2 -SACs demonstrate attractive multiple enzyme-mimicking activities based on atomically dispersed Fe active structures, which are analogous to those of natural antioxidant enzymes, iron superoxide dismutase, human erythrocyte catalase, and ascorbate peroxidase. Further, in vitro and in vivo experiments show that FeN 4 O 2 -SACs can effectively ameliorate psoriasis-like symptoms and prevent the relapse with augmented efficacy compared with the clinical drug calcipotriol. Mechanistically, estrogen receptor 1 (ESR1) is identified as the core protein upregulated in psoriasis treatment through RNA sequencing and bioinformatic analysis. Together, this study provides a proof of concept of psoriasis catalytic therapy (PCT) and multienzyme-inspired bionics (MIB).
研究领域:
药学
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材料科学
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生物医学工程
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皮肤科
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REPRODUCTIVE TOXICOLOGY
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2021
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IF 3.143
Jiadong Chen,Lian Kang,Junke Wang,Yuhao Wu,Lindong Han,Xiangqin Zheng,Yuexin Wei,Tianxin Zhao,Lianju Shen,Chunlan Long,Guanghui Wei,Shengde Wu
Di-(2-ethylhexyl) phthalate (DEHP) is an environmental endocrine disruptor that accumulates in organisms in various ways and induces male reproductive system disorders. In this study, we established a testicular injury model by gavage with different concentrations of DEHP. The testes were then collected for RNA sequencing (RNA-seq), and the results were analyzed by bioinformatics and verified by experiments. Our research results show that different concentrations of DEHP interfere with testicular development differently. Weighted gene coexpression network analysis (WGCNA) generated sixteen modules and identified the turquoise module as key. Then, estrogen receptor 1 (ESR1), filamin A (Flna) and Furin were identified as hub genes. qPCR and immunohistochemistry results revealed that all three hub genes were upregulated. We detected the locations of these genes by immunohistochemistry. ESR1 was mainly located in Leydig cells; Flna immunostaining is observed in the Leydig and some germ cells and Furin staining was seen in almost all types of testicular cells. Furthermore, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses showed enrichment mainly in MAPK signaling pathways, p53 signaling pathways, HIF-1 signaling pathways, protein processing in the endoplasmic reticulum, apoptosis, the cell cycle, RNA degradation, etc. This is the first study using WGCNA to investigate the mechanism of DEHP-induced injury in the prepubertal testis, providing new research angles to further understand the mechanism of DEHP-induced injury in the prepubertal testis.
研究领域:
毒理学
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生殖生物学
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分子生物学
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生物信息学
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PubMed
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Journal of Functional Foods
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2024
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IF 3.8
Xiaotian Xu,Xinhui Li,Xingshu Wei,Xiaoqun Duan,Yuhui Wang
Passion fruit peel fermentation extract (PFPFE) increased gastrointestinal transport power and fecal moisture content, protected the structural integrity of colon tissue, and reduced inflammatory infiltration. PFPFE also increased secretion of the ET-1, GAS, MTL, and SP, and decreased secretion of the inhibitory SS and VIP. In addition, PFPFE alleviated perirectal redness and hemorrhage in hemorrhoid mice, and downregulated levels of the serum inflammatory factors tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β). In this study, we also analyzed the main active components and core targets of PFPFE for alleviating constipation and hemorrhoids through network pharmacology, and predicted its mechanism of action. Finally, we carried out Western blot experiments to verify that PFPFE and its active component kae alleviates constipation and hemorrhoids in mice by downregulating ESR1 and PI3K/Akt pathways. These results provide a scientific basis for the development of PFPFE as a functional food for alleviating constipation and hemorrhoids.
研究领域:
药理学
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胃肠病学
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分子生物学
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ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
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2025
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IF 6.1
Biyu Wu,Zirui Cheng,Xiang Li,Minxing Liang,Xue Wang,Duan Pi,Jiayi Liu,Huiling Li,Jun Zhao,Junjie Wang,Fang Liang,Xuegeng Wang
As a major substitute for the bisphenol A (BPA), the use of the bisphenol F (BPF) has increased dramatically in recent years. Growing evidence suggest that BPF shares numerous toxicological properties with BPA, raising the concerns about its potential impact on the health of organisms. However, the developmental toxicity of BPF remains poorly understood. In this study, we conducted a 5-day BPF exposure experiment on zebrafish ( Danio rerio ) from blastula stage at concentrations of 2, 20, 200, and 2000 µg/L. Our results demonstrated a significant increase in hatching rates across all treatment groups at 2 days post-fertilization (dpf). The esr1 was significantly upregulated at 2000 µg/L by 5 dpf, while no significant change was observed in ar . The frequency of operculum loss significantly increased at exposure concentrations of 20, 200, and 2000 µg/L, and a notable increase in notochord loss was observed at 2000 µg/L. To explore the underlying mechanisms, transcriptomic analysis was performed to identify differentially expressed genes (DEGs). GO and KEGG pathway enrichment analysis revealed that the toxic effects of BPF were closely associated with osteoclast differentiation, the FoxO signaling pathway, and the MAPK signaling pathway. These pathways influenced critical biological processes, including response to stimuli, animal organ morphogenesis, detoxification, and biomineralization. This study provides evidence that BPF exposure at environmentally relevant concentrations (2 µg/L) is harmful to hatching, concentrations above 20 µg/L exhibit estrogenic-disrupting activity and exert toxicological effects on the development of the head skeleton in zebrafish. These effects are particularly linked to disruptions in osteoclast differentiation.
研究领域:
环境毒理学
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分子生物学
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PubMed
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Biomed Research International
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2022
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IF 3.246
Shisheng Jiang,Chaoming Huang,Shulin Wang,Biyun Huang,Dan Wu,Guodong Zheng,Yi Cai
Objective. Through a network pharmacology method, we screened the main active compounds of Citri Reticulatae Pericarpium (CRP), constructed a drug-ingredient-disease-target network, explored the molecular mechanism of its treatment of myocardial hypertrophy, and validated it by using molecular biology approach. Methods. Traditional Chinese Medicine Systems Pharmacology (TCMSP) and GeneCards were utilised to collect the effective component in CRP and the targets of CRP and myocardial hypertrophy. The STRING database constructed the protein interaction network. The drug-ingredient-disease-target network was outlined by the Cytoscape 3.9.0 software. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted using the Metascape database. Real-time PCR (RT-PCR) and Western blotting were utilised to determine the mRNA and protein level of the critical targets of CRP therapy for myocardial hypertrophy. Results. We found that five practical components of CRP exerted therapeutic effects on myocardial hypertrophy by modulating 41 targets. Further analysis revealed that naringenin was the essential active compound in CRP that regulated myocardial hypertrophy. In addition, we showed that the active compounds of CRP might exert antihypertrophy effects via regulating essential target proteins such as AKT1-, MAPK3-, PPARA-, PPARG-, and ESR1-mediated signaling pathways such as cell proliferation, nuclear receptor activation, and oxidative stress. The molecular biology experiments demonstrated that naringenin inhibited the mRNA level of NPPA and NPPB induced by Ang II and regulated related targets such as AKT1, MAPK3, PPARA, PPARG, and ESR1. Conclusion. CRP could inhibit myocardial hypertrophy through multitarget and multiapproach.
研究领域:
药理学
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分子生物学
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中医药学
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心脏病学
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PubMed
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PHYTOMEDICINE
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2025
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IF 8.3
Yufeng Yao,Lijun Shao,Ziqi Li,Jiahao Liang,Chenchen Zhu,Shumei Wang,Chaozhan Lin,Fangle Liu
Background Interstitial pneumonia, particularly usual interstitial pneumonia (UIP) and idiopathic pulmonary fibrosis (IPF), is a disease with progressive and fatal disorder, and limited treatment options. Xiebai San (XBS), a classical Chinese herbal formula, has shown clinical promise but its mechanism of action remains unclear. Purpose To clarify the effects and mechanism of XBS on interstitial pneumonia. Methods The in vivo pharmacochemical analysis (UPLC-Q-Exactive-Orbitrap MS/MS), network pharmacology, and GEO database analysis (GSE10667) were applied to predict potential targets of XBS on interstitial pneumonia. BLM-induced mice received XBS (1.4, 2.8, 5.6 g/kg) or dexamethasone (0.5 mg/kg) for 21 days. Lung index, histopathology observation (H&E, Collagen-1 IHC), pulmonary function, and biomarkers of inflammation, oxidative stress and fibrosis were used to evaluated the efficacy of XBS. Reverse-phase protein microarray (RPPM), RT-qPCR, and Western blotting were integrated to clarify its mechanism. Results Thirty-seven components of XBS were identified in vivo , and they were associated with 237 potential targets for interstitial pneumonia. And GEO analysis confirmed the upregulation of key nodes (NCOA2, ESR1, and ESR2) in patients. XBS significantly attenuated BLM-induced lung damage, evidenced by reduced lung index, improved pulmonary function (Penh, EEP, PIF, PEF), decreased inflammatory infiltrates, collagen deposition, and alveolar destruction. XBS suppressed proinflammatory cytokines (TNF-α, IL-1β), oxidative stress (MDA, MPO), restored antioxidants (GSH, SOD), and inhibited fibrotic factors (TGF-β1, α-SMA, Collagen-1/3). Mechanistically, XBS downregulated the mRNA and protein expression of NCOA2 and ESR1/2, subsequently inhibiting glycolytic metabolic reprogramming (G6PC, PFKFB3, HIF-1α) and the TGF-β1/ERK1/2-Smad7 pro-fibrotic signaling pathway. Conclusion XBS alleviates BLM-induced interstitial pneumonia via NCOA2-ESR1/2-driven glycolytic metabolic reprogramming and TGF-β1/ERK1/2-Smad7 fibrotic signaling, offering a mechanistic rationale for interstitial pneumonia.
研究领域:
药理学
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中医方剂学
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呼吸病学
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分子生物学
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系统生物学
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PubMed
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PHYTOCHEMICAL ANALYSIS
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2026
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IF 2.9
Yu Xia,Xinyi Zhong,Chenggang Zhang
Background Hypoxia is a core pathological factor in myocardial injury and is involved in the development of various cardiovascular diseases. Although baicalein shows cardiovascular protective potential, its mechanism against hypoxic injury remains unclear. Methods H9c2 cardiomyocytes were exposed to sodium sulfite to establish a chemical hypoxia model. Network pharmacology, molecular docking, molecular dynamics simulation, and molecular biology assays were employed to predict the core target and investigate the underlying mechanism. Results Network pharmacology identified ESR1 as a core target, with stable binding to baicalein confirmed by molecular docking and dynamics simulations. Baicalein alleviated hypoxia-induced oxidative stress by elevating key antioxidant markers and reducing malondialdehyde levels. It also ameliorated energy metabolism disorders, reduced lactate dehydrogenase release, suppressed reactive oxygen species production, and decreased cell apoptosis. Furthermore, baicalein upregulated hypoxia-suppressed ESR1 protein expression and enhanced its co‑localization with the antiapoptotic protein BCL-XL. The cytoprotective effects were abolished by the ESR1 inhibitor fulvestrant. Conclusion These findings demonstrate that baicalein protects cardiomyocytes against hypoxic injury through an ESR1‑dependent mechanism by modulating the BCL‑XL/BAX apoptotic balance, mitigating oxidative stress, and improving energy metabolism.
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INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
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2026
·Vol. 27
·期 16
·7218
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IF 5.6
Li Xie,Shanliang Yuan,Lu Gan,Rongheng Ma,Lei Tang,Qiang Xu,Weihong Li
Bisphenols (BPs) are widespread environmental endocrine disruptors, but their potential depression-related neurotoxicity has not been systematically assessed. Here, we combined machine learning (ML), network toxicology, molecular docking, and in vivo experiments to screen 26 bisphenols for depression-related neurotoxic risk. We first integrated bisphenol A (BPA)-related targets with depression-related genes to build a chemical-gene-phenotype-disease network and an adverse outcome pathway (AOP) framework. We then used nine ML algorithms to rank the predicted risk of the 26 bisphenols. Molecular docking showed that the predicted high-risk compounds had strong binding affinity for estrogen receptor 1 (ESR1). The AOP analysis further suggested the involvement of the ESR1–cAMP response element-binding protein 1 (CREB1)–glutamate ionotropic receptor N-methyl-D-aspartate type subunit 2B (GRIN2B) pathway. In vivo experiments showed that BPA exposure caused neuronal damage in the cornu ammonis 3 (CA3) region of the rat hippocampus and significantly reduced the messenger RNA (mRNA) expression of the corresponding genesEsr1,Creb1, andGrin2bin hippocampal tissue. Overall, this study screened and prioritized the model-predicted depression-related neurotoxic risk of 26 bisphenols, supports a role for the ESR1–CREB1–GRIN2B pathway in BPA-induced neurotoxicity, and provides mechanistic evidence for bisphenol risk assessment.
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Journal of Translational Medicine
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2026
·Vol. 24
·期 1
·492
·
IF 9.7
Li Ze,Ling Yimin,Xiao Wei,Li JiaZheng,Rong JiaHui,Zhang Zewen,Wei Yan,Huo Zhongchao,Li Dong
Background Scutellarin (SCU) is a natural flavonoid compound exhibiting anti-tumor activity. This study aimed to elucidate the molecular mechanism underlying SCU’s therapeutic effects in liver cancer. Methods An integrated approach combining network pharmacology and transcriptomic analysis was employed to identify SCU-related targets, followed by the identification of core targets through protein–protein interaction (PPI) network construction and topological analysis using MCC and MCODE algorithms. A circular RNA (circRNA)-mediated competing endogenous RNA (ceRNA) regulatory network was constructed by integrating data from databases including miRWALK and circBANK with whole-transcriptome sequencing. Molecular interactions were experimentally validated using Western blotting, dual-luciferase reporter assays, and RNA immunoprecipitation (RIP). In Huh7 and HepG2 cells, overexpression and knockdown models of key RNAs were established to evaluate their functional roles, with cell proliferation, cell cycle distribution, and apoptosis assessed via CCK-8, colony formation, and flow cytometry assays. To investigate in vivo anti-tumor efficacy and associated mechanisms, a subcutaneous xenograft tumor model was established in nude mice. Results Integrated network pharmacology and transcriptomic analysis identified 11 core genes significantly enriched in the estrogen signaling pathway, among which ESR1 was validated as a key target. SCU downregulated ESR1 expression in a dose-dependent manner. Mechanistically, SCU upregulated miR-2682-5p while downregulating circSRBD1. Dual-luciferase reporter assays confirmed that miR-2682-5p directly binds to the 3′UTRs of both circSRBD1 and ESR1, supporting the existence of a circSRBD1/miR-2682-5p/ESR1 ceRNA regulatory axis. Functional studies demonstrated that overexpression of circSRBD1 attenuated SCU-induced cell cycle arrest, apoptosis, and suppression of proliferation, whereas silencing circSRBD1 enhanced these effects. Furthermore, SCU and fulvestrant exhibited synergistic anti-tumor activity both in vitro and in vivo. Conclusion This study identifies a novel circSRBD1/miR-2682-5p/ESR1 ceRNA regulatory axis that plays a critical role in mediating SCU’s inhibitory effects on liver cancer progression, highlighting the potential therapeutic value of combining SCU with fulvestrant. Clinical trial number Not applicable.
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npj Science of Food
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2025
·Vol. 9
·期 1
·1-14
·
IF 7.8
Guo Xichuang,Chen Xi,Zeng Mingwei,Xuan Tianming,Xue Jing,Chen Kang,Gong Jinyan,Song Gongshuai,Shen Qing
Medicinal food homology substances have served as a traditional means of overcoming many health complications, and gained increasing attention. Fritillaria Bulbus is used as an edible herbal food with medicinal food homology; however, its antioxidant efficacy substantially varies among different species. In this study, an integrated approach of UHPLC-Q-Exactive Orbitrap MS/MS-based metabolomics, network pharmacology, and molecular docking was used to compare the antioxidant activities of four FBs and identify the active compounds and potential mechanisms. A total of 143 metabolites were identified, predominantly comprising alkaloids. In vitro antioxidant tests revealed a positive correlation between alkaloids and their antioxidant capabilities. Network pharmacology predicted 17 differential and 44 shared compounds. Molecular docking assessed that seven alkaloids (peimisine、imperialine、peimine、solasodine、veratramine、cyclopamine and jervine) exhibited good affinity for the antioxidant targets. Key therapeutic targets AKT1 and ESR1 mediate antioxidant mechanisms through PI3K/AKT signaling. These findings provide insights into interspecies differences in FB’s antioxidant properties.
研究领域:
生药学
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药物化学
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系统生物学
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分析化学
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天然产物研究
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DOI
PubMed
高影响因子
MOLECULES
·
2026
·Vol. 31
·期 12
·2158
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IF 5.1
Jingran Cui,Xuting Song,Heran Liu,Zhenhai Cui,Mengmeng Sun,Min He,Meiying Jin
Background: Glucocorticoid-induced osteoporosis (GIOP) is marked by impaired osteogenesis and reduced bone formation. Isobavachin (IBA), a flavonoid from Psoralea corylifolia, shows multiple potentials in anti-inflammatory and bone metabolism regulations, but its effects against GIOP remain unclear. This study investigated the osteoprotective effects and potential mechanism of IBA using zebrafish GIOP model. Methods: osteoprotective effects of IBA was assessed by fluorescence imaging in a prednisolone-induced zebrafish model, following with osteogenic gene expressions measured by RT-qPCR. Potential targets and pathways of IBA was filtered and predicted by network pharmacology, molecular docking, and molecular dynamics (MD) simulations, and finally validated with a pharmacological rescue experiment using a PI3K-specific inhibitor. Results: IBA improved bone mineralization and upregulated osteogenesis-related genes. Network pharmacology identified the PI3K-Akt pathway as a key pathway, with ESR1, GSK3B, MTOR, and CCND1 as core targets. PI3K inhibition attenuated the osteoprotective effects of IBA and suppressed downstream osteogenic gene expression. Conclusions: IBA alleviates GIOP by modulating the ESR1-associated PI3K-Akt signaling pathway and may serve as a multi-target therapeutic candidate for osteoporosis.
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JOURNAL OF ETHNOPHARMACOLOGY
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2022
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IF 5.195
Ying-Li Cai,Feng Zhang,Xiu-Xiu Dou,Hua-Wu Zeng,Gao-Song Wu,Yan-Lin Liang,Xi-Ke Xu,Jing Zhao,Ji Ye,Wei-Dong Zhang
Ethnopharmacological relevance Dingkun Pill (DKP), a traditional Chinese medicine prescription, was modified from Bujing decoction and Xusijiangsheng pill by the imperial physician in the Qing dynasty (1700′ s). It was believed to treat various gynecological diseases by nourishing qi and blood. Accumulating evidence indicates that it is effective in treating polycystic ovary syndrome (PCOS). However, the therapeutic efficacy and mechanism of action DKP against PCOS need to be further elucidated. Aim of the study To investigate the therapeutic effect and action mechanism of DKP against PCOS using an integrated approach of metabolomics and network pharmacology . Materials and methods The rat model of PCOS was established by dehydroepiandrosterone . An integrated metabolomics and network pharmacology strategy was applied to systemically clarify the mechanism of DKP against PCOS. Theca cells were prepared to evaluate the effect of DKP and its ingredients on testosterone synthesis in vitro. Results The pharmacological experiments demonstrated that DKP could effectively convert the disordered estrous cyclicity, decrease the level of testosterone and the luteinizing hormone/follicle stimulating hormone ratio, and inhibit abnormal follicle formation in PCOS rats. By metabolomics analysis, 164 serum endogenous differential metabolites and 172 urine endogenous differential metabolites were tentatively identified. Steroid hormone biosynthesis and ovarian steroidogenesis were the most significantly impacted pathways. Based on network pharmacology and metabolomics studies, the ingredient-target-pathway network of DKP in the treatment of PCOS was constructed. Among the 10 key targets, CYP17A1 , CYP19A1 , STS, AR, ESR1, and MYC were closely involved in ovarian androgen synthesis. In theca cell-based assay of testosterone synthesis, DKP and its two active compounds (ligustilide and picrocrocin) showed inhibitory effects. Conclusion DKP effectively improved symptoms in rats with dehydroepiandrosterone-induced PCOS. The mechanism of DKP in the treatment of PCOS is related to the CYP17A1 enzyme required for androgen synthesis.
研究领域:
药理学
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中医
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妇科
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代谢组学
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网络药理学
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高影响因子
危险品化学品经营许可证（带存储）