Scientific Reports
·
2025
·Vol. 15
·期 1
·1-11
·
IF 3.9
Bie Songtao,Yuan Hui,Shi Chen,Li Chunshuang,Lu Ming,Yao Ze,Liu Ruobing,Lu Ding,Ma Tenglong,Yu Heshui
In chronic infections caused by Staphylococcus aureus , biofilm is a major virulence factor. In Staphylococcus aureus biofilms, bacteria are embedded in a matrix of extracellular polymeric substances and are highly tolerant to antimicrobial drugs. However, the lack of effective solutions to inhibit biofilm formation remains a challenge, and the mechanism of inhibition of biofilm formation targeting extracellular polymeric substances is unclear. The aim of the present study was to investigate the inhibitory mechanisms of Plumbagin against Staphylococcus aureus biofilms formation by affecting secretion of extracellular polymeric substances using the high-content screening. Our results showed Plumbagin (16 µg/mL) inhibited biofilm formation, revealing a significant reduction in both biomass and bacterial metabolic activity, and disrupted the biofilm structure, leading to a significant decrease in both biological volume and average thickness ( P ≤ 0.01). High-content screening imaging indicated that the Plumbagin treatment induced alterations in the extracellular polymeric substances of Staphylococcus aureus biofilm, significantly reducing the quantities of extracellular polysaccharide, proteins and extracellular DNA. Interestingly, extracellular DNA within the matrix was found to be the most sensitive to Plumbagin treatment. Extracellular DNA formation was significantly inhibited at a concentration of 4 µg/mL, whereas the inhibition of extracellular polysaccharide and proteins required a higher concentration of 8 µg/mL. Overall, these results demonstrated the inhibitory effects of Plumbagin on Staphylococcus aureus biofilm formation and extracellular polymeric substances secretion, suggesting that extracellular DNA may be a potential target for the anti-biofilm activity of Plumbagin. These findings will provide new insights into the mode of action of Plumbagin in treating infections caused by Staphylococcus aureus biofilms.
研究领域:
微生物学
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药理学
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感染病学
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产品关联
DOI
PubMed
高影响因子
PHYTOMEDICINE
·
2017
·
IF 3.526
Jian Lu,Daozhi Liu,Xiaojing Zhou,Ang Chen,Zhenran Jiang,Xiyun Ye,Mingyao Liu,Xin Wang
Background Cytochrome P450 2J2 (CYP2J2) is not only highly expressed in many kinds of human tumors, but also promotes tumor cell growth via regulating the metabolism of arachidonic acids . CYP2J2 inhibitors can significantly reduce proliferation, migration and promote apoptosis of tumor cells by inhibiting epoxyeicosatrienoic acids (EETs) biosynthesis . Therefore screening CYP2J2 inhibitors is a significant way for the development of anti-cancer drug. Purpose The aim of this study was to identify a new CYP2J2 inhibitor from fifty natural compounds obtained from plants. Study design CYP2J2 inhibitor was screened from a natural compounds library and further the inhibitory manner and mechanism were evaluated. Its cytotoxicity against HepG2 and SMMC-7721 cell lines was also estimated. Methods The inhibitory effect was evaluated in rat liver microsomes (RLMs), human liver microsomes (HLMs) and recombinant CYP2J2 (rCYP2J2), using astemizole as a probe substrate and inhibitory mechanism was illustrated through molecular docking . The cytotoxicity was detected using SRB. Results In all candidates, plumbagin showed the strongest inhibitory effect on the CYP2J2-mediated astemizole O -demethylation activity. Further study revealed that plumbagin potently inhibited CYP2J2 activity with IC 50 value at 3.82 µM, 3.37 µM and 1.17 µM in RLMs, HLMs and rCYP2J2, respectively. Enzyme kinetic studies showed that plumbagin was a mixed-type inhibitor of CYP2J2 in HLMs and rCYP2J2 with K i value of 1.88 µM and 0.92 µM, respectively. Docking data presented that plumbagin interacted with CYP2J2 mainly through GLU 222 and ALA 223. Moreover, plumbagin showed strongly cytotoxic effects on hepatoma cell lines, such as HepG2 and SMMC-7721, with lower toxicity on rat primary hepatocytes. Plumbagin had no effect on the protein expression of CYP2J2 in HepG2 and SMMC-7721, while down-regulated the mRNA level of anti-apoptosis protein Bcl-2. Conclusion This study found out a new CYP2J2 inhibitor plumbagin from fifty natural compounds. Plumbagin presented a potential of anti-cancer pharmacological activity .
研究领域:
药理学
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肿瘤学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Scientific Reports
·
2016
·Vol. 6
·期 1
·1-12
·
IF 5.228
Chen Ang,Zhou Xiaojing,Tang Shuowen,Liu Mingyao,Wang Xin
Plumbagin (5-hydroxy-2-methyl-1,4-naphthoquinone), a natural naphthoquinone compound isolated from roots of Plumbago zeylanica L., has drawn a lot of attention for its plenty of pharmacological properties including antidiabetes and anti-cancer. The aim of this study was to investigate the effects of plumbagin on CYP1A2, CYP2B1/6, CYP2C9/11, CYP2D1/6, CYP2E1 and CYP3A2/4 activities in human and rat liver and evaluate the potential herb-drug interactions using the cocktail approach. All CYP substrates and their metabolites were analyzed using high-performance liquid chromatography–tandem mass spectrometry (LC-MS/MS). Plumbagin presented non-time-dependent inhibition of CYP activities in both human and rat liver. In humans, plumbagin was not only a mixed inhibitor of CYP2B6, CYP2C9, CYP2D6, CYP2E1 and CYP3A4, but also a non-competitive inhibitor of CYP1A2, with K i values no more than 2.16 μM. In rats, the mixed inhibition of CYP1A2 and CYP2D1, and competitive inhibition for CYP2B1, CYP2C11 and CYP2E1 with K i values less than 9.93 μM were observed. In general, the relatively low K i values of plumbagin in humans would have a high potential to cause the toxicity and drug interactions involving CYP enzymes.
研究领域:
药理学
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分析化学
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毒理学
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产品关联
DOI
PubMed
高影响因子
BIOFOULING
·
2025
·
IF 2
Hui Yuan,Ming Lu,Chen Shi,Chunshuang Li,Ze Yao,Hui Shang,Xiang Li,Heshui Yu,Songtao Bie
Plumbagin, also known as 5-hydroxy-2-methyl-1,4-naphthoquinone (PLB), is a naturally occurring naphthoquinone molecule that has demonstrated strong antibacterial and antibiofilm properties against Staphylococcus aureus (S. aureus). However, the potential of PLB to eradicate mature biofilms and the underlying mechanisms involved remain unclear. In this study explored the effects of PLB on disrupting mature S. aureus biofilms, focusing on its impact on the extracellular polymeric substances (EPS) and potential mechanisms of action. Crystal violet (CV) and XTT assays demonstrated that PLB significantly reduced both the biomass and metabolic activity of mature S. aureus biofilms in a concentration-dependent manner. High-content screening (HCS) imaging demonstrated that PLB treatment induced significant alterations in the biofilm EPS architecture, leading to a substantial reduction in overall biomass and average thickness, with disruption severity correlating positively with PLB concentration. Using molecular fluorescence probing techniques, this study found that treatment with PLB resulted in a marked reduction in EPS components, including extracellular polysaccharides (PIA), proteins, and extracellular DNA (eDNA), compared to untreated controls. Molecular docking analysis revealed that PLB strongly interacts with several key S. aureus proteins involved in EPS production, such as IcaA, IcaD, IcaB, IcaC, Bap, ClfB, and CidA, particularly binding strongly to the active sites of IcaA and Bap. Furthermore, gene expression analysis indicated that PLB downregulated genes associated with biofilm EPS production. Overall, these findings suggest that PLB effectively disrupts S. aureus biofilms by targeting the EPS. These results highlight PLB as a promising candidate for targeting mature S. aureus biofilms in chronic infections.
研究领域:
微生物学
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抗菌研究
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生物膜生物学
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药学
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分子对接
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传染病学
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产品关联
DOI
PubMed
高影响因子
RSC Advances
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2022
·Vol. 12
·期 25
·16046-16050
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IF 4.036
Yang Wang,Xin Sun,Yi Wang
Covalent organic frameworks have attracted increasing attention in the fields of nanotechnology and nanoscience. However, the biomedical applications of COFs still remain less explored. Here, a new type of nanoscale covalent organic framework (COF-366) composite was prepared by a facile solvothermal method. The obtained material was characterized by powder X-ray diffraction (XRD), Fourier transform-infrared spectroscopy (FTIR), and scanning electron microscopy (SEM). The results showed that the COF-366 nanocarriers possess uniform spherical morphology with a diameter of 150 nm, which make them favourable for drug delivery. After the plumbagin encapsulation, an effective pH responsive release, high adsorption capacity, and good biocompatibility were achieved. These characteristics make nanoscale COF-366 an ideal material for drug delivery and reveal its promising application in biomedical applications.
研究领域:
纳米技术
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生物医药材料
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药物递送系统
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产品关联
DOI
PubMed
高影响因子
PLoS One
·
2024
·Vol. 19
·期 1
·e0297493
·
IF 2.9
Songtao Bie,Qiuyue Mo,Chen Shi,Hui Yuan,Chunshuang Li,Tong Wu,Wenlong Li,Heshui Yu
Staphylococcus aureus is the main culprit, causing a variety of severe clinical infections. At the same time, clinics are also facing the severe situation of antibiotic resistance. Therefore, effective strategies to address this problem may include expanding the antimicrobial spectrum by exploring alternative sources of drugs or delaying the development of antibiotic resistance through combination therapy so that existing antibiotics can continue to be used. Plumbagin (PLU) is a phytochemical that exhibits antibacterial activity. In the present study, we investigated the in vitro antibacterial activity of PLU. We selected five antibiotics with different mechanisms and inhibitory activities against S . aureus to explore their interaction with the combination of PLU. The interaction of combinations was evaluated by the Bliss independent model and visualized through response surface analysis. PLU exhibited potent antibacterial activity, with half maximal inhibitory concentration (IC 50 ) and minimum inhibitory concentration (MIC) values against S . aureus of 1.73 μg/mL and 4 μg/mL, respectively. Synergism was observed when PLU was combined with nitrofurantoin (NIT), ciprofloxacin (CPR), mecillinam (MEC), and chloramphenicol (CHL). The indifference of the trimethoprim (TMP)-PLU pairing was demonstrated across the entire dose-response matrix, but significant synergy was observed within a specific dose region. In addition, no antagonistic interactions were indicated. Overall, PLU is not only a promising antimicrobial agent but also has the potential to enhance the growth-inhibitory activity of some antibiotics against S . aureus , and the use of the interaction landscape, along with the dose-response matrix, for analyzing and quantifying combination results represents an improved approach to comprehending antibacterial combinations.
研究领域:
药理学
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微生物学
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抗菌研究
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF FISH DISEASES
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2022
·Vol. 45
·期 6
·815-823
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IF 2.58
Ai-Guo Huang,Lin-Jun Su,Wei-Hao He,Fa-Li Zhang,Chao-Shuai Wei,Ying-Hui Wang
Streptococcus agalactiae , also known as Group B Streptococcus (GBS), can infect humans, terrestrial animals and fish. The emergence of bacterial resistance of S. agalactiae to antibiotics leads to an urgent need of exploration of new antimicrobial agents. In the study, the antibacterial activity of natural component plumbagin (PLB) against S. agalactiae was investigated in vitro and in vivo. The results showed that the minimal inhibitory concentration (MIC) of PLB against S. agalactiae was 8 mg/L. The growth curve assay revealed that PLB could inhibit the growth of S. agalactiae . In addition, the time-killing curve showed that S. agalactiae was killed almost completely by 2-fold MIC of PLB within 12 h. Transmission electron microscopy results showed obvious severe morphological destruction and abnormal cells of S. agalactiae after treated with PLB. The pathogenicity of S. agalactiae to zebrafish was significantly decreased after preincubation with PLB for 2 h in vitro, further indicating the bactericidal activity of PLB. Interestingly, PLB could kill S. agalactiae without inducing resistance development. Furthermore, pretreatment and post-treatment assays suggested that PLB also exhibited the antibacterial activity against S. agalactiae infection in vivo by effectively reducing the bacterial load and improving the survival rate of S. agalactiae -infected zebrafish. In summary, PLB had potent antibacterial activity against S. agalactiae in vitro and in vivo, and it could be an excellent antimicrobial candidate to prevent and control S. agalactiae infection.
研究领域:
微生物学
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药物开发
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感染病学
✓ 已验证
DOI
高影响因子
Drug Design Development and Therapy
·
2026
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IF 6.1
Dong Fan,Zongming Wang,Shixue Luo,Xuanhao Huang,Xingyi Yuan,Yanan Wang,Zhongyu Wang,Huitong Chen,Weiwen Wang,Yuxin Ma,Chang Zhou,Xiaobao Jin,Jing Liu,Xin Wang
Background: Nonfunctioning pituitary adenoma (NFPA) is among the most prevalent intracranial tumors. As surgical resection remains the primary treatment, there is a need for new therapeutic strategies. Plumbagin (PLB), a bioactive naphthoquinone compound derived from the roots of Plumbaginaceae Juss, has been used in anti-tumor research in recent years, but its mechanism remains controversial.Purpose: The aim of this study was to explore the molecular mechanism of PLB-induced ferroptosis in NFPA.Methods: The cell viability of PLB against PDFS cells was first assessed by CCK-8, colony formation, and EDU assays. Network pharmacology, molecular docking, and molecular dynamics were then used to screen out targets associated with ferroptosis. Finally, the Nrf2/FTH1 pathway was validated by a 3D multicellular tumour spheroids (MCTSs) model, q-PCR, and Western blot in vitro and in vivo.Results: Compared to temozolomide (TMZ), PLB more potently inhibited the viability of PDFS cells. In vitro, PLB treatment was associated with downregulation of the Nrf2/FTH1 pathway, accompanied by increased lipid peroxidation and labile iron pool (LIP) accumulation. Furthermore, PLB treatment led to the upregulation of NCOA4 and an increase in intracellular free iron, consistent with ferritinophagy activation. These effects collectively point to the induction of ferroptosis.Conclusion: This study demonstrates that PLB may induce ferroptosis in PDFS cells. The mechanism involves suppression of the Nrf2/FTH1 pathway, subsequent upregulation of NCOA4, and ferritinophagy-driven iron overload. These results identify PLB as a potential ferroptosis inducer and warrant further investigation into its therapeutic potential for NFPA. The image shows a biochemical pathway illustrating ferritinophagy and ferroptosis. Iron in the form of Fe superscript 3 is transported by transferrin into the cell, where it is stored in ferritin. Ferritin is directed to the autolysosome, facilitated by Lamp2, where iron is released as Fe superscript 2. NCOA4 and LC3 are involved in ferritinophagy, leading to the labile iron pool. The Fenton reaction produces reactive oxygen species, contributing to ferroptosis. Nrf2 regulates FTH1, with arrows indicating promotion and inhibition. Plumbagin is shown affecting the pathway, with an illustration of a mouse receiving an injection, highlighting the interaction between NCOA4, FTH1 and Nrf2 in the brain. Arrows indicate promotion and inhibition effects within the pathway.Diagram of ferritinophagy and ferroptosis: iron regulation, NCOA4, FTH1, Nrf2 and plumbagin effects.
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DOI
PubMed
高影响因子
JOURNAL OF MATERIALS SCIENCE
·
2025
·
IF 3.9
Wang Kexin,Li Mingyang,Geng Yiming,Fu Xiao,Chen Zhanwei
Chronic non-healing wounds typically arise from bacterial adhesion and colonization. Plumbagin (PLB), a secondary metabolite derived from Droseraceae , Plumbaginaceae , and Ebenceae, exhibits potent antibacterial activity. In this study, zeolite imidazole framework-8 (ZIF-8) was utilized to encapsulate Plumbagin, constructing the nanoparticle PLB@ZIF. In both in vitro antibacterial experiments and in vivo wound healing assays , PLB@ZIF demonstrated effective synergistic therapy against methicillin-resistant S. aureus (MRSA) and Escherichia coli ( E. coli ). In addition, compared to PLB or ZIF-8 alone, PLB@ZIF exhibited superior antibacterial efficacy. These results suggested that ZIF-8 significantly enhances the antibacterial efficiency of Plumbagin in wound healing, highlighting the broad application potential of PLB@ZIF for treating wound infection caused by MRSA and E. coli .
研究领域:
纳米技术
·
药剂学
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微生物学
·
生物医学工程
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
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2025
·
IF 4.9
Chunshuang Li,Ming Lu,Ze Yao,Ruobing Liu,Ding Lu,Tenglong Ma,Xiang Li,Hui Shang,Songtao Bie
Bacterial biofilms play a critical role in chronic wound infections by significantly delaying wound healing. Staphylococcus aureus , one of the most prevalent biofilm-forming pathogens, secretes extracellular polymeric substances that effectively protect it from host immune defenses and antibiotic treatments. To address this challenge, nanoscale antibacterial strategies have attracted increasing attention in recent years. By encapsulating antibacterial agents within nanocarriers, drug penetration into biofilms can be enhanced, thereby improving bioavailability. In this study, we synthesized bovine serum albumin-functionalized carbon nanoparticles (CB) via the functionalization method. The antibacterial agent plumbagin (PLB) was subsequently loaded onto them to form nanocomposites (CB-PLB). We comprehensively characterized their physicochemical properties, including particle size, polydispersity index, morphology, drug-loading efficiency, thermal behavior (differential scanning calorimetry, DSC), crystallinity (X-ray diffraction, XRD), spectroscopic features, solubility, and in vitro drug-release profiles. Specifically, we examined the impact of CB-PLB on both biofilm formation and established mature biofilms of Staphylococcus aureus . In comparison to PLB, CB-PLB showed better antibacterial and anti-biofilm activity against formed and matured biofilm using crystal violet staining and XTT assay. High-content screening imaging analyses confirmed that CB-PLB exerted potent disruptive effects, including reduction of biomass, mean thickness, and alteration of biofilm roughness. Furthermore, molecular docking analysis confirmed specific interactions among carbon nanoparticles (CNP), PLB, and bovine serum albumin (BSA). These findings highlight the synergistic interaction between CB and PLB, suggesting that CB is a promising nanocarrier for hydrophobic antibacterial agents.
研究领域:
纳米医学
·
药剂学
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微生物学
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分子生物学
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生物材料
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感染性疾病
✓ 已验证
产品关联
DOI
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2024
·
IF 5.3
Chenyu Cao,Yifei Li,Fangzhou Shi,Shanshan Jiang,Yutong Li,Leilei Yang,Xinyi Zhou,Yuqiong Gao,Feiyan Tang,Huan Li,Shulan Han,Zhuo Yu,Yifang Zou,Jianfeng Guo
Doxorubicin (DOX) is a chemotherapy drug used for hepatocellular carcinoma (HCC) treatment, but its effectiveness can be dramatically dampened by cancer cell chemoresistance. Signal transducer and activator of transcription 3 (STAT3) is implicated with drug resistance in a range of cancers (e.g., HCC), and the STAT3 inhibition can reverse the resistance of cancer cells to chemotherapeutic drugs. In the present study, a combination regimen to improve the efficiency of DOX was provided via the STAT3 blockade using plumbagin (PLB). A poly(lactic-co-glycolic acid) decorated by polyethylene glycol and aminoethyl anisamide was produced in the present study with the hope of generating the nanoparticles for co-delivery of DOX and PLB. The resulting co-formulation suppressed the STAT3 activity and achieved the synergistic chemotherapy, which led to tumor inhibition in the mice with subcutaneous DOX-resistant HCC, without causing any toxicity. The present study reveals the synergism of DOX and PLB, and demonstrates a promising combinatorial approach for treating HCC.
研究领域:
肿瘤学
·
药理学
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纳米医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PHARMACOLOGICAL RESEARCH
·
2026
·
IF 12.2
Minglv Fang,Ying Liu,Yongli Han,Yashi Xu,Jing Yu,Yingxuan Yan,Zhigang Jin,Xiaojun Wu,Cheng Huang,Shengjie Fan
Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system (CNS) with limited therapeutic options. Stress granules (SGs), membraneless organelles formed via liquid-liquid phase separation (LLPS) in response to cellular stress, function as a cytoprotective mechanism against stress induced apoptosis and pyroptosis. SGs can counteract NLRP3 inflammasome by sequestering dead-box helicase 3 X-linked (DDX3X), thereby promoting the survival of pyroptotic cells. Here, we identified that plumbagin (PL), a natural naphthoquinone with antioxidant and anti-inflammatory properties, as a novel SG inducer. In microglia, PL induced SGs that suppressed NLRP3-mediated pyroptosis and subsequent mitochondrial dysfunction, with DDX3X as a potential target. Furthermore, PL alleviated neuroinflammation and demyelination and suppressed oxidative stress in the CNS of both the cuprizone (CPZ) and experimental autoimmune encephalomyelitis (EAE) mouse models. Our findings reveal that PL can mitigate neuroinflammation and myelin damage by modulating the DDX3X-SG axis, supporting a novel therapeutic strategy for MS.
✓ 已验证
DOI
PubMed
高影响因子
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