INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2025
·
IF 8.5
Qiang Ma,Meinuo Chen,Zhimeng Zhang,Jianuo Cen,Shiqi Chen,Qiqi Wang,Ke Han,Zhiyue Feng,Congming Wu,Chongshan Dai,Yougang Zhong,Sihan Wang,Haiyang Jiang
Methicillin-resistant Staphylococcus aureus (MRSA) represents a serious global health challenge due to its resistance to multiple antibiotics, especially β-lactams, which limits treatment options and results in high morbidity and mortality rates. Thus, there is an urgent need for effective antibacterial agents and a deeper understanding of their mechanisms of action to combat the increasingly severe threat of bacterial resistance. In this study we have performed microbiological, molecular biology experiments and molecular dynamics simulations to investigate the antimicrobial efficacy of the sanguinarine (SAN) against MRSA and its conformational modulation of the Filamentous temperature-sensitive mutant Z (FtsZ). Our findings indicate that SAN exhibits promising anti-MRSA activity and spontaneously targets the nucleoid binding domain (NBD) of SaFtsZ to inhibit bacterial division. Additionally, SAN induces multiple single-nucleotide polymorphisms (SNPs) in the SaFtsZ coding gene, including Asp187, and site-directed mutagenesis confirms the critical role of this residue in binding. Notably, SAN causes the unfolding of SaFtsZ, significantly reducing the structural flexibility required for polymerization and triggering conformational changes. At higher dimensions, SAN disrupts protofilaments assembly, ultimately inhibiting septum formation and division. These findings provide multidimensional, high-resolution insights into the interaction between SAN and SaFtsZ, offering effective strategies for the prevention and eradication of MRSA.
研究领域:
微生物学
·
药理学
·
生物化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PHYTOMEDICINE
·
2025
·
IF 8.3
Qianwei Qu,Xingyu Huang,Zhenxin Zhu,Jun Wang,Mengmeng Zhao,Wenqiang Cui,Yadan Zheng,Yanyan Liu,Xueying Chen,Zhiyun Zhang,Na Dong,Chunliu Dong,Yanhua Li
Background Staphylococcus aureus is an opportunistic pathogen capable of readily forming biofilms, which can result in life-threatening infections involving different organs. Sanguinarine are benzo[c]phenanthridine alkaloids extracted from the Sanguinaria canadensis L. (Papaveraceae), which have a wide range of biological activities. Previous reports have shown that sanguinarine is able to induce an elevation of ROS to exert an anti- S. aureus effect. Nevertheless, the specific mechanism of action of sanguinarine against S. aureus biofilms remains unexplored. Purpose The objective of this study was to elucidate the target site of sanguinarine in S. aureus , as well as to investigate its mechanism of antimicrobial action and its interference with biofilm formation. Additionally, the study aimed to provide further evidence supporting the use of sanguinarine as an alternative to traditional antibiotics. Methods Initially, we assessed the in vitro anti- S. aureus properties of sanguinarine through a series of methodologies, including MIC assays, time-dependent assays, and resistance development studies. Secondly, we explored the antimicrobial mechanism of sanguinarine using TEM, membrane permeability assays, and membrane fluidity assays. Subsequently, the mechanism by which sanguinarine interferes with S. aureus biofilm formation was preliminarily analyzed in vitro . Additionally, the interaction between sanguinarine and imidazoleglycerol-phosphate dehydratase (IGPD) was investigated using bio-layer interferometry assays, circular dichroism spectroscopy, molecular docking, and site-directed mutagenesis to further elucidate the role of sanguinarine in biofilm disruption. Finally, the therapeutic efficacy of sanguinarine was evaluated in vivo using mouse models of biofilm and bacteremia. Results Herein, sanguinarine demonstrated notable antimicrobial properties and interfering effects on biofilm formation. Mechanistic investigations revealed that sanguinarine exerts its antimicrobial action by dissipating the proton motive force in bacteria and compromising the integrity and functionality of the cytoplasmic membrane. Furthermore, sanguinarine was found to regulate IGPD expression and inhibit L-histidine synthesis, thereby interfering S. aureus biofilm formation. Consequently, due to its polypharmacological effect, sanguinarine significantly reduced the S. aureus load in mouse organs and the formation of biofilm on the surface of implants in vivo without any resistance. Conclusions In this study, we demonstrated that sanguinarine can exert antibacterial and interfere with biofilm formation by disrupting the cell membrane of S. aureus and targeting IGPD. These findings suggest that sanguinarine holds potential for further development as a novel antibiotic to combat biofilm-associated infections.
研究领域:
微生物学
·
药理学
·
感染与免疫
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Analytical Methods in Chemistry
·
2021
·
IF 2.193
Shi-han Qin,Yuan Xu,Kai-lin Li,Kai-yan Gong,Jie Peng,Si-lin Shi,Fang Yan,Wei Cai
Aurantio-obtusin (AO) is a major anthraquinone compound isolated from Cassiae Semen or Duhaldea nervosa, which possesses diverse pharmacological effects. Previous studies have shown that it has a good effect on lowering blood lipids and treating various diseases. A few studies have also reported about its metabolites. A rapid and reliable method using ultra-high-performance liquid chromatography-Q-Exactive Orbitrap mass spectrometry and multiple data-processing technologies was established to investigate the metabolites of AO in the plasma and various tissues of rats, including the heart, liver, spleen, lung, kidneys, and brain. Finally, a total of 36 metabolites were identified in the plasma of rats, which could be very beneficial for understanding the effective form of AO metabolites leading to new drug discovery. The result demonstrated that this strategy, especially parallel reaction monitoring, has shown a wide range of applications in the identification of metabolites.
研究领域:
药理学
·
分析化学
·
代谢组学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF FOOD COMPOSITION AND ANALYSIS
·
2022
·
IF 4.52
Mi Wei,Huiyin Liu,Zhilin Zhang,Xuemin Chen,Zhenhua Guo,Xiangxia Yang
As a specialty food that is medicinal and edible, Anoectochilus roxburghii contains many active ingredients. Herein, optimal conditions to preserve A. roxburghii samples and obtain high physiological activity have been studied. The contents of polysaccharides , kinsenoside, and flavonoids of A. roxburghii were monitored during post-harvest storage for a period of eight months at 25 °C with different packaging methods such as stacking, multilayer pocket and vacuum. The results indicated that packaging method and storage time have significant influences on the preservation of active compounds. Polysaccharides, kinsenoside and flavonoids exhibited a general descending trend during storage for a period of eight months in all packaging conditions. However, the vacuum method is more effective in preservation of polysaccharides and flavonoids than stacking and multilayer pockets methods due to the lower activity of microbial community under vacuum condition. Interestingly, kinsenoside, a characteristic compound of A. roxburghii , responsive for the hypoglycemic function, was not affected by packaging methods. This is because kinsenoside was mainly affected by plant endogenous enzymes instead of microbial community. Two-factor variance analysis showed that packaging method and storage time have significant interactions in preservation. It was further disclosed that the changes of active components were closely related to the plant endogenous enzymes, microbial community and their functions. The findings in this study will shed some light on the storage of A. roxburghii and other herb products.
研究领域:
食品科学
·
药理学
·
植物学
·
微生物学
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF SEPARATION SCIENCE
·
2023
·Vol. 46
·期 7
·2200823
·
IF 3.1
Gaodan Liu,Simin Feng,Minghui Sui,Bilian Chen,Peilong Sun
In this study, quartz sand with particularly sharp nanoscale edges acted like a nanoscale knife physically cut cells of Polygonatum cyrtonema Hua into nanosized particles and was synergized with natural deep eutectic solvent to extract steroidal saponins of Polygonatum cyrtonema Hua. The natural deep eutectic solvent (choline chloride-lactic acid)-synergistic quartz sand-assisted extraction was optimized using response surface methodology. The steroidal saponins purified with AB-8 macroporous resin were identified using ultra-high-performance liquid chromatography-triple time of flight mass spectrometry. The results showed that the experimental total saponins content value (36.97 ± 0.12 mg dioscin equivalent/g dry weight) at optimal extraction conditions with a temperature of 68°C, a rotational speed of 20 400 rpm, shear time of 4.3 min, the liquid-solid ratio of 38 ml/g, was close to the maximum possible theoretical value (36.64 mg dioscin equivalent/g dry weight). A total of 20 steroidal saponins were identified, among which the content of (25 R )-Kingianoside E was the highest (102.66 ± 3.47 mg/g). Furthermore, a new steroid saponin (3 β ,25 S )-26-( β -D-glucopyranosyloxy)-22-hydroxyfurost-5-en-3-yl 4- O - β -D-glucopyranosyl- β -D-galactopyranoside+Glc was found for the first time. These results revealed that natural deep eutectic solvent-synergistic quartz sand-assisted extraction was an efficient and green method to extract a variety of steroidal saponins.
研究领域:
药学化学
·
分析化学
·
植物科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）