JOURNAL OF ETHNOPHARMACOLOGY
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2021
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IF 4.36
Junyu Tao,Shilun Yan,Chuyue Zhou,Qiong Liu,Hui Zhu,Zhen Wen
Ethanopharmacological relevance Potentilla kleiniana Wight et Arn is a wide-spread wild plant in the mountainous areas in southern China. The whole herb has been used as a traditional herbal medicine to treat fever, arthritis , malaria, insect and snake bites , hepatitis, and traumatic injury. In vitro studies have reported the antibacterial activity use of the plant in traditional medicinal systems. Aim of the study The aim of this study was to investigate the inhibitory activity of total flavonoid from Potentilla kleiniana Wight et Arn (TFP) on methicillin-resistant Staphylococcus aureus (MRSA) in planktonic state and biofilm state. Materials and methods Antibacterial activities of TFP on planktonic MRSA were determined by agar diffusion method, microtiter plate assay and time-kill curve assay. Electrical conductivity, membrane permeability, membrane potential and autoaggregation were analyzed to study TFP effects on planktonic MRSA growth. Crystal violet (CV) staining and confocal laser scanning microscopy (CLSM) were analyzed to study TFP effects on aggregation and maturation of MRSA biofilm. After TFP treatment, extracellular polymeric substances (EPS) production were examined. Morphological changes in planktonic and MRSA biofilm following TFP treatment were determined with scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Moreover, α-Toxin protein expression and adhesion-related gene expression were also determined. Results The minimum inhibitory concentration (MIC) of TFP against MRSA was 20 μg/mL. The agar diffusion method and time-kill curve assay results indicated that TFP inhibited planktonic MRSA growth. TFP treatment significantly inhibited planktonic MRSA growth by inhibiting autoaggregation, α-hemolysin activity, α-Toxin protein expression, but increasing electrolyte leakage, membrane permeability and membrane potential and impacting cell structure. Moreover, TFP treatment significantly inhibited aggregation and maturation on MRSA biofilm by decreasing surface hydrophobicity , EPS production and adhesion-related gene expression. Conclusion The results of this trial provide scientific experimental data on the traditional use of Potentilla Kleiniana Wight et Arn for traumatic injury treatment and further demonstrate the potential of TFP to be developed as a novel anti-biofilm drug.
研究领域:
药理学
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微生物学
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民族药理学
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植物科学
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高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
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2024
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IF 4.8
Qing-Yu Lu,Zhao-Jie Wang,Li-Yu Bai,Wen-Biao Zu,Zhong-Shun Zhou,Yan-Yan Zhu,Yun-Li Zhao,Xiao-Dong Luo
Ethnopharmacological relevance Caryopteris trichosphaera W. W. Sm., a traditional ethnic medicine, was recorded in the Compendium of Materia Medica for treating wound infection by pathogenic infection. However, its antibacterial potential and bioactive compositions against drug-resistant bacteria need to be validated. Aim of the study To investigate the chemical constituents of C. trichosphaera and explore its anti-MRSA component in vitro and in vivo , together with the antibacterial mechanism. Materials and methods Bioactive constituents investigation was carried out by phytochemical method and antibacterial screening. The antibacterial mechanism was predicted by network pharmacology, which was further validated by time-kill analysis, membrane function tests, multigenerational resistance induction assay and biofilm test, and metabolomics analysis in vitro. In addition, MRSA-induced epidermal infection in mice was selected to evaluate its pharmacological effect in vivo . Results Six antibacterial diterpenoids against MRSA and VRE with MIC values 4–32 μg/mL from C. trichosphaera were reported for the first time, in which the major compound cativic acid ( 1 ) disrupted MRSA cell membranes by modulating permeability, depolarization, and fluidity while increasing reactive oxygen species (ROS) and malondialdehyde (MDA) levels. It also displayed remarkable anti-biofilm activity without inducing bacterial resistance or cytotoxicity. Moreover, cativic acid affected MRSA biosynthesis of cofactors, amino acid biosynthesis, nucleotide metabolism by metabolomics analysis. Furthermore, cativic acid accelerated wound healing in MRSA-infected mouse skin wounds, even better than vancomycin. Conclusions The results supported the traditional use of C. trichosphaera , and presented unreported anti-MRSA agent, cativic acid, as a plant-derived bactericide in vitro and in vivo for the first time.
研究领域:
药理学
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微生物学
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民族药理学
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植物化学
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传染病学
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高影响因子
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
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2019
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IF 3.532
Yong Guo,Ting Xu,Chongnan Bao,Zhiyan Liu,Jiangping Fan,Ruige Yang,Shangshang Qin
Toward the search of new antibacterial agents to control methicillin-resistant Staphylococcus aureus (MRSA), a class of new norfloxacin-1,3,4-oxadiazole hybrids were designed and synthesized. Antibacterial activities against drug-sensitive bacteria S. aureus and clinical drug resistant isolates of MRSA were evaluated. Compound 5k exhibited excellent antibacterial activities against S. aureus (MIC: 2 μg/mL) and MRSA1–3 (MIC: 0.25–1 μg/mL). The time-kill kinetics demonstrated that compound 5k had an advantage over commonly used antibiotics vancomycin in killing S. aureus and MRSA. Moreover, compound 5k could inhibit the bacteria and destroy their membranes in a short time, and showed very low cytotoxicity to NRK-52E cells. Some interesting structure-activity relationships (SARs) were also discussed. These results indicated that these norfloxacin-1,3,4-oxadiazole hybrids could be further developed into new antibacterial agents against MRSA.
研究领域:
药物化学
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微生物学
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药理学
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PubMed
高影响因子
ADVANCED FUNCTIONAL MATERIALS
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2024
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IF 18.5
Hao Cheng,Yongqiang Yang,Yueyue Wang,Jiqiang Guo,Xiong Jiao,Di Huang,Meiwen An,Xiaohong Yao,Paul K. Chu,Xiangyu Zhang
The hypoxic environment of deep tissue and the weak energy of microwave (MW) are still the major limitations of MW catalytic therapy. In this work, an MW-responsive nano-platform consisting of an Mn-doped porphyrin metal–organic framework loaded with calcium peroxide (Mn 0.1 PCC) is designed to regulate the microenvironment of the injection site and enhance the generation of reactive oxygen species. The excellent MW absorbing properties of Mn 0.1 PCC improve the Fenton reaction between hydrogen peroxide formed by the hydrolysis of calcium peroxide and released Mn 2+ generating more hydroxyl radicals under MW. This process does not consume the oxygen substrate and even produces oxygen to improve the hypoxic environment. Therefore, at a low and safe concentration (125 µg mL −1 ), the antibacterial rate of Mn 0.1 PCC against 4 × 10 8 CFU mL −1 of methicillin-resistant Staphylococcus aureus (MRSA) after MW irradiation for 15 min is 99.71% ± 0.18%. Mn 0.1 PCC, upon exposure to MW, prevents the recurrence of bacterial infections and overcomes drug resistance by inhibiting quorum sensing and the two-component system of MRSA. It can also induce macrophage M1 polarization, up-regulate the pro-inflammatory factor tumor necrosis factor-α, and enhance the phagocytosis of macrophage to bacteria. This strategy provides insights into the development of high-performance MW-responsive nanocomposites for the treatment of infections in deep tissues.
研究领域:
纳米技术
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生物医学工程
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传染病学
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材料科学
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药学
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高影响因子
ACS Applied Materials & Interfaces
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2025
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IF 8.2
Xingyue Yang,Ren Fang,Xiaotian Li,Weihao Kong,Yubao Jin,Ruohan Jiao,Zhenggong Liu,Meiqi Zhang,Qixian Peng,Yumiao Zhang,Ningning Song
The clinical treatment of hospital-acquired persistent osteomyelitis caused by methicillin-resistant Staphylococcus aureus (MRSA) presents two major challenges: ineffective drug delivery into deep tissues and counteracting the rapid establishment of an immunosuppressive microenvironment. Indeed, MRSA can evade immunosurveillance and undermine both innate and adaptive immune responses. Herein, the engineered nanovesicles, functioning by combining sonodynamic therapy (SDT) with immune modulation, were constructed for the precise and noninvasive removal of MRSA in deep tissue and activation of the antimicrobial immune response using a newly engineered nanovesicle. Macrophage-derived M1 phenotypic microvesicles (M1-MW) internalized vancomycin-cross-linked micelles with the acoustic sensitizer indocyanine green (ICG) (VCG micelles). The vesicles of M1-MW were grafted with PEGylated mannose, allowing for targeted accumulation at the infection site. The VCG micelles were responsive to the highly reducing environment and released ICG to generate ROS after exposure to ultrasounds. This effect was combined with the presence of vancomycin to kill MRSA. In an osteomyelitis infection model, we observed an improved survival rate and reprogramming of macrophages to a pro-inflammatory M1 phenotype. The latter promoted T-cell activation and immune defense against MRSA-camouflaged homologous cell-transferred infections. Thus, our study presents a noninvasive and efficient treatment (VCG@MMW) for deep osteomyelitis with improved bacterial clearance and reduced risk of recurrence with enhanced immune response.
研究领域:
纳米技术
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传染病学
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免疫学
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药学
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生物医学工程
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PubMed
高影响因子
ACS Applied Materials & Interfaces
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2021
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IF 9.229
Pengpeng Deng,Feixiang Chen,Haodong Zhang,Yun Chen,Jinping Zhou
The abuse of antibiotics induces the emergence of drug-resistant bacteria, which greatly increases the difficulty of clinical treatment of infected wounds. It is urgent to design a multifunctional wound dressing independent of antibiotics. In this work, we designed multifunctional hydrogels based on lignin and cellulose in natural polymers. Lignin with antioxidant properties could reduce silver nanoparticles in situ and could also be used as a crosslinking agent to construct hydrogels between hydroxypropyl cellulose modified with phenylboric acid by a dynamic borate bond. Hydrogels have excellent properties such as self-healing, shape adaptability, biocompatibility, blood compatibility, antioxidant properties, excellent broad-spectrum antimicrobial properties, good tissue adhesion, and electrical conductivity. The tissue adhesion of hydrogels endows them with an excellent hemostasis property in a rat liver injury model. In vivo experiments demonstrated that hydrogels can maintain a moist healing environment, reduce inflammatory cell infiltration, promote M2 macrophage polarization, accelerate collagen deposition, promote the regeneration of new blood vessels, and significantly speed up the wound healing of methicillin-resistant Staphylococcus aureus (MRSA)-infected wounds. Therefore, these multifunctional hydrogels are an excellent candidate to treat multiple stages of wound healing and have a broad application prospect in the medical field.
研究领域:
材料科学
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生物材料
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纳米技术
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伤口愈合
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抗菌治疗
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生物医学工程
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PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2025
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IF 8.5
Mingzhen Kang,Mojtaba Koosha,Tianduo Li,Xiwen Geng
In this study, pullulan was oxidized by NaIO 4 into low, medium and high oxidation degrees (OPL1,OPL2,OPL3) and used as a crosslinker to enhance physicochemical and biological properties of the wound dressings based on polyvinyl alcohol(PVA)/chitosan/collagen (FPL,FOPL1,FOPL2,FOPL3). Physicochemical, mechanical and biological properties of OPL samples as well as crosslinked films were characterized. The results showed that OPL not only increased the cell viability of human skin fibroblasts but also promoted antibacterial activity. Fourier transform infrared spectroscopy, rheological and gel content results proved the crosslinking effect of OPL. Mechanical properties of FOPL2 and FOPL3 films was >2 times higher than FPL film. The viability of human skin fibroblast cells was higher than the control for all films, and antibacterial activity of the film FOPL3 was significantly higher compared to other films. Wound healing effect of FOPL3 film was evaluated in a methicillin-resistant staphylococcus aureus (MRSA) infected full-thickness skin defect model in mice. The results showed a significantly lower wound area after 7,10,14 days of treatment compared to the control group treated by normal saline. The findings of this research enlighten wound healing potentials of oxidized pullulan to be used as a multifunctional ingredient for the development of future skin care biomaterials.
研究领域:
生物材料学
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医学
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微生物学
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PubMed
高影响因子
ACS Applied Materials & Interfaces
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2023
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IF 9.5
Ling Cai,Li Zhang,Jing Yang,Xinyi Zhu,Wei Wei,Minghui Ji,Huijun Jiang,Jin Chen
With the increasing prevalence of microbial infections, which results in prolonged inflammation and delayed wound healing, the development of effective and safe antimicrobial wound dressings of multiple properties remains challenging for public health. Despite their various formats, the available developed dressings with limited functions may not fulfill the diverse demands involved in the complex wound healing process. In this study, multifunctional sandwich-structured electrospinning nanofiber membranes (ENMs) were fabricated. According to the structural composition, the obtained ENMs included a hydrophilic inner layer loaded with curcumin and gentamicin sulfate, an antibacterial middle layer consisting of bovine serum albumin stabilized silver oxide nanoparticles, and a hydrophobic outer layer. The prepared sandwich-structured ENMs (SNM) exhibited good biocompatibility and killing efficacy on Escherichia coli, Staphylococcus aureus, and Methicillin-resistant S. aureus (MRSA). In particular, transcriptomic analysis revealed that SNM inactivated MRSA by inhibiting its carbohydrate and energy metabolism and reduced the bacterial resistance by downregulating mecA. In the animal experiment, SNM showed improved wound healing efficiency by reducing the bacterial load and inflammation. Moreover, 16S rDNA sequencing results indicated that SNM treatment may accelerate wound healing without observed influence on the normal skin flora. Therefore, the constructed sandwich-structured ENMs exhibited promising potential as dressings to deal with the infected wound management.
研究领域:
材料科学
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纳米技术
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生物医学工程
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药学
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微生物学
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PubMed
高影响因子
Acta Biomaterialia
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2021
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IF 8.947
Shuocheng Huang,Shibo Xu,Yanan Hu,Xingjun Zhao,Linna Chang,Zhenhua Chen,Xifan Mei
Multidrug-resistant (MDR) bacteria-induced infection is becoming a huge challenge for clinical treatment, especially for non-healing diabetic wound infections, which increase patient mortality. MRSA infections and delayed wound healing (methicillin-resistant Staphylococcus aureus) accounted for a higher proportion. Although surgical debridement and continuous use of antibiotics are still the main clinical treatments, new multifunctional therapeutic nanoplatform are attractive for MIDW. Thus, in the present study, black phosphorus quantum dots (BPQDs) encapsulated in hydrogel ( [email protected] ) were utilized as nanoplatforms for MIDW treatment to achieve the multifunctional properties of NIR (near infrared) responsiveness, ROS (reactive oxygen species) generation and antibacterial activity . Upon NIR irradiation, the temperature of the [email protected] MIDW area rapidly increased up to 55 °C for sterilization. In vitro experiments showed that [email protected] exerted a synergistic effect on inhibiting MRSA by producing of ROS, lipid peroxidation , glutathione , adenosine triphosphate accumulation and bacterial membrane destruction upon NIR irradiation. The resulting [email protected] achieved an effective sterilization rate of approximately 90% for MRSA. Furthermore, animal experiments revealed that [email protected] achieved an effective closure rate of 95% for MIDW after 12 days by reducing the inflammatory response and regulating the expression of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF). Meanwhile, intravenous circulation experiments showed good biocompatibility of BPQDs, and no obvious damage to rat major organs was observed. The obtained results indicated that [email protected] achieved the synergistic functions of NIR-responsiveness, ROS generation, and antibacterial activity and promoted wound healing, suggesting that they are promising multifunctional nanoplatforms for MIDW healing. Statement of significance 1. NIR-triggered ROS-generating and antibacterial nanoplatforms are attractive in the wound healing field. 2. In this work, black phosphorus quantum dots encapsulated in a hydrogel were used as a nanoplatform for treating MRSA infected wounds. 3. The obtained materials have achieved an effective sterilization rate for MRSA and effective wound closure rate.
研究领域:
纳米技术
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生物医学工程
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药学
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材料科学
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细菌学
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伤口愈合
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PubMed
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International Journal of Nanomedicine
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2023
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IF 8
Jihui Lu,Zhijia Wang,Desheng Cai,Xiaoyu Lin,Xuemei Huang,Zhihua Yuan,Yaozhi Zhang,Haimin Lei,Penglong Wang
Background Deaths from bacterial infections have risen year by year. This trend is further aggravated as the overuse antibiotics and the bacterial resistance to all known antibacterial agents. Therefore, new therapeutic alternatives are urgently needed.Methods Enlightenment the combination usage of traditional herb medicine, one carrier-free binary nanoparticles (GA-BBR NPs) was discovered, which was self-assembled from gallic acid and berberine through electrostatic interaction, π-π stacking and hydrophobic interaction; and it could be successfully prepared by a green, cost-effective and “one-pot” preparation process.Results The nanoparticles exhibited strong antibacterial activity and biofilm removal ability against multidrug-resistant S. aureus (MRSA) by downregulating mRNA expression of rpsF, rplC, rplN, rplX, rpsC, rpmC and rpsH to block bacterial translation mechanisms in vitro and in vivo, and it had well anti-inflammatory activity and a promising role in promoting angiogenesis to accelerate the wound healing on MRSA-infected wounds model in vivo. Additionally, the nanoparticles displayed well biocompatibility without cytotoxicity, hemolytic activity, and tissue or organ toxicity.Conclusion GA-BBR NPs originated from the drug combination has potential clinical transformation value, and this study provides a new idea for the design of carrier-free nanomedicine derived from natural herbals.
研究领域:
药学
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纳米技术
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微生物学
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伤口愈合
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中医药
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生物医学工程
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DOI
PubMed
高影响因子
Frontiers in Microbiology
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2021
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IF 5.64
Xu Lanlan,She Pengfei,Chen Lihua,Li Shijia,Zhou Linying,Hussain Zubair,Liu Yaqian,Wu Yong
Staphylococcus aureus is an important pathogen causing hospital-acquired infections. Methicillin-resistant S. aureus (MRSA), biofilms, and persisters are highly tolerant to traditional antibiotics and make it difficult to treat. Therefore, new antimicrobial agents are urgently needed to treat hard-to-eradicate diseases caused by this bacterium. In this study, candesartan cilexetil (CC), an angiotensin hypertension drug, had strong antimicrobial activity against S. aureus with minimal inhibitory concentrations (MICs) and minimal bactericidal concentrations (MBCs) of 8–16 μg/ml and 16–32 μg/ml. CC exhibited limited cytotoxicity and low potential to induce drug resistance. In addition, it showed a synergistic antibacterial effect when combined with gentamicin and tobramycin. The effective concentrations to inhibit MRSA biofilm formation were 16–64 μg/ml, and intractable persisters were killed at 4–8 × MIC. Through the analysis of its mechanism of action, it was evident that the membrane permeability was disrupted as well as the cell structure was damaged. Furthermore, we demonstrated that CC had antibacterial effects in vivo in MRSA-infected murine skin abscess models. In conclusion, these results imply that CC might be a potential antibacterial agent for the treatment of S. aureus-associated infections.
研究领域:
药理学
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微生物学
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传染病学
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DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
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2026
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IF 12.5
Shuailin Liu,Mengna Wang,Yujie Shen,Yinghui Song,Baojun Yang,Jifeng Liu,Xia Gao
OG/ICG, an intelligent nano-prodrug, is engineered by conjugating OPC with GEN, and ICG loading. • OG/ICG remains inert systemically but switches charge and dissociates in acidic infections. • The efficacy of GEN against MRSA was restored through the synergistic action of OPC and photothermia. • Combined chemical, physical, and targeting actions enable full eradication of GEN-resistant MRSA. The waning efficacy of aminoglycosides, like gentamicin (GEN), against methicillin-resistant Staphylococcus aureus (MRSA) necessitates strategies that transcend the protracted pipeline of de novo antibiotic discovery. Herein, we present a “resensitization” strategy enabled by a carrier-free, supramolecular nano-prodrug (OG/ICG NPs), engineered via the oxidative co-assembly of oligomeric proanthocyanidin (OPC) and GEN, followed by indocyanine green (ICG) loading. Distinct from conventional inert delivery systems, this bioactive platform remains stable physiologically but undergoes charge reversal and rapid dissociation within the acidic infection microenvironment. Mechanistically, the released OPC functions as a potent resistance-breaking adjuvant by disrupting cell wall integrity and inhibiting efflux pumps, thereby facilitating massive intracellular GEN accumulation. Under near-infrared (NIR) irradiation, localized hyperthermia synergizes with this chemical attack to compromise membrane permeability and trigger pronounced metabolic collapse, characterized by disrupted fatty acid degradation and ATP depletion, as revealed by both transcriptomic and phenotypic profiling. Furthermore, the nanoplatform promotes regulating macrophage polarization from M1 to M2 phenotype, accelerating abscess resolution and tissue regeneration. This work establishes a robust, dual-responsive paradigm that not only eradicates resistant pathogens through metabolic and structural disruption but also orchestrates an immune-favorable microenvironment for wound healing.
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高影响因子
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