Polymyxin B as an inhibitor of lipopolysaccharides contamination of herb crude polysaccharides in mononuclear cells

Lu, Xiaoxiao; Jiang, Yifan; Li, Hong; Ou, Ying-Ye; Zhang, Zhi-De; Di, Hong-Ye; Chen, Daofeng; Zhang, Yunyi

doi:10.1016/s1875-5364(17)30074-2

Cited by 16 publications

(7 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Indeed, G3KL (10 μM, 72 μg/mL) blocked TNF-α expression induced by LPS (0.1 μg/mL) when the experiment was performed in DMEM containing 1% FBS, similarly to the effect observed by PMB (10 μM, 14 μg/mL) (Figure B). When the experiment was performed in the presence of 10% FBS, in contrast, we only observed TNF-α inhibition by PMB as previously reported, , while G3KL was inactive, suggesting a weaker and less selective binding to LPS versus serum proteins compared to PMB (Figure C).…”

Section: Resultssupporting

confidence: 86%

Fluorescence Imaging of Bacterial Killing by Antimicrobial Peptide Dendrimer G3KL

et al. 2019

View full text Add to dashboard Cite

We recently discovered that peptide dendrimers such as G3KL ((KL)8(KKL)4(KKL)2 KKL, K = branching l-lysine) exert strong activity against Gram-negative bacteria including Pseudomonas aeruginosa, Acinetobacter baumannii, and Escherichia coli. Herein, we report a detailed mechanistic study using fluorescence labeled analogs bearing fluorescein (G3KL-Fluo) or dansyl (G3KL-Dansyl), which show a similar bioactivity profile as G3KL. Imaging bacterial killing by super-resolution stimulated emission depletion (STED) microscopy, time-lapse imaging, and transmission electron microscopy (TEM) reveals that the dendrimer localizes at the bacterial membrane, induces membrane depolarization and permeabilization, and destroys the outer leaflet and the inner membrane. G3KL accumulates in bacteria against which it is active; however, it only weakly penetrates into eukaryotic cells without inducing significant toxicity. G3KL furthermore binds to lipopolysaccharide (LPS) and inhibits the LPS induced release of TNF-α by macrophages, similarly to polymyxin B. Taken together, these experiments show that G3KL behaves as a potent membrane disruptive antimicrobial peptide.

show abstract

Section: Resultssupporting

confidence: 86%

Fluorescence Imaging of Bacterial Killing by Antimicrobial Peptide Dendrimer G3KL

et al. 2019

View full text Add to dashboard Cite

show abstract

“…LPS (100 ng/mL) was treated with mygalin (50, 150, or 450 µM) for 45 min in a water bath at 37 • C. The mixture was used to stimulate macrophages for 24 h, and the supernatants were collected to measure the NO production. Polymyxin (30 µg/mL) was used under the same conditions as a positive control to block the biological effects of LPS [37].…”

Section: Neutralization Assay Of Lps By Mygalinmentioning

confidence: 99%

Acylpolyamine Mygalin as a TLR4 Antagonist Based on Molecular Docking and In Vitro Analyses

et al. 2020

View full text Add to dashboard Cite

Toll-like receptors (TLRs) are transmembrane proteins that are key regulators of innate and adaptive immune responses, particularly TLR4, and they have been identified as potential drug targets for the treatment of disease. Several low-molecular-weight compounds are being considered as new drug targets for various applications, including as immune modulators. Mygalin, a 417 Da synthetic bis-acylpolyamine, is an analog of spermidine that has microbicidal activity. In this study, we investigated the effect of mygalin on the innate immune response based on a virtual screening (VS) and molecular docking analysis. Bone marrow-derived macrophages and the cell lines J774A.1 and RAW 264.7 stimulated with lipopolysaccharide (LPS) were used to confirm the data obtained in silico. Virtual screening and molecular docking suggested that mygalin binds to TLR4 via the protein myeloid differentiation factor 2 (MD-2) and LPS. Macrophages stimulated by mygalin plus LPS showed suppressed gene expression of tumor necrosis factor (TNF-α), interleukine 6 (IL-6), cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS), as well as inhibition of signaling protein p65 of the nuclear factor κB (NF-κB), resulting in decreased production of nitric oxide (NO) and TNF-α. These results indicate that mygalin has anti-inflammatory potential, being an attractive option to be explored. In addition, we reinforce the importance of virtual screening analysis to assist in the discovery of new drugs.

show abstract

“…After macrophages were activated, a large number of bioactive molecules were induced, such as costimulatory molecules and cytokines. 44 Antigen-presenting cells upregulated the expression of costimulatory molecules (CD80, CD86) and then induced the activation of T-cell. 45 As shown in Figure 5A C , the expressions of CD80 and CD86 costimulatory molecules in CYPP-PEI nanoparticles group were significantly upregulated, which suggested the activation of macrophages was enhanced by CYPP-PEI nanoparticles.…”

Section: Discussionmentioning

confidence: 99%

<p>The Immunoenhancement Effects of Polyethylenimine-Modified Chinese Yam Polysaccharide-Encapsulated PLGA Nanoparticles as an Adjuvant</p>

Zhang¹,

Gu²,

Wusiman³

et al. 2020

IJN

View full text Add to dashboard Cite

Background: Poly(lactic-co-glycolic acid) (PLGA) has been extensively applied for sustained drug delivery and vaccine delivery system. However, vaccines delivered by PLGA nanoparticles alone could not effectively activate antigen-presenting cells (APCs) to induce strong immune responses. Purpose: The aim of the present study was to design polyethylenimine (PEI)-modified Chinese yam polysaccharide (CYP)-encapsulated PLGA nanoparticles (CYPP-PEI) as a vaccine delivery system and evaluate the adjuvant activities in vitro and in vivo. Materials and Methods: Cationic-modified nanoparticles exhibited high antigen absorption and could be efficiently taken by APCs to enhance the immune responses. Therefore, PEI-modified CYP-encapsulated PLGA nanoparticles (CYPP-PEI) were prepared. The storage stability and effective adsorption capacity for porcine circovirus-2 (PCV-2) antigen of these antigen-absorbed nanoparticles were measured for one month. Furthermore, the adjuvant activity of CYPP-PEI nanoparticles was evaluated on macrophages in vitro and through immune responses triggered by PCV-2 antigen in vivo. Results: The PCV-2 absorbed CYPP-PEI nanoparticles showed excellent storage stability and high absorption efficiency of PCV-2 antigen. In vitro, CYPP-PEI nanoparticles promoted antigen uptake, enhanced surface molecular expressions of CD80 and CD86, and improved cytokine secretion of TNF-α, IFN-γ, and IL-12p70 in macrophages. After immunization with CYPP-PEI/PCV-2 formulation in mice, the expressions of surface activation markers on dendritic cells which located in draining lymph nodes were increased, such as MHCI, MHCII, and CD80. In addition, CYPP-PEI nanoparticles induced dramatically high PCV-2-specific IgG levels which could last for a long time and stimulated the secretion of subtype antibodies and cytokines. The results showed that CYPP-PEI could induce Th1/Th2 mixed but Th1-biased type immune responses. Conclusion: Polyethylenimine-modified Chinese yam polysaccharide-encapsulated PLGA nanoparticle was a potential vaccine delivery system to trigger strong and persistent immune responses.

show abstract

Polymyxin B as an inhibitor of lipopolysaccharides contamination of herb crude polysaccharides in mononuclear cells

Cited by 16 publications

References 37 publications

Fluorescence Imaging of Bacterial Killing by Antimicrobial Peptide Dendrimer G3KL

Fluorescence Imaging of Bacterial Killing by Antimicrobial Peptide Dendrimer G3KL

Acylpolyamine Mygalin as a TLR4 Antagonist Based on Molecular Docking and In Vitro Analyses

<p>The Immunoenhancement Effects of Polyethylenimine-Modified Chinese Yam Polysaccharide-Encapsulated PLGA Nanoparticles as an Adjuvant</p>

Contact Info

Product

Resources

About