M1/M2 re-polarization of kaempferol biomimetic NPs in anti-inflammatory therapy of atherosclerosis

Zhao, Jianzhou; Ling, Longbing; Zhu, Wei; Ying, Tianhao; Yu, Tao; Sun, Mengmeng; Zhu, Xuan; Du, Yuan; Zhang, Leiming

doi:10.1016/j.jconrel.2022.12.041

Cited by 34 publications

(24 citation statements)

References 47 publications

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“…Therefore, repolarizing M1 macrophage into M2 phenotype has become a promising strategy to alleviate the development of AS. Interestingly, we and other research groups have shown that nanomaterials that can simultaneously suppress inflammation and scavenge cytosolic ROS possess the capability to promote the M1-to-M2 phenotype switch. ,, Given this fact, we also tested such an effect of CpG-AgNPs. The typical M1 markers CD80 and CD206 were detected by flow cytometry and quantified.…”

Section: Resultsmentioning

confidence: 99%

CpG-Conjugated Silver Nanoparticles as a Multifunctional Nanomedicine to Promote Macrophage Efferocytosis and Repolarization for Atherosclerosis Therapy

Tang,

Wang,

Guo

et al. 2023

ACS Appl. Mater. Interfaces

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Atherosclerosis (AS) is a major contributor to cardiovascular diseases, necessitating the development of novel therapeutic strategies to alleviate plaque burden. Macrophage efferocytosis, the process by which macrophages clear apoptotic and foam cells, plays a crucial role in plaque regression. However, this process is impaired in AS lesions due to the overexpression of CD47, which produces a "do not eat me" signal. In this study, we investigated the potential of CpG, a toll-like receptor 9 agonist, to enhance macrophage efferocytosis for AS therapy. We demonstrated that CpG treatment promoted the engulfment of CD47-positive apoptotic cells and foam cells by macrophages. Mechanistically, CpG induced a metabolic shift in macrophages characterized by enhanced fatty acid oxidation and de novo lipid biosynthesis, contributing to its pro-efferocytic effect. To enable in vivo application, we conjugated CpG on silver nanoparticles (AgNPs) to form CpG-AgNPs, which could protect CpG from biological degradation, promote its cellular uptake, and release CpG in response to intracellular glutathione. Combining the intrinsic antioxidative and anti-inflammatory abilities of AgNPs, such nanomedicine displayed multifunctionalities to simultaneously promote macrophage efferocytosis and repolarization. In an ApoE −/− mouse model, intravenous administration of CpG-AgNPs effectively targeted atherosclerotic plaques and exhibited potent therapeutic efficacy with excellent biocompatibility. Our study provides valuable insights into CpG-induced macrophage efferocytosis and highlights the potential of CpG-AgNPs as a promising therapeutic strategy for AS.

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Section: Resultsmentioning

confidence: 99%

CpG-Conjugated Silver Nanoparticles as a Multifunctional Nanomedicine to Promote Macrophage Efferocytosis and Repolarization for Atherosclerosis Therapy

Tang,

Wang,

Guo

et al. 2023

ACS Appl. Mater. Interfaces

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“…Several studies have demonstrated that luteolin prevents AS by regulating oxidative stress, reducing triglyceride and low-density lipoprotein (LDL) cholesterol levels, and inhibiting plaque development ( Makino et al., 2016 ; Li et al., 2018 ; Ding et al., 2019 ). In atherosclerotic ApoE −/− mice, kaempferol targeted the plaque areas and inhibited macrophage-mediated inflammation, accompanied by a decrease in TNF-α proinflammatory cytokines and repolarization of M1 to M2 macrophages ( Jianing et al., 2022 ). A study reported the antioxidant, anti-inflammatory, and cardioprotective effects of kaempferol and suggested its potential as a drug candidate for treating and preventing AS ( Chen et al., 2022b ).…”

Section: Discussionmentioning

confidence: 99%

Key ingredients in Verbena officinalis and determination of their anti-atherosclerotic effect using a computer-aided drug design approach

Chen

Gan

et al. 2023

Front. Plant Sci.

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Lipid metabolism disorders may considerably contribute to the formation and development of atherosclerosis (AS). Traditional Chinese medicine has received considerable attention in recent years owing to its ability to treat lipid metabolism disorders using multiple components and targets. Verbena officinalis (VO), a Chinese herbal medicine, exhibits anti-inflammatory, analgesic, immunomodulatory, and neuroprotective effects. Evidence suggests that VO regulates lipid metabolism; however, its role in AS remains unclear. In the present study, an integrated network pharmacology approach, molecular docking, and molecular dynamics simulation (MDS) were applied to examine the mechanism of VO against AS. Analysis revealed 209 potential targets for the 11 main ingredients in VO. Further, 2698 mechanistic targets for AS were identified, including 147 intersection targets between VO and AS. Quercetin, luteolin, and kaempferol were considered key ingredients for the treatment of AS based on a potential ingredient target–AS target network. GO analysis revealed that biological processes were primarily associated with responses to xenobiotic stimuli, cellular responses to lipids, and responses to hormones. Cell components were predominantly focused on the membrane microdomain, membrane raft, and caveola nucleus. Molecular functions were mainly focused on DNA-binding transcription factor binding, RNA polymerase II-specific DNA-binding transcription factor binding, and transcription factor binding. KEGG pathway enrichment analysis identified pathways in cancer, fluid shear stress, and atherosclerosis, with lipid and atherosclerosis being the most significantly enriched pathways. Molecular docking revealed that three key ingredients in VO (i.e., quercetin, luteolin, and kaempferol) strongly interacted with three potential targets (i.e., AKT1, IL-6, and TNF-α). Further, MDS revealed that quercetin had a stronger binding affinity for AKT1. These findings suggest that VO has beneficial effects on AS via these potential targets that are closely related to the lipid and atherosclerosis pathways. Our study utilized a new computer-aided drug design to identify key ingredients, potential targets, various biological processes, and multiple pathways associated with the clinical roles of VO in AS, which provides a comprehensive and systemic pharmacological explanation for the anti-atherosclerotic activity of VO.

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“…The experimental cells (0.5 × 10 4 per well) were cultured for 24 h, pretreated with 5c or HSS for 2 h and cotreated with 1 μg/mL LPS for another 6 h (for TNF-α) or 24 h (for IL-1β). The supernatant cytokine levels were next assessed using ELISA kits (Elabscience, Wuhan, China) based on the manufacturer’s instructions [ 41 ].…”

Section: Methodsmentioning

confidence: 99%

Design, Synthesis, and Anti-Inflammatory Activities of 12-Dehydropyxinol Derivatives

Wang

et al. 2023

Molecules

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Pyxinol skeleton is a promising framework of anti-inflammatory agents formed in the human liver from 20S-protopanaxadiol, the main active aglycone of ginsenosides. In the present study, a new series of amino acid-containing derivatives were produced from 12-dehydropyxinol, a pyxinol oxidation metabolite, and its anti-inflammatory activity was assessed using an NO inhibition assay. Interestingly, the dehydrogenation at C-12 of pyxinol derivatives improved their potency greatly. Furthermore, half of the derivatives exhibited better NO inhibitory activity than hydrocortisone sodium succinate, a glucocorticoid drug. The structure–activity relationship analysis indicated that the kinds of amino acid residues and their hydrophilicity influenced the activity to a great extent, as did R/S stereochemistry at C-24. Of the various derivatives, 5c with an N-Boc-protected phenylalanine residue showed the highest NO inhibitory activity and relatively low cytotoxicity. Moreover, derivative 5c could dose-dependently suppress iNOS, IL-1β, and TNF-α via the MAPK and NF-κB pathways, but not the GR pathway. Overall, pyxinol derivatives hold potential for application as anti-inflammatory agents.

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M1/M2 re-polarization of kaempferol biomimetic NPs in anti-inflammatory therapy of atherosclerosis

Cited by 34 publications

References 47 publications

CpG-Conjugated Silver Nanoparticles as a Multifunctional Nanomedicine to Promote Macrophage Efferocytosis and Repolarization for Atherosclerosis Therapy

CpG-Conjugated Silver Nanoparticles as a Multifunctional Nanomedicine to Promote Macrophage Efferocytosis and Repolarization for Atherosclerosis Therapy

Key ingredients in Verbena officinalis and determination of their anti-atherosclerotic effect using a computer-aided drug design approach

Design, Synthesis, and Anti-Inflammatory Activities of 12-Dehydropyxinol Derivatives

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