β-Hydroxyisovalerylshikonin regulates macrophage polarization
            <i>via</i>
            the AMPK/Nrf2 pathway and ameliorates sepsis in mice

Chang, Yabin; He, Ming; He, Zhiyao; Jiang, Jun; Ren, Xue; Zhang, Fang

doi:10.1080/13880209.2022.2046111

Cited by 10 publications

(2 citation statements)

References 48 publications

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“…In the current study, we found that the production of proinflammatory cytokine, TNF-α, was induced obviously in E. faecalis infection mice, while the underlying mechanism needs further investigation. TNF-α is a marker of M1 macrophage, which elicits rapid proinflammatory responses to infection and tissue damages ( Yoon et al, 2017 ; Pan et al, 2022 ). TNF release is typically activated by a variety of chemicals, the most active of which is bacterial LPS endotoxin ( Wang et al, 2023 ).…”

Section: Discussionmentioning

confidence: 99%

Investigations into the antibacterial effects and potential mechanism of gambogic acid and neogambogic acid

Chen

Wang

et al. 2022

Front. Microbiol.

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The growing threat of antibiotic-resistant bacterial infections to public health necessitates the development of novel antibacterial agents. Inhibiting bacterial cell wall synthesis has remained a key focus for antibiotic development. Our search for inhibitors of undecaprenyl diphosphate synthase (UPPS), an essential enzyme required for bacterial cell wall formation, revealed that two primary components of gamboge, gambogic acid (GA) and neogambogic acid (NGA), significantly inhibited the activity of Enterococcus faecalis UPPS (EfaUPPS) with the half maximal inhibitory concentrations (IC50) of 3.08 μM and 3.07 μM, respectively. In the in vitro antibacterial assay, both GA and NGA also exhibited inhibitory activities against E. faecalis with the minimal inhibitory concentrations (MICs) of 2 μg/mL. Using microscale thermophoresis, molecular docking, and enzymatic assays, we further confirmed that GA and NGA occupy the substrate binding pocket of EfaUPPS with micro-molar binding affinity, preventing the natural substrates farnesyl diphosphate (FPP) from entering. Mutagenesis analysis revealed that L91 and L146 are two key residues in the binding between GA/NGA and UPPS. Furthermore, we also demonstrated that GA and NGA can improve E. faecalis-induced undesirable inflammation in a mouse infection model. Taken together, our findings provide a basis for structural optimization of GA/NGA to develop improved antibiotic leads and enhance treatment success rates in clinical practice.

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Section: Discussionmentioning

confidence: 99%

Investigations into the antibacterial effects and potential mechanism of gambogic acid and neogambogic acid

Chen

Wang

et al. 2022

Front. Microbiol.

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“…A small amount of bronchoalveolar lavage fluid (BALF) was used to count the total number of cells, and cell survival was assessed using trypan blue staining. 12 According to the experimental requirements, the cell concentration was adjusted to 1×10 5 cells/mL. After aspiration and mixing, the cells were moved into a 24-well plate covered with round slides, cultured in a 5% CO 2 incubator at 37°C for 2 h, and washed with D-hanks liquid (a balanced salt solution without calcium and magnesium ions; Boster Biological Technology Co. Ltd, Pleasanton, CA, US).…”

Section: Methodsmentioning

confidence: 99%

Role of the Notch signaling pathway in regulating macrophage polarization in a rat model of fibrotic pigeon breeder’s lung

Wang,

Shen,

Leng

et al. 2023

Eur J Inflamm

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Objectives: The Notch signaling pathway serves as the key regulator of the biological functions of macrophages and may affect the role of macrophages in the development of pigeon breeder’s lung (PBL). This study investigated the possible association of the Notch signaling pathway with the development of fibrotic PBL based on regulation of the polarization of macrophages. Methods: Normal Sprague‒Dawley rats and rats with pigeon exfoliation-induced fibrotic hypersensitivity pneumonitis were selected. DAPT was used to inhibit the Notch signaling pathway in rats, and pulmonary fibrosis, the Notch signaling pathway, macrophage polarization, and dynamic changes in the Th1/Th2 ratio were observed. Results: The levels of key proteins in the Notch signaling pathway were higher in the lung tissues of rats with fibrotic hypersensitivity pneumonitis than in those of normal controls ( p < 0.05). The mRNA expression levels of the M1 marker genes tumor necrosis factor (TNF)-α and inducible nitric oxide synthase (iNOS) were lower in the lung macrophages of rats with fibrotic hypersensitivity pneumonitis than in those of normal controls. In contrast, the mRNA expression levels of the M2 marker genes Mrc2 and Arg-1 in macrophages were higher in the rats with pneumonitis than in normal controls ( p < 0.05). The bronchoalveolar lavage fluid Th1/Th2 ratio was lower in the fibrotic hypersensitivity pneumonitis group than in the control group, but this trend was reversed DAPT application ( p < 0.05). Conclusion: Notch pathway receptors and ligands activate the inflammatory response of macrophages and participate in the polarization of macrophages to the M1 type. Inhibition of the Notch signaling pathway plays a role in Th1/Th2 imbalance.

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AMPK Regulates M1 Macrophage Polarization through the JAK2/STAT3 Signaling Pathway to Attenuate Airway Inflammation in Obesity-Related Asthma

Lei,

Shu,

Zhu

et al. 2024

Inflammation

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β-Hydroxyisovalerylshikonin regulates macrophage polarization via the AMPK/Nrf2 pathway and ameliorates sepsis in mice

Cited by 10 publications

References 48 publications

Investigations into the antibacterial effects and potential mechanism of gambogic acid and neogambogic acid

Investigations into the antibacterial effects and potential mechanism of gambogic acid and neogambogic acid

Role of the Notch signaling pathway in regulating macrophage polarization in a rat model of fibrotic pigeon breeder’s lung

AMPK Regulates M1 Macrophage Polarization through the JAK2/STAT3 Signaling Pathway to Attenuate Airway Inflammation in Obesity-Related Asthma

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