Buyang huanwu decoction (BYHWD) alleviates sepsis-induced myocardial injury by suppressing local immune cell infiltration and skewing M2-macrophage polarization

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OBJECTIVE: To investigate the therapeutic effect of Buyang huanwu decoction (BYHWD) on sepsis-induced myocardial injury (SIMI) and explore the mechanism by which BYHWD mitigates SIMI.

METHODS: The Lipopolysaccharide (LPS)-induced SIMI mouse model was established to detect the effect of BYHWD-low (1 mg/kg), BYHWD-middle (5 mg/kg), and BYWHD-high (20 mg/kg) on SIMI. The survival of these BYHWD-treated septic mice was investigated. The histology of myocardial tissues was determined by hematoxylin and eosin (H&E) staining. The apoptotic index and inflamed microenvironment of myocardial tissues were assessed by immunofluorescent staining (IF) and flow cytometry analysis. Liquid chromatography-mass spectrometry (LC-MS/MS) was employed to determine the key chemical components in the serum of BYHWD-loaded septic mice. Immunoblotting assay was utilized to detect NF-κB and TGF-β signaling activity, and M1/M2-macrophage markers using RAW264.7 cells.

RESULTS: The high dosage of BYHWD (BYHWD-high, 20 mg/Kg) significantly attenuated SIMI and improved the survival of septic mice. The BYHWD-high solution markedly reduced myocardial cell apoptosis and mitigated the inflamed microenvironment by suppressing CD45+ immune cell infiltration. Importantly, BYHWD decreased macrophage accumulation and promoted an M2-macrophage polarization. Paeoniflorin (PF) and calycosin-7-O-β-glucoside (CBG) were identified as the key molecules in BYWHD with therapeutic effect. PF (10 μM) and CBG (1 μM) inhibited NF-κB signaling, meanwhile they upregulated the TGF-β pathway, thereby facilitating an M2-macrophage phenotypic transition in RAW264.7 cells.

CONCLUSIONS: BYHWD, with two effective components PF and CBG, can mitigate SIMI by suppressing the inflamed myocardial microenvironment and skewing an immunosuppressive M2-macrophage phenotype.

Medienart:

Artikel

Erscheinungsjahr:

2023

Erschienen:

2023

Enthalten in:

Zur Gesamtaufnahme - volume:15

Enthalten in:

American journal of translational research - 15(2023), 4 vom: 16., Seite 2389-2406

Sprache:

Englisch

Beteiligte Personen:

Xiao, Lingling [VerfasserIn]
Xi, Xixiang [VerfasserIn]
Zhao, Meng [VerfasserIn]
Zhang, Lifen [VerfasserIn]
Zhang, Kai [VerfasserIn]
Xu, Zhenyu [VerfasserIn]

Themen:

Buyang huanwu decoction (BYHWD)
Inflamed microenvironment
Journal Article
M2-macrophage
NF-κB signaling
Sepsis-induced myocardial injury (SIMI)
TGF-β signaling

Anmerkungen:

Date Revised 19.05.2023

published: Electronic-eCollection

Citation Status PubMed-not-MEDLINE

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM356957756