Calycosin Attenuates LPS-Induced Cardiomyocyte Injury Through Regulation of the PPARγ/NF-κB Signaling Pathway.
- 1College of Pharmacy, Gansu University of Chinese Medicine, Lanzhou 730000, China.
Abstract
Calycosin (CAL) is an isoflavone monomer derived from Astragalus membranaceus that possesses potent anti-inflammatory and antioxidative pharmacological activities. However, the specific role of CAL in lipopolysaccharide (LPS)-induced inflammatory injury in cardiomyocytes remains to be elucidated. In this study, we established an in vitro inflammatory injury model using LPS-stimulated H9c2 cardiomyocytes to evaluate the cardioprotective effects of CAL. We assessed cell viability, live/dead cell staining, oxidative stress markers, inflammatory cytokine profiles, and cardiac injury biomarkers to characterize the protective efficacy of CAL. Quantitative proteomics combined with bioinformatics analysis was employed to explore the underlying mechanisms. Molecular docking and molecular dynamics simulations were performed to analyze the predicted binding affinity and complex stability between CAL and the target proteins PPARγ and NF-κB. PPARγ and NF-κB mRNA and protein levels were measured by qPCR and Western blotting, and rescue experiments with the PPARγ-specific inhibitor GW9662 were performed to validate target dependency. Our results demonstrated that CAL exerted significant protective effects against LPS-induced cardiomyocyte injury, effectively enhancing cell viability, reducing cell death, alleviating intracellular ROS accumulation, modulating oxidative stress-related parameters, suppressing excessive inflammatory responses, and decreasing the release of cardiac injury biomarkers. Proteomic analysis revealed that differentially expressed proteins were significantly enriched in the PPAR signaling pathway. Molecular simulations predicted that CAL binds stably to both PPARγ and NF-κB. PCR and Western blotting results showed that CAL upregulated PPARγ and suppressed NF-κB-mediated pro-inflammatory gene expression at both the mRNA and protein levels. Notably, pharmacological blockade of PPARγ with GW9662 partially abolished the cardioprotective effects of CAL. Collectively, these findings indicate that CAL ameliorates LPS-induced inflammatory injury in H9c2 cardiomyocytes through a protective mechanism that depends on activation of PPARγ and subsequent inhibition of the NF-κB signaling pathway.
Related
- PP2Acα deficiency attenuates doxorubicin-induced cardiac injury by suppressing cardiomyocyte apoptosis
- NF-κB signaling as a central integrator of inflammation, stress-induced metabolic dysfunction, and cardiomyocyte fate in sepsis-induced myocardial injury
- Bovine milk-derived osteopontin attenuates hyperoxia-induced lung injury associated with NLRP3 inflammasome regulation in neonatal mice with bronchopulmonary dysplasia
- Central relaxin-3/RXFP3 signaling potently drives orexigenic behaviors and attenuates cisplatin-induced anorexia and body weight loss
- Astragaloside IV attenuates post-ischemic neuroinflammation associated with Treg-related regulation of CD86/CD206-associated brain myeloid phenotypic responses and PI3K/AKT signaling alterations
BibTeX
@article{zhao2026calycosin,
title = {{Calycosin Attenuates LPS-Induced Cardiomyocyte Injury Through Regulation of the PPARγ/NF-κB Signaling Pathway.}},
author = {Rui Zhao and Zhiwang Wang and Wuzhou Liu and Keke Liang},
journal = {International journal of molecular sciences},
year = {2026},
month = sep,
doi = {10.3390/ijms27198505},
url = {https://europepmc.org/article/MED/42883753},
note = {CC BY},
}
RIS
TY - JOUR
TI - Calycosin Attenuates LPS-Induced Cardiomyocyte Injury Through Regulation of the PPARγ/NF-κB Signaling Pathway.
AU - Rui Zhao
AU - Zhiwang Wang
AU - Wuzhou Liu
AU - Keke Liang
PY - 2026
DA - 2026/09/23
JO - International journal of molecular sciences
DO - 10.3390/ijms27198505
UR - https://europepmc.org/article/MED/42883753
AB - Calycosin (CAL) is an isoflavone monomer derived from Astragalus membranaceus that possesses potent anti-inflammatory and antioxidative pharmacological activities. However, the specific role of CAL in lipopolysaccharide (LPS)-induced inflammatory injury in cardiomyocytes remains to be elucidated. In this study, we established an in vitro inflammatory injury model using LPS-stimulated H9c2 cardiomyocytes to evaluate the cardioprotective effects of CAL. We assessed cell viability, live/dead cell staining, oxidative stress markers, inflammatory cytokine profiles, and cardiac injury biomarkers to characterize the protective efficacy of CAL. Quantitative proteomics combined with bioinformatics analysis was employed to explore the underlying mechanisms. Molecular docking and molecular dynamics simulations were performed to analyze the predicted binding affinity and complex stability between CAL and the target proteins PPARγ and NF-κB. PPARγ and NF-κB mRNA and protein levels were measured by qPCR and Western blotting, and rescue experiments with the PPARγ-specific inhibitor GW9662 were performed to validate target dependency. Our results demonstrated that CAL exerted significant protective effects against LPS-induced cardiomyocyte injury, effectively enhancing cell viability, reducing cell death, alleviating intracellular ROS accumulation, modulating oxidative stress-related parameters, suppressing excessive inflammatory responses, and decreasing the release of cardiac injury biomarkers. Proteomic analysis revealed that differentially expressed proteins were significantly enriched in the PPAR signaling pathway. Molecular simulations predicted that CAL binds stably to both PPARγ and NF-κB. PCR and Western blotting results showed that CAL upregulated PPARγ and suppressed NF-κB-mediated pro-inflammatory gene expression at both the mRNA and protein levels. Notably, pharmacological blockade of PPARγ with GW9662 partially abolished the cardioprotective effects of CAL. Collectively, these findings indicate that CAL ameliorates LPS-induced inflammatory injury in H9c2 cardiomyocytes through a protective mechanism that depends on activation of PPARγ and subsequent inhibition of the NF-κB signaling pathway.
SN - 1422-0067
ER -