Sodium Danshensu stabilizes atherosclerotic vulnerable plaques by targeting IKKβ mediated inflammation in macrophages - 13/08/23
, Wenyun Zeng c, ⁎ Abstract |
Background |
The primary cause of acute cardiovascular events with high mortality is the rupture of atherosclerotic plaque followed by thrombosis. Sodium Danshensu (SDSS) has shown potential in inhibiting the inflammatory response in macrophages and preventing early plaque formation in atherosclerotic mice. However, the specific targets and detailed mechanism of action of SDSS are still unclear.
Objective |
This study aims to investigate the efficacy and mechanism of SDSS in inhibiting inflammation in macrophages and stabilizing vulnerable plaques in atherosclerosis (AS).
Materials and Methods |
The efficacy of SDSS in stabilizing vulnerable plaques was demonstrated using various techniques such as ultrasound, Oil Red O staining, HE staining, Masson staining, immunohistochemistry, and lipid analysis in ApoE -/- mice. Subsequently, IKKβ was identified as a potential target of SDSS through protein microarray, network pharmacology analysis, and molecular docking. Additionally, ELISA, RT-qPCR, Western blotting, and immunofluorescence were employed to measure the levels of inflammatory cytokines, IKKβ, and NF-κB pathway-related targets, thereby confirming the mechanism of SDSS in treating AS both in vivo and in vitro. Finally, the impact of SDSS was observed in the presence of an IKKβ-specific inhibitor.
Results |
Initially, the administration of SDSS led to a decrease in the formation and area of aortic plaque, while also stabilizing vulnerable plaques in ApoE -/- mice. Furthermore, it was identified that IKKβ serves as the primary binding target of SDSS. Additionally, both in vivo and in vitro experiments demonstrated that SDSS effectively inhibits the NF-κB pathway by targeting IKKβ. Lastly, the combined use of the IKKβ-specific inhibitor IMD-0354 further enhanced the beneficial effects of SDSS.
Conclusions |
SDSS stabilized vulnerable plaques and suppressed inflammatory responses by inhibiting the NF-κB pathway through its targeting of IKKβ.
Le texte complet de cet article est disponible en PDF.Graphical Abstract |
Highlights |
• | SDSS administration decreased the formation and area of aortic plaque. |
• | SDSS administration stabilized vulnerable plaques in ApoE -/- mice. |
• | IKKβ is the key binding target of SDSS. |
• | SDSS inhibits NF-κB pathway through targeting IKKβ in vivo and in vitro. |
• | The IKKβ-specific inhibitor IMD-0354 enhanced the effect of SDSS. |
Abbreviations : AS, ApoE -/- , BP, CCK-8, CC, DAB, GO, HDL-C, HE, IL-1R, IKK, KEGG, LDL-C, LDH, MOMA-2, MF, NF-κB, Ox-LDL, OCT, PPI, PVDF, PEG, SDSS, SPF, SNR, SDS-PAGE, SD, SMC, TC, TG, TNFR, TLR, α-SMA
Keywords : Atherosclerosis, Sodium Danshensu, IKKβ, Inflammation, Macrophage
Plan
Vol 165
Article 115153- septembre 2023 Retour au numéro
Article précédent
- Discovery of a chalcone derivative as an anti-fibrotic agent targeting transforming growth factor-β1 signaling: Potential therapy of renal fibrosis
- Wanangkan Poolsri, Rattikarn Noitem, Promsuk Jutabha, Manasanan Raveesunthornkiat, Ade Danova, Warinthorn Chavasiri, Chatchai Muanprasat
- Polyphenol-enriched Desmodium elegans DC. ameliorate scopolamine-induced amnesia in animal model of Alzheimer’s disease: In Vitro, In Vivo and In Silico approaches
- Mater H. Mahnashi, Muhammad Ashraf, Abdulaziz Hassan Alhasaniah, Hammad Ullah, Alam Zeb, Mehreen Ghufran, Shah Fahad, Muhammad Ayaz, Maria Daglia
Bienvenue sur EM-consulte, la référence des professionnels de santé.
L’accès au texte intégral de cet article nécessite un abonnement.
Déjà abonné à cette revue ?