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Updated: Jun 29, 2025
Induction of Atherosclerotic Plaques Through Activation of Mineralocorticoid Receptors in Apolipoprotein E-deficient Mice
Published on: September 26, 2018
Morus alba L. (Sangzhi) alkaloids mitigate atherosclerosis by regulating M1/M2 macrophage polarization
Dandan Peng1, Fen Zhuge2, Mingwei Wang3
1Department of Endocrinology, Children's Hospital Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, Zhejiang, China; Guizhou Medical University, Guiyang, Guizhou, China.
Background:
Atherosclerosis (AS) is an important cause of cardiovascular disease, posing a substantial health risk. Recognized as a chronic inflammatory disorder, AS hinges on the pivotal involvement of macrophages in arterial inflammation, participating in its formation and progression. Sangzhi alkaloid (SZ-A) is a novel natural alkaloid extracted from the mulberry branches, has extensive pharmacological effects and stable pharmacokinetic characteristics. However, the effects and mechanisms of SZ-A on AS remain unclear.
Purpose:
To explore the effect and underlying mechanisms of SZ-A on inflammation mediated by macrophages and its role in AS development.
Methods:
Atherosclerosis was induced in vivo in apolipoprotein E-deficient mice through a high-fat and high-choline diet. We utilized macrophages and vascular endothelial cells to investigate the effects of SZ-A on macrophage polarization and its anti-inflammatory properties on endothelial cells in vitro. The transcriptomic analyses were used to investigate the major molecule that mediates cell-cell interactions and the antiatherogenic mechanisms of SZ-A based on AS, subsequently validated in vivo and in vitro.
Results:
SZ-A demonstrated a significant inhibition in vascular inflammation and alleviation of AS severity by mitigating macrophage infiltration and modulating M1/M2 macrophage polarization in vitro and in vivo. Moreover, SZ-A effectively reduced the release of the proinflammatory mediator C-X-C motif chemokine ligand (CXCL)-10, predominantly secreted by M1 macrophages. This reduction in CXCL-10 contributed to improved endothelial cell function, reduced recruitment of additional macrophages, and inhibited the inflammatory amplification effect. This ultimately led to the suppression of atherogenesis.
Conclusion:
SZ-A exhibited potent anti-inflammatory effects by inhibiting macrophage-mediated inflammation, providing a new therapeutic avenue against AS. This is the first study demonstrating the efficacy of SZ-A in alleviating AS severity and offers novel insights into its anti-inflammatory mechanism.
Insights
Sangzhi alkaloid (SZ-A) effectively reduces vascular inflammation and atherosclerosis severity by inhibiting macrophage-driven inflammatory responses. This natural compound offers a promising new therapeutic strategy for cardiovascular disease.
Area of Science:
- Cardiovascular Research
- Immunology
- Pharmacology
Background:
- Atherosclerosis (AS) is a chronic inflammatory disease and a major cause of cardiovascular disease.
- Macrophages play a critical role in AS development and progression.
- The therapeutic potential of Sangzhi alkaloid (SZ-A) in AS is currently unknown.
Purpose of the Study:
- To investigate the anti-inflammatory effects of SZ-A on macrophages.
- To elucidate the mechanisms by which SZ-A influences AS development.
- To evaluate SZ-A as a potential therapeutic agent for AS.
Main Methods:
- Atherosclerosis was induced in apolipoprotein E-deficient mice.
- In vitro studies assessed SZ-A's effects on macrophage polarization and endothelial cells.
- Transcriptomic analysis identified key molecular pathways involved in SZ-A's antiatherogenic effects.
Main Results:
- SZ-A significantly reduced vascular inflammation and AS severity in vivo and in vitro.
- SZ-A modulated M1/M2 macrophage polarization and decreased pro-inflammatory mediator CXCL-10.
- SZ-A improved endothelial cell function and inhibited inflammatory amplification, suppressing atherogenesis.
Conclusions:
- SZ-A demonstrates potent anti-inflammatory properties by targeting macrophage-mediated inflammation.
- SZ-A represents a novel therapeutic avenue for treating atherosclerosis.
- This study provides new insights into the anti-inflammatory mechanisms of SZ-A in AS.
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