Simiaoyong'an decoction alleviates atherosclerosis by inhibiting adipose tissue inflammation through PPARγ...

Obesity-associated adipose tissue inflammation exacerbates atherosclerosis (AS) by inducing endothelial dysfunction. Simiaoyong'an Decoction (SMYA), a traditional Chinese medicine (TCM) is highly effective in managing AS-related cardiovascular diseases, but the underlying mechanisms are unclear.

This study used network pharmacology, molecular docking, and AS model mice and cells to determine the mechanisms by which SMYA alleviates AS progression and attenuates visceral adipose tissue (VAT) inflammation.

Bioactive components of SMYA were identified using UHPLC-LTQ-Orbitrap-MS. An AS mouse model was established through high-fat-diet (HFD) feeding combined with perivascular carotid collar placement (PCCP). Therapeutic effects of SMYA were evaluated by histochemical staining, MOMA-2/α-SMA immunohistochemistry, and Enzyme-linked immunosorbent assay. SMYA targets against AS and adipose tissue inflammation were identified by network pharmacology and molecular docking, followed by mechanistic validation in animal models and an in vitro LPS-induced 3T3-L1-HUVECs coculture system. Western blotting analysis was used to elucidate the molecular mechanism underlying therapeutic effects of SMYA.

UHPLC-LTQ-Orbitrap-MS analysis identified 23 bioactive components in SMYA. SMYA treatment significantly reduced plaque vulnerability and systemic inflammation (TNF-α and IL-6) in the AS model mice and cells. SMYA protected against endothelial cell injury by significantly enhancing PPARγ expression, increasing adiponectin secretion, inhibiting NF-κB, and downregulating endothelial injury markers (VCAM-1 and ICAM-1). These effects were reversed by PPARγ inhibitors.

SMYA protects vascular endothelial function and stabilizes atherosclerotic plaques by suppressing adipose tissue inflammation through PPARγ activation, thereby increasing adiponectin release. Therefore, SMYA is a promising new candidate for treating AS.