The Polyphenol-Enriched Salix songarica Extract Alleviate High-Fat, High-Cholesterol Diet-Induced Inflammation via the LPC18:1/GPR120/β-Arrestin-2/NLRP3 Signaling Pathway.

Salix songarica Andersson (S. songarica), a medicinal plant endemic to Xinjiang, exhibits high polyphenol content in its floral tissues. Although it shows anti-inflammatory potential, the underlying mechanisms remain unclear. This study investigated the therapeutic effects of polyphenol-enriched S. songarica flower extract (SSFP) on inflammation and dyslipidemia in high-fat, high-cholesterol diet (HFHCD)-fed ApoE-/- mice. SSFP administration significantly improved serum lipid profiles, hepatic function, and systemic inflammatory biomarkers in these mice, while also attenuating histopathological inflammation in the liver, kidney, and colon. Furthermore, SSFP treatment upregulated the expression of GPR120 and β-arrestin-2 and suppressed NLRP3 inflammasome activation. In vitro experiments further showed that the anti-inflammatory effect of LPC18:1 was consistent with SSFP. Together, our results demonstrate that SSFP alleviates inflammation through the LPC18:1/GPR120/β-arrestin-2/NLRP3 signaling axis, supporting its potential application as a natural functional food ingredient.