ETHNOPHARMACOLOGICAL RELEVANCE: As an important component of the cell wall of Gram-negative bacteria, lipopolysaccharide (LPS) is an important inducer of inflammation in humans. Smilax china L. is known for its diverse bioactive functions, particularly its anti-inflammatory effects. AIM OF THE STUDY: This study aimed to investigate the bioactive function of Smilax china L. polyphenols (SCLP) on LPS-induced inflammation. MATERIALS AND METHODS: Inflammation in RAW264.7 macrophages and mice were induced using LPS. The cytotoxicity of SCLP was investigated by MTT assay. Inflammatory factors were detected by ELISA and RT-PCR. The expression of NF-κB pathway-related proteins was analyzed by Western Blotting. RESULTS: The results demonstrated that SCLP significantly reduced the levels of pro-inflammatory factors (TNF-α, IL-1β, and IL-6) and inhibited M1 polarization of macrophages in both RAW264.7 macrophages and mice (p <
0.05). Western Blotting analysis revealed that the levels of NF-κB signaling pathway-associated proteins (p-p65, p-IKB, p-IKK) were significantly reduced (p <
0.05). Notably, SCLP significantly downregulated the expression of pro-apoptotic proteins, while upregulating the expression of anti-apoptotic proteins in RAW264.7 macrophages (p <
0.05). Additionally, the levels of antioxidant enzymes were enhanced in mice, suggesting a potential reduction in the inflammatory response. CONCLUSIONS: These findings indicated that SCLP might inhibit LPS-induced M1 polarization through the NF-κB signaling pathway, thereby reducing inflammation. Consequently, SCLP might serve as a promising bioactive substance for preventing inflammation-related injury.