Smilax china L. Rhizome extract enhances anti-tumor immune responses by resetting M2-like macrophages and tumor-associated macrophages to M1-like via ERK1/2 signaling
- J Ethnopharmacol. 2025 Jun 12:349:119983. doi: 10.1016/j.jep.2025.119983.
- 1. Second Clinical Medical College, Jinhua Academy, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, 310053, China.
- 2. School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, 311402, China.
- 3. Zhezhong Laboratory, Zhejiang Chinese Medical University, Jinhua, Zhejiang, 310053, China; School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, 311402, China.
- 4. Zhezhong Laboratory, Zhejiang Chinese Medical University, Jinhua, Zhejiang, 310053, China.
- 5. Second Clinical Medical College, Jinhua Academy, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, 310053, China; Zhezhong Laboratory, Zhejiang Chinese Medical University, Jinhua, Zhejiang, 310053, China. Electronic address: [email protected].
- 6. Second Clinical Medical College, Jinhua Academy, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, 310053, China. Electronic address: [email protected].
Ethnopharmacological relevance: Smilax china L. is a traditional Chinese herb. Smilax china L. Rhizome (SCR) have historically been used in ethnomedicine for their anti-inflammatory, anti-tumor, and immunomodulatory properties.
Aim of the study: This study aimed to evaluate the anti-tumor efficacy of SCR in the MMTV-PyMT mouse mammary tumor model and elucidate its immunomodulatory mechanisms within the tumor microenvironment (TME).
Materials and methods: SCR was administered to MMTV-PyMT mice to assess its effects on tumor progression and metastasis. Immune cell profiling (M1/M2-like macrophages, CD8+ T cells) was conducted via flow cytometry. In vitro macrophage polarization assays under IL-4 stimulation and mechanistic studies (MAPK/ERK signaling) were performed using Western blot and pharmacological inhibitors. Diosgenin, a key SCR constituent, was identified and validated through phytochemical analysis and functional assays.
Results: SCR treatment significantly slowed primary tumor growth and reduced lung metastases. SCR induces a shift in macrophage polarization from immunosuppressive M2-like to proinflammatory M1-like and promotes increased CD8+ T cell infiltration. In vitro, SCR inhibited IL-4-induced M2 polarization and suppressed ERK1/2 phosphorylation, a critical node in the MAPK pathway. Diosgenin was identified as a pivotal bioactive compound contributing to SCR's anti-tumor and immunomodulatory effects.
Conclusions: These findings provide a theoretical basis for the potential clinical application of SCR in Cancer treatment, highlighting its critical role in remodeling the tumor immune microenvironment.