Anti-tumor effect of flavonoids isolated from Bidens Pilosa L. by regulating the activity of myeloid-derived suppressor cells within the tumor microenvironment in mice

  • J Ethnopharmacol. 2025 Sep 23;355(Pt A):120635. doi: 10.1016/j.jep.2025.120635.
Yang Tao  1 ,  Maoxin Du  2 ,  Meihua Zhu  1 ,  Weiqing Sun  3 ,  Guiyuan Zeng  1 ,  Jiayan Xiong  1 ,  Jinmin Li  1 ,  Ziyi Yang  1 ,  Baomin Fan  4 ,  Ruyi Zhang  5 ,  Guangzhi Zeng  6
Affiliations
  • 1. Key Laboratory of Chemistry in Ethnic Medicinal Resources, State Ethnic Affairs Commission and Ministry of Education, Yunnan Minzu University, Kunming, 650504, China; Yunnan Key Laboratory of Chiral Functional Substance Research and Application, Yunnan Minzu University, Kunming, 650504, China.
  • 2. Key Laboratory of Chemistry in Ethnic Medicinal Resources, State Ethnic Affairs Commission and Ministry of Education, Yunnan Minzu University, Kunming, 650504, China; Yunnan Key Laboratory of Chiral Functional Substance Research and Application, Yunnan Minzu University, Kunming, 650504, China; Pharmacy Intravenous Admixture Service, Zibo Central Hospital, Zibo, 255036, China.
  • 3. Key Laboratory of Chemistry in Ethnic Medicinal Resources, State Ethnic Affairs Commission and Ministry of Education, Yunnan Minzu University, Kunming, 650504, China.
  • 4. Key Laboratory of Chemistry in Ethnic Medicinal Resources, State Ethnic Affairs Commission and Ministry of Education, Yunnan Minzu University, Kunming, 650504, China; Yunnan Key Laboratory of Chiral Functional Substance Research and Application, Yunnan Minzu University, Kunming, 650504, China. Electronic address: [email protected].
  • 5. Key Laboratory of Chemistry in Ethnic Medicinal Resources, State Ethnic Affairs Commission and Ministry of Education, Yunnan Minzu University, Kunming, 650504, China. Electronic address: [email protected].
  • 6. Key Laboratory of Chemistry in Ethnic Medicinal Resources, State Ethnic Affairs Commission and Ministry of Education, Yunnan Minzu University, Kunming, 650504, China; Yunnan Key Laboratory of Chiral Functional Substance Research and Application, Yunnan Minzu University, Kunming, 650504, China. Electronic address: [email protected].
PMID: 40998135 DOI: 10.1016/j.jep.2025.120635
Abstract

Ethnopharmacological relevance: Colon Cancer is one of the most common malignant tumors worldwide. Bidens pilosa L., an annual herb of the Asteraceae, has long been used to treat inflammatory-related illnesses, including Cancer. As a population of immunosuppressive cells in the TME, MDSCs play a pivotal role in tumorigenesis and progression, and the effect of B. pilosa on MDSCs has rarely been reported.

Aim of study: To investigate the anti-tumor effect of a mixture of two Flavonoids, MTF, isolated from B. pilosa, which showed immunotherapeutic activity in regulating the function of MDSCs in colon Cancer.

Materials and methods: The regulatory effects of the flavonoid MTF on MDSCs differentiation and immune function were tested by qRT-PCR and flow cytometry. Its underlying immunotherapeutic mechanism, cytotoxicity, and anti-angiogenic activity were investigated using SIE luciferase/Western blot, CCK-8/Apoptosis, and MDSC-HUVEC co-culture assays, respectively. The in vivo anti-tumor activity of MTF was subsequently investigated in both CT26. WT and CT26. WT/MDSCs syngeneic models.

Results: MTF and its components effectively depleted MDSCs by inhibiting their differentiation and inducing Apoptosis, thereby restoring suppressed CD4+ T cell function. In vivo, MTF not only reduced intratumoral MDSCs but also counteracted MDSC-driven angiogenesis, leading to inhibited tumor growth and enhanced sensitivity to 5-FU treatment.

Conclusion: Flavonoid MTF showed a good anti-tumor effect in mice by regulating MDSCs activity within the TME, which contributes to the clinical use of this traditional herb.

Keywords
Bidens pilosa L.; Flavonoids; Immunosuppression; Myeloid-derived suppressor cells; Tumor immunotherapy; Tumor microenvironment.
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