"Shihu" promote T-cell immunity against breast cancer through bioactive constituent THMB enhancing JAK3-STAT1 signal

  • J Ethnopharmacol. 2026 Oct 28:369:121888. doi: 10.1016/j.jep.2026.121888.
Miao Xia  1 ,  Xue-Meng Liu  1 ,  Xiao-Long Shi  1 ,  Fu-Rao Liu  1 ,  Xin-Hui Wang  1 ,  Meng-Jiao Yang  1 ,  Li-Xing Zhao  1 ,  Yun-Li Zhao  1 ,  Zhi Dai  2 ,  Xiao-Dong Luo  3
Affiliations
  • 1. Yunnan Characteristic Plant Extraction Laboratory, Key Laboratory of Medicinal Chemistry for Natural Resource, Ministry of Education, Yunnan Key Laboratory of Research and Development for Natural Products, School of Pharmacy, Yunnan University, Kunming, 650500, PR China.
  • 2. Yunnan Characteristic Plant Extraction Laboratory, Key Laboratory of Medicinal Chemistry for Natural Resource, Ministry of Education, Yunnan Key Laboratory of Research and Development for Natural Products, School of Pharmacy, Yunnan University, Kunming, 650500, PR China. Electronic address: [email protected].
  • 3. Yunnan Characteristic Plant Extraction Laboratory, Key Laboratory of Medicinal Chemistry for Natural Resource, Ministry of Education, Yunnan Key Laboratory of Research and Development for Natural Products, School of Pharmacy, Yunnan University, Kunming, 650500, PR China. Electronic address: [email protected].
PMID: 42202911 DOI: 10.1016/j.jep.2026.121888
Abstract

Ethnopharmacological relevance: Dendrobium, commonly known as "Shihu", are the well-known Chinese traditional medicine with the ability of strengthening "Yin", tonify five viscera, lighten the body, prolong life span that were involved in immunity regulation. However, their T-cell-mediated cellular immune function was kept unknown.

Aim of the study: To investigate its T-cell-mediated cellular immune function, and reveal bioactive constituents and mechanism.

Materials and methods: The eliminating of mutant cells (Cancer cells) by T-cell-mediated cellular immune was used to evaluate T-cell immunomodulation function through the non-traditional cytotoxicity T-cell immunomodulatory anti-tumor model combination with bioactivity-guided isolation. The LDH killing and ELISA analysis were used to examine killing efficacy and cytokines. The vaccine Adjuvant model of mouse breast Cancer was used to evaluate T-cell immunomodulation efficacy in vivo. The proteome and phosphoproteome analysis were used to mechanism research combined with blocking rescue analysis.

Results: "Shihu" fraction (YD198-6) showed the T-cell immunomodulation killing Cancer cells bioactivity among the seven extracts, and fifteen known compounds were identified by bioactivity-guided isolation, which revealed the compound 3,4',5-trihydroxy-3'-methoxybiphenyl (THMB) was a better bioactive constituent. Further mechanism research suggested THMB regulated T-cell against multiple tumor cells major through enhancing JAK3-STAT1 signal to upregulate granzyme B, perforin, IL-1β. Moreover, in mice TNBC model, the primary tumor growth was significantly inhibited about 62%, and lung metastasis was reduced about 51% accompanied with significantly improving overall survival (54 days vs 37 days, p < 0.05).

Conclusion: These results demonstrated that "Shihu" could enhance T-cell mediated cellular immune function to protect health, and revealed its bioactive constituent and mechanism.

Keywords
3,4′,5-trihydroxy-3′-methoxybibenzy (THMB); Cancer cells; Dendrobium nobile Lindl.; Shihu; T-cell immune; Triple-negative breast cancer (TNBC).
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