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Background <p>Immunosuppression is a critical clinical challenge, and wheat-grain moxibustion (WGM) is a TCM therapy hypothesized to modulate immune function. However, the&#xa0;dose-dependent effects of WGM&#xa0;and its&#xa0;mechanistic link to the JAK2–STAT3 pathway&#xa0;remain understudied.</p> Objectives <p>To investigate the immunopotentiating effects of different dosages of WGM (3, 6, and 9 zhuang) at Guanyuan (CV4) and Zusanli (ST36) on the cyclophosphamide (CTX)-induced immunosuppressed rats, and elucidate its association with the JAK2–STAT3 signaling pathway.</p> Methods <p>Forty-five Sprague–Dawley (SD) rats were randomized into 5 groups: blank control (CON), MG (Model group), and WGM groups (LOW: 3 zhuang, MID: 6 zhuang, and HIGH: 9 zhuang). WGM was applied daily for 7&#xa0;days. Immune function was assessed via&#xa0;peripheral blood counts (WBC and CD4+/CD8+),&#xa0;organ indices (spleen, thymus),&#xa0;histopathology (HE staining), and&#xa0;molecular markers (JAK2/STAT3 protein/mRNA, cytokines: IgG, IgM, TNF-α, IFN-γ, IL-6, and IL-10).</p> Results <p>Compared to MG, all WGM groups increased WBC counts (<i>p</i> &lt; 0.05), but the&#xa0;MID (6 zhuang) and HIGH (9 zhuang) groups showed a 1.8-fold and 2.1-fold higher WBC count&#xa0;(<i>p</i> &lt; 0.01), respectively. Flow cytometry revealed a&#xa0;2.3-fold increase in CD4+/CD8+ ratio&#xa0;in the HIGH group (<i>p</i> &lt; 0.01) vs. MG. Histopathology showed restored spleen marginal zones and thymic corticomedullary structure in WGM groups, with the HIGH group exhibiting the least lymphocyte necrosis. Mechanistically, WGM upregulated JAK2/STAT3 phosphorylation (p-JAK2: <i>p</i> &lt; 0.01 in HIGH vs. MG; p-STAT3: <i>p</i> &lt; 0.05 in HIGH vs. MG; <i>p</i> &lt; 0.01) and downstream cytokines (e.g., IFN-γ: in HIGH vs. MG; <i>p</i> &lt; 0.01). Notably,&#xa0;IL-10 (anti-inflammatory) was downregulated in the HIGH group&#xa0;(<i>p</i> &lt; 0.01), suggesting a shift from immunosuppression to immune activation.</p> Conclusions <p>WGM at Guanyuan and Zusanli ameliorates MG-induced immunosuppression in a&#xa0;dose-dependent manner, with 9 zhuang (HIGH) being the most effective for restoring cellular (CD4+/CD8+) and molecular (JAK2–STAT3) immune function. These findings provide&#xa0;quantitative evidence&#xa0;for optimizing WGM dosage in clinical settings and reveal a novel mechanistic link between TCM therapy and modern immunology.</p> Graphical abstract <p>A graphical abstract that can encompass all the content of this article.</p> <p></p>

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Dose-Dependent Immunomodulation by Wheat-Grain Moxibustion at Guanyuan (CV4) and Zusanli (ST36) via JAK2/STAT3 Signaling in Cyclophosphamide-Induced Immunosuppressed Rats

  • 期刊论文

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  • 发表日期：

    2025年11月27日

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  • Tingting Liu,
  • Xiangyue Zhang,
  • Jing Qin,
  • Jianguo Li,
  • Muhammad Shahzad Aslam,
  • Huichao Xu,
  • Xiuqing Zhang,
  • Fang Wang,
  • Xiaoxu Wang,
  • Xianjun Meng,
  • Tiansheng Zhang

摘要

Background

Immunosuppression is a critical clinical challenge, and wheat-grain moxibustion (WGM) is a TCM therapy hypothesized to modulate immune function. However, the dose-dependent effects of WGM and its mechanistic link to the JAK2–STAT3 pathway remain understudied.

Objectives

To investigate the immunopotentiating effects of different dosages of WGM (3, 6, and 9 zhuang) at Guanyuan (CV4) and Zusanli (ST36) on the cyclophosphamide (CTX)-induced immunosuppressed rats, and elucidate its association with the JAK2–STAT3 signaling pathway.

Methods

Forty-five Sprague–Dawley (SD) rats were randomized into 5 groups: blank control (CON), MG (Model group), and WGM groups (LOW: 3 zhuang, MID: 6 zhuang, and HIGH: 9 zhuang). WGM was applied daily for 7 days. Immune function was assessed via peripheral blood counts (WBC and CD4+/CD8+), organ indices (spleen, thymus), histopathology (HE staining), and molecular markers (JAK2/STAT3 protein/mRNA, cytokines: IgG, IgM, TNF-α, IFN-γ, IL-6, and IL-10).

Results

Compared to MG, all WGM groups increased WBC counts (p < 0.05), but the MID (6 zhuang) and HIGH (9 zhuang) groups showed a 1.8-fold and 2.1-fold higher WBC count (p < 0.01), respectively. Flow cytometry revealed a 2.3-fold increase in CD4+/CD8+ ratio in the HIGH group (p < 0.01) vs. MG. Histopathology showed restored spleen marginal zones and thymic corticomedullary structure in WGM groups, with the HIGH group exhibiting the least lymphocyte necrosis. Mechanistically, WGM upregulated JAK2/STAT3 phosphorylation (p-JAK2: p < 0.01 in HIGH vs. MG; p-STAT3: p < 0.05 in HIGH vs. MG; p < 0.01) and downstream cytokines (e.g., IFN-γ: in HIGH vs. MG; p < 0.01). Notably, IL-10 (anti-inflammatory) was downregulated in the HIGH group (p < 0.01), suggesting a shift from immunosuppression to immune activation.

Conclusions

WGM at Guanyuan and Zusanli ameliorates MG-induced immunosuppression in a dose-dependent manner, with 9 zhuang (HIGH) being the most effective for restoring cellular (CD4+/CD8+) and molecular (JAK2–STAT3) immune function. These findings provide quantitative evidence for optimizing WGM dosage in clinical settings and reveal a novel mechanistic link between TCM therapy and modern immunology.

Graphical abstract

A graphical abstract that can encompass all the content of this article.