Journal of Exercise & Organ Cross Talk
Journal of Eexercise & Organ Cross Talk

Modulatory effects of aerobic exercise and Urtica dioica hydroalcoholic extract on tumor growth and Interleukin-10 levels in a Murine melanoma model

Document Type : Original Article

Authors

Saeed Sadeghi 1
Hossein Abednatanzi 2
Shahram Soheily 3

1 Department of Physical Education and Sport Sciences, SR.C, Islamic Azad University, Tehran, Iran.

2 Assistant Prof., Dept. of Professional Physical Education and Sport Science, Science, and Research Branch, Islamic Azad University, Tehran, Iran

3 Department of Physical Education and Sport Sciences, Shahr-e-Qods Branch, Islamic Azad University, Tehran, Iran.

https://doi.org/10.22122/jeoct.2026.581673.1203
Abstract
To investigate the individual and combined effects of six weeks of aerobic exercise and hydroalcoholic extract of Urtica dioica (nettle) on tumor volume, body weight, and interleukin-10 (IL-10) levels in both serum and tumor tissue in male C57BL/6 mice bearing B16F10 melanoma tumors. Thirty-two male C57BL/6 mice (6–8 weeks old, 12–14 g) were randomly assigned to four equal groups (n=8): Control, Aerobic Exercise (AE), Nettle Extract (NE), and Combined (AE+NE). Melanoma was induced via surgical implantation of B16F10 tumor fragments. The AE protocol consisted of treadmill running for 6 weeks (5 days/week, progressing from 20 to 30 minutes/session at 6–16 m/min). The NE group received intraperitoneal injections of hydroalcoholic nettle extract (200 mg/kg body weight). The combined group received both interventions. The combined AE+NE group showing a significant reduction in tumor volume compared to the control group (p=0.0186). One-way ANOVA revealed significant differences in serum IL-10 across groups (F=9.811, p=0.0001), with significant increases observed in the AE (p=0.0003) and AE+NE (p = 0.0005) groups compared to controls. For tumor IL-10, a significant difference was also found across groups (F=3.047, p= 0.0451), with the combined AE+NE group showing a significant decrease (p =0.0435) compared to the control group. No significant correlation was found between serum and tumor IL-10 levels in any group (p>0.05). The combined intervention significantly suppressed tumor growth compared to controls and was associated with increased serum IL-10 levels but decreased IL-10 levels within the tumor microenvironment, suggesting a complex, compartment-specific immunomodulatory effect.

What is already known on this subject?

Melanoma progression is strongly influenced by the interaction between the tumor microenvironment and systemic immune regulation, and both aerobic exercise and plant-derived bioactive compounds have been shown to modulate inflammatory and anti-inflammatory cytokines, including IL-10, in ways that may affect tumor growth. Tissue crosstalk is now recognized as a key biological mechanism in disease, meaning signals exchanged between tumor tissue, immune cells, and distant organs can shape cancer behavior rather than acting in isolation.

 

What this study adds?

This study adds evidence that aerobic exercise combined with Urtica dioica extract can suppress melanoma growth producing a 53.4% reduction in tumor volume while producing a compartment-specific IL-10 response, with higher serum IL-10 but lower tumor IL-10, suggesting that systemic and local immune signaling are regulated differently. This is the first demonstration that the combination of exercise and nettle extract achieves statistically significant tumor suppression where neither intervention alone reaches significance, supporting a synergistic interaction. It also supports the idea that beneficial crosstalk between muscle activity, phytochemical exposure, and the tumor microenvironment may contribute to anti-tumor effects through coordinated immunomodulation rather than a single isolated pathway.

Keywords

Exercise
Melanoma
IL-10
Nettle extract
Subjects

Acknowledgements

None.

Funding

None.

Data availability

The data that support the findings of this study are available from the corresponding author upon reasonable request.

Compliance with ethical standards

Conflict of interest The authors declare that there is no conflict of interest in the present research.

Ethical approval All procedures were approved by the Institutional Animal Care and Use Committee of Islamic Azad University, Tehran, Iran (Ethical code: IR.IAU.M.REC.1399.008). 

 Informed consent Animal study. 

Author contributions 

Conceptualization: S.S., Methodology: S.Sh., Software: S.S., Validation: H.A.,; Formal analysis: S.S.,; Investigation: S.Sh.,; Resources: S.S.,; Data curation: H.A.,; Writing - original draft: S.S.,; Writing–review & editing S.Sh.,; Visualization: S.S.,; Supervision: H.A.; Project administration: S.Sh.,.; Funding acquisition: H.A.        

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Journal of Exercise & Organ Cross Talk
Volume 6, Issue 2
Spring 2026
Pages 107-115

  • Receive Date 14 April 2026
  • Revise Date 05 June 2026
  • Accept Date 09 June 2026

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