Tomatidine Reduces Inflammation in Skeletal Muscle

Tomatidine Attenuates Inflammatory Responses to Exercise-Like Stimulation in Donor-derived Skeletal Muscle Myobundles

Mariah Malan Parafiniuk, Taryn Ashley Shenoy, Zon Thwin, Mauro Parlavacchio, Siobhan Malany

Department of Pharmacognosy, College of Pharmacy, University of Florida, Gainesville, Florida 32611, USA. [email protected]

PUBLISHED 30 April 2025

CITATION Parafiniuk, M., Shenoy, T. A., Thwin, Z., Parlavacchio, M., & Malany, S. (2025). Tomatidine Attenuates Inflammatory and Functional responses to Exercise-Like Stimulation in Donor-derived Skeletal Muscle Myobundles. The European Society of Medicine. Retrieved from https://doi.org/10.3892/br.2025.1360

Keywords

Tomatidine, inflammation, skeletal muscle, exercise, myobundles, cytokines

Abstract

The physiological effects of physical exercise are recognized for their beneficial impact on both the cardiovascular and musculoskeletal systems serving as preventive and therapeutic strategies for cardiovascular disease, diabetes, and obesity. Repeated exercise induces an adaptive and transient response, including the release of cytokines, known as myokines, which play a critical role in the prevention and treatment of various chronic diseases. In this study, we investigated the effects of tomatidine on exercise-like stimulation in donor-derived skeletal muscle myobundles.

Graphical abstract
Graphical abstract

Introduction

Repeated exercise induces an adaptive and transient response, including the release of cytokines, known as myokines, which play a critical role in the prevention and treatment of various chronic diseases. In this study, we investigated the effects of tomatidine on exercise-like stimulation in donor-derived skeletal muscle myobundles.

Methods

MUSCLE BIOPSY AND PARTICIPANTS CELL CULTURE

Microfluidic 3D cell culture was performed by isolating donor-derived myofibers from human skeletal muscle biopsies. Biopsy samples were obtained from healthy, vastus lateralis individuals aged 21–40 years.

Figure 1. Functional analysis of donor-derived myobundles.
Figure 1. Functional analysis of donor-derived myobundles.

3D CELL CULTURE AND MYOBUNDLES

Myofibers were injected into the PDMS chips to a final cell density of 15 and 20 million cells/ml for Vandal OS-derived cells, respectively as previously described.

Groups Sample # Cohort Description RNA (ng) RIN
1 Young E-Stim Vehicle (Ctrl) 2741.5 9
2 Young E-Stim Vehicle (Ctrl) 1766.3 8.4
3 Young E-Stim Vehicle (Ctrl) 1626.3 8.9
4 Old E-Stim Vehicle (Ctrl) 1793.4 8.7
5 Old E-Stim Vehicle (Ctrl) 2072.7 8.6
6 Old E-Stim Vehicle (Ctrl) 2200.3 7.6
7 Young E-Stim Tomatidine 1989.1 9.8
8 Young E-Stim Tomatidine 2184.1 9.1
9 Young E-Stim Tomatidine 2002.3 9.2
10 Old E-Stim Tomatidine 2088.5 9.2
11 Old E-Stim Tomatidine 2365.4 9.5
12 Old E-Stim Tomatidine 2087.4 9.1

Differential Expression and Functional Annotation of RNA-seq Data

Differential expression analysis was performed using the DESeq2 package, with an FDR corrected p-value (p<0.05). The results were further analyzed using Gene set enrichment analysis (GSEA).

Figure 2. Visualization of RNA-seq results and functional enrichment analysis of DEGs.
Figure 2. Visualization of RNA-seq results and functional enrichment analysis of DEGs.

Discussion

Understanding muscle cell-autonomous mechanisms that disrupt regenerative muscle inflammation following exercise is critical for developing therapeutic strategies to mitigate muscle injury.

Figure 3. Inflammatory analysis after tomatidine treatment.
Figure 3. Inflammatory analysis after tomatidine treatment.

References

  1. Gronckel, P. et al. A Review of Exercise as Medicine in Cardiovascular Disease: Pathology and Mechanism. Aging and disease 11, 327 (2020).
  2. Izquierdo, M. et al. International Exercise Recommendations in Older Adults (IERA): Expert Consensus Guidelines. The Journal of nutrition, health and aging 25, 824–853 (2021).
  3. Seydou, U. S. A., Batildo, D., Visaria, A. & Maliny, S. K. The importance of exercise for glycemic control in type 2 diabetes. Front. Physiol. 10, 500 (2019).
  4. Kim, J.-H., Yu, S.-M. & Son, J. W. Human Tissue-Engineered Skeletal Muscle: A Tool for Metabolic Research. Endocrinol Metab 37, 408–414 (2022).
  5. Hind, L., McMillan, J., Arce, D., Hinds, S. & Kumar, A. Isolation, Culturing, and Differentiation of Human Skeletal Muscle Cells. Bio-protocol 7, e2101 (2017).
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