In a groundbreaking new study published in Food Science and Biotechnology, researchers uncovered the remarkable effects of two plant-derived lignans, lariciresinol and secoisolariciresinol, on muscle cell development and energy metabolism. These compounds were found to significantly promote myogenic differentiation—the process by which precursor cells evolve into mature muscle fibers—and enhance mitochondrial biogenesis within C2C12 myotubes, a model system extensively used to study muscle physiology in vitro. The findings may open novel avenues in the pursuit of therapeutic interventions for muscle degenerative diseases and metabolic disorders.
At the core of the study lies the intricate biology of skeletal muscle cells, which require efficient differentiation and a high density of mitochondria to sustain proper function. Mitochondria, often dubbed the “powerhouses” of the cell, generate ATP through oxidative phosphorylation, fueling muscle contraction and regeneration. Disruptions in mitochondrial biogenesis or myogenesis are hallmarks of various muscular dystrophies and age-related sarcopenia. Therefore, agents capable of augmenting these processes possess tremendous therapeutic potential. Lariciresinol and secoisolariciresinol, which belong to the class of plant lignans found abundantly in foods such as flaxseed, sesame seeds, and whole grains, have long been studied for their antioxidant and anti-inflammatory properties. However, their direct effects on muscle cell biology remained obscure until now.
The research team utilized C2C12 myoblasts, a murine muscle precursor cell line that differentiates into myotubes under defined conditions, to delineate the molecular mechanisms underpinning the effects of lariciresinol and secoisolariciresinol. By administering these lignans to differentiating cells, the investigators observed a pronounced increase in myotube formation compared to controls. Quantitative assessments, including immunocytochemical analyses and expression profiles of myogenic regulatory factors such as MyoD and myogenin, confirmed that the lignans significantly accelerated the differentiation process.
Mitochondrial biogenesis was assessed by examining mitochondrial DNA content, expression levels of key biogenic regulators, and mitochondrial functional assays. The results demonstrated a robust upregulation of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), nuclear respiratory factors, and mitochondrial transcription factors, confirming that lariciresinol and secoisolariciresinol foster a cellular environment conducive to mitochondrial expansion. This coordinated enhancement of muscle fiber maturation and mitochondrial proliferation underscores a synergistic mechanism whereby muscle tissue gains both structural and energetic advantages.
Beyond the primary cellular assays, the study elucidated signaling pathways implicated in the lignans’ mode of action. Notably, activation of AMP-activated protein kinase (AMPK) and sirtuin 1 (SIRT1) pathways emerged as critical mediators. AMPK is a sensor of cellular energy status that, when activated, promotes catabolic pathways and mitochondrial biogenesis. SIRT1, a NAD+-dependent deacetylase, modulates transcriptional regulators involved in metabolic homeostasis and cellular differentiation. The engagement of these pathways indicates that lariciresinol and secoisolariciresinol may mimic exercise-like stimuli at a molecular level, enhancing muscle cell metabolism and regenerative capacity.
Implications of these findings are wide-ranging, as they suggest dietary lignans could be harnessed as natural supplements to combat muscle wasting in aging populations or pathological conditions such as cachexia associated with cancer or chronic illness. Importantly, the ability to simultaneously augment muscle differentiation and mitochondrial content could improve muscle function and endurance, thereby enhancing quality of life.
However, the authors caution that while C2C12 cells provide a valuable model for fundamental muscle biology, further in vivo research is necessary to translate these promising results into clinical practice. It remains to be seen how these lignans are metabolized and whether they reach effective concentrations within muscle tissue when ingested through diet or supplementation. Future studies incorporating animal models and eventually clinical trials will be imperative to ascertain safety, bioavailability, and efficacy.
The study also provokes intriguing questions regarding potential synergisms with other nutraceuticals or pharmaceuticals targeting muscle health. For example, could lignans augment the effects of exercise or potentiate the repair mechanisms following muscle injury? Likewise, their anti-inflammatory and antioxidant actions may complement scenarios where oxidative stress impairs muscle regeneration.
Moreover, these discoveries align with a broader trend examining the intersection of nutrition, metabolism, and regenerative medicine. The concept that naturally derived compounds influence mitochondrial biogenesis and stem cell differentiation has gained traction, offering avenues for non-invasive therapeutic strategies. The identification of naturally occurring bioactive molecules such as lariciresinol and secoisolariciresinol with multifunctional, mechanistically defined benefits reinforces the potential of diet-based interventions in chronic disease management and healthspan extension.
Beyond muscle tissue, mitochondria play fundamental roles in many cell types, suggesting that lignans’ influence on mitochondrial biogenesis might extend to metabolic organs such as the liver, heart, or brain. Inter-disciplinary research could explore possible applications in neurodegenerative diseases or metabolic syndromes where mitochondrial dysfunction is central.
The research utilized cutting-edge molecular biology techniques, including western blotting for protein quantification, RT-qPCR for gene expression analysis, and fluorescence microscopy to visualize mitochondrial networks—a robust experimental design underscoring the rigor of the study. Such comprehensive evaluation of both phenotypic outcomes and underlying signaling pathways provides a convincing narrative of lignans’ multifaceted effects on muscle cell biology.
It is worth noting that the study contributes to the evolving understanding of lignan bioactivity beyond their classical roles. Historically studied for hormone modulation and cardiovascular benefits, this research pivots towards regenerative cell biology, potentially redefining the scope of lignans in human health interventions.
In the context of global aging demographics and rising prevalence of chronic diseases accompanied by muscle loss and frailty, the discovery of bioactive compounds capable of promoting muscle regeneration and function is of profound importance. Nutritional strategies that can be easily integrated into daily life offer scalable and affordable means to support musculoskeletal health across populations.
While enthusiasm for such findings is warranted, a prudent approach necessitates careful evaluation of pharmacodynamics, optimal dosing regimens, and potential side effects in longer-term settings. Additionally, considerations of interindividual variability in response due to genetic or microbiome differences will shape future translational pathways.
Overall, this study by Jeong, Jeun, Yoon, and colleagues represents a significant advance in muscle biology and nutraceutical science. By illuminating the role of lariciresinol and secoisolariciresinol in enhancing myogenic differentiation and mitochondrial biogenesis, the research sets a promising foundation for novel therapeutic and preventive strategies aimed at mitigating muscle degeneration and improving metabolic health.
As research progresses, the integration of plant-derived lignans into clinical and lifestyle frameworks could emerge as a versatile and natural tool in the fight against muscle wasting, recovery after injury, and possibly age-related decline in muscle function. This could herald a new paradigm where food components transcend nutrition and become vital adjuncts in regenerative medicine.
This study not only enriches the scientific literature on natural compounds but also encourages a reexamination of diet’s critical role in cellular and tissue health, inspiring both researchers and clinicians to explore nature’s pharmacopeia for solutions to unexplored biological challenges.
Subject of Research: Effects of plant lignans lariciresinol and secoisolariciresinol on muscle cell differentiation and mitochondrial biogenesis in C2C12 myotubes.
Article Title: Lariciresinol and secoisolariciresinol enhance myogenic differentiation and mitochondrial biogenesis in C2C12 myotubes.
Article References:
Jeong, H.Y., Jeun, J., Yoon, Y. et al. Lariciresinol and secoisolariciresinol enhance myogenic differentiation and mitochondrial biogenesis in C2C12 myotubes. Food Sci Biotechnol (2025). https://doi.org/10.1007/s10068-025-02014-7
Image Credits: AI Generated
DOI: https://doi.org/10.1007/s10068-025-02014-7
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