15/03/2026
MicroRNAs (miRNAs) are very small pieces of RNA, about 20 nucleotides long, that do not make proteins but instead help control how genes are used. They act like fine tuners, adjusting how much protein a cell produces by attaching to messenger RNA (mRNA) and either blocking it from being translated or marking it for breakdown. Each miRNA can influence many different genes at once, and each gene can be influenced by several miRNAs, creating a web of regulation that helps keep cells stable and balanced.
MicroRNAs are involved in many normal processes, including growth, development, immune function, metabolism, and brain activity. When their levels become too high or too low, health problems can arise. Changes in miRNA patterns have been linked to cancer, heart disease, neurological conditions and autoimmune disorders. Because miRNAs circulate in the bloodstream in a stable form, they are also being studied as potential blood-based markers to help detect or monitor a range of diseases. Researchers are exploring treatments that either replace missing miRNAs or block harmful ones, although safely delivering these therapies remains a challenge. Overall, miRNAs represent an important layer of control in the body, helping shape how genes are expressed and how health and disease unfold.
The effects of foods and herbs on miRNA expression in people remain unclear. A randomised, double blind, placebo-controlled exploratory trial from Japan investigated whether onion extract tablets (OET) could alter circulating miRNA profiles in humans. Nineteen healthy Japanese adults aged 30 to 65 years with mild stress were assigned to OET (n=10) or placebo (n=9) for 2 weeks. The intervention consisted of tablets providing 30 mg/day of onion sulfur-containing amino acids. Plasma miRNAs were measured before and after treatment using next-generation sequencing. The primary aim was biomarker-based, specifically, identifying miRNA changes associated with onion extract intake, rather than assessing symptom or disease outcomes.
Onions are chemically distinctive because of their sulfur-containing amino acids, many of which are not present in meaningful amounts in other common foods. These compounds are responsible for onion’s pungency, its characteristic “tear inducing factor,” and—more interestingly for clinicians—its cardiometabolic and other health effects. The main sulfur amino acids in onions are isoalliin (trans-(+)-S-1-propenyl-L-cysteine sulfoxide), methiin (S-methyl-L-cysteine sulfoxide) and propiin (S-propyl-L-cysteine sulfoxide).
Compared with placebo, OET produced significantly greater increases in miR-106b-5p, miR-339-3p, and miR-181b-5p. The authors reported that these miRNAs, particularly when combined as a panel, could readily discriminate between the OET and placebo groups. Collectively, these miRNAs converge on key physiological domains including cell turnover, inflammatory control, metabolic balance and vascular function.
No adverse or unexpected effects were observed during the intervention. Importantly, however, the study did not demonstrate any changes in clinical symptoms or physiological endpoints; it remained focused on the molecular biomarkers. The authors performed pathway prediction analyses suggesting possible biological relevance, but no direct functional validation was conducted.
Strengths of the study include its randomised, double blind, placebo-controlled design and the use of objective, high-throughput miRNA sequencing. However, the trial was limited by its very small sample size (n=19) and short duration (2 weeks).
While this appears to be the first human trial specifically showing onion extract alters plasma miRNAs, it is not the first clinical study demonstrating that plant-derived interventions can influence circulating miRNA profiles. However, it is an important contribution to this emerging field as only few such studies exist.
The miRNA dimension opens an evolving and potentially transformative vista on how herbs may influence human physiology. Rather than viewing herbal medicines purely through receptor binding, enzyme inhibition and so on, this emerging evidence suggests they may also act at the level of post-transcriptional gene regulation, subtly reshaping patterns of gene expression across entire biological networks. Because each microRNA can influence dozens to hundreds of genes, even modest shifts may translate into coordinated changes in inflammatory tone, metabolic balance, vascular reactivity, stress signalling or tissue repair. This aligns closely with the long-observed “multi-system” effects of herbal medicines that have often been difficult to explain through single-target pharmacology.
However, this field is still in its infancy. Most current studies are small, short-term and biomarker-focused. We need larger, well-controlled clinical trials that correlate miRNA shifts with meaningful clinical endpoints—symptom change, inflammatory markers, metabolic indices or disease progression. Dose-response data, tissue-specific profiling (not just plasma), and longitudinal studies examining durability of miRNA modulation are also essential. Mechanistic validation, demonstrating that observed miRNA changes directly influence predicted pathways, remains largely uncharted territory.
In short, the miRNA lens offers a compelling systems-level explanation for herbal network effects, but it demands far more rigorous and expansive research before its clinical implications can be confidently defined and exploited.
For more information see: https://pubmed.ncbi.nlm.nih.gov/41224950/
