Drug Pipeline
SYSTEMATIC REVIEW
● Sys. Review
Preclinical Review Suggests TCM Formulas Target Multiple Pathways in Dry Eye Disease Models
Frontiers in Medicine
Published April 1, 2026
DOI ↗
A systematic review examined preclinical evidence on the molecular mechanisms of Traditional Chinese Medicine (TCM) interventions for dry eye disease (DED). The analysis focused on cellular and animal models, reviewing TCM-derived metabolites, botanical drug extracts, and TCM formulas. The main reported finding is that these TCM interventions target multiple signaling pathways—including PI3K/AKT, MAPK, NF-κB, NLRP3, Nrf2, SIRT, AMPK, and VEGF—which are involved in the inflammation, oxidative stress, and apoptosis underlying DED pathology. The direction of effect is proposed to counteract these pathological processes and promote tear film stability. No specific effect sizes, absolute numbers, or statistical measures were reported for these mechanistic findings.
No data on adverse events, serious adverse events, discontinuations, or tolerability were reported, as the review did not include clinical trials. The evidence is entirely from preclinical models; no human safety profile exists from this analysis.
Key limitations stem from the nature of the evidence. The review synthesizes findings from cellular and animal studies only. No clinical trial data, human outcomes, or direct measures of clinical efficacy in patients were included. The certainty of the evidence is therefore limited to preclinical mechanisms. The practice relevance is restrained: the review describes molecular mechanisms and offers a theoretical framework for intervention optimization and future clinical translation. It does not support any clinical recommendations for patient care at this stage.
Researchers reviewed existing scientific studies to understand how Traditional Chinese Medicine (TCM) might work against dry eye disease. They looked at TCM formulas, plant extracts, and natural compounds, focusing on how they affect cells and animals in laboratory settings. The review did not involve human patients or test treatments on people.
The main finding was that, in these lab models, TCM formulas are reported to interact with several specific biological pathways inside cells. These pathways are involved in the inflammation, oxidative stress, and cell death processes thought to contribute to dry eye disease. The review suggests these molecular interactions could form a theoretical basis for future treatments.
It is very important to understand that all the evidence discussed comes from preclinical research—meaning studies done on cells in dishes or in animals. The review did not include any results from clinical trials with human patients. Therefore, we do not know if these TCM formulas are safe, effective, or work the same way in people with dry eye disease.
Readers should take this as an early look at the science behind how these natural compounds might work. It explains potential mechanisms but does not prove any treatment works for patients. More research, especially well-designed human trials, is needed to translate these laboratory findings into real-world therapies.
What this means for you: Lab studies suggest how TCM might affect dry eye biology, but human safety and effectiveness are still unknown.
View Original Abstract ↓
Dry eye disease (DED) is a prevalent global health issue that negatively impacts quality of life. It is also associated with the risk of corneal ulceration, scarring, and even blindness in severe cases. The complex, multifactorial pathology of DED, often conceptualized as a vicious cycle involving tear film instability, hyperosmolarity, inflammation, and apoptosis, complicates treatment. Traditional Chinese Medicine (TCM) offers a potential therapeutic approach by targeting multiple components and pathways. This review systematically describes the mechanisms by which TCM-derived metabolites, botanical drug extracts, and TCM formulas are reported to modulate interconnected pathological processes underlying DED to establish a theoretical framework for intervention optimization. A systematic literature search was conducted on 23 April 2025, across seven electronic databases (PubMed, Web of Science, Embase, SinoMed, CNKI, Wanfang, and VIP) using a comprehensive strategy combining MeSH terms and keywords related to DED, TCM, and signaling pathways. DED involves alterations in several important signaling pathways associated with inflammation, oxidative stress, and apoptosis. These include PI3K/AKT, MAPK, NF-κB, NLRP3, Nrf2, SIRT, AMPK, and VEGF. TCM formulas represent a multi-target approach with an ability to simultaneously target single or multiple signaling pathways involved in DED pathology. This is proposed to counteract key interlinked processes of inflammation, apoptosis, and oxidative stress, and promotes tear film stability in cellular and animal models, thereby highlighting its pharmacological potential. The multi-component, multi-target, and multi-pathway approach of TCM may offer a strategic advantage for managing the multifactorial pathology of DED through the potential to simultaneously regulate multiple interactive signaling networks. This review describes the molecular mechanisms underlying these traditional treatment practices and offers a robust foundation for future clinical translation.