Abstract:AIM: To systematically summarize the efficacy and safety of flavonoids in the treatment of dry eye disease (DED), and review their mechanisms of action, and provide a scientific foundation for clinical translation. METHODS: To retrieve papers published from the establishment of the database through May 12, 2025, eight databases were searched: the Chinese National Knowledge Infrastructure (CNKI), the China Biomedical Literature Database (CBM), the Wanfang Database, the China Science, Technology Journal Database, PubMed, the Cochrane Library, Embase, and the Web of Science. Two independent researchers conducted the literature selection and information extraction processes, utilizing the SYRCLE tool to assess the risk of bias. The results of eligible studies were subjected to narrative analysis. RESULTS: A total of 11 animal studies were included in this review, encompassing research conducted in China, the United States, Republic of Korea, and Japan. These studies involved six flavonoid-rich substances, such as Buddleja officinalis and purple corn extract (PCE), as well as four individual flavonoids including quercetin and daidzin, etc. The findings indicated that flavonoids have the potential to enhance tear secretion. Following interventions with quercetin eye drops and PCE administered at varying doses and time intervals, a significant increase in tear secretion was observed, which approached normal levels. Additionally, these interventions demonstrated a capacity to mitigate damage to the corneal epithelium. For instance, maqui berry extract (MBE) were found to improve corneal fluorescein staining scores while reducing damage to the corneal surface. Flavonoids significantly alleviate dry eye symptoms in animal models by enhancing tear secretion and mitigating corneal epithelial damage. The observed efficacy is attributed to a range of mechanisms, including anti-inflammatory, antioxidant, hormonal regulation, and anti-apoptotic effects. CONCLUSION: The consistent therapeutic outcomes noted in both mouse and rat models further underscore the translational potential of these compounds. Consequently, flavonoids are regarded as highly promising natural agents for ocular health. However, additional pharmacokinetic studies and clinical trials are necessary to confirm their efficacy and safety in human subjects with dry eye syndrome.
