As the prevalence of metabolic diseases such as diabetes and obesity continue to rise, the search for more effective and convenient treatments has become a crucial issue in medical research. Microneedles (MNs), as an innovative drug delivery system, have shown advantages in the treatment of metabolic diseases in recent years. MNs-based drug delivery system, which use MNs to deliver drugs directly to the subcutaneous tissue, improve drug bioavailability and reduce systemic side effects. This review aims to summarize the latest concepts, designs, and types of MNs, and to investigate the materials and manufacturing methods used in their construction. Subsequently, the mechanisms of drug delivery and graded release of MNs and recent research progress are further summarized. This article focuses on the application of MNs in the treatment of common metabolic diseases, with a special emphasis on the progress and optimization of diabetic and anti-obesity MNs. The main challenges and future perspectives in the production and evaluation of MNs, as well as in enhancing treatment efficacy and improving safety, are elucidated.

Introduction: Accumulating evidence has multilaterally proved the indispensable contribution of inflammation in mediating various diseases over the last decade, including sepsis, obesity, diabetes, and neurological disorders. This established correlation between inflammation and disease progression has positioned anti-inflammatory intervention as a promising therapeutic strategy for disease prevention and treatment. Naturally occurring flavonoids have emerged as a subject of extensive investigation due to their well-documented anti-inflammatory properties and molecular mechanisms. The current review provides a comprehensive analysis of isoliquiritigenin (ISL), a bioactive flavonoid compound isolated from Glycyrrhiza glabra (licorice), with particular emphasis on its pharmacological activities and molecular mechanisms in modulating inflammation- associated disorders. Methods: A systematic literature review was executed across the PubMed and Google Scholar electronic databases spanning the period from January 2000 to December 2024, employing the following keyword combination: “isoliquiritigenin” (MeSH) AND “inflammation” (MeSH). Results: ISL was found to exhibit significant therapeutic potential in mitigating both acute and chronic inflammatory responses. Particular attention was devoted to elucidating ISL's multi-target regulatory mechanisms in acute organ injury models, including neurological, pulmonary, hepatic, and renal systems. Furthermore, the compound's therapeutic effects were found to extend to chronic inflammatory pathologies associated with metabolic and neurodegenerative disorders, notably diabetes mellitus, obesity-related complications, and Alzheimer's disease-associated tissue damage, particularly manifesting in ocular, pulmonary, and cardiovascular systems. Systematic characterization of ISL's molecular targets and associated signalling cascades, like MAPK, JAK/STAT3, Nrf2, and SIRT1 pathways, substantially enhanced our mechanistic understanding of its anti-inflammatory properties. Discussion: ISL demonstrated extensive protection in many inflammatory models. Its multi-target action implied broad therapeutic applicability. However, despite its excellent anti-inflammatory efficacy and safety profile, further study is required to investigate its effectiveness for clinical translation. Conclusion: This comprehensive analysis has provided a pharmacological foundation for developing ISL-based therapeutic interventions against inflammation-driven human pathologies.