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Transdermal anti-inflammatory effects and mechanisms of hydrogel patches containing seco-iridoids from Gentiana macrophylla Pall

Huan Liu,Yao Zhong,Rong Huang,Shian Meng,Guang Chen

Gentiana macrophylla Pall. (GMP), known as “Qinjiao” in the Chinese Pharmacopeia, has a long history of clinical application in treating rheumatoid arthritis, primarily due to its iridoid components. However, the transdermal anti-inflammatory efficacy, active ingredients, and underlying mechanisms of these components remain under-investigated. This study aimed to clarify the transdermal anti-inflammatory effects and mechanisms of seco-iridoids from GMP by establishing a hydrogel patch transdermal drug delivery system. Using crude and refined GMP iridoid extracts as active components, the hydrogel patch system was established based on physicochemical properties, skin irritation tests, in vitro drug release, and skin permeation. The anti-inflammatory efficacy of these iridoid hydrogel patches was assessed using a carrageenan-induced paw edema model in mice. Content analysis and skin permeation studies identified gentiopicroside (GPS) and swertiamarin (SWE) as the key bioactive constituents. The hydrogel patch system demonstrated superior skin permeation and sustained drug release profiles compared to oral administration, addressing issues of poor bioavailability and rapid metabolism. Mechanistic studies revealed that these seco-iridoids exert their anti-inflammatory effects primarily through modulation of the iNOS/COX-2/NF-κB signaling cascade. Pharmacokinetic evaluations showed significant improvements in bioavailability and prolonged drug release, highlighting the clinical advantages of the transdermal approach. This work lays a solid foundation for the further optimization and clinical translation of GMP-based transdermal formulations, providing a framework for the investigation of iridoid transdermal systems and their therapeutic applications in inflammatory conditions.