(P03-040-23) Therapeutic Potential of Umbelliferone on Hyperglycemia-Driven Skin Barrier Dysfunctions With Impairment of Dermal Integrity in Diabetic Skins

Objectives: Diabetic wounds are one of the complications of diabetes mellitus (DM) that can lead to amputation. Dermal fibroblasts (DF) are critical for effective wound healing in skin regeneration and repair. This study was aimed to explore that hyperglycemia triggers skin barrier dysfunction with alterations of dermal integrity, induced significant changes of extracellular matrix (ECM) components and dermal water content, which was attenuated by umbelliferone, widely spread in plants in nature especially in herbs such as celery, parsley and hogweed.

Methods: Primary human skin dermal Fibroblasts were cultured in media containing 33 mM glucose for 3 days in the presence of 1-20 μM umbelliferone. The in vivo animal study employed db/db mice orally administrated with 10 mg/kg umbelliferone. Cell lysates and mouse eye tissue extracts were prepared for Western blotting, in which antibodies of Collagen 1,3 , MMP 1,3, AQP3, HYAL1, HAS 2, ZO-1 and Occludin were used.

Results: Hyperglycemia enhanced the activity of matrix metalloproteinases in fibroblast cells, which was inhibited by umbelliferone. Exposure of fibroblast to high glucose declined the ECM components, evidenced by deactivation of collagen1,3 and fibronectin. Furthermore, prolonged high glucose lead to lessen induction of AQP3, HYAL1 and HAS 2 skin dryness related markers. Consistently, oral administration of umbellierone to db/db mice curtailed the skin tissue levels of ECM components and skin dryness related proteins.

Conclusions: Umbelliferone may be a potent skinprotective agent allaying diabetes-mediated skin barrier dysfunctions leading to dermal integrity.

Funding Sources: This work was supported by the National Research Foundation of Korea (NRF) grants funded by the Korea government (2022R1I1A1A01067661 and 2021R1 I1A0104231612).