Ursodeoxycholic Acid May Inhibit Environmental Aging-Associated Hyperpigmentation

Abstract

Extrinsic aging of the skin caused by ultraviolet (UV) light or particulate matter is often manifested by hyperpigmentation due to increased melanogenesis in senescent skin. Ursodeoxycholic acid (UDCA), which has been commonly used as a health remedy for liver diseases, is known to possess antioxidant properties. This study was done to investigate whether UDCA inhibits cellular aging processes in the cells constituting human skin and it reduces melanin synthesis. ROS, intracellular signals, IL-1α, IL-8, TNF-α, cyclooxygenase (COX)-2, type I collagen, and matrix metalloproteinases (MMPs) levels were measured in human dermal fibroblasts treated with or without UDCA after UV exposure. Melanin levels and mechanistic pathways for melanogenesis were investigated. UDCA decreased ROS, senescence-associated secretory phenotype (SASP), and proinflammatory cytokines induced by UV treatment. UDCA reduced melanogenesis in normal human melanocytes cocultured with skin constituent cells. Our results suggest that UDCA could be a comprehensive agent for the treatment of environmental aging-associated hyperpigmentation disorders.

TMBIM6 deficiency leads to bone loss by accelerating osteoclastogenesis

“…OCP cells were cultured in 96-well black/clear bottom plates with M-CSF (30 ng/mL) and RANKL (100 ng/mL) for 24 h. To detect intracellular ROS, the cells were preloaded with 5 μM of 2',7'-dichlorofluorescin diacetate (DCF-DA) in phenol red-free MEM-α for 1 h in the dark, and then treated with RANKL (100 ng/mL) for 30 min. The DCF fluorescence was measured on a fluorescence plate reader at excitation/emission wavelengths of 485/538 nm in endpoint mode [ [43] , [44] , [45] , [46] ]. Additionally, CellROXTM Deep Red Reagent (Molecular Probes) was used to detect intracellular ROS following the manufacturer's instructions.…”

SMILE Downregulation during Melanogenesis Induces MITF Transcription in B16F10 Cells

“…Therefore, targeting SMILE in local skin could be a potential treatment for hyperpigmentation or hypopigmentation. It is also worth noting that several small molecules with antimelanogenic properties in the skin can also induce SMILE expression in other tissues [ 20 , 21 , 22 , 23 ]. For instance, metformin, a drug used to treat diabetes, suppresses the expression of MITF and melanogenic genes by reducing cAMP/PKA/CREB signaling, thereby inhibiting melanin production in vivo and in human reconstituted epidermis [ 24 ].…”