Baicalein, a bioactive flavonoid, has poor water solubility, thereby limiting its use in a wide range of biological applications. In the present study, we used inclusion complexes of cysteinyl β-cyclodextrin (β-CD) with baicalein to enhance the stability and solubility of baicalein in aqueous solution. We examined the effects of inclusion complexes of cysteinyl β-CD on collagen synthesis following ultraviolet (UV) irradiation, as well as the mechanisms underlying its effects. Our findings demonstrated that baicalein significantly restored collagen synthesis in the UVexposed human fibroblast Hs68 cells. In addition, synthetic cysteine functionalized β-CDs were found to promote baicalein-induced collagen synthesis. Inclusion complexes of cysteinyl β-CDs with baicalein significantly upregulated the protein expression of type I collagen and activated the transcription of type I, II, and III collagen. Inclusion complexes of cysteinyl β-CDs with baicalein also downregulated matrix metalloproteinase -1 and -3, and α-smooth muscle actin expression. In addition, inclusion complexes of cysteinyl β-CDs with baicalein attenuated the expression of caveolin-1, but this treatment enhanced the UV-induced phosphorylation of Smad in the transforming growth factor-β pathway. These results suggested that the newly synthesized derivative of CD can be used as a complexing agent to enhance the bioavailability of flavonoids such as baicalein, especially in restoring collagen synthesis.baicalein, collagen, cysteinyl β-cyclodextrin (β-CD), inclusion complex, ultraviolet-exposed fibroblast 1 | INTRODUCTION Collagen plays an important role in maintaining the skin and is largely responsible for its strength and resilience. Skin aging is inevitably associated with disturbances in collagen metabolism, such as decreased synthesis and increased degradation. 1 Skin aging is influenced by both intrinsic (genetics) and extrinsic factors (environmental exposure). Ultraviolet (UV) irradiation is particularly important extrinsic risk factor. 2 Skin aging involves the degradation of dermal collagen fibrils in the extracellular matrix by matrix metalloproteinases (MMPs). 3 UV irradiation of the connective tissue in the skin induces the production of MMP-1, MMP-3, and MMP-9 in the normal human skin in vivo. This leads to collagen degradation, especially of type I procollagen (COLI), the J Cell Biochem. 2019;120:4032-4043. wileyonlinelibrary.com/journal/jcb 4032 |