Beneficial Regulation of Elastase Activity and Expression of Tissue Inhibitors of Matrixmetalloproteinases, Fibrillin, Transforming Growth Factor-, and Heat Shock Proteins by P. leucotomos in Nonirradiated or Ultraviolet-Radiated Epidermal Keratinocytes
There is loss of the structural integrity of the extracellular matrix (ECM) with intrinsic aging as well as photoaging, largely due to reactive oxygen species (ROS). The structural ECM proteins include the microfibrils that are composed of fibrillin. The structural ECM proteins are primarily degraded by the matrixmetalloproteinases (MMPs) and elastase enzymes. The MMPs are inhibited by the tissue inhibitors of MMPs (TIMPs). A primary regulator of the ECM proteins is transforming growth factor- (TGF- ), and the chaperone proteins important for its formation are the heat shock proteins (HSP). P. leucotomos extract beneficially regulates of MMPs, TIMPs, and TGF- in nonirradiated or ultraviolet (UV) radiated fibroblasts and melanoma cells. The hypothesis of this research was that the antioxidant activity or chemistry of P. leucotomos extract would also directly inhibit elastase activity, stimulate the cellular expression of TIMPs, fibrillins, and TGF- , and regulate HSPs in nonirradiated and UVA or UVB radiated epidermal keratinocytes. P. leucotomos directly inhibited elastase activity, stimulated the cellular expression of TIMPs, fibrillins, and TGF- , and differentially regulated HSPs in nonirradiated and UVA or UVB radiated epidermal keratinocytes. We infer that the P. leucotomos extract strengthens the ECM and is effective in the prevention or treatment of intrinsic and photoaging of skin. 1. Introduction Cellular oxidative stress from increased reactive oxygen species (ROS) occurs with intrinsic aging, and more so from the exposure of skin to ultraviolet (UV) radiation. The UV radiation includes the long-wavelength UV-A light (320–400？nm), which increases cellular ROS and ROS mediated cellular/extracellular matrix (ECM) damage, and the short-wavelength UV-B light (290–320？nm), which directly damages DNA as well as cells/ECM through ROS. The ROS facilitate the degradation/remodeling of the ECM that leads to skin aging or cancer. The ECM proteins include the microfibrillar network that is composed of the fibrillin, synthesized by the epidermal keratinocytes and the dermal fibroblasts. The degradation of the ECM proteins is primarily by the matrixmetalloproteinases (MMPs) and elastase, which are inhibited by the cellular inhibitors of MMPs, tissue inhibitors of MMPs (TIMPs). The primary regulator of the ECM is transforming growth factor- (TGF- ). Antioxidants remove ROS, and thereby have the potential to inhibit ROS mediated skin aging or cancer. Polypodium leucotomos is a topical fern plant of the order polypodiaceae. P. leucotomos is rich in polyphenols
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