Fernblock, a nutriceutical with photoprotective properties and potential preventive agent for skin photoaging and photoinduced skin cancers.
Many phytochemicals are endowed with photoprotective properties, i.e., the capability to prevent the harmful effects of excessive exposure to ultraviolet
(UV) light. These effects include photoaging and skin cancer, and immunosuppression. Photoprotection is endowed through two major modes of action: UV
absorption or reflection/scattering; and tissue repair post-exposure. We and others have uncovered the photoprotective properties of an extract of the fern
Polypodium leucotomos (commercial name Fernblock). Fernblock is an all-natural antioxidant extract, administered both topically (on the skin) or orally. It
inhibits generation of reactive oxygen species (ROS) production induced by UV including superoxide anion. It also prevents damage to the DNA, inhibits
UV-induced AP1 and NF-kB, and protects endogenous skin natural antioxidant systems, i.e., CAT, GSH, and GSSR. Its photoprotective effects at a cellular
level include a marked decrease of UV-mediated cellular apoptosis and necrosis and a profound inhibition of extracellular matrix remodeling. These
molecular and cellular effects translate into long-term inhibition of photoaging and carcinogenesis that, together with its lack of toxicity, postulate its
use as a novel-generation photoprotective nutriceutical of phytochemical origin.
Int J Mol Sci.
Molecular mechanisms of retinoid actions in skin.
For more than 40 years, it has been appreciated that vitamin A is a critical regulator of growth and differentiation of developing and adult mammalian and
avian skin. Vitamin A deficiency and hypervitaminosis A cause disruption of normal cellular homeostatic mechanisms, resulting in impairment of skin barrier
function. More recent studies demonstrating all-trans retinoic acid as the major biologically active form of vitamin A, and nuclear retinoid receptors as
the major mediators of all-trans retinoic acid actions, have provided exciting new insights into the molecular basis of vitamin A actions. These recent
insights have been the driving force for important advances in the many areas of retinoid research made during the past 6 years. Nowhere has this new
knowledge been more extensively applied than toward understanding the molecular basis of retinoid physiology and pharmacology in skin. This article will
review these recent findings and attempt to synthesize their meaning to provide a view into the mechanisms whereby retinoids participate in regulation of
Molecular Mechanisms of UV-Induced Apoptosis and Its Effects on Skin Residential Cells: The Implication in UV-Based Phototherapy.
The human skin is an integral system that acts as a physical and immunological barrier to outside pathogens, toxicants, and harmful irradiations.
Environmental ultraviolet rays (UV) from the sun might potentially play a more active role in regulating several important biological responses in the
context of global warming. UV rays first encounter the uppermost epidermal keratinocytes causing apoptosis. The molecular mechanisms of UV-induced
apoptosis of keratinocytes include direct DNA damage (intrinsic), clustering of death receptors on the cell surface (extrinsic), and generation of ROS.
When apoptotic keratinocytes are processed by adjacent immature Langerhans cells (LCs), the inappropriately activated Langerhans cells could result in
immunosuppression. Furthermore, UV can deplete LCs in the epidermis and impair their migratory capacity, leading to their accumulation in the dermis.
Intriguingly, receptor activator of NF-kB (RANK) activation of LCs by UV can induce the pro-survival and anti-apoptotic signals due to the upregulation of
Bcl-xL, leading to the generation of regulatory T cells. Meanwhile, a physiological dosage of UV can also enhance melanocyte survival and melanogenesis.
Analogous to its effect in keratinocytes, a therapeutic dosage of UV can induce cell cycle arrest, activate antioxidant and DNA repair enzymes, and induce
apoptosis through translocation of the Bcl-2 family proteins in melanocytes to ensure genomic integrity and survival of melanocytes. Furthermore, UV can
elicit the synthesis of vitamin D, an important molecule in calcium homeostasis of various types of skin cells contributing to DNA repair and
immunomodulation. Taken together, the above-mentioned effects of UV on apoptosis and its related biological effects such as proliferation inhibition,
melanin synthesis, and immunomodulations on skin residential cells have provided an integrated biochemical and molecular biological basis for phototherapy
that has been widely used in the treatment of many dermatological diseases.
Int J Mol Sci.
2013 Mar 20;14(3):6414-35
Skin barrier in atopic dermatitis.
The skin represents the largest organ of the body and provides a vital interface between the body and the environment. Hereditary and acquired alterations
of structural proteins and lipids of the stratum corneum and epidermal tight junctions leading to a diminished skin barrier function are major causative
factors for a number of skin diseases, in particular atopic dermatitis (AD). This review summarizes current knowledge on the role of the skin barrier in AD
with regard to pathogenesis and treatment, on the relationship between skin barrier abnormalities and immune aberrations, and on potential therapies aimed
at repair of the skin barrier. Furthermore recent advances in the genetics of AD will be addressed.
Front Biosci (Landmark Ed).
2014 Jan 1;19:542-56
Photoprotection: part I. Photoprotection by naturally occurring, physical, and systemic agents.
The acute and chronic consequences of ultraviolet radiation on human skin are reviewed. An awareness of variations in naturally occurring photoprotective
agents and the use of glass, sunglasses, and fabric can lead to effective protection from the deleterious effects of ultraviolet radiation. New systemic
agents, including Polypodium leucotomos, afamelanotide, and antioxidants have potential as photoprotective agents.
J Am Acad Dermatol.
e1-12; quiz 865-6
UV-induced free radicals in the skin detected by ESR spectroscopy and imaging using nitroxides.
Reactive free radicals and reactive oxygen species (ROS) induced by ultraviolet irradiation in human skin are strongly involved in the occurrence of skin
damages like aging and cancer. In the present work an ex vivo method for the detection of free radicals/ROS in human skin biopsies during UV irradiation is
presented. This method is based on the Electron Spin Resonance (ESR) spectroscopy and imaging and uses the radical trapping properties of nitroxides. The
nitroxides 2,2,6,6-Tetramethylpiperidine-1-oxyl (TEMPO), 3-Carba moyl-2,2,5,5-tetramethyl pyrrolidine-1-oxyl (PCM), and
3-Carboxy-2,2,5,5-tetramethylpyrrolidine-1-oxyl (PCA), were investigated for their applicability of trapping reactive free radicals and reactive oxygen
species in skin during UV irradiation. As a result of the trapping process the nitroxides were reduced to the EPR silent hydroxylamins. The reduction rate
of TEMPO was due to both the UV radiation and the enzymatic activity of the skin. The nitroxides PCM and PCA are sufficiently stable in the skin and are
solely reduced by UV-generated free radicals/ROS. The nitroxide PCA was used for imaging the spatial distribution of UV-generated free radicals/ROS. As a
result of the homogeneous distribution of PCA in the skin, it was possible to estimate the penetration of UVA and UVB irradiation: The UV irradiation
decreased the PCA intensity corresponding to its irradiance and penetration into the skin. This reduction was shown to be caused mainly by UVA radiation
Free Radic Biol Med.
2003 Jul 1;35(1):59-67
Photoprotection of human skin beyond ultraviolet radiation.
Photoprotection of human skin by means of sunscreens or daily skin-care products is traditionally centered around the prevention of acute (e.g. sunburn)
and chronic (e.g. skin cancer and photoaging) skin damage that may result from exposure to ultraviolet rays (UVB and UVA). Within the last decade, however,
it has been appreciated that wavelengths beyond the ultraviolet spectrum, in particular visible light and infrared radiation, contribute to skin damage in
general and photoaging of human skin in particular. As a consequence, attempts have been made to develop skin care/sunscreen products that not only protect
against UVB or UVA radiation but provide photoprotection against visible light and infrared radiation as well. In this article, we will briefly review the
current knowledge about the mechanisms responsible for visible light/infrared radiation-induced skin damage and then, based on this information, discuss
strategies that have been successfully used or may be employed in the future to achieve photoprotection of human skin beyond ultraviolet radiation. In this
regard we will particularly focus on the use of topical antioxidants and the challenges that result from the task of showing their efficacy.
Photodermatol Photoimmunol Photomed.
Radical protection by sunscreens in the infrared spectral range.
One essential reason for skin ageing is the formation of free radicals by excessive or unprotected sun exposure. Recently, free radical generation in skin
has been shown to appear not only after irradiation in the UV wavelength range but also in the infrared (IR) spectral range. Sunscreens are known to
protect against radicals generated by UV radiation; however, no data exist for those generated by IR radiation. This paper has investigated four different,
commercially available sunscreens and one COLIPA standard with regard to radical formation in the skin after IR irradiation, using electron paramagnetic
resonance spectroscopy. The use of sunscreens has led to reduced amounts of radicals compared to untreated skin. Furthermore, absorption and scattering
properties and the radical protection factor of the formulations were determined to investigate their influence on the radical protection of the skin. None
of these formulations contained an optical absorber in the IR range. The protection efficiency of the sunscreens was shown as being induced by the high
scattering properties of the sunscreens, as well as the antioxidants contained in the formulations.
2011 Mar-Apr;87(2): 452-6