Qualia Skin: The Building of a Comprehensive Supplement for Better Skin

Qualia Skin: The Building of a Comprehensive Supplement for Better Skin

Qualia Skin—Skin Health and Beauty from Within

When thinking about the most important organs of the human body, the first that come to anyone’s mind are probably the brain, heart, and lungs, and then maybe the kidneys and the liver... And it makes sense: these are absolutely essential for health and even life—they’re our vital organs. But there is an organ that we often take for granted and whose importance should probably be more acknowledged: the skin.

The skin is our shield; it protects our body—and all those important vital organs—from many of the aggressions we are exposed to in our environment: friction, damaging radiation, extreme temperatures, noxious chemicals… Add to this the fact that the skin is also a sensory organ that allows us to perceive the outside world, and it starts to come into focus just how important the skin is. 

The skin is a complex and dynamic organ whose health is influenced by all sorts of things: from genetics, hormones, metabolism, and how these change as we age—factors that are chronological and intrinsic to our biology—to diet, exercise, stress, pollution, smoking, and sun exposure—factors that are environmental or lifestyle-related, i.e., that are extrinsic to our biology but that influence our biological processes [1,2]. 

Poor skin health has a negative impact on many skin functions that are essential for our general health, particularly its barrier functions. Not only is the skin a physical barrier that envelops the body, it is also a chemical, selectively permeable, immunological, and thermal barrier that insulates and protects our internal organs and that has an irreplaceable role in maintaining the body in a state of balanced equilibrium or homeostasis. 

Only healthy skin is able to carry out its functions optimally, which is why taking care of our skin is so important.

Why We Created Qualia Skin

We created Qualia Skin, first and foremost, because we believe the skin is worthy of special attention. Because we know how important skin health is for our general wellness, we wanted to develop a skincare product that would support healthy skin physiology and that, by doing so, would support the skin’s protective, regulatory, and metabolic functions.*

But we are also aware of the sensory function of the skin—not only of its role in how we perceive and respond to the outside world, but also of the huge part skin health plays in how the outside world perceives and responds to us. There’s a social function to the skin that we believe should not be undervalued. Therefore, we also aimed to support skin beauty by working from the inside out: improving skin appearance as a natural outcome of healthier skin physiology. 

Furthermore, there are significant physiological changes the skin goes through as we age—changes in gene expression, cellular metabolism, permeability, vascularity, thermoregulation, immune function, repair capacity, and sensory perception. These age-related changes affect the skin’s susceptibility to injury and dysfunction and all these processes are susceptible to influence from all types of physiological stressors. Therefore, we also wanted to support the skin’s resilience against stressors. We aimed to design a product that would support a healthier skin aging process and natural skin beauty at all ages.*

In developing Qualia Skin, our purpose was to build a formula that targets multiple intersecting and complementary aspects of skin physiology. We believe taking this systems approach is important when the goal is comprehensive support of skin health and healthy skin aging.* 

To design Qualia Skin, we studied skin structure and function, the physiology of the integumentary system, and the changes the skin goes through as it ages. This allowed us to identify physiological processes and mechanisms to target for intervention. We then selected a set of ingredients that could support skin structure and function, the physiological processes that are most affected by environmental stressors, and the main mechanisms involved in healthy skin aging.* We did so following the same formulation philosophy and dosing principles that have guided the design of all our products. 

The result is a selection of ingredients that, as we’ll see, provide nourishment from within, through complementary and synergistic mechanisms, to support comprehensive skin health and healthy skin aging. These ingredients are:

  • Aloe Vera Inner Leaf Juice Powder
  • Amla (Emblica officinalis) Fruit Extract
  • Sea Buckthorn (Hippophae rhamnoides) Fruit Extract
  • L-Ornithine (as L-ornithine hydrochloride)
  • AstaPure® Haematococcus pluvialis Microalgae Extract (3% astaxanthin)
  • Pomanox® Pomegranate Fruit Extract
  • Red Orange Complex® (Citrus sinensis Fruit Extract)
  • SoyLife™ Soy Germ Extract
  • BioVin® French Red Grapes Extract
  • Rosemary (Rosmarinus officinalis) Leaf Extract
  • HydroPeach™ Ceramides (Peach Fruit Extract)
  • Bamboo Stem & Leaf Extract
  • Lycopene (from Tomato Fruit Extract)
  • Biotin
  • Iron (from inactive Koji Aspergillus oryzae culture)
  • Zinc (from inactive Koji Aspergillus oryzae culture)
  • Selenium (from inactive Koji Aspergillus oryzae culture)
  • Copper (from inactive Koji Aspergillus oryzae culture)
  • Manganese (from inactive Koji Aspergillus oryzae culture)
  • Chromium (from inactive Koji Aspergillus oryzae culture)
  • Molybdenum (from inactive Koji Aspergillus oryzae culture)

If you want to learn about the physiology of skin and how Qualia Skin supports it in more detail, check our articles on Biohacking For Better Skin*: Understanding the Structure and Function of the Skin, Factors That Influence Skin Health and Aging, and Understanding Skin Aging Mechanisms


Figure 1 - Structure of the skin. Source: Sean P Doherty. Wikimedia Commons. License: CC BY-SA 4.0

Supporting Epidermal Health and Skin Barrier Function 

The epidermis is the superficial layer of the skin, responsible for most of its protective functions. It creates the physical barrier that isolates and protects our body against the external environment, the chemical barrier that keeps noxious chemicals out, the selective permeability barrier that allows some chemicals in and that maintains internal hydration, and the immunological barrier that blocks microbial invasion.

The main type of cells of the epidermis are keratinocytes. They are responsible for the production of keratin, the protein that gives the skin its physical properties and resistance. Keratinocytes originate from skin stem cells at the base of the epidermis. As they differentiate, they are pushed outwards by newer keratinocytes and accumulate keratin in their cytosol, acquiring a fibrous structure in this process known as keratinization. 

In the most superficial layers of the epidermis, keratinocytes become corneocytes, heavily keratinized dead cells surrounded by a lipid-rich, impermeable coating. Corneocytes are continuously shed at the epidermal surface as the epidermis renews. In healthy skin, corneocyte shedding is imperceptible, but changes in hydration and lipid content can result in abnormal corneocyte desquamation, giving the skin a rough feel [3].

Skin lipids have a sealing action on the skin and are thus essential to its barrier function and water-retaining properties. The major lipids of the skin are ceramides. Ceramides and other skin lipids (e.g., cholesterol, fatty acids) help to maintain skin hydration by blocking transepidermal water loss (TEWL), i.e., the amount of water that evaporates from the surface of the skin, which, in healthy skin, is directly proportional to skin hydration [3]. 

As we age, one of the major structural changes of the skin is the progressive thinning of the epidermis due to a decreased proliferation and turnover of keratinocytes [1,2]. Water and lipid content in the epidermis also reduces with age, leading to a reduction of the hydration capacity of the skin [1,2]. 

Maintaining healthy epidermal structure and skin barrier function is essential for the maintenance of the skin’s selective permeability and physical shield functions, as well as for skin hydration and skin smoothness. Qualia Skin includes a set of ingredients that support these properties of the skin.* 

Zinc (from inactive Koji Aspergillus oryzae culture) is necessary for epidermal proliferation and keratinocyte differentiation, and plays a major role in keratinocyte cell survival and skin morphogenesis, repair, and maintenance [4–6]. Selenium (from inactive Koji Aspergillus oryzae culture) is part of selenoproteins that play important roles in keratinocyte function [2]; selenium protects keratinocyte stem cells against senescence [7]. Iron (from inactive Koji Aspergillus oryzae culture) has an important role in the regulation of mitochondrial DNA synthesis in the highly metabolically active cells of the basal epidermis, which undergo a continuous sequence of maturation and loss at the skin surface [8].* 

Aloe Vera Inner Leaf Juice Powder supports skin barrier function by restoring epidermal tight junctions [9]. Sea Buckthorn (Hippophae rhamnoides) Fruit Extract influences the fatty acid composition of epidermal lipids [10]. AstaPure® Astaxanthin Haematococcus pluvialis Microalgae Extract supports healthy epidermal structure [11] by regulating corneocyte desquamation [12] and supporting healthy skin lipid content, thus supporting barrier function [12]. Lycopene (from Tomato Fruit Extract) supports sebum production [13] and epidermal structure [13].*

HydroPeach™ (Peach Fruit Extract) provides ceramides, which are the major lipids of the skin barrier [14,15]. Ceramides are necessary for maintaining barrier and water-retaining properties of the skin. In addition to providing ceramides for the skin, HydroPeach™ Ceramides (Peach Fruit Extract) supports skin ceramide synthesis [16–19] and epidermal ceramide levels [20], thereby supporting epidermal structure [21–23], and skin barrier function [19,22,24]. The outcome of these actions is a support of skin hydration [25–28] and healthy transepidermal water loss (TEWL) levels [16,21–23,28–32], along with the support of skin smoothness [28,32].*

Healthy transepidermal water loss (TEWL) is further supported by Aloe Vera Inner Leaf Juice Powder [33,34] and AstaPure® Astaxanthin Haematococcus pluvialis Microalgae Extract  [35,36]. In line with this action, skin hydration is also supported by Aloe Vera Inner Leaf Juice Powder [33,34,37,38] and AstaPure® Astaxanthin Haematococcus pluvialis Microalgae Extract  [39–41], as well as by Sea Buckthorn (Hippophae rhamnoides) Fruit Extract [42], Pomanox® Pomegranate Fruit Extract [43], and Silicon (in Bamboo Stem & Leaf Extract) [44].*

A smooth skin texture is further supported by AstaPure® Astaxanthin Haematococcus pluvialis Microalgae Extract [39] Sea Buckthorn (Hippophae rhamnoides) Fruit Extract [42], Pomanox® P30 Pomegranate Extract [43,45], and Silicon (in Bamboo Stem & Leaf Extract) [44,46].* 

Supporting Healthy Skin Pigmentation

Melanin is the pigment (i.e., a colored molecule that absorbs light) responsible for skin, hair, and eye color. In the skin, melanin is produced by a specialized type of epidermal cells called melanocytes in a process known as melanogenesis. Melanin is then transferred to keratinocytes, where it accumulates [47]. 

Among other functions, melanin is the key molecule of the skin’s photochemical barrier—it absorbs light, with its production increased when we are exposed to sunlight. The number of enzymatically active melanocytes decreases with age, and their activity becomes irregular; some become overactive, creating the uneven pigmentation often observable in older skin, known as age spots. 

Qualia Skin provides a few ingredients that support melanocyte function and melanin synthesis, thereby contributing to the maintenance of a more uniform pigmentation of the skin and supporting normal skin adaptive responses to sunlight. Copper (from inactive Koji Aspergillus oryzae culture) is a cofactor of tyrosinase [48] (tyrosinase is the rate-limiting enzyme for making melanin). Sea Buckthorn Extract influences melanin synthesis [49]. Healthy melanin synthesis and a more uniform skin pigmentation are also supported by Pomanox® Pomegranate Fruit Extract [50,51], Red Orange Complex® (Citrus sinensis Fruit Extract) [52], AstaPure® Astaxanthin [53,54], BioVin® French Red Grapes Extract [55–60], and HydroPeach™ Ceramides [32].*

Supporting Dermal Health and ECM Structure

The dermis is the skin’s connective tissue layer, located beneath the epidermis. It has a fibrous extracellular matrix (ECM) that gives structure and elasticity to the skin. The most important structural components of the dermal ECM are collagen, elastin, proteoglycans, and glycosaminoglycans (GAGs, of which hyaluronic acid is the most well-known example). Fibroblasts, the main cell type in the dermis, are the cells that produce ECM molecules, and are therefore responsible for the structural integrity of the dermis. 

Collagen is a particularly important molecule of the ECM, as it makes up around 90% of the skin’s dry weight. Collagen fibers create the structural framework of the skin and are responsible for the skin’s tensile strength and other mechanical properties [61]. The network of elastin-rich elastic fibers provides the “bounce back” or the elasticity of the skin [47]. GAGs have key roles in maintaining the water content of the skin [62]. Hyaluronic acid is particularly efficient, being able to retain water molecules up to 1000-fold its molecular weight [63]. 

As the skin ages, there is a progressive decrease in collagen, elastin, and hyaluronic acid and other GAGs. There is also an accumulation of oxidative changes in these molecules that affect their structure and physical properties, leading to progressive changes in the skin that include loss of tensile strength and recoil capacity, loss of elasticity and hydration, and wrinkle formation, for example [1,2,64]. 

Furthermore, there’s an increase in the enzymatic degradation of ECM proteins by proteolytic enzymes called matrix metalloproteinases (MMPs) produced by epidermal keratinocytes and dermal fibroblasts [65–67]. Two of the more important types of MMPs, when it comes to skin aging, are collagenases (these enzymes break down native collagen) and elastase (breaks down elastin). An important “beauty from within” goal is to counter the greater age-related expression and activity of these enzymes.*

Let’s use collagen as an example. One way to promote healthier collagen levels in skin would be to provide nutrition that supports the building of collagen. Another way—the indirect way, and possibly the more important way as we get older—would be to counter the expression and activity of collagenases to limit the breakdown of collagen.* 

Figure 2 - Changes in skin structure associated with chronological aging. Source (adapted): Orioli D. & Dellambra E. Cells 2018, 7(12), 268. License: CC BY 4.0

Qualia Skin includes a set of ingredients that support dermal function and structure and that help to support the biosynthetic capacity of the dermis and its ability to healthily respond to age-related changes.* 

L-Ornithine (as L-ornithine hydrochloride) is a precursor for the synthesis of L-proline, which is one of the primary amino acids in collagen; it supports skin levels of collagen-constituting amino acids [68] and collagen deposition [69]. [Note: We did not include collagen in Qualia Skin because it is not a vegan ingredient; L-ornithine offers an alternative to support collagen production in a vegan-friendly way.]*

Copper (from inactive Koji Aspergillus oryzae culture) supports the synthesis of collagen and elastin fiber components by fibroblasts and supports signaling by TGF-β, an inducer of collagen synthesis [70]; it also supports the levels of HSP47, a protein that plays an important role in collagen structure stabilization and that is downregulated in aged skin [71]. Manganese (from inactive Koji Aspergillus oryzae culture) is required for the activation of prolidase, an enzyme that can provide the amino acid proline for collagen synthesis in human skin cells [72,73]; GAG synthesis also requires manganese-activated enzymes [74]. Silicon (in Bamboo Stem & Leaf Extract) is important for collagen synthesis, GAG synthesis, and the activation of enzymes that support skin strength and elasticity [75]; accordingly, silicon supports skin collagen levels [76] and skin firmness [44]. The skin contains high concentrations of Vitamin C, which has well-known roles in supporting collagen synthesis and as a skin antioxidant [77]. Both Red Orange Complex® (Citrus sinensis Fruit Extract) and Amla (Emblica officinalis) Fruit Extract are good food sources of vitamin C.*

Fibroblast function and ECM structural molecule levels are supported by several other ingredients: Aloe Vera Inner Leaf Juice Powder supports collagen and hyaluronic acid levels [33,34,37,38,78–84]; Amla (Emblica officinalis) Fruit Extract supports fibroblast proliferation [85] and collagen and hyaluronic acid synthesis [85–89]; Pomanox® Pomegranate Fruit Extract supports dermal collagen and hyaluronan levels [43,45,50,90]; SoyLife™ Soy Germ Extract supports fibroblast renewal and collagen, elastic fiber, and hyaluronic acid levels [91–97]; AstaPure® Astaxanthin Haematococcus pluvialis Microalgae Extract supports collagen levels [11,98,99].*

The activity of ECM breakdown enzymes (e.g., collagenases, elastase) is influenced by Pomanox® Pomegranate Extract [43,45,50,90,100–103], Red Orange ComplexTM [104], SoyLife™ Soy Germ Extract [91,95,96]; AstaPure® Astaxanthin Haematococcus pluvialis Microalgae Extract [36,40,98,105], and Rosemary (Rosmarinus officinalis) Leaf Extract [106]. Healthy dermal ECM structure in general is also supported by BioVin® French Red Grapes Extract [107–110] and Lycopene (from Tomato Extract) [111,112].* 

One of the main outcomes of supporting fibroblast cell function, and both the synthesis of ECM structural molecules and a more youthful expression and activity of collagenase and elastase enzymes, is the support of the mechanical properties of the skin, particularly skin elasticity. This is an outcome that several ingredients in Qualia Skin may support, namely Aloe Vera Inner Leaf Juice Powder [33,78,84,113], Sea Buckthorn (Hippophae rhamnoides) Fruit Extract [42], SoyLife™ Soy Germ Extract [114], AstaPure® Astaxanthin Haematococcus pluvialis Microalgae Extract [35,41], and HydroPeach™ Ceramides (Peach Fruit Extract) [26,115].*

Supporting Hair and Nail Health

Hair and nails are specialized skin appendages derived from skin cells and formed through processes of keratinization somewhat similar to that of the epidermis. As such, they also benefit from the support of skin health.* 

Hairs are formed within hair follicles, where keratinocytes born from stem cells form the matrix of the elongating hair. As they divide, keratinocytes undergo keratinization, melanin accumulation, and migration as they are pushed outward by new keratinocytes. Keratinocytes in the hair bulb produce a hard and compact form of keratin that will form the heavily keratinized hair shaft that extends beyond the skin surface [47]. 

Nails are formed at the nail root, which is the area covered by the fold of skin from which the cuticle extends. The nail plate forms as keratinocytes divide and become heavily keratinized and hardened. Continuous growth in the nail matrix pushes the nail plate forward over an epidermal nail bed [47].

Because we wanted to include some ingredients that could specifically support hair and nail health, Qualia Skin provides two minerals and a vitamin that nutritionally support hair and nail structure: Iron (from inactive Koji Aspergillus oryzae culture) supports mitochondrial DNA synthesis and therefore provides essential support for the continuous turnaround of new cells for the growth, maintenance, and normal physiology of hair and nails [8]. Silicon (in Bamboo Stem & Leaf Extract) is one of the main minerals in nails and is therefore essential for nail health [46,75]. Hair health—thickness, tensile strength, elasticity, break load—is also supported by silicon, and hair strands with higher silicon content tend to have lower falling rate and higher brightness [46,75,116]. Vitamin B7, or Biotin, also supports nail structure and health [117–119] and hair health [120]. In addition to these nutrients, Qualia Skin includes Aloe Vera Inner Leaf Juice Powder, which supports nail structure and health [34].* 

Supporting Skin Blood Flow and Nourishment

The epidermis is avascular—it does not have any blood vessels, not even microvasculature. Therefore, epidermal cells must receive nutrients and oxygen by diffusion from the dermis, which has a rich vascular network, including a nutritive capillary network just beneath the epidermis [121]. However, the density of the cutaneous microvasculature reduces with age, which leads to poorer nutritional support of the skin [122].

Supporting the skin’s microvasculature and its capacity to produce new blood vessels (i.e., angiogenesis) helps to ensure that the skin has adequate blood flow and that both the dermis and the epidermis are properly nourished. Only with an adequate supply of nutrients and oxygen can the skin maintain healthy levels of cellular division and biosynthesis of structural molecules.* 

In addition to the nutritive function, the cutaneous vasculature also has an important role in thermoregulation. The dilation and constriction of cutaneous vasculature controls the amount of heat that is lost through the skin, helping to maintain a constant body temperature [123]. Therefore, supporting healthy skin blood flow also contributes to the thermal homeostasis of the body.

Qualia Skin supports healthy skin blood flow by supporting dermal vascularity, through the action of Aloe Vera Inner Leaf Juice Powder [79], SoyLife™ Soy Germ Extract [94], and AstaPure® Astaxanthin Haematococcus pluvialis Microalgae Extract [11].* 

Supporting Skin Mitochondria and Cell Energy Production 

The skin is an organ that is exposed to inordinate amounts of environmental stress and is therefore heavily reliant on energy-demanding protection, repair, and regeneration processes for normal tissue maintenance. Also, the epidermis is constantly renewing, with dead corneocytes being shed as new keratinocytes are born; this constant cell division is another energy-demanding process. ATP is the molecule that powers any cell function that requires energy input and mitochondria are the cellular organelles responsible for ATP production. Therefore, mitochondria are essential for skin health.


 

Figure 3 - Mitochondria. Source: National Human Genome Research Institute - National Institutes of Health. Public Domain.

Cellular energy levels and mitochondrial function decline naturally as we age, and their decline is among the main drivers of aging [124]. Mitochondrial inefficiency decreases the output of cell energy required for activities such as DNA repair, for example, and can be a cause of cell dysfunction in epidermal keratinocytes and dermal fibroblasts [125,126]. The decline of mitochondrial function also contributes to the production of reactive oxygen species (ROS) and to the development of oxidative stress, thus contributing to the oxidative processes that underlie skin aging [127].

One of the consequences of oxidative stress is the oxidative damage to cellular molecules, including mitochondrial DNA (mtDNA), which can negatively impact mitochondrial efficiency [125] and further increase ROS production. This means that mitochondria are involved in a vicious circle in which they are part of both the causes and the consequences of skin health decline and aging. In fact, changes in skin cells’ mitochondria may be one of the key factors in premature skin aging [128,129].

Supporting healthy mitochondrial function contributes to the maintenance of a healthy cell energy production process and helps to prevent excessive ROS production by mitochondria. For this reason, the ability to support healthy mitochondrial function was one of the criteria for choosing some of the ingredients in Qualia Skin.* 

Iron (from inactive Koji Aspergillus oryzae culture) is important for mitochondrial respiration by participating in the electron transfer reactions of the electron transport chain. Iron also regulates mtDNA synthesis [8]. Manganese (from inactive Koji Aspergillus oryzae culture) supports the activity of MnSOD, the principal antioxidant enzyme in mitochondria [130]. Red Orange Complex® (Citrus sinensis Fruit Extract), a blood orange extract, is rich in two compounds that support skin mitochondrial function: cyanidin-3-glucoside [131] and hesperidin [132]. Mitochondrial function is also supported by Pomanox® Pomegranate Fruit Extract [133–145], AstaPure® Astaxanthin Haematococcus pluvialis Microalgae Extract [146–148], and BioVin® French Red Grapes Extract [149–161].*

Supporting Skin Immune Function

The skin is an immune organ that plays a very important part in our immunological arsenal [162,163]. First off, it forms a physical immune barrier that blocks the entry of external substances and microorganisms, which is, in and of itself, a major defense mechanism. 

But the skin also forms a functional immune barrier. It has its own immune system, with a set of innate and adaptive immune cells, both resident and recruited, that populate the dermis and the epidermis. They monitor the skin to identify friendly and potentially unfriendly organisms, making sure we get along well with the former, while devising responses against the latter. 

[If you want to learn more about the immune system, take a look at our overviews of the innate immune system and the adaptive immune system].

The epidermis has its own specific type of resident dendritic cells (a type of cells of the innate immune system) called Langerhans cells. Langerhans cells recognize microbial molecules and signal their presence to other immune cells by releasing signaling molecules. They also present microbial antigens to epidermal T lymphocytes (the main cells of cell-mediated adaptive immunity) to trigger more elaborate immune responses that are able to eliminate possible threats. 

Keratinocytes also carry out immune functions. In addition to creating a physical barrier that acts as an innate immune barrier, they play an immune surveillance and recognition role, produce antimicrobial peptides, and signal their presence to cells of the immune system. Melanocytes also participate in immune signaling and antigen presentation to T-cells.

In the dermis, other types of immune cells can also be found, including dendritic cell subpopulations, macrophages, neutrophils, mast cells, natural killer cells, B cells, and different types of T cells [162–164]. 


Figure 4 - Immune cells in the skin. Source: Rachel Cotton, PLOS Blogs ECR Community. License: CC BY 4.0

Skin immune function is thus important for surface skin health. But the skin’s immune defenses are not only skin deep; they are also important for our systemic immune health, which is why supporting healthy immune responses was one of our goals.*

Qualia Skin supports skin immune fuction through the action of Sea Buckthorn Extract [165] and Pomanox® Pomegranate Extract [166]. Other ingredients in Qualia Skin that are known to support general immune function and thereby contribute to the skin’s immune health include Zinc (from inactive Koji Aspergillus oryzae culture) [167–169] and Selenium (from inactive Koji Aspergillus oryzae culture) [170–173].*

Supporting The Skin Microbiome

The skin is an interface between the internal and external environments. Therefore, it is naturally exposed to the myriad microbes that are out there. In fact, the skin is home to a large community of microbes, which are known as the skin microbiota. These microbes, their genes, and their products, by-products, and metabolites—collectively called the skin microbiome—have an important role in maintaining skin homeostasis, i.e., a state of balance in the skin’s biology and physiological processes [174,175].

Our skin microbes live in symbiosis with us—we help each other. The skin microbiota contribute to skin health by modulating different aspects of skin physiology: they support skin barrier function by processing skin proteins, free fatty acids, and sebum, for example. Importantly, the skin microbiota collaborates with the skin’s immune system in supporting the detection of less friendly microbes [174–177]. 

Therefore, it was important for us to keep our symbionts in mind when designing Qualia Skin. The ability to support healthy skin microbiome was one of the reasons why we chose AstaPure® Astaxanthin Haematococcus pluvialis Microalgae Extract [12], Pomanox® Pomegranate Fruit Extract [13], and Lycopene (from Tomato Fruit Extract) [13] for our formula.*

Supporting Skin Endocrine Signaling

Estrogens are a group of steroid hormones known for their role in the promotion of female sex characteristics and reproduction. But estrogens also have a role in male reproductive function, as well as in a number of other physiological functions in several tissues of the human body (regardless of biological sex), including the skin [178].  

Estrogens bind a type of receptors known as nuclear estrogen receptors (ER), which regulate gene expression [179]. The predominant subtype of ER in the skin is ERβ, found in keratinocytes and fibroblasts [180,181]. Estrogen signaling via ERβ supports skin health and regulates ROS production, antioxidant enzyme expression, and oxidative stress [179]; it also supports skin immune function [182,183]. In addition to activating these protective pathways, ERβ can also directly influence the skin’s structural integrity by modulating collagen deposition and dermal thickness [184]. Therefore, estrogens can have a significant influence on skin structure and function.

Threshold levels of estrogen signaling are critical for the maintenance of skin integrity. Supporting estrogen levels supports skin quality and dermal health in both women and men [185]. But naturally, this is particularly important in postmenopausal women, for whom skin aging can be significantly delayed with the support of estrogen signaling [186]. 

The importance of estrogen signaling for skin health is the reason why we wanted to include a source of phytoestrogens in Qualia Skin. Phytoestrogens are compounds that occur naturally in plants and that have a chemical structure similar to that of estrogen. They are thus able to bind to and activate estrogen receptors, thereby acting as estrogen-like signaling molecules and exerting estrogen-like actions in the human body. While phytoestrogens are often described as “weak” estrogens, it may be more accurate to think of them as supporting homeostatic or balanced estrogen signaling [187,188].*

The main source of phytoestrogens in Qualia Skin is SoyLife™ Soy Germ Extract. Soy is rich in isoflavones, a type of polyphenolic compounds that act as phytoestrogens. Soy isoflavones are phytoestrogens that preferentially bind to and activate ERβ, the predominant subtype of ER in the skin. By activating ERβ, isoflavones may mimetize some of the physiological actions of estrogen on the skin, thereby supporting healthy skin structure and function [189]. Through ERβ signaling, soy isoflavones support the redox balance of the skin via the Nrf2 signaling pathway [190,191], support antioxidant defenses [95,96], counter oxidative stress [92,97,192,193], influence skin degenerative signaling pathways (AP-1, NF-κB) [194–196], and support dermal ECM structure (collagen, elastic fibers, hyaluronic acid levels) [91–97]. Isoflavones have also been shown to inhibit the expression of human skin aging biomarkers [95]. In accordance with these mechanisms of action, soy isoflavones support healthy skin structure and skin elasticity, and may help with the appearance of fine lines and wrinkles [91,94,114,197]. Resveratrol (in BioVin® French Red Grapes Extract) also acts as a phytoestrogen [198].* 

Supporting Antioxidant Defenses

Reactive oxygen species (ROS) have a central role in the mechanisms of skin aging. Both intrinsic and extrinsic factors of skin aging involve the generation of ROS, either as byproducts of oxidative metabolism in mitochondria, in the case of chronological aging, or as products of environmental stress.*

ROS are continually generated in skin cells as part of natural physiological processes. Healthy young skin has the ability to maintain ROS levels under control and to respond and protect itself from ROS accumulation and oxidative stress through its own endogenous antioxidant defenses—antioxidant enzymes such as superoxide dismutase (SOD), redox systems such as glutathione (GSH), and antioxidant molecules such as vitamin E (α-tocopherol) and vitamin C (ascorbic acid). However, these defenses decline naturally with age, which contributes to a rise in ROS levels and an increased susceptibility to the oxidation of lipids, proteins, and DNA [199,200]. 

ROS production and oxidative stress can be countered by many of the ingredients in Qualia Skin, either by supporting the skin’s natural antioxidant defenses or through the action of bioactive antioxidant molecules. Zinc, Copper, and Manganese (from inactive Koji Aspergillus oryzae culture) support the activity of the antioxidant enzyme SOD, which exists in cells in two forms: a copper and zinc-dependent SOD (CuZnSOD), the main cytosolic form of SOD, and a manganese-dependent SOD (MnSOD), the mitochondrial form [130]. Selenium (from inactive Koji Aspergillus oryzae culture) can be converted by the liver into selenocysteine and be used in the biosynthesis of selenoproteins, which includes the antioxidant defense enzymes glutathione peroxidase and thioredoxin reductase [5].* 

The botanical extracts found in Qualia Skin are rich in bioactive molecules with antioxidant activity and that support the skin’s antioxidant defenses and counter ROS production and oxidative stress in the skin. That’s the case with Aloe Vera Inner Leaf Juice Powder [201], Amla (Emblica officinalis) Fruit Extract [86,89,202], Sea Buckthorn (Hippophae rhamnoides) Fruit Extract [203], Pomanox® Pomegranate Extract [43,45,102,103,143,166], Red Orange Complex® (Citrus sinensis Fruit Extract) [204–207], SoyLife® Soy Isoflavones [92,95,97,192], AstaPure® Astaxanthin Haematococcus pluvialis Microalgae Extract [12,208,209], BioVin® French Red Grapes Extract [108,109,210,211], and Rosemary Extract [212].*

Because ROS are signaling molecules, excessive ROS production can also dysregulate cell signaling. ROS generation leads to the activation of signaling pathways and transcription factors that cause changes in gene expression and that drive age-associated alterations in the skin, particularly dermal ECM degeneration [213]. Two major transcription factors activated by ROS and involved in ECM changes are activator protein-1 (AP-1) and nuclear factor-kappa B (NF-κB) [214].

Signaling through AP-1 and NF-κB triggers a cascade of events that involves immune signaling and a feedback loop of additional ROS production and that leads to the production of matrix-degrading enzymes (matrix metalloproteinases—MMPs) by dermal fibroblasts; this accelerates the degeneration of the dermal ECM and leads to the functional decline and aging of the skin [213,215–218]. 

With the goal of minimizing the impact of ROS signaling on skin physiology, Qualia Skin includes a set of ingredients that influence skin degenerative signaling pathways via AP-1 and NF-κB: Sea Buckthorn Extract [219,220], Pomanox® Pomegranate Fruit Extract [166,221], Red Orange ComplexTM [104,205,206,222–224], SoyLife® Soy Isoflavones [194–196], AstaPure® Astaxanthin Haematococcus pluvialis Microalgae Extract [225], BioVin® French Red Grapes Extract [226–230], and Rosemary (Rosmarinus officinalis) Leaf Extract [106,231,232].* 

Another signaling molecule with key functions in skin antioxidant defenses is the transcription factor nuclear factor erythroid 2-like 2 (Nrf2), a master regulator of the antioxidant response. Nrf2 regulates skin homeostasis and redox balance by activating cytoprotective genes in response to oxidative stress [233]. Nrf2 activates a protection system that regenerates endogenous antioxidant molecules and upregulates antioxidant and detoxifying enzymes (phase II detoxification enzymes) that promote cell adaptation to oxidative stress [234–236]. Nrf2 also controls the bioavailability of mitochondrial electron transport chain substrates [237], thereby having a role in the regulation of oxidative metabolism, and consequently, ROS production as metabolic byproducts. 

The activity of Nrf2 declines during the aging process [238]. Older adults have lower nuclear content and diminished Nrf2 activation than younger individuals and this is associated with a decrease in the levels of Nrf2 target genes, along with an increase in several NF-κB target genes [239]. Therefore, age-related Nrf-2 downregulation can decrease the skin’s natural defenses against oxidative stress [240]. 

There are many ingredients in Qualia Skin that influence Nrf-2 signaling and that, by doing so, support the skin’s antioxidant and detox defenses and redox homeostasis. Nrf-2 signaling is supported by Aloe Vera Inner Leaf Juice Powder [201], Sea Buckthorn (Hippophae rhamnoides) Fruit Extract [203], Pomanox® Pomegranate Extract [103,143], Red Orange Complex® (Citrus sinensis Fruit Extract) [224], SoyLife® Soy Isoflavones [190,191], AstaPure® Astaxanthin Haematococcus pluvialis Microalgae Extract [208,209,241–243], BioVin® French Red Grapes Extract [107,210,244], Rosemary Extract [212,245], and Lycopene (from Tomato Extract) [246].*

Supporting Skin Youthfulness

To design Qualia Skin, we studied the physiology of healthy skin and how it changes with age in order to understand how to best support the structure and function of aging skin. We found that, although skin aging is inevitable, many of its negative impacts on the skin can be delayed and minimized with proper care.*

Skin aging produces consistent structural and functional changes that manifest as those visual changes in the skin we all recognize: the skin becomes thinner and dryer, loses elasticity and becomes saggy, fine lines and wrinkles appear, skin tonality becomes more irregular, and age spots accumulate [1,247]. 


 

But aged skin also goes through less visible alterations, including changes in cellular metabolism, sensory function, permeability, immunity, response to injury, and repair capacity [1,2].

These invisible changes have a marked impact on skin health. But supporting the physiological pathways that underlie them may help to delay these changes and to maintain the skin healthy and functionally youthful for longer. And because the skin shows its health, supporting functional youthfulness may manifest a more youthful skin appearance.* 

Skin health is visible—skin that is healthy looks healthy.

Science-Backed Ingredients for Skin Health

Qualia Skin was designed to support skin health, healthy skin aging, and healthy skin appearance. Every ingredient in Qualia Skin is backed by scientific research showing support for relevant elements or mechanisms of healthy skin structure and function. Many of the ingredients in Qualia Skin were shown to support skin health structure in scientific studies in humans.* 

Aloe Vera is a succulent plant whose fleshy leaves are filled with a gel that contains hundreds of bioactive compounds, including polysaccharides, vitamins, enzymes, minerals, and antioxidant compounds such as α-tocopherol (vitamin E), ascorbic acid (vitamin C), carotenoids, flavonoids and tannins. Aloe Vera has a long history of use in traditional medicine for skin health. In human studies, Aloe Vera has supported dermal collagen content [33,34], fine lines and wrinkle depth [34,37,78], skin elasticity [33,78,113], hydration [33,34,37], healthy skin water-retaining functions  [33,34], and fingernail strength [34].*

The fruit from Amla (Emblica officinalis) Fruit Extract is one of the most commonly used ingredients in Ayurvedic Medicine and is considered to be a rasayana (i.e., rejuvenator). Amla is rich in bioactive compounds, including tannins, alkaloids, polyphenols, minerals, and vitamins, including high levels of vitamin C. In human studies, Amla was shown to support skin elasticity, skin thickness, stratum corneum water content, and the appearance of fine lines when used in combination with lingonberry [248].*

Sea Buckthorn (Hippophae rhamnoides) fruits are small yellow-orange berries with substantial antioxidant activity, because they are rich in vitamin C, vitamin E, polyphenols, flavonoids, and carotenoids; they’re also rich in healthy fatty acids that support skin health. Sea Buckthorn has been used in many traditional medical systems for supporting skin health. Sea Buckthorn influences the fatty acid composition of epidermal glycerophospholipids [10]. In human studies, it supported skin hydration, elasticity and texture [42].*

AstaPure® is a branded Haematococcus pluvialis microalgae extract. H. pluvialis is the most concentrated natural source of astaxanthin, a carotenoid produced by some freshwater and marine algae and microorganisms as a defense compound against environmental stress such as sunlight. Since it is fat-soluble, astaxanthin is active in places with high lipid content, such as the skin, where it’s a powerful antioxidant. In human studies, astaxanthin supported skin elasticity [35,41] and texture [39], fine lines and wrinkles [35,40,41], markers of skin hydration and water-retaining properties [35], antioxidant status [12], healthy skin lipids [12], and the skin microbiota [12].*

Pomanox® is a Pomegranate Fruit Extract. Pomegranate is rich in ellagitannins, a type of polyphenol, which are potent antioxidants and modulators of cellular signaling pathways involved in healthy aging. The ellagitannin punicalagin is the largest known polyphenol and is responsible for most of pomegranate’s antioxidant potential [249–252]. In human studies, pomegranate modulated the skin microbiota [253]. When combined with grape extract, selenium, and silica (all found in Qualia Skin) pomegranate supported the skin’s antioxidant power, skin hydration, elasticity, and smoothness, fine lines and wrinkles, and uniform skin pigmentation [254].*

Red Orange Complex® (Citrus sinensis Fruit Extract) is a standardized powder extract obtained from the juice of three pigmented varieties of Sicilian blood orange—Moro, Tarocco and Sanguinello—grown exclusively in a particular area surrounding Europe’s most active volcano, Mt. Etna. They are rich in anthocyanins, hydroxycinnamic acids, flavanones, and vitamin C, the combination of which supports the antioxidant defenses that help maintain healthy skin when stressed by external environmental factors. In human studies, Red Orange Complex® supported a uniform skin pigmentation [52].*

SoyLife™ Soy Germ Extract is rich in isoflavones, which, as we’ve discussed, exert estrogen-like actions in the skin. By activating ERβ, isoflavones may mimetize some of the physiological actions of estrogen on the skin, thereby supporting healthy skin structure and function [189]. Soybean isoflavones also influence androgen signaling in the skin [255]. In human studies, isoflavones helped with the appearance of fine lines and wrinkles [91,114,197] and supported skin elasticity [114] and healthy skin structure [94].*

BioVin® French Red Grapes Extract is made from the juice, seeds, and skins of French red grapes and provides a full spectrum of grape’s skin health-promoting compounds, from resveratrol to oligomeric proanthocyanidins. In human studies, grape extract supported a uniform skin pigmentation [55]. The combination of grape extract, pomegranate extract, selenium, and silica (all Qualia Skin ingredients) supported the skin’s antioxidant power, supported skin hydration, elasticity, and smoothness, helped with the apparent depth of wrinkles, and supported more uniform skin pigmentation [254].*

Rosemary (Rosmarinus officinalis) contains a range of polyphenols that support skin health, including diterpenes (e.g., carnosol, carnosic acid, rosmarinic acid), triterpenes (e.g., ursolic acid), and flavonoids (e.g., luteolin). The diterpenes carnosol and carnosic acid are potent antioxidants that account for over 90% of the antioxidant activity in rosemary leaves [256]. In human studies, rosemary in combination with lycopene-rich tomato extract (also included in Qualia Skin) supported skin brightness and tonality, skin hydration, and overall skin condition [257].*

HydroPeach™ Ceramides (Peach Fruit Extract) is a branded and clinically studied source of phytoceramides extracted from Japanese peaches, help support healthy skin function and appearance. Ceramides, whose levels decrease with age, are necessary for maintaining barrier and water-retaining properties of the skin. HydropeachTM works by naturally increasing skin levels of ceramides, thereby supporting skin barrier function and overall skin health. Oral supplementation with HydroPeach™ which may support water retention in the skin and strengthens skin permeability layers, thereby supporting skin hydration and smoothness [28].*

Lycopene (from Tomato Fruit Extract) is a carotenoid found in large amounts in tomatoes and tomato products where it is produced as a defense compound against environmental stress such as sunlight. Lycopene is found in human skin, where it has important antioxidant actions, but its levels decrease with age. Supplementation with lycopene results in a sharp increase of lycopene concentrations in the skin surface. In human studies, lycopene supported healthy skin responses to sunlight exposure [111,258,259], epidermal structure, and skin lipid production [13]. In combination with rosemary extract (also included in Qualia Skin) it supported skin brightness and tonality, skin hydration, and overall skin condition [257].*

L-Ornithine is an amino acid and a precursor for the synthesis of L-proline, which is one of the primary amino acids in collagen. Ornithine supports collagen production in a vegan friendly way. In an animal study, adding low amounts of L-ornithine to the diet results in rapid increases in the concentrations of l-proline and glycine in the skin, and enhances collagen deposition and strength [68]. L-ornithine is also a precursor in the synthesis of polyamines, which are involved in cell growth and are important in promoting skin healing and health (Moinard et al. 2005).* 

Biotin, or vitamin B7 plays important roles in cellular metabolism and energy production. Biotin was originally called vitamin H, with “H” standing in for Haar und Haut, German words for hair and skin. This is because deficiency symptoms that led to the eventual discovery of biotin included skin issues and hair loss. In human studies, biotin was shown to support healthy nails and hair [117,119,120].*

Bamboo Stem & Leaf Extract is a plant-based source of silicon in the form of silica (silicon dioxide). Silicon is the third most abundant trace element in the human body. Silicon is important for nail, hair, and skin health. It plays a role in the synthesis of collagen and is associated with the synthesis of glycosaminoglycans. Hair strands with higher silicon content tend to have lower falling rate and higher brightness. Nail health is also dependent on silicon levels, since it is one of the predominant minerals in their composition. Silicon supplementation in humans was shown to support nail and hair health [46,116] and to support skin smoothness, firmness, and hydration [44].*

Zinc, Selenium, Copper, Iron, and Manganese (from inactive Koji Aspergillus oryzae culture) are all important for skin health. Zinc is essential for keratinocyte differentiation and epidermal renewal, stabilizes cell membranes, and supports skin morphogenesis, repair, and maintenance; it also supports the activity of skin antioxidant defenses [4–6]. Selenium is part of selenoproteins that play important roles in DNA synthesis, protection from oxidative damage, keratinocyte function, skin development, and wound healing [4]. Selenium protects keratinocyte stem cells (KSCs) against senescence. Selenium supplementation supports skin homeostasis during chronological aging [7]. Copper supports the synthesis of collagen and elastin by fibroblasts [70], ECM structure stabilization [260], melanin biosynthesis [48], and skin antioxidant defenses [70]. Iron is important for the metabolism, growth, maintenance and normal physiology of the skin, hair, and nails [8]. Manganese is required for the activation of prolidase, an enzyme that can provide the amino acid proline for collagen synthesis in human skin cells [72,73].*

Qualia Skin—Nourishing Natural Beauty

Qualia Skin is designed to support beauty from the inside out. Qualia Skin is a “beauty from within” formula that combines carefully selected plant-based ingredients—superfruits, skin antioxidants, skin minerals, ceramides, phytoestrogens, carotenoids, collagen boosters—to support skin health, skin resilience against stressors, healthy skin aging, and natural skin beauty.* 

Through the combined action of our ingredients, Qualia Skin supports skin health in areas including skin elasticity, firmness, and smoothness, as well as aspects of skin appearance such as glow, gloss, luminosity, and radiance.*  

We believe Qualia Skin may be a valuable element of a self-care routine that promotes beauty as an outcome of healthy nutrition and lifestyle, allowing you to look as you feel. Health is a reflection of what we eat, and maybe nowhere is this as evident as the skin.*

Designed To:

  • Support healthy, luminous skin from the inside out*
  • Support healthy skin aging*
  • Promote glow and radiance*

Key Features

  • Supports skin hydration*
    • Promotes water retention in the skin*
    • Supports healthy ceramide levels*
    • Supports water and fat emulsion that maintains hydration*
    • Helps moisten the epidermis and supports smoother skin texture*
  • Supports skin elasticity and firmness*
    • Supports skin cell fibroblasts that produce collagen*  
    • Supports healthy collagen levels*
    • Supports healthy elastic fiber levels*
    • Supports healthy glycosaminoglycan levels (e.g., hyaluronic acid)*
    • Promotes healthy dermal fiber network that supports healthy skin structure*
  • Supports skin smoothness and texture and helps smooth fine lines and wrinkles *
    • Supports the epidermal layer that deals with environmental stress*
    • Supports skin cell keratinocytes that produce keratin*
    • Supports healthy shedding of old skin cells and epidermal renewal*
  • Promotes healthy skin pigmentation and tone*
    • Support skin cell melanocytes that produce melanin*
    • Supports healthy melanin production*
  • Supports healthy skin physiology *
    • Supports natural antioxidant defenses*
    • Supports normal skin protective and repair functions*
    • Supports healthy mitochondria that produce cell energy*
    • Supports healthy skin immune function and immune signaling*
    • Supports healthy skin microbiota*
    • Supports healthy skin endocrine signaling*
  • Supports skin nourishment*
    • Support healthy skin blood flow*
    • Support nutrient and oxygen delivery to the skin*
  • Supports healthy hair and nails*
    • Supports hair tensile strength, elasticity, break load*
    • Support hair follicle health*
    • Supports nail growth and structure*

*These statements have not been evaluated by the Food and Drug Administration. The products and information on this website are not intended to diagnose, treat, cure or prevent any disease. The information on this site is for educational purposes only and should not be considered medical advice. Please speak with an appropriate healthcare professional when evaluating any wellness related therapy. Please read the full medical disclaimer before taking any of the products offered on this site.

References:

[1]D.J. Tobin, J. Tissue Viability 26 (2017) 37–46.
[2]M.A. Farage, K.W. Miller, P. Elsner, H.I. Maibach, Adv. Wound Care 2 (2013) 5–10.
[3]G.E. Pierard, V. Goffin, T. Hermanns-Le, C. Pierard-Franchimont, Int. J. Mol. Med. 6 (2000) 217–221.
[4]D.L. Vollmer, V.A. West, E.D. Lephart, Int. J. Mol. Sci. 19 (2018).
[5]M. Richelle, M. Sabatier, H. Steiling, G. Williamson, Br. J. Nutr. 96 (2006) 227–238.
[6]Y. Ogawa, T. Kawamura, S. Shimada, Arch. Biochem. Biophys. 611 (2016) 113–119.
[7]L. Jobeili, P. Rousselle, D. Béal, E. Blouin, A.-M. Roussel, O. Damour, W. Rachidi, Aging 9 (2017) 2302–2315.
[8]A.B. Lansdown, Int. J. Cosmet. Sci. 23 (2001) 129–137.
[9]K. Na, E. Lkhagva-Yondon, M. Kim, Y.-R. Lim, E. Shin, C.-K. Lee, M.-S. Jeon, Scand. J. Immunol. 91 (2020) e12856.
[10]B. Yang, K.O. Kalimo, R.L. Tahvonen, L.M. Mattila, J.K. Katajisto, H.P. Kallio, J. Nutr. Biochem. 11 (2000) 338–340.
[11]X. Li, T. Matsumoto, M. Takuwa, M. Saeed Ebrahim Shaiku Ali, T. Hirabashi, H. Kondo, H. Fujino, Biomedicines 8 (2020).
[12]N.E. Chalyk, V.A. Klochkov, T.Y. Bandaletova, N.H. Kyle, I.M. Petyaev, Nutr. Res. 48 (2017) 40–48.
[13]M. Wiese, Y. Bashmakov, N. Chalyk, D.S. Nielsen, Ł. Krych, W. Kot, V. Klochkov, D. Pristensky, T. Bandaletova, M. Chernyshova, N. Kyle, I. Petyaev, Biomed Res. Int. 2019 (2019) 4625279.
[14]H.J. Cha, C. He, H. Zhao, Y. Dong, I.-S. An, S. An, Int. J. Mol. Med. 38 (2016) 16–22.
[15]M.H. Meckfessel, S. Brandt, J. Am. Acad. Dermatol. 71 (2014) 177–184.
[16]H. Shimoda, S. Terazawa, S. Hitoe, J. Tanaka, S. Nakamura, H. Matsuda, M. Yoshikawa, J. Med. Food 15 (2012) 1064–1072.
[17]J. Ishikawa, S. Takada, K. Hashizume, Y. Takagi, M. Hotta, Y. Masukawa, T. Kitahara, Y. Mizutani, Y. Igarashi, J. Dermatol. Sci. 56 (2009) 220–222.
[18]Y. Shirakura, K. Kikuchi, K. Matsumura, K. Mukai, S. Mitsutake, Y. Igarashi, Lipids Health Dis. 11 (2012) 108.
[19]J. Duan, T. Sugawara, M. Hirose, K. Aida, S. Sakai, A. Fujii, T. Hirata, Exp. Dermatol. 21 (2012) 448–452.
[20]Y. Tokudome, N. Masutani, S. Uchino, H. Fukai, Nutrients 9 (2017).
[21]T. Hasegawa, H. Shimada, T. Uchiyama, O. Ueda, M. Nakashima, Y. Matsuoka, Lipids 46 (2011) 529–535.
[22]R. Ideta, T. Sakuta, Y. Nakano, T. Uchiyama, Biosci. Biotechnol. Biochem. 75 (2011) 1516–1523.
[23]K. Tsuji, S. Mitsutake, J. Ishikawa, Y. Takagi, M. Akiyama, H. Shimizu, T. Tomiyama, Y. Igarashi, J. Dermatol. Sci. 44 (2006) 101–107.
[24]C. Kawada, T. Hasegawa, M. Watanabe, Y. Nomura, Biosci. Biotechnol. Biochem. 77 (2013) 867–869.
[25]S. Guillou, S. Ghabri, C. Jannot, E. Gaillard, I. Lamour, S. Boisnic, Int. J. Cosmet. Sci. 33 (2011) 138–143.
[26]J. Kawamura, S. Kotoura, T. Okuyama, M. Furumoto, H. Fuchuu, K. Miake, M. Sugiyama, M. Ohnishi, Journal of The Japanese Society for Food Science and Technology 60
(2013) 218–224.
[27]M. Yeom, S.-H. Kim, B. Lee, J.-J. Han, G.H. Chung, H.-D. Choi, H. Lee, D.-H. Hahm, J. Dermatol. Sci. 67 (2012) 101–110.
[28]T. Koikeda, Y. Tokudome, M. Okayasu, Y. Kobayashi, K. Kuroda, J. Yamakawa, K. Niu, K. Masuda, M. Saito, Immunol. Endocr. Metab. Agents Med. Chem. 17 (2017).
[29]T. Uchiyama, Y. Nakano, O. Ueda, H. Mori, M. Nakashima, A. Noda, C. Ishizaki, M. Mizoguchi, J. Health Sci. 54 (2008) 559–566.
[30]K.-I. Kawano, K. Umemura, Phytother. Res. 27 (2013) 775–783.
[31]K. Miyanishi, N. Shiono, H. Shirai, M. Dombo, H. Kimata, Allergy 60 (2005) 1454–1455.
[32]S. Fukunaga, S. Wada, T. Sato, M. Hamaguchi, W. Aoi, A. Higashi, J. Nutr. Sci. Vitaminol. 64 (2018) 265–270.
[33]M. Tanaka, Y. Yamamoto, E. Misawa, K. Nabeshima, M. Saito, K. Yamauchi, F. Abe, F. Furukawa, Skin Pharmacol. Physiol. 29 (2016) 309–317.
[34]C. Kaminaka, Y. Yamamoto, M. Sakata, C. Hamamoto, E. Misawa, K. Nabeshima, M. Saito, M. Tanaka, F. Abe, M. Jinnin, J. Dermatol. 47 (2020) 998–1006.
[35]K. Tominaga, N. Hongo, M. Karato, E. Yamashita, Acta Biochim. Pol. 59 (2012) 43–47.
[36]T. Komatsu, S. Sasaki, Y. Manabe, T. Hirata, T. Sugawara, PLoS One 12 (2017) e0171178.
[37]M. Tanaka, E. Misawa, K. Yamauchi, F. Abe, C. Ishizaki, Clin. Cosmet. Investig. Dermatol. 8 (2015) 95–104.
[38]E. Misawa, M. Tanaka, M. Saito, K. Nabeshima, R. Yao, K. Yamauchi, F. Abe, Y. Yamamoto, F. Furukawa, Photodermatol. Photoimmunol. Photomed. 33 (2017) 101–111.
[39]N. Ito, S. Seki, F. Ueda, Nutrients 10 (2018) 817.
[40]K. Tominaga, N. Hongo, M. Fujishita, Y. Takahashi, Y. Adachi, J. Clin. Biochem. Nutr. 61 (2017) 33–39.
[41]L. Phetcharat, K. Wongsuphasawat, K. Winther, Clin. Interv. Aging 10 (2015) 1849–1856.
[42]B. Yang, A. Bonfìgli, V. Pagani, L.T. von-Knorring Asa, A.V.-P.J. Jutila, Journal of Applied Cosmetology 27 (2009) 13–35.
[43]S.-J. Kang, B.-R. Choi, S.-H. Kim, H.-Y. Yi, H.-R. Park, C.-H. Song, S.-K. Ku, Y.-J. Lee, Exp. Ther. Med. 14 (2017) 1023–1036.
[44]C.L. Petersen Vitello Kalil, V. Campos, S. Cignachi, J. Favaro Izidoro, C. Prieto Herman Reinehr, C. Chaves, J. Cosmet. Dermatol. 17 (2018) 814–820.
[45]J.-Y. Bae, J.-S. Choi, S.-W. Kang, Y.-J. Lee, J. Park, Y.-H. Kang, Exp. Dermatol. 19 (2010) e182–90.
[46]A. Barel, M. Calomme, A. Timchenko, K. De Paepe, N. Demeester, V. Rogiers, P. Clarys, D. Vanden Berghe, Arch. Dermatol. Res. 297 (2005) 147–153.
[47]L. Junqueira, J. Carneiro, in: A.L. Mescher (Ed.), Junqueira’s Basic Histology Text and Atlas, McGraw-Hill Education, 2018.
[48]C. Olivares, F. Solano, Pigment Cell Melanoma Res. 22 (2009) 750–760.
[49]J. Zhang, C. Wang, C. Wang, B. Sun, C. Qi, Food Funct. 9 (2018) 5402–5416.
[50]S.J. Kang, B.R. Choi, S.H. Kim, H.Y. Yi, H.R. Park, S.J. Park, C.H. Song, J.H. Park, Y.J. Lee, S. Kwang, J. Cosmet. Sci. 66 (2015) 145–159.
[51]M. Kanlayavattanakul, W. Chongnativisit, P. Chaikul, N. Lourith, Planta Med. 86 (2020) 749–759.
[52]C. Puglia, A. Offerta, A. Saija, D. Trombetta, C. Venera, Journal of Cosmetic Dermatology 13 (2014) 151–157.
[53]T. Niwano, S. Terazawa, H. Nakajima, Y. Wakabayashi, G. Imokawa, Cytokine 73 (2015) 184–197.
[54]H. Nakajima, K. Fukazawa, Y. Wakabayashi, K. Wakamatsu, K. Senda, G. Imokawa, Arch. Dermatol. Res. 304 (2012) 803–816.
[55]J. Yamakoshi, A. Sano, S. Tokutake, M. Saito, M. Kikuchi, Y. Kubota, Y. Kawachi, F. Otsuka, Phytother. Res. 18 (2004) 895–899.
[56]J. Yamakoshi, F. Otsuka, A. Sano, S. Tokutake, M. Saito, M. Kikuchi, Y. Kubota, Pigment Cell Res. 16 (2003) 629–638.
[57]Y.-S. Lin, H.-J. Chen, J.-P. Huang, P.-C. Lee, C.-R. Tsai, T.-F. Hsu, W.-Y. Huang, Biomed Res. Int. 2017 (2017) 5232680.
[58]T.H. Lee, J.O. Seo, S.-H. Baek, S.Y. Kim, Biomol. Ther. 22 (2014) 35–40.
[59]Q. Liu, C. Kim, Y.H. Jo, S.B. Kim, B.Y. Hwang, M.K. Lee, Molecules 20 (2015) 16933–16945.
[60]R.A. Newton, A.L. Cook, D.W. Roberts, J.H. Leonard, R.A. Sturm, J. Invest. Dermatol. 127 (2007) 2216–2227.
[61]T. Quan, G.J. Fisher, Gerontology 61 (2015) 427–434.
[62]J.-H. Oh, Y.K. Kim, J.-Y. Jung, J.-E. Shin, K.H. Kim, K.H. Cho, H.C. Eun, J.H. Chung, J. Dermatol. Sci. 62 (2011) 192–201.
[63]U. Anderegg, J.C. Simon, M. Averbeck, Exp. Dermatol. 23 (2014) 295–303.
[64]D.H. Lee, J.-H. Oh, J.H. Chung, J. Dermatol. Sci. 83 (2016) 174–181.
[65]R. Bosch, N. Philips, J.A. Suárez-Pérez, A. Juarranz, A. Devmurari, J. Chalensouk-Khaosaat, S. González, Antioxidants (Basel) 4 (2015) 248–268.
[66]S. Freitas-Rodríguez, A.R. Folgueras, C. López-Otín, Biochim. Biophys. Acta Mol. Cell Res. 1864 (2017) 2015–2025.
[67]P. Pittayapruek, J. Meephansan, O. Prapapan, M. Komine, M. Ohtsuki, Int. J. Mol. Sci. 17 (2016).
[68]D. Harada, S. Nagamachi, K. Aso, K. Ikeda, Y. Takahashi, M. Furuse, Biochem. Biophys. Res. Commun. 512 (2019) 712–715.
[69]H.P. Shi, R.S. Fishel, D.T. Efron, J.Z. Williams, M.H. Fishel, A. Barbul, J. Surg. Res. 106 (2002) 299–302.
[70]N. Philips, P. Samuel, H. Parakandi, S. Gopal, H. Siomyk, A. Ministro, T. Thompson, G. Borkow, Connect. Tissue Res. 53 (2012) 373–378.
[71]M. Pyo, J.S. Park, Y.H. Lee, D.H. Lee, J.H. Chung, S.-T. Lee, J. Dermatol. Sci. 86 (2017) e92.
[72]R. Besio, M.C. Baratto, R. Gioia, E. Monzani, S. Nicolis, L. Cucca, A. Profumo, L. Casella, R. Basosi, R. Tenni, A. Rossi, A. Forlino, Biochim. Biophys. Acta 1834 (2013) 197–204.
[73]A. Lupi, R. Tenni, A. Rossi, G. Cetta, A. Forlino, Amino Acids 35 (2008) 739–752.
[74](2014).
[75]L.A. de Araújo, F. Addor, P.M.B.G.M. Campos, An. Bras. Dermatol. 91 (2016) 331–335.
[76]M.R. Calomme, D.A. Vanden Berghe, Biol. Trace Elem. Res. 56 (1997) 153–165.
[77]J.M. Pullar, A.C. Carr, M.C.M. Vissers, Nutrients 9 (2017).
[78]S. Cho, S. Lee, M.-J. Lee, D.H. Lee, C.-H. Won, S.M. Kim, J.H. Chung, Ann. Dermatol. 21 (2009) 6–11.
[79]A. Atiba, M. Nishimura, S. Kakinuma, T. Hiraoka, M. Goryo, Y. Shimada, H. Ueno, Y. Uzuka, Am. J. Surg. 201 (2011) 809–818.
[80]P. Chithra, G.B. Sajithlal, G. Chandrakasan, J. Ethnopharmacol. 59 (1998) 179–186.
[81]P. Chithra, G.B. Sajithlal, G. Chandrakasan, Mol. Cell. Biochem. 181 (1998) 71–76.
[82]F. Ali, N. Wajid, M.G. Sarwar, A.M. Qazi, Curr. Pharm. Biotechnol. (2020).
[83]R. Yao, M. Tanaka, E. Misawa, M. Saito, K. Nabeshima, K. Yamauchi, F. Abe, Y. Yamamoto, F. Furukawa, J. Food Sci. 81 (2016) H2849–H2857.
[84]M. Saito, M. Tanaka, E. Misawa, R. Yao, K. Nabeshima, K. Yamauchi, F. Abe, Y. Yamamoto, F. Furukawa, Biosci. Biotechnol. Biochem. 80 (2016) 1416–1424.
[85]T. Fujii, M. Wakaizumi, T. Ikami, M. Saito, J. Ethnopharmacol. 119 (2008) 53–57.
[86]S. Pientaweeratch, V. Panapisal, A. Tansirikongkol, Pharm. Biol. 54 (2016) 1865–1872.
[87]M.D. Adil, P. Kaiser, N.K. Satti, A.M. Zargar, R.A. Vishwakarma, S.A. Tasduq, J. Ethnopharmacol. 132 (2010) 109–114.
[88]P. Chanvorachote, V. Pongrakhananon, S. Luanpitpong, B. Chanvorachote, S. Wannachaiyasit, U. Nimmannit, J. Cosmet. Sci. 60 (2009) 395–403.
[89]M. Majeed, B. Bhat, S. Anand, A. Sivakumar, P. Paliwal, K.G. Geetha, J. Cosmet. Sci. 62 (2011) 49–56.
[90]H.M. Park, E. Moon, A.-J. Kim, M.H. Kim, S. Lee, J.B. Lee, Y.K. Park, H.-S. Jung, Y.-B. Kim, S.Y. Kim, Int. J. Dermatol. 49 (2010) 276–282.
[91]S.-Y. Kim, S.-J. Kim, J.-Y. Lee, W.-G. Kim, W.-S. Park, Y.-C. Sim, S.-J. Lee, J. Am. Coll. Nutr. 23 (2004) 157–162.
[92]E. Duchnik, J. Kruk, I. Baranowska-Bosiacka, A. Pilutin, R. Maleszka, M. Marchlewicz, Postepy Dermatol Alergol 36 (2019) 760–766.
[93]K. Miyazaki, T. Hanamizu, R. Iizuka, K. Chiba, Skin Pharmacol. Appl. Skin Physiol. 16 (2003) 108–116.
[94]A. Accorsi-Neto, M. Haidar, R. Simões, M. Simões, J. Soares Jr, E. Baracat, Clinics 64 (2009) 505–510.
[95]R. Gopaul, H.E. Knaggs, E.D. Lephart, Biofactors 38 (2012) 44–52.
[96]E.D. Lephart, Pharm. Biol. 51 (2013) 1393–1400.
[97]P. Sienkiewicz, A. Surazyński, J. Pałka, W. Miltyk, Acta Pol. Pharm. 65 (2008) 203–211.
[98]H.-Y. Chou, C. Lee, J.-L. Pan, Z.-H. Wen, S.-H. Huang, C.-W.J. Lan, W.-T. Liu, T.-C. Hour, Y.-C. Hseu, B.H. Hwang, K.-C. Cheng, H.-M.D. Wang, Int. J. Mol. Sci. 17 (2016).
[99]J. Meephansan, A. Rungjang, W. Yingmema, R. Deenonpoe, S. Ponnikorn, Clin. Cosmet. Investig. Dermatol. 10 (2017) 259–265.
[100]F. Afaq, M.A. Zaid, N. Khan, M. Dreher, H. Mukhtar, Exp. Dermatol. 18 (2009) 553–561.
[101]J.K. Seok, J.-W. Lee, Y.M. Kim, Y.C. Boo, Skin Pharmacol. Physiol. 31 (2018) 134–143.
[102]M.A. Zaid, F. Afaq, D.N. Syed, M. Dreher, H. Mukhtar, Photochem. Photobiol. 83 (2007) 882–888.
[103]B. Baek, S.H. Lee, K. Kim, H.-W. Lim, C.-J. Lim, Korean J. Physiol. Pharmacol. 20 (2016) 269–277.
[104]H.J. Lee, A.-R. Im, S.-M. Kim, H.-S. Kang, J.D. Lee, S. Chae, BMC Complement. Altern. Med. 18 (2018) 39.
[105]K. Suganuma, H. Nakajima, M. Ohtsuki, G. Imokawa, J. Dermatol. Sci. 58 (2010) 136–142.
[106]M. Park, J. Han, C.S. Lee, B.H. Soo, K.-M. Lim, H. Ha, Exp. Dermatol. 22 (2013) 336–341.
[107]J. Kim, J. Oh, J.N. Averilla, H.J. Kim, J.-S. Kim, J.-S. Kim, J. Food Sci. 84 (2019) 1600–1608.
[108]E.D. Lephart, M.B. Andrus, Exp. Biol. Med. 242 (2017) 1482–1489.
[109]E.D. Lephart, J.M. Sommerfeldt, M.B. Andrus, J. Funct. Foods 10 (2014) 377–384.
[110]J. Wittenauer, S. Mäckle, D. Sußmann, U. Schweiggert-Weisz, R. Carle, Fitoterapia 101 (2015) 179–187.
[111]M. Rizwan, I. Rodriguez-Blanco, A. Harbottle, M.A. Birch-Machin, R.E.B. Watson, L.E. Rhodes, Br. J. Dermatol. 164 (2011) 154–162.
[112]S. Grether-Beck, A. Marini, T. Jaenicke, W. Stahl, J. Krutmann, Br. J. Dermatol. 176 (2017) 1231–1240.
[113]M. Tanaka, Y. Yamamoto, E. Misawa, K. Nabeshima, M. Saito, K. Yamauchi, F. Abe, F. Furukawa, Clin. Cosmet. Investig. Dermatol. 9 (2016) 435–442.
[114]T. Izumi, M. Saito, A. Obata, M. Arii, H. Yamaguchi, A. Matsuyama, J. Nutr. Sci. Vitaminol. 53 (2007) 57–62.
[115]M. Hori, S. Kishimoto, Y. Tezuka, H. Nishigori, K. Nomoto, U. Hamada, Y. Yonei, Anti-Aging Med 7 (2010) 129–142.
[116]R.R. Wickett, E. Kossmann, A. Barel, N. Demeester, P. Clarys, D. Vanden Berghe, M. Calomme, Arch. Dermatol. Res. 299 (2007) 499–505.
[117]V.E. Colombo, F. Gerber, M. Bronhofer, G.L. Floersheim, J. Am. Acad. Dermatol. 23 (1990) 1127–1132.
[118]G.L. Floersheim, Z. Hautkr. 64 (1989) 41–48.
[119]L.G. Hochman, R.K. Scher, M.S. Meyerson, Cutis 51 (1993) 303–305.
[120]D.P. Patel, S.M. Swink, L. Castelo-Soccio, Skin Appendage Disord 3 (2017) 166–169.
[121]I.M. Braverman, J. Investig. Dermatol. Symp. Proc. 5 (2000) 3–9.
[122]M. El-Domyati, W. Medhat, in: M.A. Farage, K.W. Miller, H.I. Maibach (Eds.), Textbook of Aging Skin, Springer Berlin Heidelberg, Berlin, Heidelberg, 2017, pp. 469–484.
[123]N. Charkoudian, Mayo Clin. Proc. 78 (2003) 603–612.
[124]C. López-Otín, M.A. Blasco, L. Partridge, M. Serrano, G. Kroemer, Cell 153 (2013) 1194–1217.
[125]M.A. Birch-Machin, H. Swalwell, Mutagenesis 25 (2010) 101–107.
[126]M.A. Birch-Machin, E.V. Russell, J.A. Latimer, Br. J. Dermatol. 169 Suppl 2 (2013) 9–14.
[127]R. Gniadecki, T. Thorn, J. Vicanova, A. Petersen, H.C. Wulf, J. Cell. Biochem. 80 (2001) 216–222.
[128]J. Krutmann, P. Schroeder, J. Investig. Dermatol. Symp. Proc. 14 (2009) 44–49.
[129]M. Greco, G. Villani, F. Mazzucchelli, N. Bresolin, S. Papa, G. Attardi, FASEB J. 17 (2003) 1706–1708.
[130]Y. Sheng, I.A. Abreu, D.E. Cabelli, M.J. Maroney, A.-F. Miller, M. Teixeira, J.S. Valentine, Chem. Rev. 114 (2014) 3854–3918.
[131]Y. Hu, Y. Ma, S. Wu, T. Chen, Y. He, J. Sun, R. Jiao, X. Jiang, Y. Huang, L. Deng, W. Bai, Front. Pharmacol. 7 (2016) 301.
[132]S.R.K. Madduma Hewage, M.J. Piao, K.A. Kang, Y.S. Ryu, X. Han, M.C. Oh, U. Jung, I.G. Kim, J.W. Hyun, Biomol. Ther. 24 (2016) 312–319.
[133]M. Kujawska, M. Jourdes, M. Kurpik, M. Szulc, H. Szaefer, P. Chmielarz, G. Kreiner, V. Krajka-Kuźniak, P.Ł. Mikołajczak, P.-L. Teissedre, J. Jodynis-Liebert, Int. J. Mol. Sci. 21 (2019).
[134]P.A. Andreux, W. Blanco-Bose, D. Ryu, F. Burdet, M. Ibberson, P. Aebischer, J. Auwerx, A. Singh, C. Rinsch, Nat Metab 1 (2019) 595–603.
[135]W. Sun, C. Yan, B. Frost, X. Wang, C. Hou, M. Zeng, H. Gao, Y. Kang, J. Liu, Sci. Rep. 6 (2016) 34246.
[136]S. Tan, C.Y. Yu, Z.W. Sim, Z.S. Low, B. Lee, F. See, N. Min, A. Gautam, J.J.H. Chu, K.W. Ng, E. Wong, Sci. Rep. 9 (2019) 727.
[137]K. Cao, J. Xu, W. Pu, Z. Dong, L. Sun, W. Zang, F. Gao, Y. Zhang, Z. Feng, J. Liu, Sci. Rep. 5 (2015) 14014.
[138]X. Zou, C. Yan, Y. Shi, K. Cao, J. Xu, X. Wang, C. Chen, C. Luo, Y. Li, J. Gao, W. Pang, J. Zhao, F. Zhao, H. Li, A. Zheng, W. Sun, J. Long, I.M.-Y. Szeto, Y. Zhao, Z. Dong, P. Zhang, J. Wang, W. Lu, Y. Zhang, J. Liu, Z. Feng, Antioxid. Redox Signal. 21 (2014) 1557–1570.
[139]C. Yan, W. Sun, X. Wang, J. Long, X. Liu, Z. Feng, J. Liu, Mol. Nutr. Food Res. 60 (2016) 1139–1149.
[140]S. Atashbar, T. Sabzalipour, A. Salimi, Drug Res. (2020).
[141]R. Ebrahimi, M.R. Sepand, S.A. Seyednejad, A. Omidi, M. Akbariani, M. Gholami, O. Sabzevari, Daru 27 (2019) 721–733.
[142]E. Keshtzar, M.J. Khodayar, M. Javadipour, M.A. Ghaffari, D.L. Bolduc, M. Rezaei, Hum. Exp. Toxicol. 35 (2016) 1060–1072.
[143]Y.-C. Hseu, C.-W. Chou, K.J. Senthil Kumar, K.-T. Fu, H.-M. Wang, L.-S. Hsu, Y.-H. Kuo, C.-R. Wu, S.-C. Chen, H.-L. Yang, Food Chem. Toxicol. 50 (2012) 1245–1255.
[144]J.M. Hwang, J.S. Cho, T.H. Kim, Y.I. Lee, Biomed. Pharmacother. 64 (2010) 264–270.
[145]A.M. Toney, R. Fan, Y. Xian, V. Chaidez, A.E. Ramer-Tait, S. Chung, Obesity 27 (2019) 612–620.
[146]S.H. Kim, H. Kim, Nutrients 10 (2018).
[147]A.M. Wolf, S. Asoh, H. Hiranuma, I. Ohsawa, K. Iio, A. Satou, M. Ishikura, S. Ohta, J. Nutr. Biochem. 21 (2010) 381–389.
[148]J.S. Park, B.D. Mathison, M.G. Hayek, J. Zhang, G.A. Reinhart, B.P. Chew, J. Anim. Sci. 91 (2013) 268–275.
[149]C. Rodriguez Lanzi, D.J. Perdicaro, M.S. Landa, A. Fontana, A. Antoniolli, R.M. Miatello, P.I. Oteiza, M.A. Vazquez Prieto, J. Nutr. Biochem. 56 (2018) 224–233.
[150]H. Asseburg, C. Schäfer, M. Müller, S. Hagl, M. Pohland, D. Berressem, M. Borchiellini, C. Plank, G.P. Eckert, Neuromolecular Med. 18 (2016) 378–395.
[151]L. Bao, X. Cai, X. Dai, Y. Ding, Y. Jiang, Y. Li, Z. Zhang, Y. Li, Food Funct. 5 (2014) 1872–1880.
[152]X. Cai, L. Bao, J. Ren, Y. Li, Z. Zhang, Food Funct. 7 (2016) 805–815.
[153]L. Bao, X. Cai, Z. Zhang, Y. Li, Br. J. Nutr. 113 (2015) 35–44.
[154]S. Timmers, E. Konings, L. Bilet, R.H. Houtkooper, T. van de Weijer, G.H. Goossens, J. Hoeks, S. van der Krieken, D. Ryu, S. Kersten, E. Moonen-Kornips, M.K.C. Hesselink, IKunz, V.B. Schrauwen-Hinderling, E. Blaak, J. Auwerx, P. Schrauwen, Cell Metab. 14 (2011) 612–622.
[155]M. Lagouge, C. Argmann, Z. Gerhart-Hines, H. Meziane, C. Lerin, F. Daussin, N. Messadeq, J. Milne, P. Lambert, P. Elliott, B. Geny, M. Laakso, P. Puigserver, J. Auwerx, Cell 127 (2006) 1109–1122.
[156]T.D. Scribbans, J.K. Ma, B.A. Edgett, K.A. Vorobej, A.S. Mitchell, J.G.E. Zelt, C.A. Simpson, J. Quadrilatero, B.J. Gurd, Appl. Physiol. Nutr. Metab. 39 (2014) 1305–1313.
[157]J.A. Baur, K.J. Pearson, N.L. Price, H.A. Jamieson, C. Lerin, A. Kalra, V.V. Prabhu, J.S. Allard, G. Lopez-Lluch, K. Lewis, P.J. Pistell, S. Poosala, K.G. Becker, O. Boss, D. Gwinn, M. Wang, S. Ramaswamy, K.W. Fishbein, R.G. Spencer, E.G. Lakatta, D. Le Couteur, R.J. Shaw, P. Navas, P. Puigserver, D.K. Ingram, R. de Cabo, D.A. Sinclair, Nature 444 (2006) 337–342.
[158]N.L. Price, A.P. Gomes, A.J.Y. Ling, F.V. Duarte, A. Martin-Montalvo, B.J. North, B. Agarwal, L. Ye, G. Ramadori, J.S. Teodoro, B.P. Hubbard, A.T. Varela, J.G. Davis, B. Varamini, A. Hafner, R. Moaddel, A.P. Rolo, R. Coppari, C.M. Palmeira, R. de Cabo, J.A. Baur, D.A. Sinclair, Cell Metab. 15 (2012) 675–690.
[159]J.-H. Um, S.-J. Park, H. Kang, S. Yang, M. Foretz, M.W. McBurney, M.K. Kim, B. Viollet, J.H. Chung, Diabetes 59 (2010) 554–563.
[160]B. Dasgupta, J. Milbrandt, Proc. Natl. Acad. Sci. U. S. A. 104 (2007) 7217–7222.
[161]J.M. Ajmo, X. Liang, C.Q. Rogers, B. Pennock, M. You, Am. J. Physiol. Gastrointest. Liver Physiol. 295 (2008) G833–42.
[162]S. Eyerich, K. Eyerich, C. Traidl-Hoffmann, T. Biedermann, Trends Immunol. 39 (2018) 315–327.
[163]J.A.S. Quaresma, Clin. Microbiol. Rev. 32 (2019).
[164]F. Abdallah, L. Mijouin, C. Pichon, Mediators Inflamm. 2017 (2017) 5095293.
[165]X. Wang, S. Li, J. Liu, D. Kong, X. Han, P. Lei, M. Xu, H. Guan, D. Hou, BMC Complement Med Ther 20 (2020) 263.
[166]F. Afaq, N. Khan, D.N. Syed, H. Mukhtar, Photochem. Photobiol. 86 (2010) 1318–1326.
[167]J. Duchateau, G. Delepesse, R. Vrijens, H. Collet, Am. J. Med. 70 (1981) 1001–1004.
[168]S. Sazawal, S. Jalla, S. Mazumder, A. Sinha, R.E. Black, M.K. Bhan, Indian Pediatr. 34 (1997) 589–597.
[169]A.S. Prasad, F.W.J. Beck, B. Bao, J.T. Fitzgerald, D.C. Snell, J.D. Steinberg, L.J. Cardozo, Am. J. Clin. Nutr. 85 (2007) 837–844.
[170]C.S. Broome, F. McArdle, J.A.M. Kyle, F. Andrews, N.M. Lowe, C.A. Hart, J.R. Arthur, M.J. Jackson, Am. J. Clin. Nutr. 80 (2004) 154–162.
[171]W.C. Hawkes, D.S. Kelley, P.C. Taylor, Biol. Trace Elem. Res. 81 (2001) 189–213.
[172]J.C. Avery, P.R. Hoffmann, Nutrients 10 (2018).
[173]O.M. Guillin, C. Vindry, T. Ohlmann, L. Chavatte, Nutrients 11 (2019).
[174]E.A. Grice, J.A. Segre, Nat. Rev. Microbiol. 9 (2011) 244–253.
[175]A.L. Byrd, Y. Belkaid, J.A. Segre, Nat. Rev. Microbiol. 16 (2018) 143–155.
[176]Y.E. Chen, M.A. Fischbach, Y. Belkaid, Nature 553 (2018) 427–436.
[177]R.R. Roth, W.D. James, Annu. Rev. Microbiol. 42 (1988) 441–464.
[178]R.J. Santen, E. Simpson, Endocrinology 160 (2019) 605–625.
[179]J.R. Rettberg, J. Yao, R.D. Brinton, Front. Neuroendocrinol. 35 (2014) 8–30.
[180]G. Pelletier, L. Ren, Histol. Histopathol. 19 (2004) 629–636.
[181]M.J. Thornton, A.H. Taylor, K. Mulligan, F. Al-Azzawi, C.C. Lyon, J. O’Driscoll, A.G. Messenger, Exp. Dermatol. 12 (2003) 181–190.
[182]S. Widyarini, D. Domanski, N. Painter, V.E. Reeve, Proc. Natl. Acad. Sci. U. S. A. 103 (2006) 12837–12842.
[183]K.C.N. Chang, Y. Wang, I.G. Oh, S. Jenkins, L.P. Freedman, C.C. Thompson, J.H. Chung, S. Nagpal, Mol. Pharmacol. 77 (2010) 744–750.
[184]M. Markiewicz, S. Znoyko, L. Stawski, A. Ghatnekar, G. Gilkeson, M. Trojanowska, J. Invest. Dermatol. 133 (2013) 120–127.
[185]R.L. Jackson, J.S. Greiwe, R.J. Schwen, Exp. Dermatol. 20 (2011) 879–882.
[186]D.F. Archer, Gynecol. Endocrinol. 28 Suppl 2 (2012) 2–6.
[187]J. Gujarathi, R. Gujarathi, (n.d.).
[188]C.S. Hwang, H.S. Kwak, H.J. Lim, S.H. Lee, Y.S. Kang, T.B. Choe, H.G. Hur, K.O. Han, J. Steroid Biochem. Mol. Biol. 101 (2006) 246–253.
[189]M. Messina, Nutrients 8 (2016).
[190]T. Zhang, X. Liang, L. Shi, L. Wang, J. Chen, C. Kang, J. Zhu, M. Mi, PLoS One 8 (2013) e79075.
[191]E.B. Froyen, F.M. Steinberg, J. Nutr. Biochem. 22 (2011) 843–848.
[192]M.A. Rahman Mazumder, P. Hongsprabhas, Biomed. Pharmacother. 82 (2016) 379–392.
[193]V.A. Terra, F.P. Souza-Neto, M.A.C. Frade, L.N.Z. Ramalho, T.A.M. Andrade, A.A.C. Pasta, A.C. Conchon, F.A. Guedes, R.C. Luiz, R. Cecchini, A.L. Cecchini, J. Photochem. Photobiol. B 144 (2015) 20–27.
[194]N.J. Kang, K.W. Lee, E.A. Rogozin, Y.-Y. Cho, Y.-S. Heo, A.M. Bode, H.J. Lee, Z. Dong, J. Biol. Chem. 282 (2007) 32856–32866.
[195]J.S. Kang, Y.D. Yoon, M.H. Han, S.-B. Han, K. Lee, M.R. Kang, E.-Y. Moon, Y.J. Jeon, S.-K. Park, H.M. Kim, Biochem. Pharmacol. 71 (2005) 136–143.
[196]T.H. Lee, M.H. Do, Y.L. Oh, D.W. Cho, S.H. Kim, S.Y. Kim, J. Agric. Food Chem. 62 (2014) 8962–8972.
[197]A. Oyama, T. Ueno, S. Uchiyama, T. Aihara, A. Miyake, S. Kondo, K. Matsunaga, Menopause 19 (2012) 202–210.
[198]T. Cornwell, W. Cohick, I. Raskin, Phytochemistry 65 (2004) 995–1016.
[199]J.H. Rabe, A.J. Mamelak, P.J.S. McElgunn, W.L. Morison, D.N. Sauder, J. Am. Acad. Dermatol. 55 (2006) 1–19.
[200]R.M. Tyrrell, Photochem. Photobiol. Sci. 11 (2012) 135–147.
[201]L. Yuan, X. Duan, R. Zhang, Y. Zhang, M. Qu, J. Dermatolog. Treat. 31 (2020) 300–308.
[202]R.K. Chaudhuri, Skin Pharmacol. Appl. Skin Physiol. 15 (2002) 374–380.
[203]A. Gęgotek, A. Jastrząb, I. Jarocka-Karpowicz, M. Muszyńska, E. Skrzydlewska, Antioxidants (Basel) 7 (2018).
[204]A. Saija, A. Tomaino, R. Lo Cascio, P. Rapisarda, J.C. Dederen, Int. J. Cosmet. Sci. 20 (1998) 331–342.
[205]P. Pratheeshkumar, Y.-O. Son, X. Wang, S.P. Divya, B. Joseph, J.A. Hitron, L. Wang, D. Kim, Y. Yin, R.V. Roy, J. Lu, Z. Zhang, Y. Wang, X. Shi, Toxicol. Appl. Pharmacol. 280 (2014) 127–137.
[206]Y. He, Y. Hu, X. Jiang, T. Chen, Y. Ma, S. Wu, J. Sun, R. Jiao, X. Li, L. Deng, W. Bai, J. Photochem. Photobiol. B 177 (2017) 24–31.
[207]G. Chandra Jagetia, Transcriptomics 03 (2015).
[208]E. Camera, A. Mastrofrancesco, C. Fabbri, F. Daubrawa, M. Picardo, H. Sies, W. Stahl, Exp. Dermatol. 18 (2009) 222–231.
[209]X.-L. Xue, X.-D. Han, Y. Li, X.-F. Chu, W.-M. Miao, J.-L. Zhang, S.-J. Fan, Stem Cell Res. Ther. 8 (2017) 7.
[210]J. Soeur, J. Eilstein, G. Léreaux, C. Jones, L. Marrot, Free Radic. Biol. Med. 78 (2015) 213–223.
[211]Y. Ido, A. Duranton, F. Lan, K.A. Weikel, L. Breton, N.B. Ruderman, PLoS One 10 (2015) e0115341.
[212]A.C. Carvalho, A.C. Gomes, C. Pereira-Wilson, C.F. Lima, Free Radic. Biol. Med. 83 (2015) 262–272.
[213]A. Kammeyer, R.M. Luiten, Ageing Res. Rev. 21 (2015) 16–29.
[214]S.J. Cooper, G.T. Bowden, Curr. Cancer Drug Targets 7 (2007) 325–334.
[215]E.C. Naylor, R.E.B. Watson, M.J. Sherratt, Maturitas 69 (2011) 249–256.
[216]C.C. Zouboulis, E. Makrantonaki, Clin. Dermatol. 29 (2011) 3–14.
[217]D.J. Haustead, A. Stevenson, V. Saxena, F. Marriage, M. Firth, R. Silla, L. Martin, K.F. Adcroft, S. Rea, P.J. Day, P. Melton, F.M. Wood, M.W. Fear, Sci. Rep. 6 (2016) 26846.
[218]G.J. Fisher, S. Kang, J. Varani, Z. Bata-Csorgo, Y. Wan, S. Datta, J.J. Voorhees, Arch. Dermatol. 138 (2002) 1462–1470.
[219]A. Balkrishna, S.S. Sakat, K. Joshi, K. Joshi, V. Sharma, R. Ranjan, K. Bhattacharya, A. Varshney, Front. Pharmacol. 10 (2019) 1186.
[220]D.-J. Kwon, Y.-S. Bae, S.M. Ju, A.R. Goh, S.Y. Choi, J. Park, Biochem. Biophys. Res. Commun. 409 (2011) 780–785.
[221]F. Afaq, A. Malik, D. Syed, D. Maes, M.S. Matsui, H. Mukhtar, Photochem. Photobiol. 81 (2005) 38–45.
[222]S. Wu, Y. Hu, Z. Li, W. Bai, J. Zhao, C. Huang, Q. Li, C. Fan, L. Deng, D. Lu, Photodermatol. Photoimmunol. Photomed. 34 (2018) 224–231.
[223]M. Ding, R. Feng, S.Y. Wang, L. Bowman, Y. Lu, Y. Qian, V. Castranova, B.-H. Jiang, X. Shi, J. Biol. Chem. 281 (2006) 17359–17368.
[224]H. Parhiz, A. Roohbakhsh, F. Soltani, R. Rezaee, M. Iranshahi, Phytother. Res. 29 (2015) 323–331.
[225]S. Terazawa, H. Nakajima, M. Shingo, T. Niwano, G. Imokawa, Exp. Dermatol. 21 Suppl 1 (2012) 11–17.
[226]V.M. Adhami, F. Afaq, N. Ahmad, Neoplasia 5 (2003) 74–82.
[227]S. Pastore, D. Lulli, R. Maurelli, E. Dellambra, C. De Luca, L.G. Korkina, PLoS One 8 (2013) e59632.
[228]J.K. Kundu, Y.-J. Surh, Mutat. Res. 555 (2004) 65–80.
[229]X. Zhu, Q. Liu, M. Wang, M. Liang, X. Yang, X. Xu, H. Zou, J. Qiu, PLoS One 6 (2011) e27081.
[230]M.-H. Tsai, L.-F. Hsu, C.-W. Lee, Y.-C. Chiang, M.-H. Lee, J.-M. How, C.-M. Wu, C.-L. Huang, I.-T. Lee, Int. J. Biochem. Cell Biol. 88 (2017) 113–123.
[231]L. Tong, S. Wu, Sci. Rep. 8 (2018) 3574.
[232]J. Oh, T. Yu, S.J. Choi, Y. Yang, H.S. Baek, S.A. An, L.K. Kwon, J. Kim, H.S. Rho, S.S. Shin, W.S. Choi, S. Hong, J.Y. Cho, Mediators Inflamm. 2012 (2012) 781375.
[233]M. Yamamoto, T.W. Kensler, H. Motohashi, Physiol. Rev. 98 (2018) 1169–1203.
[234]L. Baird, A.T. Dinkova-Kostova, Arch. Toxicol. 85 (2011) 241–272.
[235]M. Rojo de la Vega, A. Krajisnik, D.D. Zhang, G.T. Wondrak, Nutrients 9 (2017).
[236]M. Schäfer, S. Werner, Free Radic. Biol. Med. 88 (2015) 243–252.
[237]K.M. Holmström, L. Baird, Y. Zhang, I. Hargreaves, A. Chalasani, J.M. Land, L. Stanyer, M. Yamamoto, A.T. Dinkova-Kostova, A.Y. Abramov, Biol. Open 2 (2013) 761–770.
[238]J.H. Suh, S.V. Shenvi, B.M. Dixon, H. Liu, A.K. Jaiswal, R.-M. Liu, T.M. Hagen, Proc. Natl. Acad. Sci. U. S. A. 101 (2004) 3381–3386.
[239]A. Silva-Palacios, M. Ostolga-Chavarría, C. Zazueta, M. Königsberg, Ageing Res. Rev. 47 (2018) 31–40.
[240]A. Hirota, Y. Kawachi, M. Yamamoto, T. Koga, K. Hamada, F. Otsuka, Exp. Dermatol. 20 (2011) 664–668.
[241]T. Niu, R. Xuan, L. Jiang, W. Wu, Z. Zhen, Y. Song, L. Hong, K. Zheng, J. Zhang, Q. Xu, Y. Tan, X. Yan, H. Chen, J. Agric. Food Chem. 66 (2018) 1551–1559.
[242]C.L.L. Saw, A.Y. Yang, Y. Guo, A.-N.T. Kong, Food Chem. Toxicol. 62 (2013) 869–875.
[243]Q. Fang, S. Guo, H. Zhou, R. Han, P. Wu, C. Han, Sci. Rep. 7 (2017) 41440.
[244]Y. Liu, F. Chan, H. Sun, J. Yan, D. Fan, D. Zhao, J. An, D. Zhou, Eur. J. Pharmacol. 650 (2011) 130–137.
[245]H. Kim, C.N. Ramirez, Z.-Y. Su, A.-N.T. Kong, J. Nutr. Biochem. 33 (2016) 54–62.
[246]A. Ben-Dor, M. Steiner, L. Gheber, M. Danilenko, N. Dubi, K. Linnewiel, A. Zick, Y. Sharoni, J. Levy, Mol. Cancer Ther. 4 (2005) 177–186.
[247]M. Yaar, M.S. Eller, B.A. Gilchrest, J. Investig. Dermatol. Symp. Proc. 7 (2002) 51–58.
[248]T. Uchiyama, M. Tsunenaga, M. Miyanaga, O. Ueda, M. Ogo, Biotechnol. Appl. Biochem. 66 (2019) 870–879.
[249]P. Ambigaipalan, A.C. de Camargo, F. Shahidi, J. Agric. Food Chem. 64 (2016) 6584–6604.
[250]R.P. Singh, K.N. Chidambara Murthy, G.K. Jayaprakasha, J. Agric. Food Chem. 50 (2002) 81–86.
[251]U.A. Fischer, R. Carle, D.R. Kammerer, Food Chem. 127 (2011) 807–821.
[252]B. Cerdá, P. Periago, J.C. Espín, F.A. Tomás-Barberán, J. Agric. Food Chem. 53 (2005) 5571–5576.
[253]S.M. Henning, J. Yang, R.-P. Lee, J. Huang, M. Hsu, G. Thames, I. Gilbuena, J. Long, Y. Xu, E.H. Park, C.-H. Tseng, J. Kim, D. Heber, Z. Li, Sci. Rep. 9 (2019) 14528.
[254]D. Buonocore, A. Lazzeretti, P. Tocabens, V. Nobile, E. Cestone, G. Santin, M.G. Bottone, F. Marzatico, Clin. Cosmet. Investig. Dermatol. 5 (2012) 159–165.
[255]P. Riyanto, P. Subchan, R. Lelyana, Dermatoendocrinol. 7 (2015) e1063751.
[256]G. Nieto, G. Ros, J. Castillo, Medicines (Basel) 5 (2018).
[257]E. Tarshish, K. Hermoni, S.R. Schwartz, Clinical Pharmacology & Biopharmaceutics 9 (2020).
[258]W. Stahl, U. Heinrich, S. Wiseman, O. Eichler, H. Sies, H. Tronnier, J. Nutr. 131 (2001) 1449–1451.
[259]O. Aust, W. Stahl, H. Sies, H. Tronnier, U. Heinrich, Int. J. Vitam. Nutr. Res. 75 (2005) 54–60.
[260]R.B. Rucker, T. Kosonen, M.S. Clegg, A.E. Mitchell, B.R. Rucker, J.Y. Uriu-Hare, C.L. Keen, Am. J. Clin. Nutr. 67 (1998) 996S–1002S.

No Comments Yet

Sign in or Register to Comment