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Astaxanthin in Skin Health, Repair, and Disease: A Comprehensive Review

  • Guangdong Klox Biomedical Group

Abstract and Figures

Astaxanthin, a xanthophyll carotenoid, is a secondary metabolite naturally synthesized by a number of bacteria, microalgae, and yeasts. The commercial production of this pigment has traditionally been performed by chemical synthesis, but the microalga Haematococcus pluvialis appears to be the most promising source for its industrial biological production. Due to its collective diverse functions in skin biology, there is mounting evidence that astaxanthin possesses various health benefits and important nutraceutical applications in the field of dermatology. Although still debated, a range of potential mechanisms through which astaxanthin might exert its benefits on skin homeostasis have been proposed, including photoprotective, antioxidant, and anti-inflammatory effects. This review summarizes the available data on the functional role of astaxanthin in skin physiology, outlines potential mechanisms involved in the response to astaxanthin, and highlights the potential clinical implications associated with its consumption.
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Astaxanthin in Skin Health, Repair, and Disease:
A Comprehensive Review
Sergio Davinelli 1, *ID , Michael E. Nielsen 2ID and Giovanni Scapagnini 1
1Department of Medicine and Health Sciences “V. Tiberio”, University of Molise, Via de Sanctis s.n.c,
86100 Campobasso, Italy;
2FB Dermatology, Borupvang 5C, 2750 Ballerup, Denmark;
*Correspondence:; Tel.: +39-0874-404771
Received: 26 March 2018; Accepted: 19 April 2018; Published: 22 April 2018
Astaxanthin, a xanthophyll carotenoid, is a secondary metabolite naturally synthesized
by a number of bacteria, microalgae, and yeasts. The commercial production of this pigment has
traditionally been performed by chemical synthesis, but the microalga Haematococcus pluvialis appears
to be the most promising source for its industrial biological production. Due to its collective
diverse functions in skin biology, there is mounting evidence that astaxanthin possesses various
health benefits and important nutraceutical applications in the field of dermatology. Although still
debated, a range of potential mechanisms through which astaxanthin might exert its benefits on skin
homeostasis have been proposed, including photoprotective, antioxidant, and anti-inflammatory
effects. This review summarizes the available data on the functional role of astaxanthin in skin
physiology, outlines potential mechanisms involved in the response to astaxanthin, and highlights
the potential clinical implications associated with its consumption.
astaxanthin; skin; aging; ultraviolet; antioxidant; anti-inflammatory; immune-enhancing;
DNA repair; clinical trials
1. Introduction
The ketocarotenoid astaxanthin (ASX), 3,30-dihydroxy-b,b-carotene-4,40-dione, was originally
isolated from a lobster by Kuhn and Sorensen [
]. Currently, ASX is a renowned compound for its
commercial application in various industries comprising aquaculture, food, cosmetics, nutraceuticals,
and pharmaceuticals. ASX was first commercially used for pigmentation only in the aquaculture
industry to increase ASX content in farmed salmonids and obtain the characteristic orange-red
color of the flesh. ASX is ubiquitous in nature, especially found in the marine environment as
a red-orange pigment common to many aquatic animals such as salmonids, shrimp, and crayfish.
ASX is primarily biosynthesized by microalgae/phytoplankton, accumulating in zooplankton and
crustaceans and subsequently in fish, from where it is added to the higher levels in the food chain.
Although ASX can be also synthesized by plants, bacteria, and microalgae, the chlorophyte alga
Haematococcus pluvialis is considered to have the highest capacity to accumulate ASX [
]. It is worth
mentioning that currently, 95% of ASX available in the market is produced synthetically using
petrochemicals due to cost-efficiency for mass production. Safety issues have arisen regarding the
use of synthetic ASX for human consumption, while the ASX derived from H. pluvialis is the main
source for several human applications, including dietary supplements, cosmetics, and food. There are
several ASX stereoisomers in nature ((3S, 3
S), (3R, 3
R), and (3R, 3
S)) that differ in the configuration
of the two hydroxyl groups on the molecule. The predominant form found in H. pluvialis and in
salmon species is the stereoisomer form 3S, 3
S [
]. In addition, ASX has several essential biological
functions in marine animals, including pigmentation, protection against ultraviolet (UV) light effects,
Nutrients 2018,10, 522; doi:10.3390/nu10040522
Nutrients 2018,10, 522 2 of 12
communication, immune response, reproductive capacity, stress tolerance, and protection against
oxidation of macromolecules [
]. ASX is strictly related to other carotenoids, such as zeaxanthin,
lutein, and
-carotene; therefore, it shares numerous metabolic and physiological functions attributed
to carotenoids. However, ASX is more bioactive than zeaxanthin, lutein, and
-carotene. This is mainly
due to the presence of a keto- and a hydroxyl group on each end of its molecule. Moreover, unlike other
carotenoids, ASX is not converted into vitamin A. Because of its molecular structure, ASX has unique
features that support its potential use in promoting human health. In particular, the polar end groups
quench free radicals, while the double bonds of its middle segment remove high-energy electrons.
These unique chemical properties explain some of its features, particularly a higher antioxidant
activity than other carotenoids [
]. In addition, ASX preserves the integrity of cell membranes by
inserting itself in their bilayers, protects the redox state and functional integrity of mitochondria,
and demonstrates benefits mostly at a very modest dietary intake, since its strongly polar nature
optimizes the rate and extent of its absorption [
]. Recently, ASX has attracted considerable interest
because of its potential pharmacological effects, including anticancer, antidiabetic, anti-inflammatory,
and antioxidant activities as well as neuro-, cardiovascular, ocular, and skin-protective effects [
In particular, ASX has been reported to exhibit multiple biological activities to preserve skin health
and achieve effective skin cancer chemoprevention [
]. Extensive research during the last two decades
has revealed the mechanism by which continued oxidative stress leads to chronic inflammation, which
in turn, mediates most chronic diseases including cancer and skin damage [
]. In skin, ASX has
been shown to improve dermal health by direct and downstream influences at several different
steps of the oxidative stress cascade, while inhibiting inflammatory mediators at the same time [
Molecular and morphological changes in aged skin not only compromise its protective role, but also
contribute to the appearance of skin symptoms, including excessive dryness and pruritus, as well as
increased predisposition to the formation or deepening of wrinkles, dyspigmentation, fragility and
difficulty in healing injuries, alteration in skin permeability to drugs, impaired ability to sense and
respond to mechanical stimuli, skin irritation, and tumor incidence [
]. The effects of ASX on
hyperpigmentation suppression, melanin synthesis and photoaging inhibition, and wrinkle formation
reduction have been reported in several clinical studies [
]. In the current review, we will address
some issues that highlight the overall versatility and protection offered by ASX. In particular, we will
discuss the effects of ASX on cellular and molecular mechanisms, such as the regulation of antioxidant
and anti-inflammatory activities, modulation of the immune response, prevention of skin damage,
and regulation of DNA repair.
2. Skin-Protective Mechanisms of Astaxanthin
2.1. Antioxidant Activity
Oxidative stress plays a crucial role in human skin aging and dermal damage. The mechanisms
of intrinsic (chronological) and extrinsic (photo-) aging include the generation of reactive oxygen
species (ROS) via oxidative metabolism and exposure to sun ultraviolet (UV) light, respectively.
Thus, the formation of ROS is a pivotal mechanism leading to skin aging. Oxidant events of skin
aging involve damage to DNA, the inflammatory response, reduced production of antioxidants,
and the generation of matrix metalloproteinases (MMPs) that degrade collagen and elastin in the
dermal skin layer [
]. There are many dietary or exogenous sources that act as antioxidants,
including polyphenols and carotenoids [
]. ASX has recently caught the interest of researchers
because of its powerful antioxidant activity and its unique molecular and biochemical messenger
properties with implications in treating and preventing skin disease. Comparative studies examining
the photoprotective effects of carotenoids have demonstrated that ASX is a superior antioxidant,
having greater antioxidant capacity than canthaxanthin and
-carotene in human dermal fibroblasts.
In particular, ASX inhibits ROS formation and modulates the expression of oxidative stress-responsive
enzymes such as heme oxygenase-1 (HO-1), which is a marker of oxidative stress and a regulatory
Nutrients 2018,10, 522 3 of 12
mechanism involved in the cell adaptation against oxidative damage [
]. HO-1 is regulated via
various stress-sensitive transcription factors, including nuclear factor erythroid 2-related factor (Nrf2),
which binds to antioxidant response elements in the promoter regions of enzymes of the detoxifying
metabolism [
]. Several authors demonstrated that ASX activates the Nrf2/HO-1 antioxidant pathway
by generating small amounts of ROS [
]. Consistent with these studies,
Xue et al. [25]
that ASX upregulated Nrf2 expression in irradiated cells. Furthermore, the Nrf2-targeted proteins
HO-1 and antioxidative enzymes superoxide dismutase 2 (SOD2), catalase (CAT), and glutathione
peroxidase 1 (GPX1) were significantly upregulated in irradiated cells in the presence of ASX. Therefore,
ASX exerts significant antioxidant activities not only via direct radical scavenging, but also by activating
the cellular antioxidant defense system through modulation of the Nrf2 pathway. A recent study also
demonstrated that ASX protected against early burn-wound progression by attenuating ROS-induced
oxidative stress in a rat deep-burn model. This effect involves the regulation of free radical production
by influencing xanthine oxidase (XO) and the reduced form of nicotinamide adenine dinucleotide
phosphate (NADPH) oxidase (Nox); both contribute to the generation of ROS [26].
2.2. Anti-Inflammatory Properties
Extensive research during the last two decades has revealed the mechanism by which continued
oxidative stress leads to chronic inflammation, which in turn, mediates most chronic diseases
including neurodegeneration, cancer, and skin damage [
]. It is well established that various
proinflammatory markers in skin are increased as a result of UV exposure. Keratinocytes play a crucial
role in the photodamage response after UV exposure by releasing proinflammatory mediators. It has
been shown that ASX treatment prevents the deleterious effects of UV by decreasing UV-induced
reactive nitrogen species production, inflammatory cytokine expression, and apoptosis in keratinocytes.
ASX caused a significant decrease in the levels of inducible nitric oxide (iNOS) and cyclooxygenase
(COX)-2, and decreased the release of prostaglandin E2 from keratinocytes after UV irradiation [
The inhibitory effect of ASX on the production of iNOS has important implications for the development
of anti-inflammatory drugs for skin inflammatory diseases such as psoriasis and atopic dermatitis (AD).
AD is a chronic inflammatory skin disease associated with various factors, including immunological
abnormalities that contribute to the pathogenesis and development of skin lesions. A recent report
showed that ASX inhibited the gene expression of several proinflammatory biomarkers such as
), interleukin-6 (IL-6), and tumor necrosis factor-
) in an AD animal
model [
]. Several investigators examined the inhibition of nuclear factor-kappa B (NF-
B) by ASX.
In particular, ASX has been reported to have a potent capacity to block the nuclear translocation
of the NF-
B p65 subunit and I
degradation through its inhibitory effect on N
B kinase (IKK)
activity [
]. More importantly, studies showed the ability of ASX to inhibit the production of
inflammatory mediators by blocking NF-
B activation in human keratinocytes, indicating that ASX
may offer an attractive new strategy for treating skin inflammatory diseases [33].
2.3. Immune-Enhancing Effects
Considerable evidence suggests that suppression of immune system contributes to the
development of solar UV-induced cutaneous malignancies, including melanoma and non-melanoma,
in both mouse models and humans [
]. ASX significantly influences immune function in
in vitro
in vivo
assays [
]. For example,
in vitro
studies on human lymphocytes have
demonstrated enhancement by ASX of immunoglobulin production in response to T cell-dependent
stimuli [
]. The immunomodulatory action of ASX has been also reported in dogs and cats, enhancing
both cell-mediated and humoral immune responses. In these studies, ASX increased natural killer (NK)
cell cytotoxic activity, suggesting that ASX may regulate NK cells that serve as an immunosurveillance
system against tumours and virus-infected cells [
]. Moreover, other authors have shown that
ASX increased cytotoxic T lymphocyte activity in mice. Activated T cells and NK cells produce
), which is involved in immune regulation and B cell differentiation; therefore,
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ASX may enhance immune responses and potentially exert antitumor activity [
]. In addition to
the cell-mediated immune response, as already mentioned, ASX also stimulated humoral immunity.
ASX increased antibody production in mouse splenocytes, restored humoral immune response in
old mice, and induced production of polyclonal antibodies G and M in murine spleen cells [
Although further studies are needed to better elucidate the specific mode of action of ASX in enhancing
the immune response, collectively, these observations suggest that ASX may be a potential tool against
UV-induced immunosuppression.
2.4. Effects on Skin Damage
The most important and abundant structures of the dermal extracellular matrix (ECM) are
collagen, elastin, and glycosaminoglycans (GAGs). In both intrinsic and extrinsic aging, changes in
these structures are observed. These modifications lead to the loss of tensile strength and recoil capacity,
wrinkle formation, dryness, and impaired wound healing [
]. In addition, UV-induced ROS stimulate
the synthesis of MMPs that are responsible for the degradation of ECM, and in particular, MMPs can
fully degrade collagen [
In vitro
, ASX effectively suppresses cell damage caused by free radicals
and induction of MMP-1 in skin after UV irradiation [
]. Some similar studies also reported that ASX
inhibited the expression of MMPs in different cells, including macrophages and chondrocytes [
Recently, an enriched ASX extract from H. pluvialis increased collagen content through inhibition of
MMP-1 and MMP-3 expression in human dermal fibroblasts [
]. Moreover, it should be highlighted
that ECM deregulation may affect various essential cell behaviours. Indeed, the correct regulation of
MMPs is critical in controlling the balanced turnover of collagen and in maintaining ECM integrity and
function [
]. During wound healing, the ECM at the wound site undergoes dramatic reorganization.
It has been shown that ASX is an effective compound for accelerating wound healing in full-thickness
dermal wounds in mice. ASX-treated wounds showed significantly increased expression of wound
healing biological markers such as collagen type I
1 (Col1A1) and basic fibroblast growth factor
(bFGF) [52].
2.5. Effects on DNA Repair
The exposure of the skin to UV radiation causes DNA damage. The biologically harmful effects
associated with UV radiation exposure are largely the result of errors in DNA repair, which can lead to
oncogenic mutations. The DNA photoproducts generated by UV-induced DNA damage are altered
DNA structures that activate a cascade of responses, beginning with the initiation of cell-cycle arrest
and activation of DNA repair mechanisms [
]. The nucleotide excision repair (NER) pathway is a key
mechanism utilized by mammalian cells for the repair of damaged DNA [
]. Although there are no
studies evaluating the effects of ASX on the NER pathway, ASX is reported to improve the DNA repair
capacity of cells exposed to UV radiation. In particular, ASX was capable of minimizing DNA damage
and influencing the kinetics of DNA repair. [
]. Human cells possess multiple protection mechanisms
against UV-induced ROS, either by preventing damage or by damage repair. For example, ASX inhibits
the UV-induced DNA damage and increases the expression of oxidative stress-responsive enzymes [
Moreover, ASX was shown to exert its protective effects against cyclophosphamide-induced oxidative
stress and DNA damage by activating Nrf2 and modulating NQO1 and HO-1 expressions [
Cyclophosphamide (CP), a cytotoxic alkylating agent, is extensively used in the treatment of various
cancers with high efficacy. However, it exhibits severe cytotoxicity to normal cells in humans and
experimental animals, and it is associated with toxic effects and induction of genomic instability and
DNA damage. Therefore, it is important to prevent normal cells from DNA damage induced by CP
in clinical applications. Several reports indicated that ASX decreased CP-induced oxidative stress
and subsequent oxidative DNA damage [
]. Furthermore, the AKT pathway plays key roles in
modulating genome stability and DNA damage responses. Studies have shown that inhibition of
AKT kinase activity impairs double-strand break (DSB) repair [
]. Recently, it was suggested that
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modulation of the AKT signal pathway by ASX may potentially contribute to the maintenance of
genomic stability and counteract DNA damage [60].
3. Evidence from Human Clinical Trials
in vivo
in vitro
studies have demonstrated that ASX may play a promising functional
role to treat and prevent skin aging. Although ASX displayed molecular and protective mechanisms of
action to promote and/or improve human skin health, it may not be easy to translate these results
to humans. Methodological pitfalls afflicting
in vitro
experiments and animal models need to be
considered for the interpretation of these results. In addition, the source of ASX used in cell culture and
animal studies is often of unknown origin. However, the potential skin-protective effects of ASX have
also been investigated in humans. The main source of ASX intake in humans is from seafood, with wild
sockeye salmon, for example, providing 26–38 mg/kg of flesh [
]. Human intervention studies that
have been conducted with ASX are summarized in Table 1. Immune cells are extremely vulnerable
to uncontrolled free radical production due to a high percentage of polyunsaturated fatty acids in
their membranes, and they produce more oxidative products and inflammatory mediators [
Park et al. [64]
conducted the first comprehensive study to investigate the action of dietary ASX in
modulating immune response, oxidative status, and inflammation in young healthy adult female
human subjects. After eight weeks of supplementation, ASX enhanced both cell-mediated and humoral
immune responses, including T cell and B cell mitogen-induced lymphocyte proliferation, NK cell
cytotoxic activity, and IL-6 production. ASX did not influence the concentration of plasma C-reactive
proteins, but levels of 8-hydroxy-2
-deoxyguanosine (8-OHdG) (a DNA damage biomarker) were
dramatically lower in the group fed higher doses of ASX. All of the skin aging characteristics are
associated with the oxidative metabolism and subsequent ROS production that define this unavoidable
phenomenon. In a recent study, it was demonstrated that continuous consumption of ASX for four
weeks alleviated aging-related changes of residual skin surface components (RSSC). The authors
also measured the levels of malondialdehyde (MDA), a recognized biomarker of systemic oxidative
stress. In particular, 31 middle-aged subjects received 4-mg daily doses of ASX, and the plasma
levels of MDA decreased during ASX consumption (by 11.2% on day 15 and by 21.7% on day 29).
Moreover, the analysis of RSSC samples revealed decreased levels of corneocyte desquamation and
microbial presence at the end of the study [
Tominaga et al. [66]
conducted an
in vitro
study and in
parallel, a randomized, double-blind, parallel-group, placebo-controlled study with 65 healthy female
subjects for 16 weeks to verify the effects of oral ASX supplementation (6 or 12 mg) on skin integrity.
The authors demonstrated that pre- and post-treatment with ASX dose-dependently decreased the
secretion of inflammatory cytokines and MMP-1 from UVB-irradiated keratinocytes. Furthermore,
the clinical study demonstrated that skin moisture content and deep wrinkles were not significantly
changed in the ASX-supplemented groups, whereas these parameters significantly worsened in the
placebo group during the study period. Interestingly, IL-1
levels in the stratum corneum were
maintained only in the high-dose group. In addition, skin elasticity improvements were observed
in the high-dose group compared with that of the placebo group in participants with high skin
moisture content. In 2001,
Seki et al. [67]
conducted a small pilot study with ASX from H. pluvialis
to investigate the wrinkle reduction effect on the skin of 45 healthy subjects. The authors observed
an antiwrinkle effect in female human subjects (
n= 3
), using a topical cream containing ASX combined
with other active ingredients. A dermatological assessment revealed significant reduction of wrinkles
and puffiness on the lower eye and cheeks after two weeks of use. A second preliminary human
study performed by Yamahita in 1995 [
] showed in healthy male subjects (
n= 7
) that topical natural
ASX from krill significantly reduces erythema by 60% at 98 h after UV-B exposure. In a second study,
the same author administered to 49 healthy female subjects (mean age of 47 years) 2 mg of ASX or
placebo. After six weeks of treatment, significant improvements were observed in skin moisture and
elasticity [
]. In another study by
Tominaga et al. [70]
, the effect of ASX on wrinkle reduction and
skin elasticity was investigated in 28 female subjects (20–55 years). The combined use of a dietary
Nutrients 2018,10, 522 6 of 12
supplement and a topical product containing ASX for eight weeks showed a reduction in the overall
average wrinkle depth. The latest trend in antiaging strategies is to use a combination of dietary and
oral supplements to produce extra physiologic benefits
. Several studies demonstrated that the
combined administration of ASX with other compounds, particularly collagen hydrolysate, may show
additive or synergistic effects for preventing or reversing the skin aging process [
]. Consistent with
this, a recent study with 44 healthy subjects showed that a combination of ASX (
2 mg/day
) and collagen
hydrolysate (
2 mg/day
) for 12 weeks improves elasticity and barrier integrity in human skin. These
improvements were associated with molecular changes such as the induction of procollagen type I and
decreased levels in the expression of the collagen-degrading enzyme MMP-1 and the elastin-degrading
enzyme MMP-12 [
]. In an open-label noncontrolled study, 30 healthy female subjects received for
eight weeks 6 mg per day of oral supplementation combined with 2 mL (78.9-
M solution) per day
of a topical application of ASX. Significant improvements were observed in skin wrinkle, age spot
size, elasticity, and skin texture [
]. The same authors also conducted a randomized double-blind
placebo-controlled study involving 36 healthy male subjects supplemented with 6 mg of ASX for six
weeks. At the end of the study period, ASX improved wrinkles, elasticity, transepidermal water loss
(TEWL), moisture content, and sebum oil level [
]. These results demonstrate that ASX may improve
skin condition in both men and women. Further evidence from human intervention studies is required.
In addition, we recommend additional research focused on stimulation of the endogenous antioxidant
defense systems of the skin, particularly the expression of antioxidant responsive elements associated
with the activity of detoxifying enzymes.
Table 1. Summary of human intervention studies on skin and astaxanthin.
Intervention Study Design Control Population (n) Duration Outcomes Dosage Author, Year
Administration of ASX
controlled study
Healthy female subjects
(14/diet group) 8 weeks
DNA damage biomarkers;
of NK cells, T cells, B cells,
and IL-6
2 or 8 mg Park, 2010
Administration of
ASX capsules
Monitoring of
oxidative stress
and skin aging
31 middle-aged volunteers
4 weeks MDA;
RSSC 4 mg Chalyk, 2017
Administration of
ASX capsules
Placebo 65 healthy female subjects
16 weeks Wrinkle parameters;
IL-α6 or 12 mg Tominaga, 2017
Administration of
ASX cream Pilot study None 3 healthy female subjects 2 weeks Wrinkle parameters 0.7 mg/g of
ASX cream Seki, 2001
Topical application of
ASX Pilot study None 3 healthy male subjects N/S erythema N/S Yamashita, 1995
Administration of
ASX capsules
Placebo 49 healthy female subjects
6 weeks Wrinkle parameters 2 mg Yamashita, 2006
Oral and topical
treatment with ASX N/S N/S
28 healthy female subjects
8 weeks Wrinkle parameters 6 mg Tominaga, 2009
Two oral forms
(ASX capsules;
tablets collagen)
44 healthy
female volunteers 12 weeks
viscoelastic parameters;
procollagen type I;
MMP-1 and MMP-12
2 mg Yoon, 2014
Capsules of ASX
combined with topical
application of ASX
noncontrolled None
30 healthy female subjects
8 weeks
age spot size;
skin texture
6 mg and 2 mL
78.9 µM solution
Tominaga, 2012
Administration of
ASX capsules
36 healthy male subjects 6 weeks
moisture content;
sebum oil
6 mg Tominaga, 2012
, increase;
, decrease; ASX, astaxanthin; NK, natural killer; IL-6, interleukin-6;
MDA, malondialdehyde; RSSC, residual skin surface components; N/S, not specified; TEWL, transepidermal
water loss; MMP, matrix metalloproteinase.
Nutrients 2018,10, 522 7 of 12
4. Safety and Bioavailability
4.1. Safety
ASX sourced from the microalgae H. pluvialis has been approved as a coloradditive in salmon feeds
and as a dietary supplement for human consumption in Europe, Japan, and the USA. The European
Food Safety Authority (EFSA) on Additives and Products or Substances used in Animal Feed
(FEEDAP) advised an acceptable daily intake (ADI) of 0.034 mg/kg bw of ASX (2.38 mg per day
a 70-kg human
) [
]. This scientific opinion was reiterated later by an EFSA Panel on Dietetic
Products, Nutrition and Allergies (NDA), where it was concluded that the safety of 4 mg of ASX
per day (0.06 mg/kg bw) had yet to be fully established [
]. However, no adverse effects were
reported in studies involving participants supplemented with more than 4 mg per day of ASX [
For example, the acute intake of 40 mg of ASX has also been reported as well-tolerated in 32 healthy
participants with only three mild events reported in the 48 h post-intake [
]. Also, the chronic
intake of
16 and 40 mg per day
of ASX has been suggested as safe in patients suffering with functional
dyspepsia [
]. It is also worth mentioning that the Food and Drug Administration (FDA) has approved
ASX from H. pluvialis for direct human consumption dosages up to 12 mg per day and up to 24 mg per
day for no more than 30 days [
]. In addition, supercritical CO
extracts from H. pluvialis have been
granted “novel food” status by the FDA and recognized as “GRAS” status (generally recognized as
safe) [3].
4.2. Bioavailability
Following release from the food matrix, carotenoids accumulate in the lipid droplets within the
gastric juices and then are incorporated into micelles. These micelles diffuse into the plasma membrane
of enterocytes, and carotenoids are transported in the circulation by high-density lipoprotein (HDL)
and low-density lipoprotein (LDL) [
]. The absorption of ASX and other carotenoids is influenced
by their chemical properties and several dietary and non-dietary-related parameters [
]. The ASX
content of salmon flesh ranges from 3 to 37 mg/kg; therefore, a 200-g serving of salmon provides
approximately 1 to 7 mg of ASX. Wild salmon contains the 3S, 3
S form of ASX almost exclusively [
The absorption of ASX is affected by diet and by smoking, and in particular, concomitant food
intake appears to increase the absorption and smoking appears to reduce the half-life of ASX [
The absorption of ASX from different sources has been investigated in several animal species, including
mice, rats, dogs, and humans. In a randomized and double-blind trial, 28 healthy men consumed 250 g
of wild or aquacultured salmon daily for four weeks, which provided
5 mg ASX/day
from salmon
flesh. Following six days of intervention with wild salmon (3S, 3
S isomer), plasma ASX concentrations
reached a plateau of 39 nmol/L, and of 52 nmol/L after administration of aquacultured salmon
3R, 30S
). Interestingly, at days 3, 6, 10, and 14, but not at day 28, the ASX concentrations in human
plasma were significantly greater after ingestion of aquacultured salmon. First, these results suggest
that the ASX isomer pattern in human plasma resembles that of the ingested salmon. Then, it seems
that when the intake of ASX is chronic, maximal concentrations can be achieved within the first
week of intake, even when ASX is obtained from different sources [
]. Although the bioavailability
and the configurational isomer distribution of the ASX in human plasma has been investigated in
this clinical trial, a comprehensive study regarding the pharmacokinetics and tissue distribution
of ASX in human skin has not been performed. Carotenoids are lipid-soluble molecules, and the
absorption of ASX is influenced positively by dietary lipids. It appears that a higher proportion of ASX
is absorbed when is delivered in an oil-based formulation. In an open parallel study, eight healthy male
volunteers received a single dose of 40 mg of ASX as three different lipid-based formulations (n= 8 for
each group). All three lipid-based formulations enhanced the bioavailability of ASX, but the highest
bioavailability was observed with the formulation containing the highest content of the hydrophilic
synthetic surfactant. Therefore, these results suggest that ASX should be consumed together with
dietary fats to optimize bioavailability [
]. Considering the small number of subjects included in these
Nutrients 2018,10, 522 8 of 12
bioavailability studies, future research should try to replicate these findings in doses equivalent to those
advised by the different authorities such as the EFSA and FDA. The limited literature evidence devoted
to showing improvements in ASX bioavailability reveals that the enhancement of ASX bioavailability
has not gained significant attention, especially for skin tissue. Moreover, novel delivery strategies
including various type of formulations such as nanoparticles, topical application cream, and defined
phospholipid complexes offer significant promise and are worthy of further exploration in attempts to
enhance the bioavailability of this interesting molecule.
5. Conclusions
The main components that confer an aged skin appearance are damaged structural and
functional proteins that form the ECM. Damage to these structures leads to the production of reactive
intermediates, cell death, and inflammatory responses. Moreover, UV irradiation significantly induces
pigmentation, skin wrinkling, and immunosuppression, resulting in the acceleration of photoaging.
UV-induced damage of DNA can lead to mutations, apoptosis, or malignant transformations of cells.
Although there is no health claim or therapeutic indication approved by the EFSA or FDA, ASX has
a great potential in the global market of nutraceuticals. In this article, we have provided an overview
of the cytoprotective mechanisms of ASX. Due to its involvement in diverse biological activities, ASX is
a promising compound in the field of dermatology. Additional, more comprehensive experiments
will be necessary in order to fully understand ASX activities in the skin. However, ASX inhibits
collagenases, MMP activity, inflammatory mediators, and ROS induction, resulting in potent
antiwrinkle and antioxidant effects. Moreover, ASX may prevent UV-induced immunosuppression.
Toxicological aspects have been characterized and ASX appears to be a safe and bioavailable compound.
Some clinical studies have shown a relationship between the intake of ASX and positive effects on
cutaneous physiology; however, a lot of unknown topics need to be further investigated.
We thank group members of Solgar Italia Multrinutrient S.p.A. for their thorough review and
helpful discussions during the preparation of this manuscript and for their help in elaborating the search strategy.
Author Contributions: All authors wrote the paper.
Conflicts of Interest: The authors declare no conflict of interest.
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2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access
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(CC BY) license (
... This carotenoid has potent antioxidant activity, 100-fold higher, for example, than that of α-tocopherol and 10-fold higher than that of other carotenoids, such as β-carotene and lutein [4,5]. Several studies have demonstrated that the daily intake of astaxanthin has excellent effects on human health and beauty [6][7][8][9][10]. In particular, astaxanthin has been reported to prevent ultraviolet (UV) light-induced skin damage and exhibits multiple biological activities that preserve skin health [7][8][9][10]. ...
... Several studies have demonstrated that the daily intake of astaxanthin has excellent effects on human health and beauty [6][7][8][9][10]. In particular, astaxanthin has been reported to prevent ultraviolet (UV) light-induced skin damage and exhibits multiple biological activities that preserve skin health [7][8][9][10]. For example, Li et al. (2020) reported that astaxanthin supplementation reduced UV light-induced thickening and capillary regression in the skin of hairless mice [8]. ...
... To our knowledge, no previous study has investigated the effects of oral supplementation with Z-isomer-rich astaxanthin on skin health and UV light-induced skin deterioration. As previous studies have used H. pluvialis as a source of astaxanthin [7][8][9][10], it is predicted that most astaxanthin was in the all-E-configuration [18]. This study aimed to evaluate the protective effects of astaxanthin with different Z-isomer ratios on UV light-induced skin deterioration. ...
Full-text available
The effect of oral supplementation with astaxanthin of different Z-isomer ratios on ultraviolet (UV) light-induced skin damage in guinea pigs was investigated. Astaxanthin with a high Z-isomer content was prepared from the all-E-isomer via thermal isomerization. Intact (all-E)-astaxanthin and the prepared Z-isomer-rich astaxanthin were suspended in soybean oil and fed to guinea pigs for three weeks. The UV-light irradiation was applied to the dorsal skin on the seventh day after the start of the test diet supplementation, and skin parameters, such as elasticity, transepidermal water loss (TEWL), and pigmentation (melanin and erythema values), were evaluated. The accumulation of astaxanthin in the dorsal skin was almost the same after consumption of the all-E-isomer-rich astaxanthin diet (E-AST-D; total Z-isomer ratio = 3.2%) and the Z-isomer-rich astaxanthin diet (Z-AST-D; total Z-isomer ratio = 84.4%); however, the total Z-isomer ratio of astaxanthin in the skin was higher in the case of the Z-AST-D supplementation. Both diets inhibited UV light-induced skin-damaging effects, such as the reduction in elasticity and the increase in TEWL level. Between E-AST-D and Z-AST-D, Z-AST-D showed better skin-protective ability against UV-light exposure than E-AST-D, which might be because of the greater UV-light-shielding ability of astaxanthin Z-isomers than the all-E-isomer. Furthermore, supplementation with Z-AST-D resulted in a greater reduction in skin pigmentation caused by astaxanthin accumulation compared to that of E-AST-D. This study indicates that dietary astaxanthin accumulates in the skin and appears to prevent UV light-induced skin damage, and the Z-isomers are more potent oral sunscreen agents than the all-E-isomer.
... Currently, astaxanthin is a renowned compound for its commercial application in various industries, comprising aquaculture, food, cosmetics, nutraceutical, and pharmaceutical [10]. Moreover, astaxanthin effectively suppresses cell damage caused by free radicals, and induction of matrix metalloproteinases (MMPs) in skin after UV irradiation [11]. ...
Full-text available
This study compared microbiological and chemical methods used in astaxanthin extraction from the exoskeleton of the shrimp species Penaeus japonicus and Penaeus semisulcatus. The microbiological method was performed using Saccharomyces cerevisiae (bakery yeast) or Lactobacillus acidophilus (from yogurt), followed by solvent extraction with hexane and acetone at different ratios (1:1, 1:2, and 1:3). The chemical method was performed traditionally using hexane. The highest astaxanthin yield from P. japonicus exoskeleton was obtained using either S. cerevisiae or L. acidophilus followed by solvent extraction with hexane and acetone at a ratio of 1:1 (8.5 and 8.1 mg/g waste, respectively) as well as by the chemical method (8.4 mg/g waste). Likewise, the highest astaxanthin yield from P. semisulcatus exoskeleton was obtained using either S. cerevisiae or L. acidophilus followed by solvent extraction with hexane and acetone at a ratio of 1:1 (3.0 and 4.1 mg/g waste, respectively) as well as by the chemical method (3.2 mg/g waste). The values obtained from P. semisulcatus exoskeleton were considerably lower than those attained from P. japonicus exoskeleton. In addition, the nuclear magnetic resonance (C-NMR) analysis confirmed that astaxanthin was the main carotenoid present in the extract. In conclusion, the pretreatment of exoskeleton wastes of P. japonicus using S. cerevisiae followed by solvent extraction with hexane and acetone at a ratio of 1:1 as well as the classical chemical treatment led to the highest astaxanthin content.
... Yeasts and bacteria producing astaxanthin are genetically engineered, thus their product cannot be considered for human consumption. Synthetic astaxanthin, that actually covers 95% of the market, is produced from petrochemical sources, raising issues of potential toxicity, pollution, and sustainability and posing severe health risks; hence chemically produced astaxanthin is sold in the animal feed market, but it does not meet the regulatory requirements to be used for direct human use in any country [15,17]. This limitation is pushing the production of natural astaxanthin towards microalgal cultivation. ...
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Background Astaxanthin is a ketocarotenoid with high antioxidant power used in different fields as healthcare, food/feed supplementation and as pigmenting agent in aquaculture. Primary producers of astaxanthin are some species of microalgae, unicellular photosynthetic organisms, as Haematococcus lacustris . Astaxanthin production by cultivation of Haematococcus lacustris is costly due to low biomass productivity, high risk of contamination and the requirement of downstream extraction processes, causing an extremely high price on the market. Some microalgae species are also primary producers of omega-3 fatty acids, essential nutrients for humans, being related to cardiovascular wellness, and required for visual and cognitive development. One of the main well-known producers of omega-3 fatty eicosapentaenoic acid (EPA) is the marine microalga Nannochloropsis gaditana (named also Microchloropsis gaditana ): this species has been already approved by the Food and Drug Administration (FDA) for human consumption and it is characterized by a fast grow phenotype. Results Here we obtained by chemical mutagenesis a Nannochloropsis gaditana mutant strain, called S4 , characterized by increased carotenoid to chlorophyll ratio. S4 strain showed improved photosynthetic activity, increased lipid productivity and increased ketocarotenoids accumulation, producing not only canthaxanthin but also astaxanthin, usually found only in traces in the WT strain. Ketocarotenoids produced in S4 strain were extractible in different organic solvents, with the highest efficiency observed upon microwaves pre-treatment followed by methanol extraction. By cultivation of S4 strain at different irradiances it was possible to produce up to 1.3 and 5.2 mgL ⁻¹ day ⁻¹ of ketocarotenoids and EPA respectively, in a single cultivation phase, even in absence of stressing conditions. Genome sequencing of S4 strain allowed to identify 199 single nucleotide polymorphisms (SNP): among the mutated genes, mutations in a carotenoid oxygenase gene and in a glutamate synthase gene could explain the different carotenoids content and the lower chlorophylls content, respectively. Conclusions By chemical mutagenesis and selection of strain with increased carotenoids to chlorophyll ratio it was possible to isolate a new Nannochloropsis gaditana strain, called S4 strain, characterized by increased lipids and ketocarotenoids accumulation. S4 strain can thus be considered as novel platform for ketocarotenoids and EPA production for different industrial applications.
... Natural bioactive compounds (NBC) presenting anti-inflammatory and antioxidant properties, can contribute to stopping inflammation and restoring the redox balance necessary to reestablish normal dermal conditions [5]. In this regard, the topical use of NBC such as astaxanthin [6], gallic acid [7] or curcumin [8], has been described for the treatment of some skin pathologies. ...
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This work focuses on the development and evaluation of a dual nanostructured lipid carrier (NLC)/Carbopol®-based hydrogel system as a potential transporter for the topical delivery of curcumin to the skin. Two populations of different sized negatively charged NLCs (P1, 70–90 nm and P2, 300–350 nm) were prepared and characterized by means of dynamic light scattering. NLCs presented an ovoid platelet shape confirmed by transmission electron microscopy techniques. Curcumin NLC entrapment efficiency and release profiles were assessed by HPLC (high pressure liquid chromatography) and spectrophotometric methods. Preservation and enhancement of curcumin (CUR) antioxidant activity in NLCs (up to 7-fold) was established and cell viability assays on fibroblasts and keratinocytes indicated that CUR-NLCs are non-cytotoxic for concentrations up to 10 μM and exhibited a moderate anti-migration/proliferation effect (20% gap reduction). CUR-NLCs were then embedded in a Carbopol®-based hydrogel without disturbing the mechanical properties of the gel. Penetration studies on Franz diffusion cells over 24 h in CUR-NLCs and CUR-NLCs/gels demonstrated an accumulation of CUR in Strat-M® membranes of 22% and 5%, respectively. All presented data support the use of this new dual CUR-NLC/hydrogel system as a promising candidate for adjuvant treatment in topical dermal applications.
... 51 In food and beverages sectors, carotenoids are used not only as the colourant, making them more appealing to the consumers, but also as essential heath nutrients. 19 Roles of carotenoids in skin heath are well-known, 52 and carotenoids can also provide protection against sunlight and UV. [53][54][55] Plenty of studies have shown that carotenoids have beauty-enhancing effects, and thus carotenoids are widely used in cosmetic products. ...
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The intrinsic ability of microalgae to accumulate high amounts of carotenoids has made them the preferred aquatic organisms of biotechnological exploration for carotenoid production. To continuously innovate and modify microalgal bioprocesses, aquaculture scientists have been working hard for the past decades in a forward‐looking way, and mixotrophic cultivation of microalgae is deemed as a promising strategy to decrease production cost. This review is intended to summarise the recent research advancement of carotenoids production from mixotrophically cultivated microalgae, starting from the structure, biosynthesis, physiological roles and applications of carotenoids and followed by the production processes both currently established and under development. Most importantly, the microalgal physiology of mixotrophic cultivation is reviewed in depth both in general and specifically for the most studied species, and the prospects of commercially viable mixotrophic microalgal processes for carotenoid production along with the insight of future research are of course discussed. Finally, we conclude that mixotrophy might be a promising strategy for large‐scale cultivation of microalgae to produce carotenoids although some technical obstacles need to be overcome.
... Among them, astaxanthin has been studied for its potential role in regulating oxidative stress and reducing inflammation and subsequently cardiovascular disease caused by atherosclerosis (Fassett & Coombes, 2012;Kishimoto et al., 2016;Visioli & Artaria 2017). Astaxanthin is a lipid-soluble keto-carotenoid, a class of strong antioxidants, in which commercial production of this pigment has traditionally been performed by chemical synthesis (Davinelli et al., 2018). This red-orange carotenoid pigment, first discovered in 1938 in lobsters (Kuhn & Soerensen, 1938), subsequently was approved as a color additive by the US Food and Drug Administration (USFDA) for use as a pigmentation ingredient for aquaculture (21 C.F.R. § 73.35) before USFDA approval for naturally derived astaxanthin for use as a supplement for human consumption through the New Dietary Ingredient Notifications Program (Jayaraj et al., 2008;Fakhri et al., 2018). ...
The field of research that explores the use of microalgae in biomedicine and health is complex and diverse. Numerous research avenues currently explore the use of microalgae in biomedicine and heath such as: focusing on establishing and boosting nutritional profiles for food applications; identification, characterisation and utilisation of microalgal metabolites with biological activity as functional ingredients and/or drugs; utilisation of recombinant technology to genetically modify the algae for use as production systems for enzymes, antibodies, growth factors, drugs, and vaccines; or the use of microalgae as a source of “biomaterial” for use in applications such as drug carriers or cellular scaffolds for tissue engineering. To illustrate the diversity of microalgae and its potential for utilisation in a wide variety of biomedical and heath care applications, this chapter will present a concise overview of this broad applicability of microalgae in biomedicine and health, while highlighting research that is also occurring into the production and biorefinery of these compounds to facilitate a viable transition from laboratory to commercial production. Thus, this chapter aims to bridge the knowledge gap between both existing and potentially new algae applications, in particular, the use of microalgae as a source of “biomaterials” for biomedicine and health applications.
... In particular, the polar end groups quench free radicals, while the double bonds of its middle segment remove high-energy electrons. These unique chemical properties explain some of its features, notably a higher antioxidant activity than other carotenoids (Ishikawa et al., 2015;Kishimoto et al., 2016;Davinelli et al., 2018;Brotosudarmo et al., 2020). ...
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Cincalok is a typical food from West Kalimantan made from fermented rebon shrimp containing astaxanthin, the most potent antioxidant in nature. This study investigated an efficient method for extracting astaxanthin from the cincalok using vegetable oils as solvents. Olive, sesame, grape seeds, coconut, and virgin coconut oil were used as alternative solvents. The effect of various parameters on extraction yield was also studied. N-hexane and acetone were also used for comparison. Amplitude level and extraction time were the factors investigated concerning extraction yield. Comparative studies between traditional extraction methods and extraction assisted by ultrasonication have also been carried out. The astaxanthin content as total carotenoids in oil extract was analyzed using a UV-vis spectrophotometer with a standard external method. The optimum ultrasound-assisted extraction condition of astaxanthin from cincalok was 40% amplitude for 3 minutes, with 100.62 μg/g of astaxanthin extraction yield when used virgin coconut oil as a solvent. In this way, oils enriched with astaxanthin are produced.
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Spearmint (Mentha spicata L.) has been widely studied for its diversity of compounds for product generation. However, studies describing the chemical and biological characteristics of commercial spearmint materials from different origins are scarce. For this reason, this research aimed to bioprospecting spearmint from three origins: Colombia (Col), Mexico (Mex), and Egypt (Eg). We performed a biological activity analysis, such as FRAP, DPPH, and ABTS, inhibition potential of S. pyogenes, K. pneumoniae, E. coli, P. aeuroginosa, S. aureus, S aureus Methicillin-Resistant, and E. faecalis. Furthermore, we performed chemical assays, such as total polyphenol and rosmarinic acid, and untargeted metabolomics via HPLC-MS/MS. Finally, we developed a causality analysis to integrate biological activities with chemical analyses. We found significant differences between the samples for the total polyphenol and rosmarinic acid contents, FRAP, and inhibition analyses for Methicillin-Resistant S. aureus and E. faecalis. Also, clear metabolic differentiation was observed among the three commercial materials evaluated. These results allow us to propose data-driven uses for the three spearmint materials available in current markets.
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Context: Astaxanthin (Ast), a compound used widely as a dietary supplement, has high antioxidant properties but poor oral bioavailability. To benefit from its nutritional values in cognitive function, Ast was formulated into a nanoemulsion which may improve its penetration through the blood–brain barrier (BBB). Aim: The present study aims to quantitate the Ast nanoemulsion in different regions of the brain tissue using the high-performance liquid chromatography method. Materials and Methods: Sprague–Dawley rats were fed with Ast nanoemulsion formulation daily (40, 80, and 160 mg/kg body weight, bw) for 28 days before brain tissues were harvested, extracted, and quantified. A simple, sensitive, and reliable method using high-performance liquid chromatography with an ultraviolent detector was developed and validated to quantify Ast in the brain. Statistical Analysis: Data were analyzed using the ToolPak Data Analysis in Excel for t-test and analysis of variance single factor with Tukey post hoc analysis. Results: The calibration curve demonstrated a linear regression with an r2 of 0.9998 and absolute recovery ranging from 97.8% to 109.6%. The hippocampus of the 160 mg/kg bw treatment group showed a significantly higher concentration of Ast (77.9 ± 17.3 μg/g) compared to the cortex (22.3 ± 4.2 μg/g) and cerebellum (33.1 ± 5.4 μg/g). Ast was detected in the cerebellum of the 80 mg/kg bw (29.4 ± 7.8 μg/g) treatment group with the amount not being significantly different to the 160 mg/kg bw (33.1 ± 5.4 μg/g) treatment group. Conclusions: It was evident that the Ast nanoemulsion formulated was able to cross the BBB and may provide protective benefits.
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The use of medication is effective in managing metabolic syndrome (MetS), but side effects have led to increased attention on using nutraceuticals and supplements. Astaxanthin shows positive effects in reducing the risk of MetS, but results from individual studies are inconclusive. This systematic review summarizes the latest evidence of astaxanthin in adults with risk factors of MetS. A systematic search of English and Chinese randomized controlled trials in 14 electronic databases from inception to 30 June 2021 was performed. Two reviewers independently screened the titles and abstracts, and conducted full-text review, quality appraisal, and extraction of data. Risk of bias was assessed by PEDro. A total of 7 studies met the inclusion criteria with 321 participants. Six studies were rated to have excellent methodological quality, while the remaining one was rated at good. Results show marginal effects of astaxanthin on reduction in total cholesterol and systolic blood pressure, and a significant attenuating effect on low-density lipoprotein cholesterol. Further robust evidence is needed to examine the effects of astaxanthin in adults at risk of MetS.
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Background: Skin aging is a complex biological process influenced by a combination of intrinsic and extrinsic factors, leading to cumulative alterations of skin structure, function and appearance. Polyphenols, which are secondary plant metabolites, represent one of the largest classes of compounds used in dermatology and nutricosmetics to combat skin aging. The main objective is to provide an overview of the existing literature linking skin aging and the ability of polyphenols as regulatory elements able to maintain skin homeostasis. Methods: In this review, we discuss recent progress in understanding the molecular bases of skin aging, with specific emphasis on some well known and extensively studied polyphenols which have significant anti-aging influences and photoprotective effects. Results: Although no relevant clinical data exist and standard delivery systems have not been established, promising results have been obtained in many in vitro and animal models. A wide variety of polyphenols may minimize mechanisms underlying the functional manifestations of photoaging and chronological skin aging. Conclusion: Polyphenols exert their influence mostly through their antioxidant and anti-inflammatory effects, thereby abrogating collagen degradation and/or increasing procollagen synthesis.
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The realisation that UV radiation (UVR) exposure could induce a suppressed immune environment for the initiation of carcinogenesis in the skin was first described more than 40 years ago. Van der Leun and his colleagues contributed to this area in the 1980s and 90s by experiments in mice involving UV wavelength and dose-dependency in the formation of such tumours, in addition to illustrating both the local and systemic effect of the UVR on the immune system. Since these early days, many aspects of the complex pathways of UV-induced immunosuppression have been studied and are outlined in this review. Although most experimental work has involved mice, it is clear that UVR also causes reduced immune responses in humans. Evidence showing the importance of the immune system in determining the risk of human skin cancers is explained, and details of how UVR exposure can down-regulate immunity in the formation and progression of such tumours reviewed. With increasing knowledge of these links and the mechanisms of UVR-induced immunosuppression, novel approaches to enhance immunity to skin tumours antigens in humans are becoming apparent which, hopefully, will reduce the burden of UVR-induced skin cancers in the future.
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Citicoline and homotaurine are renowned compounds that exhibit potent neuroprotective activities through distinct molecular mechanisms. The present study was undertaken to demonstrate whether cotreatment with citicoline and homotaurine affects cell survival in primary retinal cultures under experimental conditions simulating retinal neurodegeneration. Primary cultures were obtained from the retina of fetal rats and exposed to citicoline plus homotaurine (100 μ M). Subsequently, neurotoxicity was induced using excitotoxic levels of glutamate and high glucose concentrations. The effects on retinal cultures were assessed by cell viability and immunodetection of apoptotic oligonucleosomes. The results showed that a combination of citicoline and homotaurine synergistically decreases proapoptotic effects associated with glutamate- and high glucose-treated retinal cultures. This study provides an insight into the potential application of citicoline and homotaurine as a valuable tool to exert neuroprotective effects against retinal damage.
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In this study, we investigated anti-dermatitic effects of Astaxanthin (AST) in phthalic anhydride (PA)-induced atopic dermatitis (AD) animal model as well as in vitro model. AD-like lesion was induced by the topical application of 5% PA to the dorsal skin or ear of Hos:HR-1 mouse. After AD induction, 100 μl of 1 mg/ml and 2 mg/ml of AST (10 μg or 20 μg/cm2) was spread on the dorsum of ear or back skin three times a week for four weeks. We evaluated dermatitis severity, histopathological changes and changes in protein expression by Western blotting for inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and nuclear factor-κB (NF-κB) activity. We also measured tumor necrosis factor- α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), and immunoglobulinE (IgE) concentration in the blood of AD mice by enzyme-linked immunosorbent assay (ELISA). AST treatment attenuated the development of PA-induced AD. Histological analysis showed that AST inhibited hyperkeratosis, mast cells and infiltration of inflammatory cells. AST treatment inhibited expression of iNOS and COX-2, and NF-κB activity as well as release of TNF-α, IL-1β, IL-6, and IgE. In addition, AST (5, 10, and 20μM) potently inhibited lipopolysaccharide (LPS) (1 μg/ml)-induced nitric oxide (NO) production, expression of iNOS and COX-2, and NF-κB DNA binding activities in RAW 264.7 macrophage cells. Our data demonstrated that AST could be a promising agent for AD by inhibition of NF-κB signaling. This article is protected by copyright. All rights reserved.
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Jitlada Meephansan,1 Atiya Rungjang,1 Werayut Yingmema,2 Raksawan Deenonpoe,3 Saranyoo Ponnikorn3 1Division of Dermatology, Chulabhorn International College of Medicine, Thammasat University, Pathum Thani, Thailand; 2Laboratory Animal Centers, Thammasat University, Pathum Thani, Thailand; 3Chulabhorn International College of Medicine, Thammasat University, Pathum Thani, Thailand Abstract: Wound healing consists of a complex series of convoluted processes which involve renewal of the skin after injury. ROS are involved in all phases of wound healing. A balance between oxidative and antioxidative forces is necessary for a favorable healing outcome. Astaxanthin, a member of the xanthophyll group, is considered a powerful antioxidant. In this study, we investigated the effect of topical astaxanthin on cutaneous wound healing. Full-thickness dermal wounds were created in 36 healthy female mice, which were divided into a control group and a group receiving 78.9 µM topical astaxanthin treatment twice daily for 15 days. Astaxanthin-treated wounds showed noticeable contraction by day 3 of treatment and complete wound closure by day 9, whereas the wounds of control mice revealed only partial epithelialization and still carried scabs. Wound healing biological markers including Col1A1 and bFGF were significantly increased in the astaxanthin-treated group since day 1. Interestingly, the oxidative stress marker iNOS showed a significantly lower expression in the study. The results indicate that astaxanthin is an effective compound for accelerating wound healing. Keywords: astaxanthin, wound healing, reactive oxygen species, antioxidant
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Astaxanthin is a carotenoid with potent antioxidant and anti-inflammatory activity. To evaluate the anti-inflammatory effect of astaxanthin on skin deterioration, we confirmed its role in epidermal-dermal interactions in vitro. Astaxanthin treatment suppressed ultraviolet B (UVB)-induced inflammatory cytokine secretion in keratinocytes, and matrix metalloproteinase-1 secretion by fibroblasts cultured in UVB-irradiated keratinocyte medium. To verify these findings, we conducted a 16-week clinical study with 65 healthy female participants. Participants were orally administered either a 6 mg or 12 mg dose of astaxanthin or a placebo. Wrinkle parameters and skin moisture content significantly worsened in the placebo group after 16 weeks. However, significant changes did not occur in the astaxanthin groups. Interleukin-1α levels in the stratum corneum significantly increased in the placebo and low-dose groups but not in the high-dose group between weeks 0 and 16. This study was performed in Japan from August to December, when changing environmental factors, such as UV and dryness, exacerbate skin deterioration. In conclusion, our study suggests that long-term prophylactic astaxanthin supplementation may inhibit age-related skin deterioration and maintain skin conditions associated with environmentally induced damage via its anti-inflammatory effect. (UMIN Clinical Trials Registry ID: UMIN000018550)
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Astaxanthin, a carotenoid found mainly in seafood, has potential clinical applications due to its antioxidant activity. In this study, we evaluated the effect of dietary astaxanthin derived from Haematococcus pluvialis on skin photoaging in UVA-irradiated hairless mice by assessing various parameters of photoaging. After chronic ultraviolet A (UVA) exposure, a significant increase in transepidermal water loss (TEWL) and wrinkle formation in the dorsal skin caused by UVA was observed, and dietary astaxanthin significantly suppressed these photoaging features. We found that the mRNA expression of lympho-epithelial Kazal-type-related inhibitor, steroid sulfatase, and aquaporin 3 in the epidermis was significantly increased by UVA irradiation for 70 days, and dietary astaxanthin significantly suppressed these increases in mRNA expression to be comparable to control levels. In the dermis, the mRNA expression of matrix metalloprotease 13 was increased by UVA irradiation and significantly suppressed by dietary astaxanthin. In addition, HPLC-PDA analysis confirmed that dietary astaxanthin reached not only the dermis but also the epidermis. Our results indicate that dietary astaxanthin accumulates in the skin and appears to prevent the effects of UVA irradiation on filaggrin metabolism and desquamation in the epidermis and the extracellular matrix in the dermis.
Astaxanthin is a powerful antioxidant that possesses potent protective effects against various human diseases and physiological disorders. However, the mechanisms underlying its antioxidant functions in cells are not fully understood. In the present study, the effects of astaxanthin on reactive oxygen species (ROS) production and antioxidant enzyme activity, as well as mitogen-activated protein kinases (MAPKs), phosphatidylinositol 3-kinase (PI3K)/Akt, and the nuclear factor erythroid 2-related factor 2 (Nrf-2)/heme oxygenase-1 (HO-1) pathways in human umbilical vein endothelial cells (HUVECs) were examined. It was shown that astaxanthin (0.1, 1, 10 μM) induced ROS production by 9.35%, 14.8% and 18.06% compared to control respectively in HUVECs. In addition, astaxanthin increased the mRNA levels of phase II enzymes HO-1 and also promoted GSH-Px enzyme activity. Furthermore, we observed ERK phosphorylation, nuclear translocation of Nrf-2, and activation of antioxidant response element-driven luciferase activity upon astaxanthin treatment. Knockdown of Nrf-2 by small interfering RNA inhibited HO-1 mRNA expression by 60%, indicating that the Nrf-2/ARE signaling pathway is activated by ¬astaxanthin. Our results suggest that astaxanthin activates the Nrf-2/HO-1 antioxidant pathway by generating small amounts of ROS. Keywords: astaxanthin, human umbilical vein endothelial cells, reactive oxygen species, Nrf-2/HO-1 pathway, antioxidant
Oxidative stress accelerates skin aging, and dietary supplementation with antioxidants may alleviate it. Morphological analysis of the residual skin surface components (RSSCs) allows detecting age-related changes in corneocyte desquamation, microbial presence, and lipid droplet size. We hypothesized that continuous ingestion of carotenoid antioxidant astaxanthin (4 mg/d) for 4 weeks could influence RSCC morphology and evaluated RSSC samples taken from middle-aged subjects before and after this dietary intervention. The study included 31 volunteers (17 men and 14 women) over the age of 40. RSSC samples were collected from the surface of the facial skin at the beginning (day 0) and end (day 29) of the study. In addition, blood samples were taken on days 0, 15, and 29 for measuring plasma levels of malondialdehyde that allowed assessing systemic oxidative stress. The results demonstrated that plasma malondialdehyde consistently decreased during astaxanthin consumption (by 11.2% on day 15 and by 21.7% on day 29). The analysis of RSSC samples has revealed significantly decreased levels of corneocyte desquamation (P =.0075) and microbial presence (P =.0367) at the end of the study. These phenomena as well as a significant (P =.0214) increase in lipid droplet size were more strongly manifested among obese (body mass index >30 kg/m²) subjects. All described RSSC changes correspond to a shift toward characteristics of skin associated with a younger age. The results confirm our hypothesis by demonstrating that continuous astaxanthin consumption produces a strong antioxidant effect resulting in facial skin rejuvenation which is especially pronounced in obese subjects.
Astaxanthin is a high value keto-carotenoid pigment renowned for its commercial application in various industries comprising aquaculture, food, cosmetic, nutraceutical and pharmaceutical. Among the verified bio-resources of astaxanthin are red yeast Phaffia rhodozyma and green alga Haematococcus pluvialis. The supreme antioxidant property of astaxanthin reveals its tremendous potential to offer manifold health benefits among aquatic animals which is a key driving factor triggering the upsurge in global demand for the pigment. Numerous scientific researches devoted over a number of years have persistently demonstrated the instrumental role of astaxanthin in targeting several animal health conditions. This review article evaluates the current best available evidence to judge the beneficial usage of astaxanthin in aquaculture industry. Most apparent is the profound effect on pigmentation, where astaxanthin is frequently utilized as an additive in formulated diets to boost and improve the coloration of many aquatic animal species, and subsequently product quality and price. Moreover, the wide range of other physiological benefits that this biological pigment confers to these animals is also presented which include various improvements in survival, growth performance, reproductive capacity, stress tolerance, disease resistance and immune-related gene expression.