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Modern lifestyles have developed new attention on appearance and personal care which attract a huge number of consumers towards cosmetic products. The demand for a skincare product with natural ingredients is rapidly increasing. Seaweeds are major resources for in-demand active compounds with a wide variety of applications. The use of seaweed-derived ingredients in cosmetic products has increased in recent years as many scientific studies have proved the potential skincare properties of seaweed bioactive compounds. This review emphasizes possible skincare properties of seaweed bioactive compounds. The review outlines the mechanism involved in skin problems including hyperpigmentation, premature skin aging, and acne in the first part while the second part focuses on the promising application of seaweeds in skin protection by highlighting the bioactive compound responsible for their bioactivity.
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marine drugs
Review
Potential Use of Seaweed Bioactive Compounds in
Skincare—A Review
Valentina Jesumani 1, Hong Du 1,*, Muhammad Aslam 1,2, Pengbing Pei 1and Nan Huang 1
1Guangdong Provincial Key Laboratory of Marine Biotechnology College of Sciences, Shantou University,
Shantou 515063, China; tina@stu.edu.cn (V.J.); drmaslam@hotmail.com (M.A.);
peipengbing1990@126.com (P.P.); 18nhuang@stu.edu.cn (N.H.)
2Faculty of Marine Sciences, Lasbela University, Uthal 90950, Pakistan
*Correspondence: hdu@stu.edu.cn; Tel.: +86-0754-86502083
Received: 20 September 2019; Accepted: 2 December 2019; Published: 6 December 2019


Abstract:
Modern lifestyles have developed new attention on appearance and personal care which
attract a huge number of consumers towards cosmetic products. The demand for a skincare product
with natural ingredients is rapidly increasing. Seaweeds are major resources for in-demand active
compounds with a wide variety of applications. The use of seaweed-derived ingredients in cosmetic
products has increased in recent years as many scientific studies have proved the potential skincare
properties of seaweed bioactive compounds. This review emphasizes possible skincare properties
of seaweed bioactive compounds. The review outlines the mechanism involved in skin problems
including hyperpigmentation, premature skin aging, and acne in the first part while the second part
focuses on the promising application of seaweeds in skin protection by highlighting the bioactive
compound responsible for their bioactivity.
Keywords: seaweeds; hyperpigmentation; skin aging; skincare; photo-protection
1. Introduction
Cosmetics are the materials used to enhance or alter the function and appearance of the skin and
hair [
1
]. Kligman created the term “cosmeceutical” to hightlight cosmetic products that can combine
the use of both cosmetic and pharmaceutical uses [
2
]. Cosmeceuticals are often used in dermatology to
enhance the skin tone, skin glow, and provide anti-aging benefits [
3
]. The cosmeceutical industries
are most fascinating, profitable, and constantly growing in the world economy. According to reports,
an average woman spends $15,000 on beauty products in her lifetime [
4
]. The cosmetics industry has
predicted an annual gross revenue of US $170 billion according to the financial exploration stated
by a French-based company, Eurostaf [
5
]. In 2016, the European cosmetics market was top in the
world, esteemed at
77 billion in a wholesale rate, trailed by the US and Brazil [
4
]. The global beauty
market stated that the cosmetic industry will continue to develop due to the growth of the middle
class in many developing countries [
6
]. Based on this encouraging future of the cosmetics industry,
many cosmetic products without any side eects have been developed to satisfy the customers’
needs.
Currently, many synthetic
chemicals have been used in cosmetic products, many of them did
not get synthetic customer satisfaction due to high cost and unsafe nature in terms of side eects.
For example, chemicals like hydroquinone, arbutin, and kojic acid are being used as a skin whitening
agent, but they are reported to be unstable and they also cause dermatitis and induce cancer [
7
9
].
Thus, in recent years, the demand for cosmetic products that containing natural ingredients is rapidly
expanding. The advantages of natural ingredients are environmentally friendliness, fewer side eects,
and safe use [
1
,
10
]. Hence, Cosmeceutical industries are persistently seeking active compounds from
natural sources. From this perspective, the marine environment provides numerous marine organisms,
Mar. Drugs 2019,17, 688; doi:10.3390/md17120688 www.mdpi.com/journal/marinedrugs
Mar. Drugs 2019,17, 688 2 of 19
including seaweeds with potential bioactive compounds. Seaweeds are rich in bioactive compounds
that could be exploited as functional ingredients for cosmetic applications [
11
]. This review focusses on
the cosmetic properties of seaweed bioactive compounds and provides an overview of skin problems
and the potential of seaweed bioactive compounds against skin problems.
2. Structure of Skin
The skin is the major organ in the human body. Generally, the skin can be divided into epidermis,
dermis, and subcutaneous tissue. The epidermis is the uppermost layer of the skin. It has three types of
cells—namely keratinocytes, melanocytes, and Langerhans cells. Keratinocytes are made up of keratin,
which on maturation lose water and move up to the uppermost layer of the epidermis called the
‘stratum corneum’ [
12
]. The next collection of cells present in the epidermis are melanocytes, the cells
that produce melanin, the pigment accountable for skin tone and color. Langerhans cells inhibit the
penetration of unwanted foreign materials into the skin. The condition of the epidermis defines the
freshness and youthfulness of your skin. The middle layer of the skin is the dermis [
13
]. Collagen and
elastin are the main components of the extracellular matrix (ECM), covering about 90% of the dermis,
which are cross-linked and provide support for the skin. Hence, the dermis is responsible for the
structural support and elasticity of the skin. Collagen is found in the extracellular matrix of all animal
bodies [
14
]. Hyaluronic acid (HA) is also a main constituent of the dermis. HA plays an important
role in moisture absorption and moisture retention [
12
]. Subcutaneous tissue, which is the third layer
located under the dermis, is comprised of connective tissue and fat. The loss of subcutaneous tissue
due to age will also lead to facial sagging and wrinkles.
3. UV Induced Skin Damage
The ultraviolet (UV) radiation from the sun extends the earth in a significant amount. UV-C
(100–290 nm) is mostly filtered by the atmosphere, but UVA (320–400 nm) and UVB (290–320 nm) rays
extend the skin and cause suntan, wrinkles, etc. [
15
]. UV radiation induces the production of reactive
oxygen species (ROS) and also depletes the antioxidant enzymes [
16
]. These ROS can lead to skin
disorders such as hyperpigmentation (dark spots), premature aging, dryness, etc. [17,18].
3.1. Hyperpigmentation
Hyperpigmentation is usually an inoensive form in which spots of the skin become darker in
color than the regular surrounding skin. The overproduction and accumulation of melanin pigment
resulted in a change in skin color. Melanogenesis is controlled by an enzyme such as tyrosinase,
a glycoprotein [
19
] present in the membrane of the melanosome which catalyzes the conversion of
l-tyrosine to melanin [
20
]. Melanogenesis is regulated by maturation and translocation of tyrosinase.
The translocation of tyrosinases is regulated by the presence of specific carbohydrate moieties [21].
Two types of melanin are synthesized within melanosomes: eumelanin and pheomelanin.
The pathway in which melanogenesis occurs is presented in Figure 1. The enzymes such as tyrosinase
and tyrosinase related protein (TRP-1 and 2) are produced by the phosphorylation of MITF, which is
activated by several signaling pathways such as cAMP, ERK, and Wnt pathways. These signaling
pathways are upregulated by the upstream of the receptor such as KIT (ligand SCF) and MC1R (ligand
α
-MSH, ACTH, and ASP). The KIT receptor activates the cAMP pathway and MC1R activates both
cAMP and ERK pathway which further phosphorylates the MITF. This leads to the expression of
tyrosinase-related enzymes which further mediates the production of melanin [
22
26
]. The skin under
UV generates the reactive oxygen species (ROS) that activate the
α
-MSH and MC1R and enhances the
production of tyrosinase that leads to the excess generation of melanin [27,28].
Mar. Drugs 2019,17, 688 3 of 19
3.2. Skin Aging
Skin aging is a complex process that occurs in all living beings that caused by two factors.
One is intrinsic in which aging is caused by genetics [
29
]. The latter one is an extrinsic factor,
in which aging occurs due to the exposure of skin to the ultraviolet rays. This type of aging is
called photo-aging or premature aging [
30
]. Reactive oxygen species (ROS) play a key role in skin
aging. ROS triggers the various growth factors and cytokine receptors which further stimulate
mitogen-activated protein kinase (MAPK) signal transduction and P13/AKT pathway. The AKT
pathway inactivates the FoxO which suppresses the expression of antioxidant enzymes in the cell.
MAPK upregulates activator protein-1 (AP-1) and NF-
κ
B in the nucleus. The induction of AP-1 gives
rise to the MMP expressions [
31
,
32
] (Figure 2). MMPs are a collection of zinc-containing extracellular
proteinases that degrade the extracellular components, such as collagen and elastic fibers, inducing
wrinkle formation [
31
33
]. ROS also activates the expression of the hyaluronidase enzyme that
degrades hyaluronic acid. Hyaluronic acid is present in extracellular matrix, absorbing and retaining
water molecules and helping to keep the skin smooth, moist, and lubricated [3436].
Mar. Drugs 2019, 17, x FOR PEER REVIEW 3 of 19
Figure 1. Signaling pathways involved in melanin synthesis. Tyrosinase-related protein (TRP),
microphthalmia-associated transcription factor (MITF), adenosine 3,5-cyclic monophosphate (cyclic
AMP) (cAMP), cAMP response element-binding (CREB), extracellular receptor kinase (ERK),
melanocortin 1 receptor (MC1R), wingless-related integration site (Wnt), α-melanocyte-stimulating
hormone (MSH), agonist stimulating protein (ASP), and stem cell factor (SCF).
3.2. Skin Aging
Skin aging is a complex process that occurs in all living beings that caused by two factors. One
is intrinsic in which aging is caused by genetics [29]. The latter one is an extrinsic factor, in which
aging occurs due to the exposure of skin to the ultraviolet rays. This type of aging is called photo-
aging or premature aging [30]. Reactive oxygen species (ROS) play a key role in skin aging. ROS
triggers the various growth factors and cytokine receptors which further stimulate mitogen-activated
protein kinase (MAPK) signal transduction and P13/AKT pathway. The AKT pathway inactivates the
FoxO which suppresses the expression of antioxidant enzymes in the cell. MAPK upregulates
activator protein-1 (AP-1) and NF-κB in the nucleus. The induction of AP-1 gives rise to the MMP
expressions [31,32] (Figure 2). MMPs are a collection of zinc-containing extracellular proteinases that
degrade the extracellular components, such as collagen and elastic fibers, inducing wrinkle formation
[31–33]. ROS also activates the expression of the hyaluronidase enzyme that degrades hyaluronic
acid. Hyaluronic acid is present in extracellular matrix, absorbing and retaining water molecules and
helping to keep the skin smooth, moist, and lubricated [34–36].
Figure 1.
Signaling pathways involved in melanin synthesis. Tyrosinase-related protein (TRP),
microphthalmia-associated transcription factor (MITF), adenosine 30,50-cyclic monophosphate (cyclic
AMP) (cAMP), cAMP response element-binding (CREB), extracellular receptor kinase (ERK),
melanocortin 1 receptor (MC1R), wingless-related integration site (Wnt),
α
-melanocyte-stimulating
hormone (MSH), agonist stimulating protein (ASP), and stem cell factor (SCF).
Mar. Drugs 2019,17, 688 4 of 19
Mar. Drugs 2019, 17, x FOR PEER REVIEW 4 of 19
Figure 2. UV induced signaling pathway involved in premature skin aging. Mitogen-activated
protein kinase (MAPK), matrix metalloproteinase (MMP), nuclear factor kappa-light-chain-enhancer
of activated B cells (NF-κB), activator protein 1 (AP-1).
4. Bacteria-Induced Skin Damage-Acne Vulgaris
Acne vulgaris is a prevalent, chronic skin disorder which affects most of the adult and leads to
scar marks. Acne vulgaris is a formation of lesions and prevalently caused by Propionibacterium acnes.
Acne is spread by enzymes such as lipase, protease, hyaluronidase, and acid phosphatase produced
by P. acnes [37]. The infection of P. acne triggers the immune response by the release of cytokine (IL-
12 and IL-8) and the antimicrobial peptide (β-defensins) expression [38]. IL-8 stimulates neutrophils
movement which leads to the formation of acne lesions and pus. Neutrophils consequently produce
free radicals for killing the bacteria. This excess production of free radicals leads to the development
of the inflammatory responses [39]. Staphylococcus aureus and Staphylococcus epidermidis are also the
normal flora of human skin may also cause acne inflammatory response but are less significant than
P. acnes in this process [40].
5. Seaweeds a Potential Source in the Cosmetic Industry
Nowadays People prefer cosmetic products that have natural ingredients than chemical ones.
As the products with natural ingredients are safe to use without any side effects, many consumers
go in search of natural products to keep themselves look young with healthy skin. Due to this, the
cosmetic industry has also focussed on the ingredients that are derived from natural resources like
plant, algae, microbes, and their metabolites. The marine world is extremely demanding for a wide
variety of species with multiple bioactive compounds. Macroalgae are major resources for the active
compound with a wide variety of applications in many fields (Figure 3) [16].
Macroalgae or seaweeds are the aquatic, photosynthetic organisms taxonomically categorized
as algae, and they divided into three groups based on their pigment, the Rhodophyceae (red algae),
Phaeophyceae (brown algae), and Chlorophyceae (green algae). Marine algae are considered as sea
vegetables which are also used for consumption. Since ancient times seaweeds are also used as an
alternative medicine for skin-related diseases. Many studies revealed the potentiality of seaweeds
and their major role in antioxidant, antitumor, anti-inflammatory, anti-lipedemic, anti-microbial, and
also their anti-allergic properties. Wide applications of seaweeds are based on the valuable bioactive
compounds and potent bioactivity. In addition, the compounds derived from marine algae have been
given considerable importance in developing a cosmeceutical product [41]. Seaweed compounds—
Figure 2.
UV induced signaling pathway involved in premature skin aging. Mitogen-activated
protein kinase (MAPK), matrix metalloproteinase (MMP), nuclear factor kappa-light-chain-enhancer of
activated B cells (NF-κB), activator protein 1 (AP-1).
4. Bacteria-Induced Skin Damage-Acne Vulgaris
Acne vulgaris is a prevalent, chronic skin disorder which aects most of the adult and leads to
scar marks. Acne vulgaris is a formation of lesions and prevalently caused by Propionibacterium acnes.
Acne is spread by enzymes such as lipase, protease, hyaluronidase, and acid phosphatase produced by
P. acnes [
37
]. The infection of P. acne triggers the immune response by the release of cytokine (IL-12
and IL-8) and the antimicrobial peptide (
β
-defensins) expression [
38
]. IL-8 stimulates neutrophils
movement which leads to the formation of acne lesions and pus. Neutrophils consequently produce
free radicals for killing the bacteria. This excess production of free radicals leads to the development
of the inflammatory responses [
39
]. Staphylococcus aureus and Staphylococcus epidermidis are also the
normal flora of human skin may also cause acne inflammatory response but are less significant than
P. acnes in this process [40].
5. Seaweeds a Potential Source in the Cosmetic Industry
Nowadays People prefer cosmetic products that have natural ingredients than chemical ones.
As the products with natural ingredients are safe to use without any side eects, many consumers go in
search of natural products to keep themselves look young with healthy skin. Due to this, the cosmetic
industry has also focussed on the ingredients that are derived from natural resources like plant, algae,
microbes, and their metabolites. The marine world is extremely demanding for a wide variety of
species with multiple bioactive compounds. Macroalgae are major resources for the active compound
with a wide variety of applications in many fields (Figure 3) [16].
Macroalgae or seaweeds are the aquatic, photosynthetic organisms taxonomically categorized
as algae, and they divided into three groups based on their pigment, the Rhodophyceae (red algae),
Phaeophyceae (brown algae), and Chlorophyceae (green algae). Marine algae are considered
as sea vegetables which are also used for consumption. Since ancient times seaweeds are also
used as an alternative medicine for skin-related diseases. Many studies revealed the potentiality
Mar. Drugs 2019,17, 688 5 of 19
of seaweeds and their major role in antioxidant, antitumor, anti-inflammatory, anti-lipedemic,
anti-microbial, and also their anti-allergic properties. Wide applications of seaweeds are based
on the valuable bioactive compounds and potent bioactivity. In addition, the compounds derived from
marine algae have been given considerable importance in developing a cosmeceutical product [
41
].
Seaweed compounds—including phenolic compounds, polysaccharides, pigments, PUFA, sterols,
proteins, peptides, and mycosporine-like amino acid (MAA)—exhibited a wide range of bioactivity
that can be used as active ingredients in cosmetic products (Figure 3) [
7
,
42
]. Phenolic compounds
are the water-soluble secondary metabolites that have numerous biological activities [
43
]. It is a
diverse group of compounds and the common structural features shared by all the phenol groups.
Based on the number of substituents, phenolic compounds can be divided into simple phenols or
polyphenols. Flavonoids and gallic acid are the building blocks of polyphenols. Phenolic compounds
from seaweeds, like Ecklonia cava Kjellman and Ishige okamurae Yendo, are proven to have many
bioactivities—including anti-oxidant, anti-microbial, anti-inflammatory, anti-cancer, etc. Antioxidant
activity of seaweeds is mainly due to the presence of phenolic compounds [
43
,
44
]. Among the many
phenolic compounds extracted from seaweeds, phlorotannins from brown seaweed are the most
important secondary metabolites, with a wide range of functional bioactivity [
45
]. Phlorotannins are
phloroglucinol-based polyphenols found in Marine brown algae. Phloroglucinol units linked to each
other in various ways to form phlorotannins [
46
]. Marine brown algae such as Ecklonia cava Kjellman,
E. stolonifera Okamura, E. kurome Okamura, Ishige okamurae Yendo, Hizikia fusiformis (Harvey) Okamura,
Eisenia bicyclis (Kjellman) Setchell Undaria pinnatifida (Harvey) Suringar, Sargassum thunbergii (Mertens
ex Roth) Kuntze, and Laminaria japonica. Areschoug have been studied the biological activity of
phlorotannins [
47
,
48
]. Phlorotannins are well known for their wide-ranging applications which include
anti-melanogenesis, anti-aging, and antioxidant [
49
52
]. As a result of the bioactivities, the application
of phlorotannins on pharmaceutical, nutraceutical, and cosmeceutical advances [43,53,54].
Polysaccharides are the most important compounds present in seaweeds and are well documented
for its biological activity. The green seaweed-like Ulva has the high content of polysaccharide comprises
of 65% of dry weight. The other seaweeds that have a large amount of polysaccharide are Ascophyllum,
Porphyra, and Palmaria species. The important polysaccharides are ulvan from green seaweeds,
fucoidan, alginate, and laminarin from brown seaweeds, agar, and carrageenan from red seaweeds.
In this, agar and alginate are used widely in the food industry as thickening and gelling agents.
Fucoidan, ulvan, and carrageenan are sulfated polysaccharides that have wide application in many
fields. Among these polysaccharides, the fucoidan from brown seaweed has been studied enormously
for their bioactivity including antioxidant, anticancer, antimicrobial, hyperlipedemic, anti-inflammatory,
etc. [
4
]. In recent days, many studies recommend the use of polysaccharide as an active ingredient in
cosmetic formulations. Polysaccharides have a huge number of cosmetic roles such as hair conditioners,
moisturizers, emulsifiers, wound-healing agents, and as a thickening agent [55,56].
Proteins are macromolecules made up of one or more amino acids. Seaweeds are a good source of
amino acid. Amino acids are one of the important constitutes of natural moisturizing factor which
prevents the water loss in the skin [
57
]. Seaweeds have amino acids, such as alanine, proline, arginine,
serine, histidine, and tyrosine. Palmaria and Porphyra have the maximum amount of arginine, which is
considered a natural moisturizing factor that can be used in cosmetic products. Mycosporine-like
amino acids are water-soluble low molecular weight molecules. They are categorized by cyclohexane
joined with nitrogen as a substitute for amino acid, amino alcohol, or amino group [
57
]. For seaweeds
exposed to extreme stress including UV radiation, Mycosporine-like amino acids defend seaweed from
UV radiation and act as a potent photo protector candidate. It also involved in radical scavenging
and DNA repair systems. Hence, they have received more attention as UV protection and antioxidant
agents in the cosmetic industry [
3
,
16
,
58
]. Furthermore, in recent years, peptides have drawn attention
in the field of skincare due to their binding specificity to the target cells and their ability to change the
physiological functions in the skin. Bioactivity depends on the composition of amino acids.
Mar. Drugs 2019,17, 688 6 of 19
Macroalgae contain a large variety of pigments which absorb the light for photosynthesis.
The green algae contain the pigment similar to the plants namely chlorophylls a, b, and carotenoids.
The red algae have photosynthetic pigments such as chlorophyll a and the phycobilins such as
R-phycocyanin and R-phycoerythrin and carotenoids, mostly
β
-carotene, lutein, and zeaxanthin.
The brown algae pigments include the chlorophylls a and c, fucoxanthin, and carotenoids. The pigment
act as a shield to the cells from UV irradiation [
59
]. Seaweeds are an important source of vitamin A,
vitamin B, vitamin C, vitamin D, and vitamin E which are widely used in skincare.
The lipid content of seaweeds is generally low and less than 4% of the dried mass, whereas
Sargassum kjellmaniamum Yendo contains more than 6% [
60
]. Lipids such as essential fatty acid,
glycolipids, sterols, triglycerides, and phospholipids are found in seaweeds. Polyunsaturated fatty acid
(PUFA) present in seaweeds is higher than in terrestrial plants. Seaweed fatty acids have anti-allergic
and anti-inflammatory activities and also act as an emollient that protects the skin from water loss [
61
].
Mar. Drugs 2019, 17, x FOR PEER REVIEW 6 of 19
brown algae pigments include the chlorophylls a and c, fucoxanthin, and carotenoids. The pigment
act as a shield to the cells from UV irradiation [59]. Seaweeds are an important source of vitamin A,
vitamin B, vitamin C, vitamin D, and vitamin E which are widely used in skincare.
The lipid content of seaweeds is generally low and less than 4% of the dried mass, whereas
Sargassum kjellmaniamum Yendo contains more than 6% [60]. Lipids such as essential fatty acid,
glycolipids, sterols, triglycerides, and phospholipids are found in seaweeds. Polyunsaturated fatty
acid (PUFA) present in seaweeds is higher than in terrestrial plants. Seaweed fatty acids have anti-
allergic and anti-inflammatory activities and also act as an emollient that protects the skin from water
loss [61].
Figure 3. Cont.
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Figure 3. Cont.
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Figure 3. Seaweed bioactive compounds with skincare potentials. (A) Eckol; (B) Fucophloroethol; (C)
Dieckol; (D) 6,6 Bieckol; (E) Fucodiphloroethol G; (F) 7-phloroeckol; (G) Fucoxanthin; (H)
phlorofucofuroeckol; (I) Fucosterol; (J) Sargahydroquinoic acid; (K) Laminarin; (L) Porphyra 334, (M)
Sargachromenol; (N) Astaxanthin; (O) Shinorine [3,22,42,47,57].
Figure 3.
Seaweed bioactive compounds with skincare potentials. (
A
) Eckol; (
B
) Fucophloroethol;
(
C
) Dieckol; (
D
) 6,6 Bieckol; (
E
) Fucodiphloroethol G; (
F
) 7-phloroeckol; (
G
) Fucoxanthin;
(
H
) phlorofucofuroeckol; (
I
) Fucosterol; (
J
) Sargahydroquinoic acid; (
K
) Laminarin; (
L
) Porphyra 334,
(M) Sargachromenol; (N) Astaxanthin; (O) Shinorine [3,22,42,47,57].
Mar. Drugs 2019,17, 688 9 of 19
6. Skincare Application of Seaweeds
In recent years, seaweeds have been most desirable source of research for their bioactivity and
bioactive compounds like polyphenols, fucoidan, phlorotannins, carotenoids, etc. Beauty care products
have been focused on compounds with potential antioxidant activity, MMPs, and tyrosinase inhibitory
activity in order to reduce ROS caused by UV radiation and also to delay skin aging.
6.1. Tyrosinase Inhibition Activity of Seaweed
Tyrosinase is the enzyme that catalyzes the synthesis of melanin, a pigment that is responsible for
skin color. Hyperpigmentation is caused due to the abnormal accumulation of melanin pigments in the
skin. Overexposure to UV rays induces abnormal melanin synthesis which results in skin pigmentation.
Tyrosinase inhibitors may act as a candidate for the control of hyperpigmentation or skin whitening as
the tyrosinase catalyzes the melanogenesis [62]. The search for natural tyrosinase inhibitors becomes
a great interest for non-toxic and active skin whitening ingredients.
Hence, skin whitening
agents
derived from seaweeds could be advantageous for the cosmetic industry. Researchers screened various
seaweed extracts for tyrosinase inhibition activity and found that Ishige okamurae Yendo, Endarachne
binghamiae J.Agardh, Schizymenia dubyi (Chauvin ex Duby) J.Agardh,Ecklonia cava,E. stolonifera Okamura,
and Sargassum silquastrum (Mertens ex Turner) C.Agardh showed profound tyrosinase activity and
significantly reduced the content of the melanin [
63
65
]. S. polycystum hexane extract had no inhibitory
activity on mushroom tyrosinase. However, it showed potential activity on cellular tyrosinase
inhibition when examined on cellular tyrosinase [
66
]. Dieckol is a phlorotannin derivative isolated
from E. stolonifera showed the tyrosinase inhibition activity with the IC50 of 2.16
µ
g/mL [
67
,
68
].
Fucoxanthin is a carotenoid present in the seaweed exhibits tyrosinase inhibition activity when treated
orally and also applied topically in UVB-induced guinea pig [69]. Many studies proved that sulfated
polysaccharide, fucoidan extracted from Fucus sp., Sargassum sp., and Laminaria sp. can also be used
as a promising tyrosinase inhibitor [
70
72
]. Fucoidan, the polysaccharide extracted from the brown
seaweed such as Chnoospora minima (Hering) Papenfuss and Sargassum polycystum C.Agardh inhibit the
activity of collagenase, elastase and also tyrosinase [
70
]. Tyrosinase activity was increased by the low
molecular weight fucoidan extracted from Sargassum fusiforme (Harvey) Setchell [
73
].
Park et al. [74]
were also demonstrated the increased inhibitory activity in low molecular weight fucoidan in a
melanoma cell.
Several signaling pathways involved in melanin synthesis. The cAMP pathway is one of the prime
regulatory mechanism which increases the expression of microphthalmia-associated transcription
factor -MITF. MITF regulates the expression of tyrosinase, tyrosinase-related protein 1,2 which is
required for melanogenesis. Ethyl acetate fraction of Leathesia diormis Areschoug showed the eect
on melanin synthesis and cellular tyrosinase activity by downregulating the CREB, PKA, and cAMP
pathways [
75
]. ERK pathway involves in anti-melanogenesis. The phosphorylation of ERK degrades
the MITF which leads to the suppression of melanin synthesis [
23
]. Fucoidan plays a major role in
the anti-melanogenesis by ERK phosphorylation [
76
]. Another study showed the inhibitory activity
of fucoidan on cellular melanin and tyrosinase but in contrast, it lacks the inhibitory activity on the
expression of TRP1, TRP2, and MITF [
71
]. Sargahydroquinoic acid, sargachromenol, and sargaquinoic
acid from S. serratifolium (C.Agardh) C.Agardh decreased the
α
-MSH-activated melanogenesis in
melanoma cells through the inhibition of CREB signaling pathways without aecting ERK pathway [
77
].
Sulfated galactans, the polysaccharide from G. fisheri, showed no potential inhibition on tyrosinase
activity and it proved to be suppressed the activity of tyrosinase by downregulating the MITF, TRP1,2,
and tyrosinase mRNA expression, which was concluded by RT-PCR and ELISA [78].
6.2. Collagenase and Elastase Inhibition Activity of Seaweed
The MMPs are a family of degradative enzymes particularly collagenase which is responsible for
the degradation of skin matrix especially collagen due to which occurs the skin sagging. The same
Mar. Drugs 2019,17, 688 10 of 19
way enzyme elastase degrades the elastin. This process leads to wrinkles. The compound that
inhibits collagenase and elastase activity might act as an active ingredient in an anti-aging product.
Overexposure of UV produces ROS which activates the mitogen-activated protein kinases followed by
the phosphorylation of transcription factor activator protein1 results in the upregulation of MMPs.
Seaweed polysaccharides play a major role in inhibiting collagenase and elastase activity.
Sulfated polysaccharides from Sargassum fusiforme (Harvey). Setchell potentially inhibited the activity
of intracellular collagenase and elastase by regulating the NF-
κ
B, AP-1, and MAPKs pathways in
HDF cells radiated by UVB [
79
]. Fucoidans isolated from the Chnoospora minima (Hering) Papenfuss
and Sargassum polycystum C.Agardh showed elastase and collagenase inhibition in a dose-dependent
manner [
70
]. Fucoidan inhibited the expression of MMP 1 in UVB -induced dermal fibroblast cells
in a dose-dependent manner. It suppressed the expression of MMP by inhibiting the ERK pathway
and reduced the expression of MMP1 mRNA. Furthermore, Fucoidan also inhibited the activity of the
MMP1 promoter and increased the expression of Type 1 procollagen synthesis [80,81].
Ryu et al. [
82
] proved that methanol extracts of Corallina pilulifera J.V.Lamouroux that are rich
in phenolic content inhibited the MMP 2,9 expressions in a dose-dependent manner in UV-induced
dermal fibroblast cells. Phlorotannin extracted from Eisenia bicyclis (Kjellman) Setchell, Ecklonia cava
Kjellman, and E. stolonifera Okamura strongly inhibit the MMP1 expression. Similarly, phlorotannin
from E. cava inhibit the expression of MMP 2,9 and also reduced the activity of MMPs at 10
µ
g/mL.
Eckol, dieckol, dioxinodehydroeckol, and bieckol are responsible for the inhibition of MMPs in human
dermal fibroblast cells. This previous study also suggested that these phlorotannin derivatives inhibited
the expression of NF-kappa B and AP-1 reporter resulting in the suppression of MMP expression [
51
,
83
].
The results of all these studies suggest that phlorotannin may act as an active ingredient in preventing
photoaging of the skin.
The peptides, namely PYP1-5 and Porphyra 334 from Porphyra yezoensis f. coreana Ueda, increased
the production of elastin and collagen and decrease the expression of MMP protein [
84
]. PYP1-5
induced the collagen synthesis by initiate the TGF-b/Smad signaling pathway by increasing the
expression of TIMP-1,2 and TGF-b1 protein expression [
85
]. Likewise, Sargachromanol extracted from
S. horneri (Turner) C.Agardh also activated the TIMP1,2 and downregulate the expression of MMP [
86
].
The sterol compound, fucosterol from marine brown algae also enhanced the production of type I
procollagen and suppressed the expression of MMPs in human keratinocytes cell by deactivating the
MAPK pathway [
59
]. All these studies revealed the potential protection of seaweed bio compounds
towards UVA-induced collagen degradation.
6.3. Hyaluronidase Inhibition
Hyaluronidase is an enzyme that degrades the hyaluronic acid present in the extracellular matrix
which results in the skin aging process. Very few studies have been focused on Hyaluronidase
inhibition. Phlorotannins derivatives—such as fucophloroethol, fucodiphloroethol, fucotriphloroethol,
7-phloroeckol, phlorofucofuroeckol, and bieckol/dieckol extracted from Cystoseira nodicaulis (Withering)
M.Roberts exhibited the hyaluronidase activity with the IC50 of 0.73 mg/mL and also proved that the
higher molecular weight displayed the strongest activity [
87
]. Phlorotannins derivatives—such as
dieckol, eckol, bieckol, and phlorofucofuroeckol A—extracted from Eisenia bicyclis (Kjellman) Setchell
and Ecklonia kurome Okamura exhibited potent inhibition towards hyaluronidase. Among these
phlorotannin derivatives, bieckol exhibited the strongest inhibition with an IC50 value of 40 µM [88].
6.4. Photoprotection Ability
When the skin is exposed to UV radiation, UV rays penetrate into dermis and epidermis and
induce the production of ROS which cause damage to DNA. This results in hyperpigmentation,
premature aging, sunburn, skin cancer, etc. The extensive use of photoprotection products will help to
get rid of the eect caused by the sun UV rays. The macroalgae are exposed to extreme conditions
such as UV radiation and it produces the ROS. The seaweeds produce many secondary metabolites
Mar. Drugs 2019,17, 688 11 of 19
that play as an antioxidant that helps to combat those ROS. These antioxidant substances included
pigments like fucoxanthin, carotenoids, mycosporine-like amino acids (MAA), and phenols such
as phlorotannins and scytonemins [
89
,
90
]. These bioactive components are capable of absorbing
the UV radiation and keep the human fibroblast cells from UV-induced aging. These secondary
metabolites that act as UV filters/sunscreen with antioxidant activity can be extensively used in
cosmetic products. Polysaccharides such as fucoidan, laminarin, and alginate extracted from brown
algae like Fucus vesiculosus var. alternans C.Agardh, Sargassum sp, Turbinaria conoides f. laticuspidata
W.R.Taylor, possessed potent anti-oxidative activity [89].
Cardozo et al. [
91
] studied the MAA from the red algae, Gracilaria birdiae E.M.Plastino &
E.C.Oliveira, G. domingensis (Kützing) Sonder ex Dickie, and G. tenuistipitata C.F.Chang & B.-M.Xia
which exhibited the photoprotection activity. Heo et al. [
92
] studied the photoprotection ability of
fucoxanthin on UV induced human fibroblast cells and showed to significantly inhibit the cell damage
at 61.24% at 250
µ
M. Fucoxanthin successfully suppressed the cell damage and apoptotic stimulation
induced by UV-B. Fucoxanthin extracted from Sargassum fusiforme (Harvey) Setchell and S.saliquastrum
(Mertens ex Turner) C.Agardh exhibited strong antioxidant activity against DPPH and hydrogen
peroxide. Urikura et al. [
93
] reported that fucoxanthin reduced UV induced ROS in the hairless mice
and also suppress the MMP expression.
A red pigment, astaxanthin, exhibited strong antioxidant activity and protects from peroxidation
by scavenging the radicals. The activity may be due to the presence of conjugated polyene and terminal
ring moieties of astaxanthin help to trap the radicals and therefore exhibit potent antioxidative and
photoprotective agents. It also blocked cytokine production. The topical application also demonstrated
the photoprotection eect against the cell damage caused by UVB radiation [
94
]. Lyons et al. [
95
]
studied the photoprotection exhibited by the algal extract that contains astaxanthin by reducing
DNA damage and also conserve the cellular antioxidant enzymes in human cells irradiated by
UVA. Tetraprenyltoluquinol chromane meroterpenoid extracted from Sargassum muticum (Yendo)
Fensholt showed potent photoprotection against UV-A radiation and also inhibit the accumulation of
intracellular ROS in human dermal fibroblast cells [96].
Phlorotannins extracted from E. cava and E. stolonifera also provided photoprotection towards
UVB rays by reducing the cell damage caused by UVB radiation which is measured by comet assay.
It also showed the inhibition against UVB induced oxidative damage with antioxidant activities and
also upgrading in cell viability [
63
,
68
]. Phlorotannins extracted from Halidrys siliquosa (Linnaeus)
Lyngbye proved the sunscreen ability based on the sun protection factor and UV-A protection
factor. It also was shown to exhibit strong antioxidant activity and proved to have the ability to kill
bacteria [
97
].
Vo et al. [98]
isolated fucofuroeckol-A, which exhibited the photoprotection activity
against damage caused by UVB radiation. The aqueous extracts of Hydropuntia cornea (J.Agardh)
M.J.Wynne and Gracilariopsis longissima (S.G.Gmelin) Steentoft, L.M.Irvine & Farnham exhibited a
photo-protective activity with the sun protection factor of 7.5 and 4.8. The MAA Porphyra-334 and
Shinorine were extracted from Porphyra rosengurttii J.Coll & J.Cox tested for their photo-protective
activity and photo-stability without producing any free radicals. The formulated product of these two
demonstrated wide-ranging protection against UV. MAA can also absorb UV light and also act as a
sunscreen [
99
,
100
]. Porphyra-334 from the Porphyra umbilicalis Kützing reduced the intracellular ROS
induced by UV-A radiation and also suppressed the expression of MMPs. It also acts as a better UV
filter compared to synthetic sunscreens [84,101].
6.5. Moisture Retention Ability
Maintaining moisture in the skin is important to skincare and it improves the skin texture and
state, i.e., young and healthy. Extract from Undaria pinnatifida (Harvey) Suringar, Codium tomentosum
Stackhouse, Durvillea antarctica (Chamisso) Hariot, Cladosiphon okamuranus Tokida, A. nodosum
(Linnaeus) Le Jolis, Pediastrum duplex Meyen, and Polysiphonia lanosa (Linnaeus). Tandy exhibited
skin hydrating properties and protects the skin from dryness. Polysaccharides have maximum water
Mar. Drugs 2019,17, 688 12 of 19
holding capacity which can act as a humectant and moisturizer in cosmetic industry. Polysaccharides
from Laminaria japonica Areschoug were shown to have greater hydrating and moisturizing eects
than hyaluronic acid. The formulation prepared by incorporating Laminaria japonica extract shown to
improve the skin moisture [
3
,
4
,
6
]. Shao et al. [
102
] isolated sulfated polysaccharide from the green algae
Ulva fasciata Delile displayed a higher capability both in the moisture-absorption and moisture retention
for 96 h when compared with glycerol. Wang et al. [
103
] extracted the polysaccharide from Saccharina
japonica (Areschoug) C.E.Lane, C.Mayes, Druehl & G.W.Saunders; Porphyra haitanensis T.J.Chang
& B.F.Zheng; Codium fragile (Suringar) Hariot; Enteromorpha linza (Linnaeus) J.Agardh and Bryopsis
plumose (Hudson) C.Agardh and studied for the moisture absorption and retention. The authors
also proved that the sulfate content and molecular weight plays a major role in the moisture-holding
capacity [103].
6.6. Antimicrobial Activity
Antimicrobial property of the seaweeds can be used in cosmetic products as a preservative that
could delay the shelf life of the cosmetic product by killing the microorganisms especially fungi
that could spoil the product. Seaweeds exhibited antifungal activity for possible use in substituting
chemical preservations. Seaweeds such as Sargassum vulgare C.Agardh, Colpomenia sinuosa (Mertens
ex Roth) Derb
è
s & Solier, Dictyopteris membranacea Batters, Cystoseira barbata (Stackhouse) C.Agardh,
and Dictyota dichotoma (Hudson) J.V.Lamouroux, showed the strongest antifungal eect against
Cladosporium cladosporioides,Alternaria alternata,Fusarium oxysporum,Aspergillus niger,Epicoccum nigrum,
A.ochraceus,Penicillium citrinum, and A. flavus [
104
]. Extract from Halimeda tuna (J.Ellis & Solander)
J.V.Lamouroux also showed the antifungal activity against Candida albicans,Aspergillus niger,A. flavus,
Alternaria,Trichophyton rubrum,Epidermophyton floccossum,T. mentagrophytes, and Penicillium sp. [
44
].
Saidani et al. [
105
] studied the antifungal activity of seaweed, in which the seaweed, Rhodomela
confervoides (Hudson) P.C.Silva reported for the strongest inhibition against Candida albicans and
Mucor ramaniannus and the seaweed, Padina pavonica (Linnaeus) Thivy against the Candida albicans.
Phlorotannin derivative, Dieckol from E.cava showed the antifungal activity with the MIC of 200
µ
M
against Trichophyton rubrum [
106
]. Alghazeer et al. [
107
] screened the 19 seaweed extracts and tested
them for their antibacterial activity. Their data revealed that all the extracts showed inhibition against
gram-positive and gram-negative bacteria including E. coli,Staphylococcus aureus, and S. epidermis.
Among the 19 species the brown algae Cystoseira crinita Duby showed the strongest antibacterial
activity. Ulva rigidis also showed the strongest inhibition against S. aureus and Escherichia coli [
108
].
These studies confirmed the role of seaweeds and their extract as a preservative.
The skin may also be contaminated by some microorganisms which could create skin problems
that can be overcome by the antimicrobial potential of the seaweeds derived biological compounds.
Propionibacterium acnes, Staphylococcus aureus, and S. epidermis are some of the normal microflora present
in the skin. P. acnes is the main inducers of acne. S. aureus and S. epidermis are harmless microflora,
but it can enter the skin epidermis through the wound and cause infection by secreting the toxins [
109
].
This leads to pimples, abscesses, and also blisters. Therefore, the antimicrobial potential of seaweed
could be used eectively in cosmetic formulations in the prevention of skin acne [
4
,
109
]. Ruxton and
Jenkins [
110
] discussed the anti-acne activity of seaweed oligosaccharide-zinc complex extracted from
Laminaria digitata (Hudson) J.V.Lamouroux which also reduces the signs of acne by reducing the sebum
production. Ethyl acetate extraction of Fucus evanescens C.Agardh showed antibacterial ability against
methicillin-resistant S. aureus and P. acnes [
111
]. Choi et al. [
112
] screened 57 seaweed species for the
antimicrobial activity against P. acnes in which 15 species exhibited the antiacne activity. The methanol
extract of E. cava,E. kurome,Ishige sinicola (Setchell & N.L.Gardner) Chihara, and Symphyocladia latiuscula
(Harvey) Yamada showed potent activity with the maximum MIC of 0.31 mg/mL. Phlorotannins
isolated from E. bicyclis showed eective inhibitory activity against human acne producing bacteria
such as P. acnes,Staphylococcus aureus, and S. epidermidis [
113
]. Carrageenan extracted from red algae
of the genus Corallina inhibited the bacteria S. epidermidis with a MIC of 0.325 mg/mL, whereas
Mar. Drugs 2019,17, 688 13 of 19
sulfated galactan from Corallina showed the bactericidal activity against Enterococcus faecalis and
S. epidermidis [
114
]. These studies defined that the seaweed compound can act as an ingredient for the
anti-acne product due to its inhibitory activity against P. acnes,S. aureus, and S. epidermidis.
7. Conclusions
Due to the overexposure of human skin to several environmental stress—such as UV and
pollution—it increases the production of ROS that leads to many skin related problems such as
hyperpigmentation, premature aging, etc. The seaweeds in the marine environment have the
biosynthesis of secondary metabolites for its survival under stress conditions. These biologically active
components present in the seaweeds paves the way to be used as an active ingredient in the cosmetic
industries due to their potent skin protection ability. The active components from the seaweeds
could be used as an antioxidant, antibacterial whitening agent, anti-aging, and anti-acne, and also for
moisturization in cosmetic industries.
8. Future Perspectives
This review examines the potentiality of seaweed-derived compounds in applications to combat
skin whitening and aging in cosmetic industries. Though most of the seaweeds are studied for its
cosmetic properties, still many species are not explored. Hence, the standardization of cost-eective
and ecient methods to extract the bioactive compounds with higher productivity and activity is in
demand. In addition to eciency, the molecular mechanism of their activity and safety concerns of
these compounds are very significant for future challenges in the cosmetics industry.
Author Contributions:
V.J. conceived, organized, and wrote the manuscript. P.P., N.H., and M.A. analyzed the
information from the references. H.D. and M.A. revised the manuscript and H.D. contributed to the final version
of the manuscript.
Funding:
This research was supported by the China Agriculture Research System (CARS-50), Start-Up Funding
of Shantou University (NTF18004), and Department of Education of Guangdong Province (2017KQNCX076).
Conflicts of Interest: The authors declare no conflict of interest.
Abbreviations
ECM Extracellular matrix
HA Hyaluronic acid
ROS Reactive oxygen species
TRP Tyrosinase-related protein
MITF Microphthalmia-associated transcription factor
cAMP Adenosine 3’,5’-cyclic monophosphate (cyclic AMP)
CREB cAMP response element-binding
ERK Extracellular receptor kinase
ASP Agonist stimulating protein
SCF Stem cell factor
Wnt Wingless-related integration site
MC1R Melanocortin 1 receptor
α-MSH α-Melanocyte-stimulating hormone
MAPK Mitogen-activated protein kinase
MMP Matrix metalloproteinase
NF-κB Nuclear factor kappa-light-chain-enhancer of activated B cells
AP-1 Activator protein 1
IL-12 and IL-8 Interleukin 12
TLR2 Toll-like receptor 2
MAA Mycosporine-like amino acid
PUFA Polyunsaturated fatty acid
Mar. Drugs 2019,17, 688 14 of 19
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... Collagen, which is the major compound of this skin layer, is synthesized by specialized cells called fibroblasts. Elastin is the second major compound in the extracellular matrix and is most responsible for contributing to skin elasticity (Jesumani et al., 2019). The set of these fibrous compounds are called the extracellular matrix and they are responsible for the structural and mechanical skin´s properties (Dragicevic, Maibach, 2015;Norman, Menendez, 2008). ...
... The deepest layer is the hypodermis, it is mainly formed by fat cells and loose connective tissue, providing mechanical protection to the body (Dragicevic, Maibach, 2015). eventually lead to the expression of degenerative enzymes, an example of a metal and protein matrix that degrades compounds of the extracellular matrix-like collagen (Berthon et al., 2017;Jesumani et al., 2019). ...
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This study aims to evaluate the chemical and structural characterization of polysaccharide isolated from Gracilaria verrucosa and examine their anti-diabetic effect on streptozotocin (STZ)-induced diabetes mice. The yield of the polysaccharide was 17.5% and the carbohydrate, protein, ash, and moisture content were 90.05%, 0%, 20.08%, and 5.03% respectively. The carbon, hydrogen, nitrogen, and sulphur content of the polysaccharide recorded 31.07%, 4.03%, 2.09%, and 3.08% respectively. The structural characterization of the polysaccharide was analysed using FT-IR and NMR. The administration of polysaccharide resulted in a rise in body weight, insulin levels, and a decrease in glucose levels. Total cholesterol (TC), triglycerides (TG), low-density lipoprotein (LDL), and very low-density lipoprotein (VLDL) were all reduced in the polysaccharide-treated mice, whereas HDL was enhanced. The polysaccharide-treated diabetic mice demonstrated normal levels of blood glucose, insulin production, and cholesterolemic prevention. As a result, the polysaccharide from G. verrucosa has been identified as an effective anti-diabetic principle for the treatment of diabetics, which may lead to the creation of potent anti-diabetic drugs in pharmaceutical firms in the future.
... Among these, UVC rays are blocked by the ozone layer in the atmosphere, but exposure to UVA and UVB continues. Exposure to these types of radiation induces reactive oxygen species (ROS) production and tends to reduce the levels of natural body antioxidants, in turn disrupting the defense mechanism against ROS (Jesumani et al., 2019). Studies have shown that exposure of skin to UV radiation can cause mutation in the p53 gene, which in turn can lead to squamous cell carcinomas and basal cell carcinomas (Stretch et al., 1991). ...
... Nanosystems such as liposomes, ethosomes, transferosomes, and bilosomes (BS) have shown promising results in dermal drug delivery [29]. Nonetheless, despite the interest of the cosmetic market in naturally derived skin care products, the promising potential of marine-derived natural products as a source for active compounds with antiaging effects has remained relatively undiscovered until recently [12,30]. ...
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Hyperpigmentation of the skin results from excessive melanin formation in melanocytes, and overproduction of melanin frequently leads to melanoma. The aim of this study was to investigate the potential of sulfated galactans (SG) from Gracilaria fisheri to inhibit melanin formation or melanogenesis. Cellular and molecular mechanisms of inhibition were also investigated. SG was evaluated in vitro for its inhibitory effect on mushroom tyrosinase activity, cell-free tyrosinase activity, and cellular tyrosinase activity. B16F10 mouse melanoma cells were cultured with SG and their tyrosinase activity and melanin content was compared with kojic acid, a known tyrosinase inhibitor. Moreover, the levels of expression of melanogenesis-related genes and proteins were determined by quantitative RT-PCR and enzyme-linked immunosorbent assay (ELISA), respectively. The result showed that SG had no inhibitory effect on mushroom tyrosinase activity and cell-free tyrosinase activity. However, SG significantly suppressed cellular tyrosinase activity and melanin production in B16F10 melanoma cells without any apparent cytotoxicity. Quantitative RT-PCR and ELISA revealed that SG downregulated the expression of microphthalmia-associated transcription factor (MITF), tyrosinase-related protein-1 (TRP-1), tyrosinase-related protein-2 (TRP-2), and tyrosinase mRNA and proteins. Taken together, the data suggest that SG may act as an anti-melanogenic agent by inhibiting the expression of MITF and cellular tyrosinase activity. SG may show potential as an ingredient in skin-whitening cosmetics or as a topical agent for the treatment of hyperpigmentation disorders.
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Propionibacterium acnes has been recognized as a main target for medical treatment of acne since this bacterium promotes acne inflammation by inducing upregulation of pro-inflammatory cytokines production, resulting in an accumulation of neutrophils and oxygen-free radicals produced by neutrophils within acne lesion. The aims of this study were to evaluate the biological activities of Mangifera indica kernel extracts grown in Northern Thailand (Kaew-Moragot cultivar), related to anti-acne properties including antimicrobial effect against acne-inducing bacteria together with the first elucidation of the mechanism of action against Propionibacterium acnes, anti-oxidation, and anti-inflammation. The kernels of M. indica, obtained from raw and ripe fruits, were macerated using various solvents. Agar diffusion and broth microdilution methods were performed to investigate the antibacterial activities of the extracts against P. acnes, Staphylococcus aureus, and Staphylococcus epidermidis. The ethanolic fractions exhibited the strongest antimicrobial effect against P. acnes with minimum inhibitory concentration and minimum bactericidal concentration of 1.56 mg/mL and 12.50 mg/mL, respectively. Bactericidal effect against P. acnes of these extracts could be observed after 3 h of incubation from time-kill curve. The chromatograms of high-performance liquid chromatography showed that the extracts existed gallic acid with high total phenolic content. These extracts additionally showed strong free radical scavenging properties on 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS) as well as a notable inhibitory effect on linoleic acid peroxidation, which highly correlated to their antimicrobial effect, total phenolic, and gallic acid contents. The images, studied through using transmission electron microscopy, revealed that the extract certainly disrupted P. acnes cell membrane after exposure for 1 h as well as induced the consequent leakage of cytoplasmic materials. The inhibitory effects of the extracts on IL-8 secretion from LPS-inducing RAW 264.7 cells were also presented. In conclusion, the kernel extracts of raw M. indica fruit were effective against aerobic and anaerobic acne-inducing bacteria particularly P. acnes and exerted antioxidant along with anti-inflammatory activities. Therefore, the extracts might be potential agents for inflammatory acne treatment. However, clinical study is needed for further investigation.