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Bakuchiol: A Retinol-Like Functional Compound Revealed by Gene Expression Profiling & Clinically Proven to have Anti-Aging Effects.


Abstract and Figures

The study was undertaken to compare the skin care related activities of retinol and bakuchiol, a potential alternative to retinoids. Retinol is a pivotal regulator of differentiation and growth of developing as well as adult skin. Retinoic acid is the major physiologically active metabolite of retinol regulating gene expression through retinoic acid receptor - dependant and independent pathways. Comparative gene expression profiling of both substances in the EpiDerm FT full thickness skin substitute model was undertaken. Type I, III and IV collagen and aquaporin 3 synthesis in normal human dermal fibroblasts and in were analysed by ELISA and/or histochemistry in EpiDerm FT full thickness skin model were determined. Bakuchiol is a meroterpene phenol abundant in seeds and leaves of the plant Psoralea corylifolia. We present evidence that bakuchiol, having no structural resemblance to retinoids, can function as a functional analogue of retinol. Volcano plots show the great similarity of retinol and bakuchiol gene expression. Retinol-like functionality was further confirmed for the upregulation of types I, and IV collagen in DNA microarray study and also show stimulation of type III collagen in the mature fibroblast model. Bakuchiol was also formulated into a finished skin care product and was tested in clinical case study by twice-a-day facial application. The results showed that, after twelve weeks treatment, significant improvement in lines and wrinkles, pigmentation, elasticity, firmness and overall reduction in photo-damage was observed, without usual retinol therapy-associated undesirable effects. Based on these data, we propose that bakuchiol can function as an anti-aging compound through retinol-like regulation of gene expression. This article is protected by copyright. All rights reserved.
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Bakuchiol: a retinol-like functional compound revealed by gene
expression profiling and clinically proven to have anti-aging effects
R. K. Chaudhuri* and K. Bojanowski
*Sytheon Ltd., Boonton, NJ 07005, USA and
Sunny Biodiscovery, Santa Paula, CA 93060, USA
Received 04 November 2013, Accepted 25 January 2014
Keywords: anti-ageing clinical, bakuchiol, DNA microarray, histology, retinol
OBJECTIVE: The study was undertaken to compare the skin care
related activities of retinol and bakuchiol, a potential alternative to
retinoids. Retinol is a pivotal regulator of differentiation and
growth of developing as well as adult skin. Retinoic acid is the
major physiologically active metabolite of retinol regulating gene
expression through retinoic acid receptor dependant and indepen-
dent pathways.
METHODS: Comparative gene expression profiling of both sub-
stances in the EpiDerm FT full thickness skin substitute model
was undertaken. Furthermore, type I, III and IV collagen, as well
as aquaporin 3 expression was analyzed by ELISA and/or histo-
chemistry in human dermal fibroblasts and/or Epiderm FT skin
RESULTS: Bakuchiol is a meroterpene phenol abundant in seeds
and leaves of the plant Psoralea corylifolia. We present evidence that
bakuchiol, having no structural resemblance to retinoids, can func-
tion as a functional analogue of retinol. Volcano plots showed
great overall similarity of retinol and bakuchiol effects on the gene
expression profile. This similarity was confirmed by the side-by-side
comparison of the modulation of individual genes, as well as on
the protein level by ELISA and histochemistry. Retinol-like func-
tionality was further confirmed for the upregulation of types I and
IV collagen in DNA microarray study and also show stimulation of
type III collagen in the mature fibroblast model. Bakuchiol was also
formulated into a finished skin care product and was tested in clini-
cal case study by twice-a-day facial application. The results showed
that, after 12 weeks treatment, significant improvement in lines
and wrinkles, pigmentation, elasticity, firmness and overall reduc-
tion in photo-damage was observed, without usual retinol therapy-
associated undesirable effects.
CONCLUSION: Based on these data, we propose that bakuchiol
can function as an anti-ageing compound through retinol-like
regulation of gene expression.
etude a
e men
ee pour comparer les activit
es li
aux soins de la peau du r
etinol et du bakuchiol, une alternative
potentielle aux r
ıdes. Le r
etinol est un r
egulateur essentiel de
la diff
erenciation et de la croissance de la peau en d
ainsi que la peau des adultes. L’acide r
ıque est le principal
etabolite physiologiquement actif du r
etinol qui r
egule l’expres-
sion des g
enes par des voies d
ependantes et ind
ependantes du
ecepteur de l’acide r
ETHODES: Un profilage comparatif d’expression g
etique de ces
deux substances dans le mod
ele substitut de la peau EpiDerm FT a
e entrepris. La synth
ese des collag
enes de type I, III et IV et de
l’aquaporine 3 dans des fibroblastes dermiques humains normaux
e analys
es par ELISA et/ou en histochimie dans le mod
ele de
peau EpiDermTM FT.
ESULTATS: Bakuchiol est un ph
enol meroterp
ene abondant dans
les graines et les feuilles de la Psoralea corylifolia. Nous pr
des preuves que bakuchiol, n’ayant aucune ressemblance structu-
relle avec les r
ıdes, peut fonctionner comme un analogue fonc-
tionnel de r
etinol. Les diagrammes de type Volcano montrent la
grande similitude de l’effet du r
etinol et du bakuchiol sur l’expres-
sion des g
enes. Cette ressemblance a
e aussi d
ee par la
comparaison de la modulation de l’expression de g
enes particu-
laires, appartenant a de diff
erentes groupes fonctionnelles. La fonc-
etinol -like a
e confirm
ee par la r
a la hausse
du collag
ene de type I et IV et aquaporine 3 au niveau de proteines
par ELISA et histochimie. Le bakuchiol a
e formul
dans un produit de soin de la peau et a
e test
e dans une
clinique avec deux applications par jour au visage. Les r
ont montr
e que, apr
es le traitement de douze semaines, une
elioration significative a
e observ
ee dans les rides et ridules, la
pigmentation, l’
e, la fermet
eduction globale des
dommages du photo-vieillissement, sans les effets ind
esirables habi-
tuels associ
erapie au r
CONCLUSION: Sur la base de ces donn
ees, nous proposons que le
bakuchiol peut fonctionner comme un compos
e anti- vieillissement
eglementation de l’expression des g
enes similaire au
Retinoids have been first defined as a family of naturally occurring
compounds comprised of vitamin A (retinol) and its derivatives,
such as vitamin A aldehyde (retinal) or vitamin A acid (retinoic
acid). Retinoic acid is considered to be the active form of vitamin A
and is involved in gene regulation, leading to effects ranging from
hyperplasia to differentiation and apoptosis of normal and cancer
cells [1, 2]. The conversion of retinol to retinal by the retinol dehy-
drogenases is considered to be the rate-limiting step for the biosyn-
thesis of retinoic acid [3]. In addition to retinol dehydrogenases,
P450s 1A1, 1A2, 1B1 and 3A4 have been shown to be involved
Correspondence: Ratan K. Chaudhuri, Sytheon Ltd., 315 Wootton
Street, Boonton, NJ 07005, USA. Tel.: +201 303 5594; fax: +1 973
909 9922; e-mail:
©2014 Society of Cosmetic Scientists and the Soci
e Franc
ßaise de Cosm
etologie 1
International Journal of Cosmetic Science, 2014, 1–10 doi: 10.1111/ics.12117
in the metabolism of retinoic acid [4]. Human dermal fibroblasts
treated with retinol metabolize it to retinoic acid, demonstrating
the bioactivity and bioavailability of retinol in the dermis [5].
Retinol is found in a variety of foods such as beef, calf, chicken
liver, eggs and fish. It is also present in vegetables such as carrots,
squash, sweet potatoes, pumpkin and cantaloupe. Subsequent
research has resulted in a much larger class of natural and syn-
thetic compounds that are termed retinoids due to their functional
although not always structural similarity to vitamin A [6].
The epidermis is one of the major targets for the retinoic acid
signalling in adult organism. Classic retinoid activities are mainly
achieved through the transcriptional regulation of specific genes
via two classes of nuclear hormone receptors, the retinoic acid
receptors (RAR) and retinoid X receptors (RXR), each with three is-
otypes (a,b,c) and multiple isoforms [79]. All-trans retinoic acid
preferentially binds RARs and its 9-cis isomer, 9-cis retinoic acid,
binds both RARs and RXRs. The predominant retinoid receptors
found in skin are RARcand RXRa[10]. Retinoic acid receptors
exert their effects in epidermis through direct binding to epidermal
genes [11, 12] or interference with signalling of other transcription
factors [13].
Retinoic acid and its derivatives have been used as therapeutic
agents for numerous skin conditions from psoriasis to acne and
were also found to be clinically effective against wrinkles [14].
Retinol (Fig. 1A) application is believed to be a more efficient
method to deliver retinoic acid to the skin cells than direct treat-
ment with retinoic acid [15]. However, retinoid therapy using
even the newer analogues is still restricted by many undesirable
side effects, such as irritation, dryness, peeling, erythema and a
sensation of burning on the skin [16, 17]. These side effects often
result in non-compliance and discontinuation of therapy. There-
fore, there is a definite need to develop improved retinoid com-
pounds. Such compounds should have similar but not identical
gene expression pattern as compared with retinol, ideally, result-
ing in retinol-like beneficial effects, without having retinol-like
undesirable side effects. Here, we build on our preliminary findings
[18] and report that bakuchiol (Fig. 1B) a meroterpene phenol
from seeds of the plant Psoralea corylifolia [19, 20] exhibits such
retinol-like functionality.
Materials and methods
Test materials
Retinol (Fig. 1A), trade named Retinol 50 C (INCI name Retinol
and Polysorb 20), was purchased from BASF (Florham Park, NJ,
U.S.A). This product is a yellow oil containing 50% vitamin A in
polysorbate 20 and stabilizer system consisting of 3.5% BHT and
1% BHA. Bakuchiol (Phenol, 4-[1E,3S)-3-ethenyl-3,7-dimethyl-1,6-
octadinenyl; Fig. 1B)l is a phenolic compound with a monoterpene
side chain [19]. Bakuchiol belongs to a rare group of terpenoids in
which the aromatic ring system is derived from phenylpropane unit.
The material used in this study is obtained from edible seeds of Psora-
lea corylifolia, which is psoralene-depleted Bakuchiol (trade named Sy-
A; INCI name Bakuchiol) with a purity of about 95%.
DNA microarrays
EpiDerm FT tissues were obtained from Mattek (Ashland, MA,
U.S.A.; cat. no. EFT 212) and cultured according to the manu-
facturer’s instructions. The test materials Retinol (50%) and
Bakuchiol (100%) were dissolved in DMSO at 10 mg mL
nol) and 5 mg mL
(Bakuchiol), and further dilutions were made
in type I sterile water. Test materials were assayed at 10 lgmL
(Retinol) and 5 lgmL
(Bakuchiol) against 0.1% DMSO as a con-
trol. The incubation time with skin tissues was 2 days. After incu-
bation, skin tissues were harvested, frozen in liquid nitrogen and
subjected to total RNA extraction with Qiagen kit (Frederick, MD,
U.S.A). The quality of extracted RNA was validated twice by elec-
trophoresis (after extraction and before microarray analysis).
Samples were hybridized and data were analysed using human
OneArray platform from Phalanx Biotech (Palo Alto, CA, U.S.A.).
The Excel file yielding information on over 30 000 probes was then
further processed in house to retain only differences with low P
values (Pvalue cut off was 0.05) and high fold-change (the cut off
value for fold-change was 2.0).
Collagen ELISA
Retinol and bakuchiol were assayed at 10 lgmL
on normal
human fibroblasts grown in DMEM with 5% calf serum (Hyclone,
Salt Lake City, UT, U.S.A.). For type I and IV collagen quantifica-
tion, neonatal human dermal fibroblasts (low passage; American
Type Culture Collection, Manassas, VA, U.S.A. cat. no. PCS-201-
010, lot no. 58243223) were used. For type III collagen quantifi-
cation, human epidermal fibroblasts from a 68-year-old female
donor (p. 5, Zen-bio, cat. no. KR-F) was used. Cells were exposed
to test materials for 3 days (type I collagen quantification) or
7 days (type III and IV collagen quantification). Afterward, cell-
culture conditioned media were harvested and assayed for type I,
type III or type IV collagen by sandwich ELISA using affinity-purified
antibodies, followed by streptavidin-avidin-HRP conjugate and ABTS,
according to a standard ELISA protocol [21, 22]. The colorimetric
signal proportional to collagen content was quantified with the Bio-
Rad microplate spectrophotometer 3550-UV at 405 nm with back-
ground subtraction at 660 nm and analysed with Microplate
Manager v.2 software for Macintosh (BioRad, Hercules, CA, U.S.A.).
Fort type IV collagen and aquaporin three visualization retinol
and bakuchiol were dissolved at 50 mg mL
in DMSO. Test sam-
ples were then further diluted in type I sterile water and tested at
final concentrations 10 lgmL
(Retinol) and 5 lgmL
uchiol) using EpiDermFT tissues from Mattek. Tissues were equili-
brated for 24 h and incubated with test materials or water
(negative control) for 96 h, afterward they were rinsed and fixed
in 10% buffered formalin. Paraffin sections of these tissues were
stained with a biotinylated antibody against type IV collagen (cat.
Figure 1 (A) Retino l. (B) Bakuchiol.
2©2014 Society of Cosmetic Scientists and the Soci
e Franc
ßaise de Cosm
International Journal of Cosmetic Science, 1–10
A retinol-like functional compound R. K. Chaudhuri and K. Bojanowski
no. 1340-08 Southern Bio, Birmingham, AL, U.S.A.) or AQP3
(cat. no. sc-9885, Santa Cruz Biotechnology, Santa Cruz, CA,
U.S.A.) and developed with the ABC peroxidase staining compo-
nents (Santa Cruz Biotechnology). Slides were mounted in Perm-
mount and observed on Nikon (Tokyo, Japan) Eclipse TS100
inverted microscope at 100 magnifications. Microphotographs
were taken with Canon Rebel digital camera mounted on the
Nikon TS100 microscope.
Clinical study
Seventeen healthy but photo-aged subjects were recruited to this
blind study (all females; age range 4065 years). All subjects read,
understood and signed an informed consent. All subjects had
abstained from the use of moisturizing products and used only sim-
ple soap, for at least 1 week prior to treatment conditions. All test
products were supplied in identical containers. Subjects were
instructed on the use of the cream twice daily morning and even-
ing applications to the entire face for 3 months. Clinical assess-
ments of the skin of the face were performed for all participants at
baseline and following 4, 8 and 12 weeks of product use. The fol-
lowing parameters were assessed at each visit by an expert grader:
Fine Lines/Wrinkles, Roughness and Dryness, Skin Tone, Skin Elas-
ticity and Firmness, Radiance, Brightening and Overall Eye Area
Appearance. Assessment for each parameter was performed at
baseline using the following five-point ordinal severity scale:
0=None; 1 =Minimal; 2 =Mild; 3 =Moderate; 4 =Severe.
Silicone analysis profilometry
At each visit, a single silicone replica was made of the target area
and a photographic record was kept of this target for subsequent
relocation. Comparative analysis of skin profilometry was con-
ducted, using surface roughness and wrinkle depth analysis. The
heights of the replicated wrinkles were measured using Miyomoto
Surftest profilometer. Ry (depth) and Ra (mean roughness) were
recorded at each time of measuring operation. The area scanned
from each sample was clearly mapped so as to determine the same
area in respective weeks 4, 8 and 12 samples.
Photo booth
At each time point, a series of high resolution digital photographs
was collected using a photo booth equipped with Canon G7 Digital
Camera 10 MP, 69zoom. Subject positioning was reproduced
upon return visit. A light booth was used so as to provide con-
trolled reproducible light conditions. The booth consists of an array
of 8 equally spaced fluorescent tubes in a semicircular configura-
tion. The software-driven system allows the position and expression
of the test subjects to be aligned to a high degree.
Method of assessment & product application
The expert grader performed assessment of the panelist’s face and
eye area for all the parameters as described before. Photographs
were conducted using a photo booth with a three-point head
restraint with photographs taken with frontal view, 45 degrees to
the right and 45 degrees to the left at each time point (Day 0,
Weeks 4, 8 and 12). A replica ring was used to delineate the wrin-
kle site in the crow’s feet area. Silflo was applied on the site,
allowed to dry for approximately 5 min, and the replica was
removed gently from the site.
Product application
Test Materials were distributed to the subjects. Subjects were asked to
gently massage a small amount of the test material to the crow’s feet
and eye area and then smooth over the whole face. They were asked
to apply twice a day for 12 weeks. A study diary was given to the
panelists to list the time of application, the dates and any subjective
comments that they might have in regard to the test product.
Weeks 4, 8 and 12
Panellists returned to the study site after week 4, 8 and 12 of prod-
uct use. At each study visit, panellists were clinically evaluated in
the same manner as at the baseline visit.
Statistical analysis
For each of the parameters, percent improvement from baseline
was calculated to express the efficacy of the product at each time
point (4, 8 and 12 weeks). Using the t-test, the statistical signifi-
cance of the net change from baseline (pre-application) to each
subsequent time point was assessed. Statistical significance was
defined at the P=0.05 or less level (corresponding to a 95% or
greater confidence level).
Formulated product
Formulation details are given in Table V.
Results and discussion
Bakuchiol is a meroterpene phenol abundant in seeds and leaves of
the plant Psoralea corylifolia [19, 20] and has also been isolated
from other plants, such as, P. grandulosa [23, 24], P. drupaceae
[25], Ulmus davidiana [26], Otholobium pubescens [27] and Piper lon-
gum [28]. It is widely used in Indian as well as Chinese medicine to
treat a variety of diseases. Bakuchiol has been reported to possess
anti-inflammatory [24, 2931], antioxidant [3234], anti-tumor
[35, 36], anti-bacterial [37], cytotoxic [38], heptaprotective [39]
and caspase-3 depended apoptosis [40] effects. The cytotoxicity of
bakuchiol is mainly due to its DNA polymerase 1-inhibiting activity
[41]. Recently, anti-acne activity of bakuchiol has been reported
[42]. Here, we demonstrate the anti-ageing and retinol-like func-
tionalities of bakuchiol using DNA microarray, ELISA, histochemis-
try and clinical case studies.
As human skin naturally ages, it becomes thin, lax and finely
wrinkled. Of these changes, fine lines & wrinkles and uneven pig-
mentation are most easily appreciated clinically with severity corre-
lating strongly with age. We have demonstrated through a pilot
clinical study that topical 0.5% bakuchiol treatment improves clini-
cal appearance (% improvement vs. baseline) of naturally aged/
photo-aged human skin.
DNA microarrays
As retinol affects the expression of a vast array of genes, compara-
tive gene expression profiling with retinol is a suitable method to
identify retinol-like compounds [43]. Here, we applied this method
©2014 Society of Cosmetic Scientists and the Soci
e Franc
ßaise de Cosm
etologie 3
International Journal of Cosmetic Science, 1–10
A retinol-like functional compound R. K. Chaudhuri and K. Bojanowski
to reveal retinol-like properties of bakuchiol. These proprieties were
first evidenced on the whole genome scale by comparing the shapes
of volcano plots of retinol- and bakuchiol-treated skin substitutes
(Fig. 2A,B). Volcano plot is a scatter graph used to identify mean-
ingful changes in large datasets, such as data from DNA micro-
array analysis, by plotting significance versus. fold-change on the
y- and x-axes, respectively. Data points with low P-values (highly
significant) appear towards the top of the plot, and with Pvalue of
0.05 being set as the threshold for statistical significance, all points
situated above the value of 1.3 on the y axis are statistically signifi-
cant. The finding that the overall shapes of retinol and bakuchiol
volcano plots are similar was the first indication of the functional
analogy between the two compounds. This was further confirmed
by the analysis of retinoid-binding and metabolizing genes; the
expression was often but not always similarly modulated
(Table I). Interestingly, both RARB and RARG are up-regulated, as
expected, by retinol but not by bakuchiol, indicating a possible
advantage of the latter in terms of side effects. Also retinol had no
effects on CRBP II and CRBP IV, whereas bakuchiol showed signifi-
cantly higher up-regulation. Furthermore, retinol causes down reg-
ulation of CRABP1 gene whereas bakuchiol causes up-regulation,
and whereas bakuchiol showed a dramatic up-regulation (82-fold
vs. placebo) of LRAT retinol showed 12.3-fold (still a very signifi-
cant) increase. These results indicate that besides being a retinol
functional analogue, bakuchiol may enhance the availability of
endogenous retinol.
Retinol and bakuchiol also showed similar modulation of genes
implicated in ECM and DEJ (Tables II and III, respectively). ECM is
the material that forms the bulk of the dermis, excluding water and
cells. Proteins and complex sugars form most of the dermal ECM, and
they are arranged in an orderly network fibres and ground sub-
stances organized by physical entanglements, opposing ionic
charges, chemical covalent bonding and cross-linking into a
biomechanically active polymer. This scaffolding structure with
regional tensile strength provided by collagens, elasticity by elastins,
Table I Description, fold-change in the DNA microarray experiment and role of modulated retinoid binding and metabolizing genes (R: retinol; B: bakuchiol)
Gene Full name Function & comments
Cellular retinol binding
protein I, II & IV
CRBP I:R =2.6; B =4.2
CRBP II: R =NS; B =4.1
CRBP IV: R =NS; B =3.1
CRBP I mediates the cellular uptake of retinol, solubilizes and detoxifies it for further transport within the
cytoplasm and presents it to the appropriate enzymes to biosynthesize retinoic acid
N6AMT2 N-6 adenine-specific
DNA methyltransferase 2
R=NS; B =2.1
Retinoic acid resistance might be overcome by the use of epigenetic modifying agents such as DNA methyl
transferase inhibitors. Down-regulation provided by bakuchiol may reduce retinoic acid-induced toxicity
TIG1 Tazarotene-inducible gene 1 R =13.2; B =12.9
Retinoid acid (RA) receptor-responsive gene. The expression of this gene is found to be down-regulated in a
variety of human cancers as well as in acne, rosacea and psoriasis. Up-regulation by bakuchiol may provide a
solution to problem skin. Anti-acne clinical study results of bakuchiol has recently been reported [40]
DHRS9 Dehydrogenase/reductase
SDR family member
9 precursor
R=5.5; B =11.6
DHRS9 is involved in converting retinol to retinal and then to retinoic acid, the rate-limiting step for the
biosynthesis of retinoic acid
RETSAT All-trans- 13,14-dihydroretinol
R=2.9; B =2.8
RETSAT expression is involved in adipocyte differentiation
LRAT Lecithin-retinol acyltransferase R =12.3; B =82.2
Retinol esterification with long-chain fatty acid by LRAT is the key step in both absorption & storage of retinol.
Cytochrome P450 CYP1A1: R =4.0; B =4.9
CYP1A2: R =3.6; B =6.7
In addition to retinol dehydrogenase, P450s 1A1 and 1A2 genes are the major human P450s
RARB; RARG Retinoic acid receptor beta -1;
Retinoic acid receptor
gamma -1
RARB: R =5.6; B =NS
RARG: R =1.8; B =NS
The actions of retinoids are generally mediated by the retinoic acid receptors (RARs alpha, beta, and gamma) and
the retinoid X receptors (RXRs alpha, beta, and gamma). Both RARB and RARG are up-regulated, as expected
by retinol but not with bakuchiol
–3 –2 –1 0 1 2 3
–Log (P value)
Log2 (fold change)
–3 –2 –1 0 1 2 3
–Log (P value)
Log2 (fold change)
Figure 2 (A) Volcan ic plot of DNA microarray data Retinol. (B) Volcanic
plot of DNA microarray data Bakuchiol.
4©2014 Society of Cosmetic Scientists and the Soci
e Franc
ßaise de Cosm
International Journal of Cosmetic Science, 1–10
A retinol-like functional compound R. K. Chaudhuri and K. Bojanowski
adhesiveness by structural glycoproteins, compressibility by proteo-
glycans hyaluronans and communicability by transmembrane
receptors, such as integrins, which exchange information between
the cytoskeleton-bound cellular elements and between cells and the
dermal extracellular matrix, provides a unique homeostatic tenseg-
rity function to the skin [44, 45]. DEJ, in turn, provides cohesion
between dermis and epidermis. With age, both, ECM and DEJ
gradually deteriorate resulting in skin thinning and morphological
Table II Description, fold-change in the DNA microarray experiment and roles of modulated genes coding for ECM components [(R: retinol; B: bakuchiol]
Gene Full name Function & comments
Collagen 1A2;
Collagen 4A6;
Collagen 9A2;
Collagen 9A3
COL1A2: R =3.3; B =1.9
COL4A6: R =6.4; B =11.2
COL9A2: R =5.6; B =6.7
COL9A3: R =4.1; B =5.8
Collagens provide scaffolding structure with regional tensile strength and elasticity; Degradation leads to fine lines and
wrinkles. Comparable fold-change observed with four collagen genes with the exception of COL3A1. This may be due
to the use of neonatal tissue in the skin substitutes. ELISA study with mature fibroblasts showed stimulation of type III
Elastin microfibril
interface-located protein 3;
Elastin microfifibril
interface-located protein 1
EMILIN3:R =2.2 (NS); B =9.1
EMILIN1: R =3.4; B =2.4
The EMILINs are a family of glycoproteins of the extracellular matrix; Widely distributed in several tissues associated
with elastin and localized at the interface between amorphous elastin and microfibrils
PI3 Peptidase inhibitor
3/Elastase-specific inhibitor
R=2.5; B =2.7
Bakuchiol and retinol are expected to maintain the desired level of elastin required for maintaining the connective
tissue structure due to their up-regulation of elastase-specific inhibitor gene PI3
leucine-rich transmembrane
protein 2
FLRT2: R =NS; B =13.9
FLRT3: R =2.8 (NS); B =6.1
Fibronectins maintain the shape of cells and matrix stability
HAS3 Hyaluronan synthase 3 R =10.8; B =19.2
Hyaluronans are important for the maintenance of a highly hydrated extracellular matrix in tissues and is also involved
in cell adhesion and supports cell migration. It is synthesized by hyaluronan synthases, such as HAS-3
AQP3 Aquaporin 3 R =3.5; B =4.3
Aquaporin 3 is the water/glycerol transporting channel protein expressed in the epidermis which helps maintain the
right level of skin hydration, elasticity and barrier recovery. Both retinol and bakuchiol up-regulated AQP3
Table III Description, fold-change in the DNA microarray experiment and roles of modulated DEJ genes (R: retinol; B: bakuchiol)
Gene Full name Fold-change, function & comments
Collage alpha-6 (IV)
Collagen alpha-1(XVII)
COL4A6: R =6.4; B =11.2
COL17A1: R =3.6; B =8.7
Lamina densa mostly consists of type IV collagen, perlecan and nidogen. Through a complex inter- and intramolecular
interactions type IV collagen forms supra molecular networks that influence cell adhesion, migration, and
differentiation. Type XVII collagen is the protein component of anchoring fibrils that fortifies the attachment of the
epidermis to the dermis.
PLEC1 or
Plectin I
protein 1)
R=2.7; B =6.8
Plectin, a 500-KDa protein and a constituent of the intracellular component of hemidesmosomes, attaches intermediate
filaments to both hemidesmosomes and plasma membranes of basal keratocytes
Integrin beta-4;
Integrin beta-6;
Integrin beta-8;
Integrin alpha-6
ITGB4: R =3.5; B =8.0; ITGB6: R =7.5; B =7.7
ITGB8: R =0; B =3.9; ITGA6: R =0; B =3.6
Integrins are transmembrane glycoproteins and a major component of hemidesmosomes. They mediate the transfer of
information between the extracellular matrix and the interior of the cell, thereby aiding in modulating the organization of
the cytoskeleton, proliferation and differentiation. Main functions: (a) attachment of the cell to the ECM and (b) signal
transduction from ECM to the cell
Laminin subunit alpha-3
precursor; Laminin
subunit gamma-2
LAMA3: R =4.7; B =11.0;
LAMC2: R =2.7; B =7.8
Laminins are the major non-collagenous proteins in lamina densa and are integral part of the structural scaffolding in
almost every tissue; Involved in cell differentiation, migration, adhesion as well as phenotype and survival.
CDH1 E-Cadherin R =9.4; B =21.6
One of the most important and ubiquitous types of adhesive interactions required for the maintenance of solid tissues
is that mediated by E-cadherin. E-cadherin has important functions in pluripotency and maintenance of the
differentiated state of cells
©2014 Society of Cosmetic Scientists and the Soci
e Franc
ßaise de Cosm
etologie 5
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A retinol-like functional compound R. K. Chaudhuri and K. Bojanowski
flattening [46]. Retinol is a well known inhibitor of those processes,
and the finding that bakuchiol has retinol-like functionality at the
ECM and DEJ levels makes it an interesting novel candidate for
anti-ageing applications.
Validation of DNA microarray results by ELISA and histochemistry
Collagens secreted by dermal fibroblasts are major components of
the skin extracellular matrix (type I and type III collagens) and
basement membrane (type IV collagen). In aged and photodamaged
skin, the new collagen pool is decreased due to the inferior amount
and quality of dermal fibroblasts. Therefore, we chose to measure
select collagens by ELISA and histochemistry methods to validate
the data obtained by DNA microarrays. The results, summarized in
the Table IV, confirm the upregulation of types I and IV collagen
in DNA microarray study and also show stimulation of type III
collagen in this mature fibroblast model.
To determine whether the stimulation of type IV collagens in cell
culture translates into a more robust collagen expression in 3D
skin substitute tissue, EpiDermFT tissues were incubated with bak-
uchiol or retinol at 10 lgmL
, and histological sections were
stained with anti-type IV collagen antibodies (Fig. 3). The stain
revealed a stronger type IV collagen signal at the dermalepidermal
junction, as compared with the water control, further corroborat-
ing the DNA microarray and ELISA results. This collagen stimula-
tory effect observed in cell culture seems to be due to the selective
metabolic activation of collagen synthesis in fibroblasts, because at
10 lg/mL
, bakuchiol or retinol did not enhance cell proliferation
(results not shown).
Water homeostasis of the epidermis is essential for the normal
function of the skin and stratum corneum (SC) hydration. It is a
determinant of skin appearance, mechanical properties, barrier
function and metabolism. In addition, it is indispensable in main-
taining proper water balance of the body. Dehydration of SC is a
typical feature of skin ageing, especially in photo-aged skin and of
Table IV Comparative collagen stimulatory effects of bakuchiol and retinol
as determined by ELISA in human dermal fibroblasts. The stimulatory effect
is expressed as the % of water control (100%)
Test material (10 lgmL
) Collagen I Collagen III Collagen IV
Bakuchiol 147 150 119
Retinol 119 148 100
Figure 3 Effect of Retinol (B) and Bakuchiol (C) on type IV collagen expression compared with non-treat ed control (A) in human EpidermFT (full thickness)
tissue substitutes. Arrows indicate dermo-epidermal juncture (basement membrane), where collagen IV is localized. Note darker band in (B) and (C) as com-
pared to (A) at this level, indicating greater type IV collagen expression.
Figure 4 Effect of Retinol (B) and Bakuchiol (C) on aquaporin-3 expression, compared with non-treated control (A) in human EpidermFT (full thickness) tissue
substitutes. Arrows indicate aquaporin-3 staining in the basal layer, where this protein is principally localized.
6©2014 Society of Cosmetic Scientists and the Soci
e Franc
ßaise de Cosm
International Journal of Cosmetic Science, 1–10
A retinol-like functional compound R. K. Chaudhuri and K. Bojanowski
several diseases, for example, eczema, atopic dermatitis, psoriasis
and hereditary ichthyosis (retinol 3.5 fold and bakuchiol 4.3 fold,
Table II) [4750]. To determine whether the increase of the !!!
expression of water channel AQP3 gene observed in DNA micro-
arrays translates into orthotropic increase at the protein level.
EpiDermFT skin substitutes were incubated with retinol, bakuchiol
and compared with the negative (water) control using immunohis-
tochemistry. It was found that both retinol and bakuchiol increased
AQP3 expression (Fig. 4) as visualized by more intense brown col-
oration in retinol and bakuchiol treated tissues located, as
expected, at stratum spinosum and corneum level. Recently, Belle-
mere et al. [51] have shown the effects of all-trans retinoic acid
(ATRA) on AQP3 expression and function both in vitro and ex
vivo. ATRA treatment increased a rapid accumulation of AQP3
transcripts in cultured normal human epidermal keratinocytes.
Also in our model of EpiDermFT skin substitute, both retinol and
bakuchiol increased AQP3 expression.
Clinical study
Taken together, these results prompted us to test bakuchiol clinically.
The formulated product containing 0.5% bakuchiol (no moisturizer
or any other active ingredients or sunscreen included in this formu-
lated product; Table V) was applied twice daily to the whole face.
Sixteen subjects of seventeen enrolled completed the study. One sub-
ject discontinued due to protocol violation. Each of the parameters
was graded on a semi-quantitative scale from 0 to 4 (0, none; 1,
minimal; 2, mild; 3, moderate; and 4, severe). With regard to subjec-
tive evaluation by experts and panelists, the obtained results for the
entire subjects are summarized in Tables VI and VII, respectively.
Evaluations were performed at baseline and then at 4, 8 and
12 weeks and the results compared versus. the baseline.
Retinol is used widely in cosmetic products for reducing the
appearance of the signs of ageing and photo-damage [52]. Retinol
is a precursor of retinoic acid. Once it penetrates skin, it is sequen-
tially oxidized to retinoic acid, causing retinoic acid-like effects, but
is notably less irritating. Currently, most of these products contain
0.1% or lower of retinol. However, even at this low concentration,
some irritation can occur [53]. It seems that bakuchiol has accept-
able skin tolerability.
Analysing the data (Table VI vs. Table VII), it is evident that %
improvement score for roughness & dryness and radiance given by
expert is significantly higher versus. the panelists’ self-evaluation. It
is interesting to note that % improvement score given by the sub-
jects, on the other hand, for fine lines and wrinkles and eye area
appearance is significantly higher than the score given by the
expert. Most of the parameters were improved significantly more
after 8 weeks compared to 4 weeks of application of bakuchiol,
showing a certain degree of cumulative beneficial effect over time.
Results obtained from silicone replica analysis using profilometry
are summarized in Table VIII. Comparison of results of day 0 (base
line) vs. 4, 8 and 12 weeks treated skin provided 7%, 13% and
20% reduction in wrinkle depth (Ry), respectively. All three
results are statistically significant (P0.01). Comparison of results
of day 0 (baseline) versus. 4, 8 and 12 weeks treated skin yielded
Table V Formulation details of bakuchiol
Ingredient Trade name/supplier % w/w
Phase A
Glyceryl stearate
and PEG-100
Arlacel 165/Uniqema 1.50
Arachidyl alcohol,
Behenyl alcohol,
Arachidyl glucoside
Montanov 202/Seppic 4.00
Dimethyl isosorbide Arlasolve DMI/Uniqema 3.00
Isohexadecane Permethyl 101A/Presperse 8.00
Dimethicone Dow Corning 200, 100 cst/Dow Corning 2.00
Bakuchiol Sytenol A/Sytheon 0.50
Phase B
Water 69.75
Propylene Glycol Propylene glycol/Lyondell 2.00
Pentylene Glycol Hydrolite-5/Symrise 3.00
Xanthan Gum Vanzan NF/Vanderbilt 0.25
Phase C
Dicaprylylether Cetiol OE/Cognis 4.00
(and) sodium
taurate copolymer
Sepinove EMT 10/Seppic 1.00
(and) Caprylyl glycol
Optiphen or Microcare PHG 1.00
Total 100.00
Table VI Subjective evaluation by expert % improvement vs. baseline
Parameters 4 Weeks 8 Weeks 12 Weeks
Roughness & dryness 65 81 90
Fine lines/wrinkles 5 16 29
Skin tone 14 29 39
Skin elasticity/firmness 13 20 39
Radiance 24 40 52
Skin brightening 13 35 46
Eye area appearance 8 24 46
Table VII Subjective evaluation by panelists % improvement vs. baseline
Parameters 4 Weeks 8 Weeks 12 Weeks
Roughness & dryness 35 40 48
Fine lines/wrinkles 19 25 23
Skin tone 12 19 29
Skin elasticity/firmness 14 23 25
Radiance 11 17 30
Skin brightening 10 14 29
Eye area appearance 22 24 35
Table VIII Silicone replica analysis using profilometry: % reduction vs.
Parameters 4 Weeks 8 Weeks 12 Weeks
Wrinkle depth 7% 13% 20%
Skin roughness 2% 10% 21%
©2014 Society of Cosmetic Scientists and the Soci
e Franc
ßaise de Cosm
etologie 7
International Journal of Cosmetic Science, 1–10
A retinol-like functional compound R. K. Chaudhuri and K. Bojanowski
2%, 10% and 21% reduction in skin roughness (Ra), respec-
tively. The results at 8 and 12 weeks are statistically significant
The photos (Fig. 5; before and after treatment) shown here are
representative of the results that have been obtained with bakuchi-
ol treatment for 12 weeks.
Clinical grading and comparative analysis of skin profilometric
measurements were performed at baseline and after 4, 8 and
12 weeks of application. After 8 weeks of daily application, a
significant reduction in the wrinkle depth and roughness was
observed with the product vs. baseline. These changes were even
greater after 12 weeks of product application. For example, wrinkle
depth reduction (Fig. 5C) is significantly more after 8 weeks com-
pared to 4 weeks of application of bakuchiol (subject no. M572)
showing a certain degree of cumulative beneficial effect over time.
The significant improvement in fine lines and wrinkles, elasticity,
firmness and overall reduction in signs of photodamage including
even toning effects observed after 12 weeks of treatment provided
the ultimate validation of the in vitro results and were in line with
the retinoid-type functionality of bakuchiol.
Given the fact that retinol and bakuchiol do not have close struc-
tural similarities, yet they exhibit a similar gene expression profile,
especially on certain key anti-ageing genes and proteins,which is
remarkable. Bakuchiol has several substantial advantages over reti-
nol, including excellent photochemical and hydrolytic stability a
good safety profile and ease to formulate due to miscibility with a
wide variety of emollients and solubilizers [18]. Bakuchiol can be
used during the day due its photostability. Interestingly, bakuchiol
is an excellent stabilizer of retinol under photo-oxidative as well as
singlet oxygen environments (not discussed here). This property
may help reduce oxidative stress caused by retinol when combined
with bakuchiol and used at concentrations higher than the physio-
logical limit [54].
This open clinical pilot study needs further confirmation of bak-
uchiol bioactivity in vivo, from vehicle- or benchmark-controlled
studies. The similarity of gene expression and protein synthesis
stimulation observed in the comparison of bakuchiol with retinol
is, however, remarkable and suggests that similar bioactivity in vivo
is probable. Taken together, this study demonstrates the potential
of bakuchiol, a true retinol-like functional compound, to become a
key ingredient for dermatological and skin care products.
The authors would like to thank Sytheon Ltd for funding this
research and to Stephanie Ma for her dedicated assistance in this
1. Linney, E. Retinoic acid receptors: tran-
scription factors modulating gene
regulation, development, and differentia-
tion. Curr. Top. Dev. Biol. 27, 309350
2. Balmer, J.E. and Blomhoff, R. Gene expres-
sion regulation by retinoic acid. J. Lipid Res.
43, 17731808 (2002).
3. Siegenthaler, G., Saurat, J.H. and Ponec, M.
Retinol and retinal metabolism. Relationship
to the state of differentiation of cultured
human keratinocytes. Biochem. J. 268,
371378 (1990).
4. Marill, J., Cresteil, T., Lanotte, M. et al. Iden-
tification of human cytochrome P450s
involved in the formation of all-trans-reti-
noic acid principal metabolites. Mol. Phar-
macol. 58, 13411348 (2000).
5. Bailly, J., Crettaz, M., Schifflers, M.H. et al.
In vitro metabolism by human skin and
fibroblasts of retinol, retinal and retinoic
acid. Exp. Dermatol. 7,2734 (1998).
6. Barnard, J.H., Collings, J.C., Whiting, A.
et al. Synthetic retinoids: structure-activity
relationships. Chemistry 15, 1143011442
7. Mattei, M.G., Petkovich, M., Mattei, J.F.
et al. Mapping of the human retinoic acid
receptor to the q21band of chromosome17.
Hum. Genet. 80, 186188 (1988).
Base 4 weeks 8 weeks 12 weeks
Subject #M572
Figure 5 (A) Subject no. M572; Right view; Pre application. (B) Subject no.
M572; Right view; 12-week treatment. (C) Change in wrinkle depth in lm.
8©2014 Society of Cosmetic Scientists and the Soci
e Franc
ßaise de Cosm
International Journal of Cosmetic Science, 1–10
A retinol-like functional compound R. K. Chaudhuri and K. Bojanowski
8. Chambon, P. The nuclear receptor super-
family: a personal retrospect on the first two
decades. Mol. Endocrinol. 19, 14181428
9. Gann, A.A., Gates, P.B., Stark, D. et al.
Receptor isofrom specificity in a cellular
response to retinoic acid, Proc.Biol. Sci.
263, 729734 (1996).
10. Fisher, J.G., Talwar, H.S., Xiao, J.H. et al.
Immunological identification and functional
quantitation of retinoic acid and retinoid x
receptor proteins in human skin. J. Biol.
Chem. 269, 2062920635 (1994).
11. Jho, S.H., Radoja, N., Im, M.J. et al. Negative
response elements in keratin genes mediate
transcriptional repression and the cross-talk
among nuclear receptors. J. Biol. Chem.
276, 4591445920 (2001).
12. Jho, S.H., Vouthounis, C., Lee, B. et al. The
book of opposites: the role of the nuclear
receptor co-regulators in the suppression of
epidermal genes by retinoic acid and thyroid
hormone receptors. J. Invest. Dermatol. 124,
10341043 (2005).
13. Lee, D.D., Stojadinovic, O., Krzyzanowska,
A. et al. Retinoid-responsive transcriptional
changes in epidermal keratinocytes. J. Cell.
Physiol. 220, 427439 (2009).
14. Kafi, R., Kwak, H.S.R., Schumache, W. et al.
Improvement of naturally aged skin with
vitamin A (retinol). Arch. Dermatol. 143,
606612 (2007).
15. Fisher, G.J. and Voorhees, J.J. Molecular
mechanism of retinoid actions in skin.
FASEB J. 10, 10021013 (1996).
16. David, M., Hodak, E. and Lowe, N.J. Adverse
effects of retinoids. Med. Toxicol. Adverse
Drug Exp. 3, 273288 (1988).
17. Sorg, O., Kuenzli, S. and Saurat, J.H. Side
effects and pitfalls in retinoid therapy. In:
Retinoids and Carotenoids in Dermatology, 1st
edn (Vahlquist, A. and Duvic, M. eds), pp.
225248. Informa Healthcare, New York,
London (2007).
18. Chaudhuri, R.K. The miracle of retinol. Soap
Perfum. Cosmet. 2324 (2010).
19. Mehta, G., Nayak, U.R. and Dev, S. Merot-
erpenoids-I: Psoralea corylifolia L.-1. Bakuchi-
ol, a novel monoterpene phenol. Tetrahedron
29, 11191125 (1973).
20. Prakasarao, A.S.C., Bhalla, V.K., Nayak,
U.R. et al. Meroterpenoids. II. Psoralea coryli-
folia L. 2. Absolute configuration of (+)-bak-
uchiol. Tetrahedron 29, 11271130 (1973).
21. Dobak, J., Grzybowski, J., Liu, F.T. et al.
1,25-Dihydroxyvitamin D3 increases colla-
gen production in dermal fibroblasts. J. Der-
matol. Sci. 8,1824 (1994).
22. Zhao, H., Alexeev, A., Chang, E. et al.
Lycium barbarum glycoconjugates: effect on
human skin and cultured dermal fibroblasts.
Phytomedicine 12, 131137 (2005).
23. Labbe, C., Faini, F., Coll, J. et al. Bakuchiol
derivatives from the leaves of Psoralea glan-
dulosa.Phytochemistry 42, 12991303
24. Backhouse, C.N., Delporte, C.L., Negrete,
R.E. et al. Active constituents isolated from
Psoralea glandulosa L. with antiinflammatory
and antipyretic activities. J. Ethnopharmacol.
78,2731 (2001).
25. Lystvan, K., Belokurova, V., Sheludko, Y.
et al. Production of bakuchiol by in vitro sys-
tems of Psoralea drupacea Bge. Plant Cell Tiss.
Organ. Cult. 101,99103 (2010).
26. Choi, S.Y., Lee, S. and Choi, W.H. Isolation
and anti-inflammatory activity of Bakuchiol
from Ulmus davidiana var. japonica. J. Med.
Food 13, 10191023 (2010).
27. Krenisky, J.M., Luo, J., Reed, M.J. et al.
Isolation and antihyperglycemic activity of
bakuchiol from Otholobium pubescens
(Fabaceae), a Peruvian medicinal plant used
for the treatment of diabetes, Biol.Pharm.
Bull. 22, 11371140 (1999).
28. Ohno, O., Watabe, T., Nakamara, K. et al.
Inhibitory effects of Bakuchiol, Bavachin
and Isobavachalcone isolated from Piper lon-
gum on melanin production in B16 mouse
melanoma cells. Biosci. Biotechnol. Biochem.
74, 15041506 (2010).
29. Ferrandiz, M.L., Gil, B., Sanz, M.J. et al.
Effect of bakuchiol on leukocyte functions
and some inflammatory responses in mice. J.
Pharm. Pharmacol. 48, 975980 (1996).
30. Pae, H.O., Cho, H., Oh, G.S. et al. Bakuchiol
from Psoralea corylifolia inhibits the expres-
sion of inducible nitric oxide synthase gene
via the inactivation of nuclear transcription
factor-jB in RAW 264.7 macrophages. Int.
Immunopharmacol. 1, 18491855 (2001).
31. Matsuda, H., Kiyohara, S., Sugimoto, S.
et al. Bioactive constituents from Chinese
natural medicines. XXXIII. Inhibitors from
the seeds of Psoralea corylifolia on production
of nitric oxide in lipopolysaccharide-acti-
vated macrophages. Biol. Pharm. Bull. 32,
147149 (2009).
32. Adhikari, S., Joshi, R., Patro, B.S. et al. Anti-
oxidant activity of bakuchiol: experimental
evidences and theoretical treatments on the
possible involvement of the terpenoid chain.
Chem. Res. Toxicol. 16, 10621069 (2003).
33. Haraguchi, H., Inoue, J., Tamura, Y. et al.
Antioxidative components of Psoralea coryli-
folia (L.). Phytother. Res. 16, 539544
34. Haraguchi, H., Inoue, J., Tamura, Y. et al.
Inhibition of mitochondrial lipid peroxida-
tion by bakuchiol, a meroterpene from
Psoralea corylifolia.Planta Med. 66, 569571
35. Pandey, U., Bapat, K., Samuel, G. and Venk-
atesh, M. Bioevaluation studies of 125I-Bak-
uchiol in tumor bearing animals. BARC
News Lett. 285,8891 (2007).
36. Chen, Z., Jin, K., Gao, L. et al. Anti-tumor
effects of bakuchiol, an analogue of resvera-
trol, on human lung adenocarcinoma A549
cell line. Eur. J. Pharmacol. 643, 170179
37. Katsura, H., Tsukiyama, R.I., Suzuki, A.
et al. In-Vitro antimicrobial activities of Bak-
uchiol against oral microorganisms. Antimic-
rob. Agents Chemother. 45, 30093013
38. Fang, J., Xin-rui, Z., Qi, W. et al. Cytotoxic
effect and mechanism of bakuchiol and bak-
uchiol combined with psoralen on HK-2 cell.
Int. J. Autom. Comput. 24,5058 (2010).
39. Cho, H., Jun, J.Y., Song, E.K. et al. Bakuchi-
ol: a hepatoprotective compound of Psoralea
corylifolia on tacrine-induced cytotoxicity in
Hep G2 cells. Planta Med. 67, 750751
40. Park, E., Zhao, Y.Z., Kim, Y.C. et al. Bakuch-
iol-induced caspase-3-dependent apoptosis
occurs through c-Jun NH
-terminal kinase-
mediated mitochondrial translocation of Bax
in rat liver myofibroblasts. Eur. J. Pharmacol.
559, 115123 (2007).
41. Sun, N.J., Woo, S.H., Cassady, J.M. et al.
DNA polymerase and topoisomerase II inhib-
itors from Psoralea corylifolia.J. Nat. Prod.
61, 362366 (1998) Erratum in: J. Nat.
Prod., 66, 734 (2003).
42. Chaudhuri, R.K. and Marchio, F. Bakuchiol
in the management of acne-affected skin.
Cosmet. Toilet. 126, 502510 (2011).
43. Ishida, S., Shigemoto-Mogami, Y., Kagechika,
H. et al. Clinically potential subclasses of reti-
noid synergists revealed by gene expression
profiling. Mol. Cancer Ther. 2,4958 (2003).
44. Hayden, M.R., Sowers, J.R. and Tyagi, S.C.
The central role of vascular extracellular
matrix and basement membrane remodeling
in metabolic syndrome and type 2 diabetes:
the matrix preloaded. Cardiovasc. Diabetol. 4,
9 (2005).
45. Ingber, D.E. The architecture of life. Sci. Am.
278,4857 (1998).
46. Tim
ar, F., So
os, G., Szende, G.B. et al. Inter-
digitation index - a parameter for differentiat-
ing between young and older skin specimens.
Skin Res. Technol. 6,1720 (2006).
47. Takenouchi, M., Suzuki, H. and Tagami,
H. Hydration characteristics of pathologic
stratum corneumevaluation of bound
water. J. Invest. Dermatol. 87, 574576
©2014 Society of Cosmetic Scientists and the Soci
e Franc
ßaise de Cosm
etologie 9
International Journal of Cosmetic Science, 1–10
A retinol-like functional compound R. K. Chaudhuri and K. Bojanowski
48. Thune, P. Evaluation of the hydration and
the water-holding capacity in atopic skin
and so-called dry skin. Acta Derm. Venerol.
Suppl. 144, 133135 (1989).
49. Scheuplein, R.J. and Blank, I.H. Permeability
of the skin. Physiol. Rev. 51, 702747 (1975).
50. Cao, C., Wan, S., Jiang, Q. et al. All-trans reti-
noic acid attenuates ultraviolet radiation-
induced down-regulation of aquaporin-3 and
water permeability in human keratinocytes.
J. Cell. Physiol. 215, 506516 (2008).
51. Bellemere, G., Von Stetten, O. and Oddos, T.
Retinoic acid increases aquaporin 3 expres-
sion in normal human skin. J. Invest. Derma-
tol. 128, 542548 (2008).
52. Mukherjee, S., Date, A., Patravale, V. et al.
Retinoids in the treatment of skin aging: an
overview of clinical efficacy and safety. Clin.
Interv. Aging 1, 327348 (2006).
53. Oddos, T., Roure, R., Leyden, J. et al. A pla-
cebo-controlled study demonstrates the
long-lasting anti-aging benefits of a cream
containing retinol, dihydroxy methyl
chromone (DMC) and hyaluronic acid. J. Cos-
met. Dermatol. Sci. Appl. 2,5159 (2012).
54. Gimeno, A., Zaragoz
a, R., Viv
e, I.
et al. Retinol, at concentrations greater
than the physiological limit, induces oxida-
tive stress and apoptosis in human dermal
fibroblasts. Exp. Dermatol. 13,4554
10 ©2014 Society of Cosmetic Scientists and the Soci
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ßaise de Cosm
International Journal of Cosmetic Science, 1–10
A retinol-like functional compound R. K. Chaudhuri and K. Bojanowski
... Bakuchiol has recently emerged as a trendy ingredient in cosmetic skincare products, claiming to have similar efficacy to over-thecounter vitamin A derivative products [32]. In fact, although no structural similarity is observed, bakuchiol has recently been recognized as a "functional analogue of retinol" [33], being in some instances even considered a "natural substitute" of retinol with less undesirable effects [34]. ...
... Although bakuchiol is currently used in cosmetic skincare products, only a few studies have been reported in early 2019 and recently reviewed proving its significant efficacy in reducing the signs of skin aging [12,[32][33][34]. Its depigmenting efficacy was shown in two clinical studies using creams containing 0.5% bakuchiol, with good tolerability, and these findings are attributed to bakuchiol's ability to block both αmelanocyte-stimulating hormone (α-MSH) and tyrosinase activation [12,33]. ...
... Although bakuchiol is currently used in cosmetic skincare products, only a few studies have been reported in early 2019 and recently reviewed proving its significant efficacy in reducing the signs of skin aging [12,[32][33][34]. Its depigmenting efficacy was shown in two clinical studies using creams containing 0.5% bakuchiol, with good tolerability, and these findings are attributed to bakuchiol's ability to block both αmelanocyte-stimulating hormone (α-MSH) and tyrosinase activation [12,33]. In mammals, α-MSH is required for the development of pigmentation, by binding to its specific melanocortin-1 receptor and by increasing cyclic adenosine monophosphate. ...
Full-text available
Human skin aging results from intrinsic and extrinsic factors. Uneven pigmentation is one of the major changes of extrinsic aging. Many compounds have been tested for depigmenting activity but only a few are actually used by the cosmetic industry, which is continually looking for new ingredients. In this study, the trends in the use of skin depigmenting ingredients in a panel of anti-aging formulations commercialized in the Portuguese pharmacy market were analyzed, by comparing the composition of the products marketed in 2011 with products launched or reformulated in 2018 (59% and 74%, respectively). The analysis of the top 12 ingredients put forward three novelties for 2018: tranexamic acid, bakuchiol, and 4-butylresorcinol. Regarding their mechanisms of action, tranexamic acid inhibits melanin synthesis through inhibition of the plasminogen/plasmin system. Bakuchiol depigmenting efficacy was attributed to the ability to block both α-melanocyte-stimulating hormone and tyrosinase activation, while 4-butylresorcinol exerts its action through the inhibition of both tyrosinase and tyrosinase-related protein-1 (TRP-1). Industry-optimized and efficient synthetic methodologies that embrace green chemistry, reducing the environmental impact, are commonly used. This analysis aims to bring insights to both formulators, involved in the development of depigmenting cosmetic products, and chemists performing the synthesis of new and existing compounds intended for this purpose.
... It has been used in traditional Indian and Chinese medicine for centuries [16,17] and is well tolerated [18]. Bakuchiol was suggested to exhibit retinol-like functions, as in a skin substitute model, both substances show similar gene expression patterns in vitro [19] and an improvement of cutaneous photodamage in vivo [20]. Hence, it has also been referred to as a plantderived functional retinoid analogue [21]. ...
... Hence, it has also been referred to as a plantderived functional retinoid analogue [21]. Further studies demonstrated antioxidant [19,[22][23][24], anti-inflammatory [19,[25][26][27], antibacterial [28] as well as antiproliferative and antitumor effects [29,30] of bakuchiol. ...
... Hence, it has also been referred to as a plantderived functional retinoid analogue [21]. Further studies demonstrated antioxidant [19,[22][23][24], anti-inflammatory [19,[25][26][27], antibacterial [28] as well as antiproliferative and antitumor effects [29,30] of bakuchiol. ...
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Objective: Skin aging is a multifactorial process involving formation of reactive oxygen species, consecutive inflammation with reduced epidermal and dermal cell viability and resulting damage to the extracellular matrix. Effective dermocosmetic treatment modalities should ideally address these hallmarks in a holistic approach. Here, we determined the corresponding activity profile of bakuchiol, a plant-derived meroterpene, in an array of in vitro, ex vivo and in vivo studies and compared it to retinol, currently considered as gold standard in topical antiaging cosmetics. Methods: The antioxidative capacity and power of bakuchiol and retinol were analyzed by measuring 2,2'-diphenyl-1-picrylhydrazyl (DPPH) reduction via its absorption decay and electron spin resonance spectroscopy, respectively. Effects on prostaglandin E2 (PGE2), macrophage migration inhibitory factor (MIF), fibroblast growth factor 7 (FGF7), collagen type I and VII (COL1A1, COL7A1), fibronectin (FN) levels as well as the metabolization of water-soluble tetrazolium 1 (WST-1) were determined in human dermal fibroblasts. Epidermal regeneration was assessed utilizing an in vitro wound healing model. FN protein levels were analyzed ex vivo after treatment with a formulation containing bakuchiol, retinol or vehicle using suction blister fluid. Skin condition-improvement was determined in vivo in a split-face comparison study after application of bakuchiol or vehicle. Results: In contrast to retinol, bakuchiol demonstrated high antioxidative efficacy. Levels of PGE2 and MIF were significantly decreased by both bakuchiol and retinol. Bakuchiol but not retinol significantly increased FGF7 protein levels. WST-1 metabolization levels were significantly augmented by bakuchiol and retinol. Bakuchiol and retinol application led to a significant augmentation of COL1A1, COL7A1 and FN protein levels. Wounds supplemented with bakuchiol but not retinol displayed a significant increase in epidermis regeneration. Clinically, areas treated with a bakuchiol-containing formulation showed a statistically significant increase in FN protein values after a 4-week application compared to untreated areas and areas treated with vehicle. Conclusion: These data provide evidence for the multidirectional efficacy of bakuchiol against cellular hallmarks of skin aging. Its activity profile shares some common features with retinol but demonstrates several hitherto unknown biopositive effects in our studies, namely stimulation of the critical extracellular matrix component FN, and accelerated epidermal regeneration and wound healing.
... In its pure form, this natural product was reported to have skin-beneficial effects, such as anti-ageing, anti-pigmentation and anti-acne (Xin et al. 2019). At least some of these effects are believed to stem from its retinoid functionality (Chaudhuri and Bojanowski 2014) and many have been validated in clinical case studies (Draelos et al. 2020;Lyons et al. 2020;Dhaliwal et al. 2019;Jafernik et al. 2020). ...
Bakusylan (bakuchiol salicylate) is a bipartite compound obtained by merging two skin-active entities with complementary bioactivities-bakuchiol and salicylic acid-for the purpose of generating a new class of functional retinoids with enhanced skin benefits. Here, we describe its preparation process and report that pure bakusylan exhibits potential for an improved permeation through the stratum corneum, enhances type IV collagen gene expression in organotypic skin substitutes containing both epidermal and dermal layers, and upregulates this protein in adult human dermal fibroblast cultures. The mechanism of action underlying these effects appears to involve the components of the IP3K/Akt signaling pathway selectively implicated in the maintenance of skin integrity, further underlying the suitability of this ester for skin care applications requiring enhanced cutaneous permeation targeting the dermal-epidermal junction.
... Although retinol's irritation potential is more anecdotal, with little literature to conclusively state that it is irritating, it is known to be drying [19], which should be avoided in a range designed for sensitive skin. Nephelium lappaceum leaf extract plays in the same territory as other actives or compounds, for example Bakuchiol, which aim to show similar efficacy to retinol, but without its downsides [20]. A summary of formulation components and functions of key ingredients across the range can be found in Table S1. ...
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People with self-reported sensitive skin may reluctantly use performing anti-ageing skin care products as it could elicit skin discomfort. We thus aimed to design and test an anti-ageing skin care routine that is suitable for people reporting sensitive skin. Key principles for developing products for sensitive skin were applied and formulas were screened for their mildness in vitro using the Reconstructed Human Epidermis ET50 method. Anti-ageing efficacy and mildness was evaluated during a clinical study in China, with 33 female volunteers aged 40–65 years, with sensitive skin. The anti-ageing benefits were measured using Primos 3D, the cutometer and clinical evaluation. Hallmarks for sensitive skin such as skin hydration, skin barrier, skin redness and response to lactic acid were also measured. The ET50 method yielded values suggesting moderate to mild expected irritancy effect in vivo for most of them, and non-irritating effect for the serum. During the clinical study, no physical or functional signs of discomfort were reported with twice-daily usage of the routine. Instrumental evaluation of Wrinkle depth, skin elasticity/firmness, skin hydration, skin barrier and skin redness revealed improvement at 4 and 8 weeks. Clinical evaluation evidenced skin smoothness, skin suppleness and radiance improvements. The skin was less reactive to lactic acid stimuli, while the sensitive skin burden was lowered according to the dermatological quality of life index. Lastly, a separate investigation suggested the potential relief aspect of such routines to alleviate discomforts from mask wearing. With the right formulation design, the benefits of layering products from a routine can be made accessible to people with sensitive skin while simultaneously alleviating the burden of sensitive skin.
... Myung et al. reported that phenolics can prevent wrinkle formation by reducing the levels of matrix metalloproteinase and inflammatory cytokines and increasing the expression of moisturizing factors and antioxidant genes (33). A previous study has reported that phenolic substances could significantly improve skin's fine lines and wrinkles, pigmentation, elasticity, firmness, and light damage (34). The moisturizing and anti-aging effects of small molecule peptides have also been reported (23). ...
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Selenium-enriched mung bean (Se-MB) is a combination of mung bean (MB) and selenium (Se), which have a variety of potential biological activities. However, little is known about the skincare activity of Se-MB. The chemical composition of Se-MB fermentation broth (Se-MBFB) was analyzed to investigate the whitening, moisturizing, and anti-aging activities of Se-MBFB. The tyrosinase inhibition, anti-melanogenic in melanocytes (B16F10 cells), and moisturizing effect in human dermal fibroblasts (HDFs) were analyzed. Besides, the free radical scavenging activity of Se-MBFB was assessed in vitro. To verify the in vivo effects and the potential of practical applications of Se-MBFB, a clinical trial was conducted on the participants: 31 Chinese women aged 25–60 years, with no pigmentation disorder, no illness, no history of hypersensitivity reaction, and no use of skincare product on the face. The participants used an Se-MBFB masque for 15-20 min after cleaning the face. The measurement points were Week 0, 2, and 4 (W0, W2, and W4) after using the masque, and target sites were cheek and canthus. The following parameters were recorded on the target sites at each visit: melanin index, skin color, cuticle moisture content, transepidermal water loss, and crow's feet. The results demonstrated that Se-MBFB was rich in polyphenols, peptides, and γ-aminobutyric acid (GABA), displayed significant free radical scavenging and tyrosinase inhibiting activities, decreased the synthesis of melanin, and upregulated the aquaporin-3 (AQP3) expression. The test of the Se-MBFB mask showed that after 4 weeks of using the Se-MBFB facemask, the faces of the participants became whiter with reduced wrinkles and increased moisture content. Se-MB possessed the excellent whitening, moisturizing, and antioxidant efficacy, which could lay a scientific foundation for utilization and development of skincare products of Se-MB and its related industrial cosmetics products.
... Terpenes can also combine with phenylpropanoids or phloroglucinols to become 'meroterpenes', such as osthole, which is a prenyl coumarin that is often detected in essential oils [28]. Nevertheless, there are many examples of meroterpenes in the genera Peperomia [29] and Psoralea [30], such as bakuchiol (Figure 7) that are light enough and have polar head space that is low enough to enable collection by hydrodistillation, so it is just a matter of time before such essential oils will be reported in the published literature. ...
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The current text provides a comprehensive introduction to essential oils, their biosynthesis, naming, analysis, and chemistry. Importantly, this text quickly brings the reader up to a level of competence in the authentication of essential oils and their components. It gives detailed descriptions of enantiomers and other forms of stereoisomers relevant to the study of natural volatiles and essential oils. The text also describes GC-MS work and provides tips on rapid calculation of arithmetic indices, how to interpret suggested names from the NIST mass spectral library, and what additional efforts are required to validate essential oils and defeat sophisticated adulteration tactics. In brief, essential oils are mixtures of volatile organic compounds that were driven out of the raw plant material in distillation, condensed into an oil that is strongly aroma emitting, and collected in a vessel as the top layer (uncommonly bottom layer) of two phase separated liquids: oil and water. Essential oils commonly include components derived from two biosynthetic groups, being terpenes (monoterpenes, sesquiterpenes and their derivatives) and phenylpropanoids (aromatic ring with a propene tail). The current text provides details of how terpenes and phenylpropanoids are further categorised according to their parent skeleton, then recognised by the character of oxidation, which may be from oxygen, nitrogen, or sulphur, or the presence/absence of a double bond. The essential oil’s science niche is an epicentre of individuals from diverse backgrounds, such as aromatherapy, pharmacy, synthetic and analytical chemistry, or the hobbyist. To make the science more accessible to the curious student or researcher, it was necessary to write this fundamentals-level introduction to the chemistry of essential oils (i.e., organic chemistry in the context of essential oils), which is herein presented as a comprehensive and accessible overview. Lastly, the current review constitutes the only resource that highlights common errors and explains in simplistic detail how to correctly interpret GC-MS data then accurately present the respective chemical information to the wider scientific audience. Therefore, detailed study of the contents herein will equip the individual with prerequisite knowledge necessary to effectively analyse an essential oil and make qualified judgement on its authenticity.
... However, Bakuchiol was more tolerable than retinol suggesting that bakuchiol can act as functional analogue of retinol.78,79 The authors also reported significant improvement in lines and wrinkles, pigmentation, elasticity, firmness and decrease in photo-damage without undesirable effects associated with retinol therapy.80 3.2.10 ...
Hyperpigmentation is the most common complaint in the age group 40–45 years, seeking consultation for skin disorders. Hydroquinone is a commonly used depigmenting agent in clinical practice for treating hyperpigmentation. Prolonged use of hydroquinone has been associated with cancer risk and exogenous ochronosis. The CARES (The Coronavirus Aid, Relief, and Economic Security Act) Act of 2020 has instituted significant changes to hydroquinone containing OTC (over the counter) products, and consequently, many hydroquinone-based OTC products had to be withdrawn from the market. Henceforth, products containing hydroquinone would need US Food and Drug Administration approval via new drug application pathways for commercialization. Alternative treatment options to hydroquinone in clinical practice are reviewed in this paper with regard to their safety and efficacy vis a vis hydroquinone. Also, new potential treatment options such as thiamidol, Polypodium leucotomos, and glutathione are discussed. The review shows that these alternative depigmenting agents can be rationally combined to achieve desired treatment goals in the management of hyperpigmentation.
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Bakuchiol is an emblematic meroterpene class of natural product extracted from Psoralea corylifolia. It has been reported to possess a broad range of biological and pharmacological properties and is considered as a leading biomolecule. It is highly desirable to devise an efficient approach to access bakuchiol and its chemical biology applications. In this review we provided structural features, isolation methods, various chemical routes and late-stage functionalization (LSF) approaches for bakuchiol and its derivatives. Moreover, this review encompasses the structure–activity relationships (SAR), value-added contributions and future perspectives of bakuchiol.
Objective: Because they limit, even reverse, age-induced skin alterations, retinoids became a staple in cosmetology. However, their use can result in undesired secondary effects and there is a demand for natural sources of compounds with retinoid like effects. A preliminary screening identified a Harungana madagascariensis plant extract (HME) as possibly inducing genes stimulated by retinol. We analysed its effect on gene and protein expression, comparing it to retinoids. Methods: Gene expression was analysed by real-time qPCR on RNA from isolated fibroblasts subjected to retinol or the plant extract for 6, 48 or 96 hours. Skin markers were quantified in fibroblasts cultured with retinol or extract containing medium, and UV-aged skin explants subjected to topical applications of creams containing retinol, retinaldehyde or HME. Results: Real-time qPCR show that the extract induced all RARs and RXRs, even RXRγ that was not induced by retinol. Eighty-eight percent of the 25 early retinoid reaction genes induced by a concentration of retinol are induced by the extract. In fibroblasts, only the extract increased collagen III labelling, while collagen I and fibronectin labelling are increased by retinol and the extract, with higher levels for the extract. When topically applied to UV-aged skin explants, only the cream containing the HME led to increased labelling of CRABP1 in the epidermis. CRABP2 and Ki67 are induced by all three creams and no effect was detected on RXRs. In the dermis the extract containing cream increased CRABP2, total collagen, procollagen I and collagen I while creams with retinol or retinaldehyde only affected some of these proteins. Conclusions: The HME induces an overall retinol-like gene induction profile in isolated fibroblasts and retinoid-like stimulation of protein synthesis in both isolated fibroblasts and photoaged skin explants.
Background Psoralea corylifolia is a renowned medicinal plant in the arena of traditional herbal medicine. It has been extensively used in the treatment of various skin disorders, including psoriasis, vitiligo, eczema, leprosy and other maladies. P. corylifolia possesses anti-vitiligo, anti-microbial, oestrogenic, anti-tumor, anti-depression, anti-diabetic, anti-inflammatory, anti-oxidant, immunomodulatory properties, etc. which can be attributed to the presence of elite phytochemicals. Aim of the study The purpose of this study was to consolidate the information on traditional-medicinal uses, phytochemistry, pharmacological activities, toxicity trials and commercial medicinal products of P. corylifolia. Methodology Data was gathered from various engines such as Pubmed, Science Direct, Google Scholar, Scopus, etc. Information on the aforementioned topics from 266 references was meticulously organized and included in this review. Key findings A total of 155 bioactive compounds belonging to the chemical class of flavones, coumarins, meroterpenes, chalcones, stigmasterols, flavonoids etc., have been isolated from P. corylifolia plant parts. The main phytochemicals which are concerned with its anti-psoriasis property are psoralen, isopsoralen. Conclusion Although the medicinal uses and safety of P. corylifolia extracts have been time-tested, more meticulous and in-depth studies regarding its bioactive constituents' extraction regimes, stability and activity (mode of action) are still required. Future research should also focus on clinical trials related to the dosage optimization of its extracts. We hope that this compendium will serve as an easy resource and encourage future research on P. corylifolia, for better healthcare.
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Vitamin A is involved in the biosynthesis of the visual pigment rhodopsin (1), in embryogenesis (2), as well as in cell growth and differentiation (3). It exists in interconvertible forms as retinol, its esters (the main storage form in the body) and retinaldehyde, whereas the latter is irreversibly converted to retinoic acid, the biologically active form of vitamin A that binds to nuclear receptors and modulate gene expression (Fig. 1) (4,5). Retinoic acid exists as three cis/trans isomers: all-trans-, 9-cis- and 13-cis- retinoic acid; all-trans-retinoic acid (retinoic acid, tretinoin) binds to the nuclear receptors such as retinoic acid receptor (RAR)-α, β, and γ with a high affinity, 9-cis-retinoic acid (alitretinoin) binds to RAR-α, β, γ and retinoid X receptor (RXR)-α, β, γ with a high affinity, whereas 13-cis-retinoic (isotretinoin) does not bind to nuclear retinoid receptors with significant affinity (6,7).
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KEY WORDS: acne, bakuchiol, antioxidant, anti-inflammatory, antibacterial, matrix metalloprotease ABSTRACT: Bakuchiol, a meroterpene of plant origin, is shown here to act against four major pathophysiologic features that cause acne, suggesting its use to complement and/or enhance the effectiveness of current anti-acne agents. In addition, the material is non-irritating, presents no photo-or hydrolytic-stability issues and is easy to use.
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OBJECTIVE: To study the nephrotoxicity induced by bakuchiol alone and bakuchiol combined with psoralen and to explore its mechanism. METHODS: The cytotoxicities of bakuchiol and bakuchiol combined with psoralen were investigated using human renal tubular epithelial cell lines (HK-2) , in presence or absence of hepatic S9 mixture. The HK-2 cells were exposed culture medium alone (blank control), 0.5% DMSO (vehicle control), aristolochic acid I (AA I; positive control) , psoralen 5 μ-L-1 group, bakuchiol 5, 10, 20, 30 and 40 μ-L-1 groups, and bakuchiol + psoralen (20+5) , (30+5) and (40+5) μmol·L-1 groups, respectively. The cell viabilities were examined by MTT assay; cell membrane injuries were examined by detecting lactate dehydrogenase ( LDH ) release rate ; and the morphological changes in HK-2 cells were observed with contrast microscope. The rate of cell apoptosis was detected by Annexin V/PI staining, and cell cycle was detected by PI staining with flow cytometry. RESULTS: No cytotoxicity was found in psoralen 5 μmol·L-1 group. The HK-2 cell viabilities were significantly reduced after 4, 24, 48 and 72 h of exposure to either bakuchiol 20, 30 and 40 μmol·L-1 groups or bakuchiol + psoralen (20+5), (30+5) and (40+5) μmol·L-1 groups in a time- and concentration-dependent manner. The IC50 values of bakuchiol were (26.4±4.8), (21.8±0.6) and (24.1±0.8)μmol·L -1 for 24, 48 and 72 h exposure, respectively. The cytotoxicity of bakuchiol was significantly decreased in presence of hepatic S9 mixture. The LDH release rate of HK-2 cell increased significantly after 24 h of exposure to bakuchiol 20, 30 and 40 μmol·L-1 or bakuchiol + psoralen groups. With the concentration and time increasing, the HK-2 cells became more and more contracted and rounded. In bakuchiol 40 μmol·L-1 or bakuchiol + psoralen (20+5), (30+5) and (40+5) μmol·L-1 groups, HK-2 cells showed apoptotic characters. In bakuchiol or bakuchiol + psoralen groups, apoptotic cells significantly increased and cells in G 2 phase markedly decreased. CONCLUSION: Bakuchiol has a significant cytotoxicity in HK-2 cells, and combined with psoralen can not decrease its toxicity. The cytotoxicity of bakuchiol is significantly reduced in the presence of hepatic S9 mixture. The possible mechanisms of the renal cytorotoxicity of bakuchiol are as follows: Circle digit 1 direct damage to the cell membrane; Circle digit 2 inducing cell apoptosis; Circle digit 3 inhibiting intracellular DNA synthesis and block cell mitosis and proliferation.
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Retinol is an ingredient used in cosmetic products for reducing the appearance of the signs of aging and photo-damage. Currently, most of these products contain 0.1% of retinol. However, at this concentration, some irritation can occur. We have evaluated in vitro and in a clinical study the potential efficacy of a combination of actives to improve the facial skin aging signs while using low concentration of retinol. We demonstrated, in vitro, that a chromone derivative, 5,7-di-hydroxy-2-methyl chromone (DMC), is able to enhance the collagen synthesis in culture of normal human dermal fibroblasts. The enhancement of retinol anti-wrinkle efficacy by DMC was confirmed in a small scale clinical trial. Specifically, a product associating low concentration of retinol (0.04%) and DMC (0.1%) in combination with low mo-lecular weight hyaluronic acid fragments (50,000 Dalton of average molecular weight) has been applied topically for 8 weeks. Clinical results show significant improvement of various signs of facial skin aging such as wrinkles, pigmentary spots, tone unevenness, dullness and the overall photo-damage score. Improvements were still visible 4 weeks after the cessation of the test product application. This study demonstrates that significant lasting improvement of facial skin aging can be obtained with well tolerated low concentration of retinol when adequately formulated with other anti-aging ingredients.
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Bakuchiol, a terpene phenol from Psoralea corylifolia Linn has only one asymmetric centre. By suitable correlation with (+)-linalool on the one hand and, with (+)-3-methyl-3-methoxy-carbonyl-n-valeria acid on the other, it has been shown to possess (S)-chirality.
Isolation and structure elucidation of a novel monoterpene phenol, bakuchiol, from the seeds of Psoralea corylifolia Linn, is described.