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Caffeine’s Mechanisms of Action and Its Cosmetic Use


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Caffeine is being increasingly used in cosmetics due to its high biological activity and ability to penetrate the skin barrier. This alkaloid is frequently used as a hydrophilic model substance in human and animal skin penetration as well as different synthetic membrane using Franz diffusion cell experiments. The commercially available topical formulations of caffeine normally contain 3% caffeine. As for a cosmetic purpose, caffeine is used as an active compound in anti-cellulite products because it prevents excessive accumulation of fat in cells. This alkaloid stimulates the degradation of fats during lipolysis through inhibition of the phosphodiesterase activity. Caffeine has potent antioxidant properties. It helps protect cells against the UV radiation and slows down the process of photoaging of the skin. Moreover, caffeine contained in cosmetics increases the microcirculation of blood in the skin and also stimulates the growth of hair through inhibition of the 5-alpha-reductase activity. Copyright (C) 2012 S. Karger AG, Basel
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Skin Pharmacol Physiol 2013;26:8–14
DOI: 10.1159/000343174
Caffeine’s Mechanisms of Action and Its
Cosmetic Use
A. Herman a A.P. Herman b
a Academy of Cosmetics and Health Care, Warsaw , and
b The Kielanowski Institute of Animal Physiology and
Nutrition, Polish Academy of Sciences, Jabłonna , Poland
Caffeine is one of the alkaloids which can be found in
coffee, tea and some soft drinks. Caffeine is well known
as a mild stimulant of the central nervous system where
it is transported with blood after its absorption in the
stomach and small intestine. In the liver, caffeine is me-
tabolized by the cytochrome P450 oxidase system into 3
derivative dimethylxanthines: paraxanthine (speeds up
lipolysis), theobromine (expands blood vessels), and the-
ophylline (relaxes smooth muscles of the bronchi)
[1] .
These metabolites of caffeine after demethylation and ox-
idation pass to derivatives of xanthine and uric acid. Only
10% of the caffeine is excreted from the body by the kid-
neys in an unchanged form
[2] . In the brain, caffeine as a
ligand (instead of adenosine) blocks the adenosine A1
and A2 receptors
[3] . Both ligands, caffeine and adeno-
sine, show a high similarity of their chemical structures
[4] . They can affect the release of neurotransmitters such
as acetylcholine, dopamine, noradrenaline, gamma-ami-
nobutyric acid, and serotonin, which enhances mood
[5] ,
stimulates the organism, improves concentration and
eliminates physical fatigue
[6] . Caffeine also inhibits
phosphodiesterase (PDE) activity, an enzyme which is re-
Key Words
Caffeine Penetration through the skin Cellulite
Microcirculation Antioxidant
Caffeine is being increasingly used in cosmetics due to its
high biological activity and ability to penetrate the skin bar-
rier. This alkaloid is frequently used as a hydrophilic model
substance in human and animal skin penetration as well as
different synthetic membrane using Franz diffusion cell ex-
periments. The commercially available topical formulations
of caffeine normally contain 3% caffeine. As for a cosmetic
purpose, caffeine is used as an active compound in anti-cel-
lulite products because it prevents excessive accumulation
of fat in cells. This alkaloid stimulates the degradation of fats
during lipolysis through inhibition of the phosphodiesterase
activity. Caffeine has potent antioxidant properties. It helps
protect cells against the UV radiation and slows down the
process of photoaging of the skin. Moreover, caffeine con-
tained in cosmetics increases the microcirculation of blood
in the skin and also stimulates the growth of hair through
inhibition of the 5- -reductase activity.
Copyr ight © 2012 S. Karger AG, Ba sel
Recei ved: April 3, 2012
Accepted a fter revision: August 29, 2012
Publish ed online: October 11, 2012
Ann a Herman, PhD
Academy of Cosmetics and He alth Care
Podwa le 13 street
PL–00-252 Warsaw (Poland)
E-Mail anna.herman @
© 2012 S. Ka rger AG, Basel
Accessible online at:
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Caffeine’s Mechanisms of Action and Its
Cosmetic Use
Skin Pharmacol Physiol 2013;26:8–14
sponsible for the degradation of cyclic adenosine mono-
phosphate (cAMP) to the noncyclic form 5 -A MP [3] . The
inhibition of PDE increases the cAMP concentration in
cells and also elevates blood pressure
[3] . Although the
impact of caffeine on the human organism is well under-
stood, the mechanism of the cosmetic action of caffeine
has not been fully explained. Given that coffee and caf-
feine are used increasingly for the production of many
cosmetics, it seems interesting to clarify whether it is re-
ally able to improve the skin’s appearance and the hair’s
condition. The ability of caffeine to penetrate the skin
barrier is essential when discussing the mechanism of its
action on skin and hair.
Penetration of Caffeine through the Skin Barrier
The ability of active compounds from cosmetics or
pharmaceuticals to influence the metabolism of cells and
other processes occurring in the skin is largely dependent
on the capacity of these molecules to penetrate through
the skin barrier. Caffeine is frequently used as a hydro-
philic model substance in skin penetration experiments
[7–11] . Previous studies found out that caffeine penetra-
tion of the skin barrier was unchanged by occlusion
and skin thickness
[13 , 14] , but the application of 5% caf-
feine in a hydroxyethylcellulose gel for 7 days significant-
ly reduced transepidermal water loss in male skin com-
pared with female skin
[15] . The maximal absorption
rates of caffeine through the human skin were found to
be 2.24 8 1.43 g/cm 2 /h [13] , and the maximal absorp-
tion was reached at 100 min after local application in vivo
[16] . Touitou et al. [17] using quantitative skin autoradi-
ography found out that after 24 h, the greatest concentra-
tion of caffeine (280 g/tissue) was localized in the epi-
dermis, while the lowest amount of this alkaloid (50 g/
tissue) was detected in the dermis.
The penetration of caffeine was also compared in
Franz-type diffusion cell experiments with different
coated membranes, e.g. skin of humans
[8, 18, 19] and
[9, 10] or synthetic materials [20, 21] . The perme-
ation of different concentrations of caffeine (3% and 1, 3,
and 5%) through human skin and synthetic membranes
(cellulose acetate impregnated with isopropyl myristate,
silicone rubber soaked in isopropyl myristate and poly-
sulfate) using Franz
diffusion cells were compared by
Dias et al.
[20] and Mustapha et al. [21] , respectively. Both
research groups did not find a correlation between caf-
feine transfers through the synthetic membranes and
those observed through the human skin. Moreover, Mu-
stapha et al.
[21] show ed t ha t the d if fusion flux of caf feine
permeation does not depend on the concentration but
rather on the quantity of formulation applied. Also Sha-
keel and Ramadan [10] confirmed that the type of emul-
sion affects the transdermal delivery of caffeine. A sig-
nificant increase in the permeability of caffeine in Franz
diffusion cells using rat skin as permeation membrane
was observed in water-in-oil nanoemulsion formulations
as compared to aqueous solutions of caffeine
[10] .
Other studies concerned the permeation of caffeine
from microspheres applied in aqueous suspension (diam-
eter of the microspheres: 2.8 m, caffeine loading: 2.3
mg/g of particles) and from solution through in vitro dif-
fusion measurements with Franz-type diffusion cells
over 24 or 72 h
[22] . After 24 h, the total amount of caf-
feine from microspheres carried out on full-thickness
skin without hypodermis was twice as high as that from
aqueous solution (22.6 vs. 9.99%). The results suggested
that microspheres could easily penetrate through the skin
and accumulate in the receptor compartment, ensuring
continuous caffeine release. After 72 h of exposure, the
receptor fluid contained 15.3% free caffeine and 27.8%
encapsulated fractions. For the cosmetic use of caffeine,
its penetration through the skin is the key.
Anti-Cellulite Properties of Caffeine
Cellulite (gynoid lipodystrophy), commonly called
‘orange peel effect’, is a typical women’s problem, which
mainly appears on the thighs and buttocks. Cellulite is
a complex disorder involving the microcirculatory and
lymphatic systems, the extracellular matrix and the pres-
ence of excess subcutaneous fat that bulges into the der-
[23] . Lipolysis is the degradation process of triglycer-
ides from adipocytes by lipoprotein lipases, leading to
the formation of fatty acids and glycerol. Lipases located
on the fat cell membrane can be activated or inhibited
by catecholamines (noradrenaline and adrenaline) and
hormones (insulin, glucagon, and adrenocorticotropin).
Adrenaline, noradrenaline, glucagon, and adrenocorti-
cotropin activate the lipases, while insulin inhibits the
activity of these enzymes. Depending on the hormones
and type of adrenergic receptor ( or ) in adipocytes, the
lipolysis process can be activated or inhibited. Insulin
binding to the adrenergic receptor stimulates the col-
lection of fat in adipocytes, while the second receptor (
adrenergic) binds to adrenaline, noradrenaline, gluca-
gon, or adrenocorticotropin and stimulates the degrada-
tion of fats during the lipolysis process. The biological
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Skin Pharmacol Physiol 2013;26:8–14
compounds activating the lipolysis pathway induce the
conformational change in the structure of the G protein-
coupled receptor and stimulate the adenylate cyclase to
synthesize the cytosolic cAMP. An increasing level of
cAMP stimulates protein kinase A to activate hormone-
sensitive lipase (HSL) by phosphorylation. Phosphorylat-
ed HSL hydrolyzes triglycerides into diglycerides, mono-
glycerides, free fatt y acids, and glycerol. The lipolysis pro-
cess can be inhibited by a decreasing level of cAMP. PDE
activity is responsible for the degradation of cAMP into
its noncyclic form 5 -AMP [24, 25] .
Caffeine can affect the above-mentioned intracellular
signaling pathways in several ways. It may affect the se-
cretion of catecholamine, which activates adrenergic
receptors, increases the concentration of cAMP in cells
and activates HSL in the lipolysis process
[26] . This alka-
loid also blocks adrenergic receptors, preventing an
excessive accumulation of fats, and speeds up the lipoly-
sis process
[27, 28] . Caffeine also stimulates lipolysis via
the inhibition of PDE activity and by increasing the
cAMP levels in adipocytes
[29] . Then caffeine activates
HSL, which leads to the degradation of triglycerides in
4 x cAMP
4 x cAMP
Adipocyte triglyceride
lipid droplet
Adipocyte cell membrane
Glycerol FFA
reduction of adipocyte
lipid droplet size
Lipolysis (hydrolysis of
stored triglycerides)
Fig. 1. Caffeines mechanism of action
during lipolysis in adipocyte. GDP = Gua-
nosine diphosphate; GTP = guanosine tri-
phosphate; AC = adenylate cyclase; ATP =
adenosine triphosphate; PKA = protein
kinase A; HSL-P = phosphorylated hor-
mone-sensitive lipase; TG = triglyceride;
DG = diglyceride; MG = monoglyceride;
FFA = free fatty acid.
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the lipolysis process, and takes part in the reduction of
cellulite ( fig.1 ). Caffeine also stimulates the draining
lymph systems in fatty tissue by removing accumulated
fat, toxin and unnecessary substances arising during the
lipolysis process, which all together may impede the mi-
crocirculation in blood vessels and foster the emergence
of cellulite.
Pires-de-Campos et al. [30] explored the effect of gel
application on swine hypodermis (dorsal area): gel with
ultrasound treatment (3 MHz, intensity: 0.2 W/cm
2 , rate:
1 min/cm
2 ), gel with caffeine (5%, water-in-water), and
gel with caffeine and ultrasound, daily for 15 days. A pre-
specified (fifth) area received no topical application and
was used as control. Among all the experimental groups,
only caffeine treatment associated with ultrasound ther-
apy was effective. The results showed a significant reduc-
tion in the thickness of the subcutaneous adipose tissue,
as well as damage of the adipocytes, consequently de-
creasing the number of cells. Velasco et al.
[31] also exam-
ined the effect of emulsion with caffeine, caffeine and so-
dium benzoate, and siloxanetriol alginate caffeine (SAC)
on the diameter and number of fatty cells with a light mi-
croscope. Emulsion with caffeine and its derivatives was
applied topically for 21 days on Wistar female mice.
Emulsion with caffeine and SAC provoked a reduction of
the diameter of fatty cells compared with controls of 17
and 16%, respectively, while the emulsion with caffeine
and sodium benzoate did not cause alterations of the cell
diameter; moreover, sodium benzoate inhibited the effi-
ciency of caffeine. Caffeine also had a significant anti-
cellulite effect versus baseline, shown by its superiority
versus placebo in the skin’s macrorelief (it decreased the
‘orange peel’ effect), and increased the cutaneous micro-
[32] .
Caffeine’s Effect on Microcirculation of Blood
Caffeine can improve the microcirculation of blood
vessels. Some research carried out using computed to-
mography showed that a dose of 250 mg caffeine given
orally increased the circulation of blood in the human
brain by 30%
[33] and a dose of 100 mg caffeine given
orally increased the microcirculation of blood in the hu-
man ocular fundus
[34] . The study performed by Lupi et
[35] showed that a 7% caffeine solution affected the
reduction of cellulite and improved the microcircula-
tory blood flow in all women taking part in the experi-
ment. For observing the changes in the blood microcir-
culation, a noninvasive method was used – orthogonal
polarization spectral imaging, which determined capil-
lary density (number of flowing capillaries per unit area
of the skin) and centimetrical measurements of thighs
and hips. In the same study, the inf luence of tobacco,
alcohol and physical activity on the effectiveness of the
cellulite treatment was also examined. A significant re-
duction of thigh circumferences in more than 80% of the
cases and a reduction of hip circumference in 67.7% were
observed after 1 month of treatment. The capillary den-
sity after 1 month of caffeine administration was slight-
ly increased, but the changes were not statistically sig-
nificant. The results of Lupi et al.’s study
[35] showed
that smoking, alcohol consumption and regular physi-
cal activity do not affect the reduction of hip circuit in
Caffeine can effectively reduce swelling of the tissue
around the eyes. Amnuaikit et al.
[18] compared the im-
pact of both a 3% caffeine gel and a gel base on the de-
crease of puffy eyes among Thai volunteers (18 women
and 16 men, aged 19–24 years). An insignificant differ-
ence between the efficacy of caffeine gel and gel base to
reduce puffy eyes was found as only 23.5% of the volun-
teers responded to the caffeine activity.
Antioxidant Properties of Caffeine
It is well known that UV rays accelerate photoaging of
the skin, reduce the synthesis of procollagen, affect the
fiber of collagen, reduce skin elasticity, cause expansion
and cracking of skin blood vessels, stimulate the forma-
tion of wrinkles, spots and discoloration, and in extreme
cases they can lead to cancer of the skin, e.g. melanoma
[36] . UV radiation also increases the production of free
radicals, leading in consequence to cell damage. Adding
caffeine to the formula of sunscreen cosmetics raises its
protective effect against UV radiation, reduces the for-
mation of free radicals in skin cells and could be useful
in preventing UV-induced skin cancers
[37, 38] . Leon-
Carmona and Galano
[39] revealed that caffeine is an ef-
fective scavenger of hydroxyl radicals ( OH) and alkoxyl
radicals ( OCH 3 ), a poor scavenger of HOO( ) radicals,
inefficient for directly scavenging O
2 ( –) and ( )OOCH 3
radicals and most likely other alkyl peroxyl radicals.
There are also reports concerning the impact of caffeine
on the protection of skin cells from cancer caused by UV
Caffeine affects the UV-damaged cells of human
skin causing cellular divisions and apoptosis before they
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Skin Pharmacol Physiol 2013;26:8–14
begin to transform into cancer cells. Kerzendorfer and
[36] demonstrated that caffeine administered
orally or topically accelerated apoptosis of mice keratino-
cytes damaged by UVB radiation. The study performed
by Abel et al. [40] also demonstrated that daily intake of
coffee ( 1 6 cups) caused a 30% reduction in the prevalence
of nonmelanoma skin cancer in Caucasian women. Oth-
ers found that caffeine has the ability to selectively induce
apoptosis in vitro in UV-damaged keratinocytes
[41] .
Studies were carried out on p53-mutated keratinocytes,
isolated from the human skin. This cell line contains
about 4% mutated keratinocytes from all isolated kerati-
nocytes of the human skin. In comparison with the other
keratinocytes isolated from the skin, p53-mutated kerati-
nocytes are more resistant to UV-induced apoptosis.
Sunlight also acts as a tumor promoter by favoring the
clonal expansion of p53-mutated cells over the other ke-
ratinocytes of the skin. Caffeine induced apoptosis in
p53-defective cells. Lu et al.
[42] demonstrated that topi-
cal application of caffeine to mice enhanced the elimina-
tion of p53-mutated keratinocytes from the skin. Immu-
nohistochemical analyses showed that topical applica-
tions of caffeine increased apoptosis in nonmalignant
skin tumors and in squamous cell carcinomas, but there
was no effect on apoptosis in tumor-free areas of the epi-
dermis. Also Kramata et al.
[43] reported that mice oral-
ly treated with caffeine or green tea during chronic UVB
irradiation showed changes in the mutation profile of the
p53 gene in early mutant p53-positive epidermal patches.
Topical applications of caffeine after discontinuing the
chronic UVB irradiation specifically eliminated patches
harboring homozygous p53 mutations. Studies carried
out by Heffernan et al.
[44] explained the caffeine’s mech-
anism of action for these important observations. Caf-
feine at a concentration of 2 m
M inhibits cAMP PDE, in-
creases the intracellular levels of cAMP and promotes
apoptosis in UV-damaged primary human keratinocytes
[44] . Also Conney et al. [45] showed that the oral admin-
istration of green tea or caffeine to hairless SKH-1 mice
for 2 weeks stimulated apoptosis in UV-induced sun-
burnt cells in the epidermis. A similar effect was observed
when caffeine was applied topically immediately after
UV exposure. In mice pretreated with UV radiation for
22 weeks (high-risk mice without tumors), topical appli-
cations of caffeine 5 days a week for 18 weeks with no
further UV treatment inhibited carcinogenesis and stim-
ulated apoptosis in the tumors. In another next experi-
ment, Conney et al.
[46] s ho wed t ha t c af fe in e a nd ca ff ei ne
and sodium benzoate may be useful as novel inhibitors of
sunlight-induced skin cancer. They found out that the ap-
plication of caffeine and sodium benzoate was more ac-
tive as sunscreen than caffeine alone. Also caffeine and
sodium benzoate stimulated apoptosis of UVB-induced
carcinogenesis more than caffeine and they were also
highly active in inhibiting carcinogenesis in UVB-pre-
treated high-risk mice.
Caffeine’s Effects on the Growth of Hair
5- -r edu ct as e is a n enz ym e t hat conv er ts te stosterone
into the more active dihydrotestosterone (DHT), which
is responsible for baldness. Particularly sensitive to the
action of DHT are hair follicles. Its application results in
a shortened anagen phase of the hair growth cycle, most
of the hair goes into the telogen phase with fallowing hair
follicle miniaturization and reduction of hair roots. The
newly growing hair is thinner and shorter, and after sev-
eral cycles of hair growth, the hair ceases to grow. Caf-
feine inhibits the activity of the 5- -reductase enzyme
and allows a renewed growth phase of the hair
[47] . Caf-
feine in concentrations of 0.001 and 0.005% led to a sig-
nificant stimulation of human hair follicle growth in vi-
[47] . The stimulating effects of caffeine on the growth
of the hair can also be explained by its ability to inhibit
PDE enzymes. Inhibiting PDE activity increases the in-
tracellular concentration of cAMP, stimulating cellular
metabolism in a multitude of new cells
[47] . Caffeine re-
duces smooth muscle tension near the hair follicle caus-
ing an easier delivery of nutrients through the blood ves-
sels of the papillae of the hair
[47] . Caffeine also arouses
capillary vessel microcirculation in the skin of the head,
thereby contributing to nurture hair bulbs. It strength-
ens and stimulates rapid growth by regularly providing
nutrients with blood to the hair
[46] . Teichmann et al.
[48] and Lademann et al. [49] demonstrated that a 2-min
contact of a shampoo with caffeine was sufficient for the
formulation to penetrate deeply into the hair follicles and
remain there for up to 48 h, even after washing of the
hair. Otberg et al.
[50] showed that there is a quantitative
distinction between follicular penetration and interfol-
licular diffusion of a formulation containing 2.5% caf-
feine applied to the chest of male Caucasian volunteers
aged 2639 with normal body mass indices. Caffeine
(3.75 ng/ml) was detected in blood samples 5 min after
topical application, when the follicles remained open.
When the follicles were blocked, caffeine was detectable
after 20 min (2.45 ng/ml). The highest values (11.75 ng
caffeine/ml) were found 1 h after application, when the
follicles were open. The ability of caffeine to penetrate
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Skin Pharmacol Physiol 2013;26:8–14
the hair follicles and to stimulate the human hair growth
in vitro may have an important clinical impact on the
management of androgenetic alopecia, a common prob-
lem in men of all ages.
S u m m a r y
Extracts from coffee have a wide spectrum of actions;
therefore, they are used in many kinds of cosmetics. Caf-
feine stimulates the metabolism, contributes to the re-
moval of deposits of toxins from the organism, reduces
puffy eyes, accelerates the drainage of the lymph system
from fatty tissue, improves the microcirculation of the
blood in the capillary vessels, exhibits anti-cellulite prop-
erties, activates lipolysis, and releases the excess of fat
from adipocyte cells by reducing their size. Polyphenol
compounds contained in coffee have antioxidant proper-
ties (protecting against the UVB radiation), neutralize
free radicals, and therefore are used as sunscreen in anti-
wrinkle and anti-aging cosmetics. Caffeine is also used
in hair-care products because it reduces and slows down
the process of baldness and also stimulates hair growth.
All these properties make caffeine an important biologi-
cally active compound which can be used in different cos-
metic products. New findings concerning the biological
proper ties of t his alkaloid wi ll make that the spec tru m of
caffeine applications in the field of cosmetology and der-
matology in the future may be even wider. For this pur-
pose, more research is necessary to determine the appro-
priate doses and delivery systems for caffeine penetration
through the skin. There is little scientific data based on
clinical trials and none about the side effects of the cos-
metic use of caffeine. More research is needed to confirm
or deny the cosmetic application of caffeine.
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... Caffeine has also been shown to exhibit anti-oxidant activity [18,19], including the ability to inhibit lipid per-oxidation [20]. As with piroctone olamine, it is expected that follicular delivery of caffeine will enhance its anti-oxidant activity in a region that will be beneficial for hair retention. ...
Full-text available
A key factor in the prevention of hair loss is the provision of optimal conditions on the scalp. In this regard, reduction of oxidative stress on the scalp is one critical requirement to support the hair follicles to function optimally. Recently, a novel shampoo formulation technology containing anti-oxidants such as piroctone olamine has been demonstrated to improve hair retention based on micellar degradation and coacervation effects. Caffeine has also been shown to exhibit anti-oxidant activity including the ability to inhibit lipid peroxidation. As with piroctone olamine, it is expected that follicular delivery of caffeine will enhance its anti-oxidant activity in a region that will be beneficial for hair retention. In this study, two shampoo formulations as well as a control formulation were applied to the calf area of n = 9 male participants. The technique of differential tape stripping was applied to obtain the caffeine penetrated to the stratum corneum and to the hair follicles. Isotope-dilution liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) was performed to demonstrate caffeine follicular delivery from the shampoo formulas. The results showed that the percentage of caffeine recovered in the hair follicles was 8–9% of the caffeine absorbed into the skin and matched an existing caffeine-based shampoo. In conclusion, a novel shampoo formulation technology has been developed that effectively delivers beneficial anti-oxidants to improve hair retention. This new shampoo is expected to be especially useful in the goal of retaining hair during aging.
... Apart from these applications, the cosmetics industry has also developed caffeine-based products for weight loss and beauty care. Caffeine can promote skin blood microcirculation, prevent fat accumulation, and provide antioxidant benefits [20]. ...
Full-text available
Caffeine is a metabolite derived from purine nucleotides, typically accounting for 2-5% of the dry weight of tea and 1-2% of the dry weight of coffee. In the tea and coffee plants, the main synthesis pathway of caffeine is a four-step sequence consisting of three methylation reactions and one nucleosidase reaction using xanthine as a precursor. In bacteria, caffeine degradation occurs mainly through the pathways of N-demethylation and C-8 oxidation. However, a study fully and systematically summarizing the metabolism and application of caffeine in microorganisms has not been established elsewhere. In the present study, we provide a review of the biosynthesis, microbial degradation, gene expression, and application of caffeine microbial degradation. The present review aims to further elaborate the mechanism of caffeine metabolism by microorganisms and explore the development prospects in this field.
Free radicals are generated as a result of different chemical reactions occurring in living cells. Excessive production of these free radicals leads to oxidative stress. Endogenous free radical production is associated with cellular respiration, immune response, infections, inflammations, several types of cancers, and the process of aging. The mitochondrion is the primary organelle involved in the generation of reactive oxygen species (ROS). External sources involved in the generation of free radicals include heavy metals, environmental toxins, chemical solvents, specific medications, overcooking, alcohol, cigarette smoke, and radiation. ROS produced by all these endogenous and exogenous sources can damage cell membranes as a result of lipid peroxidation chain reactions. ROS can also damage protein structure by modification in the structures of amino acids. Nuclear and mitochondrial DNA are also damaged due to high levels of ROS production that lead to spontaneous mutations and cancers. In addition to different types of cancers, ROS also takes part in hypertension, Alzheimer’s disease, the process of aging, and other physiological abnormalities. Antioxidants are substances that mitigate or eliminate the effects of free radicals. Free radicals receive an electron from these antioxidants and become less reactive. Natural antioxidants are categorized as endogenous antioxidants and exogenous antioxidants. Nowadays, much focus is on those exogenous antioxidants which we get from food. Maintaining a healthy equilibrium between free radicals and antioxidants is crucial for optimal physiological functions.
The hydration structure and related dynamics of caffeine diluted in ambient liquid water have been extensively studied by performing classical molecular dynamics simulations, using our previously developed potential model of caffeine and the TIP4P/2005 water model. The results obtained have revealed that the first hydration shell of caffeine contains on average 56 water molecules. Hydrated caffeine forms in total 3 hydrogen bonds with its neighbor water molecules, with the Ocaffeine … Hwater hydrogen bonds exhibiting similar lifetimes with the ones corresponding to Owater … Hwater hydrogen bonds in liquid water. The self-diffusion coefficient of caffeine has been found to be four times lower than the corresponding value for water, being also in agreement with recent experimental measurements. The presence of water molecules inside the solvation shell of caffeine changes significantly their low-frequency intermolecular vibrations, as reflected on the calculated atomic velocity time correlation functions and corresponding spectral densities. Using the estimated average intermolecular structure of the first hydration shell of caffeine, the molecular cluster caffeine@W56 was optimized via quantum chemical calculations and subsequently the time-dependent density functional theory was used in order to predict the ultraviolet–visible and fluorescence spectra of hydrated caffeine. The results obtained are in agreement with recent experimental studies, which have proposed that such spectroscopic measurements can be used for the direct determination of alkaloids in aqueous extracts of natural products. In this framework, multi-scale molecular modelling providing accurate predictions of experimental data could also be a very useful tool, linking theoretical physical chemistry with analytical chemistry applications.
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Obesity and overweight are associated with an increasing risk of developing health conditions and chronic non-communicable diseases, including cardiovascular diseases, cancer, musculoskeletal problems, respiratory problems, and mental health, and its prevalence is rising. Diet is one of three primary lifestyle interventions. Many bioactive components in tea especially oolong tea, including flavonoids, gamma-aminobutyric acid (GABA), and caffeine were reported to show related effects in reducing the risk of obesity. However, the effects of GABA oolong tea extracts (OTEs) on high-fat diet (HFD)-induced obesity are still unclear. Therefore, this study aims to explore whether the intervention of GABA OTEs can prevent HFD-induced obesity and decipher its underlying mechanisms using male C57BL/6 J mice. The result indicated that GABA OTEs reduced leptin expression in epididymal adipose tissue and showed a protective effect on nonalcoholic fatty liver disease. It promoted thermogenesis-related protein of uncoupling protein-1 and peroxisome proliferator-activated receptor-gamma coactivator (PGC-1α), boosted lipid metabolism, and promoted fatty acid oxidation. It also reduced lipogenesis-related protein levels of sterol regulatory element binding protein, acetyl-CoA carboxylase, and fatty acid synthase and inhibited hepatic triglyceride (TG) levels. These data suggest that regular drinking of GABA oolong tea has the potential to reduce the risk of being overweight, preventing obesity development through thermogenesis, lipogenesis, and lipolysis.
Background: The development of effective cosmetic products for the reduction of the signs of skin aging is a complex process which requires an optimized combination of ingredients and specialized systems to deliver the actives to the skin layers. Aim: To evaluate the tolerance and antiaging clinical efficacy of a cosmetic formulation containing a blend of nanoencapsulated antioxidants: ascorbyl palmitate, resveratrol, tocopherol, caffeine, carnosine, and niacinamide. Methods: Clinical efficacy was determined by subjective and instrumental analyses of collagen synthesis by fluorescence spectroscopy, by three-dimensional imaging analysis of suborbital edema, and by analysis of skin hydration and sebum content by biophysical techniques-Corneometer® and Sebumeter®. Results: The studied formulation was safe and effective for the improvement of skin appearance by increasing collagen synthesis and skin moisturizing and by reducing facial blemishes, swelling, and oiliness. A preclinical exploratory approach using an experimental model of human cell and skin cultures agreed with the observed antiaging effects, identifying mechanisms related to the containment of oxidative stress, reduction of melanin production, increased synthesis of type I procollagen, and regulation of the epidermal cohesion protein filaggrin. Conclusions: The skin benefits obtained resulted from the combination of the ingredients in the formulation and the nanoencapsulation-based delivery system, which favors the solubility, safety, efficacy, and bioavailability of the preparation to the skin.
This study evaluated the effects of topical use of caffeine hydrogel on hypertrophic scar in a rabbit ear wound model. Nine rabbits were randomly divided into three groups: control group, caffeine hydrogel group and matrix group. Punched defects were established on each rabbit's ear which resulted in a hypertrophic scar. When the wound epithelialization and scar hyperplasia could be seen, control group did not do any treatment, while caffeine hydrogel group and matrix group were treated with caffeine hydrogel and hydrogel matrix, respectively. After 3 weeks of administration, the general morphological changes of scar were observed, and the scar tissue of rabbit ears was stained with HE and Masson. The relative expressions of TGF β-1, α-SMA, type Ⅰ collagen and type Ⅲ collagen in scar tissue were detected by Western blot. In all three groups, findings showed that caffeine hydrogel can inhibit scar growth by reducing the expression of TGF β-1, reducing the proliferation of fibroblasts, improving collagen arrangement and reducing collagen deposition. The overall study shows efficacy and mechanism of caffeine. It concluded that caffeine could be an effective therapeutic agent for hypertrophic scars.
The goal of this study was the development and evaluation of semisolid caffeine (CAF) loaded nanostructured lipid carriers (NLCs) for topical treatment of cellulite. CAF-loaded NLC formulations were prepared via high-speed homogenization followed by ultrasonication. A 32 full factorial design was employed for formulation optimization. The total lipid content (%) and the liquid lipid content per total lipids (%) were chosen as factors, whereas particle size (PS), polydispersity index (PDI), zeta potential (|ZP|) and viscosity (VIS) were selected as responses. The design suggested CAF-NLC3 as the optimum formulation consisting of a total lipid content of 15% w/w (palmitic acid and soft paraffin/isopropyl myristate, 7:3 w/w) and a surfactant content of 10% w/w (Tween 80/lecithin, 8:1.2 w/w). CAF-NLC3 revealed PS, PDI, ZP, VIS and CAF content values of 318.8 nm, 0.253, -41.1 mV, 18.0 Pa.s and 97.57%, respectively. It showed a pseudoplastic rheological behavior, acceptable pH value (5.25), good spreadability (1.12 mm2/g) and spherical shape employing transmission electron microscopy. Differential scanning calorimetry and X-ray diffraction demonstrated the amorphization of CAF in CAF-NLC3. CAF-NLC3 remained stable for 3 months at room and refrigeration conditions. A single topical application of CAF-NLC3 on shaved abdominal skins of Wistar rats revealed enhanced skin retention of CAF by 2-fold and 1.4-fold after 4 h when compared with plain CAF gel (CAF-P) and marketed CAF gel (CAF-M), respectively. Furthermore, CAF-NLC3 exhibited a superior anti-cellulite activity in comparison with CAF-P and CAF-M through elevating extracellular matrix components (collagen 1, elastin and hyaluronic acid) and stimulating the brown adipose tissue thermogenesis via up-regulating UCP1 and PPAR-γ expression. In addition, CAF-NLC3 prominently increased lipolysis through HSL activity and decreased pro-inflammatory cytokines such as ICAM-1 and VCAM-1 after 30 days of treatment on a high fat diet-induced cellulite rat model. These findings were further confirmed by histopathological examination supported by morphometric analysis. Therefore, incorporation of CAF in a semisolid NLC formulation would be a promising cosmetic approach for the topical treatment of cellulite.
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The eyelids are the thinnest skin in the body, leading to be easy for the blood vessels to show through the skin caused a swollen and dark appearance called puffy eyes. Placing refrigerated damp tea bags on the eyelids has been believed for a long time that it can reduce the puffy eyes due to the vasoconstriction of caffeine. This study aimed to characterize physicochemical properties and to determine in vivo efficacy in reducing puffy eyes of the prepared caffeine gels. The formulation composed of 3% caffeine, 2% ethanol, 0.3% Uniphen ® P-23, 7.5% propylene glycol, 0.5% Carbopol ® Ultrez-21 and water to 100% was selected for eye irritation test and efficacy evaluation since it possessed good characteristics and provided sustained skin permeation. The 34 volunteers (18 women, 16 men) who easily developed puffy eyes after going to bed without sleep and with no irritation to caffeine gel as well as its gel base were treated with the gels in a randomized, double-blind, placebo-controlled trial. The skin permeation profiles showed that all caffeine gels allowed caffeine to permeate through the newborn pig skin. However, the overall efficacy of the selected caffeine gel in reducing puffy eyes was not significantly different from that of its gel base. It could be concluded that the cooling effect of the hydrophilic gels was the main parameter in reduction of eye puffiness rather than the vasoconstriction of caffeine.
Full-text available
Coffee, a rich source of natural products, including caffeine, chlorogenic acid, and diterpenoid alcohols, has been part of the human diet since the 15th century. In this study, we characterized the effects of Colombian coffee extract (CE), which contains high concentrations of caffeine and diterpenoids, on a rat model of human metabolic syndrome. The 8-9 wk old male Wistar rats were divided into four groups. Two groups of rats were fed a corn starch-rich diet whereas the other two groups were given a high-carbohydrate, high-fat diet with 25% fructose in drinking water for 16 wk. One group fed each diet was supplemented with 5% aqueous CE for the final 8 wk of this protocol. The corn starch diet contained ~68% carbohydrates mainly as polysaccharides, whereas the high-carbohydrate, high-fat diet contained ~68% carbohydrates mainly as fructose and sucrose together with 24% fat, mainly as saturated and monounsaturated fat from beef tallow. The high-carbohydrate, high-fat diet-fed rats showed the symptoms of metabolic syndrome leading to cardiovascular remodeling and nonalcoholic fatty liver disease. CE supplementation attenuated impairment in glucose tolerance, hypertension, cardiovascular remodeling, and nonalcoholic fatty liver disease without changing abdominal obesity and dyslipidemia. This study suggests that CE can attenuate diet-induced changes in the structure and function of the heart and the liver without changing the abdominal fat deposition.
Interest in the molecular and mechanistic aspects of cosmetic research has grown exponentially during the past decade. Herbal Principles in Cosmetics: Properties and Mechanisms of Action critically examines the botanical, ethnopharmacological, phytochemical, and molecular aspects of botanical active ingredients used in cosmetics. Along with dermatological and cosmetic uses, the book also explores the toxicological aspects of these natural ingredients, maintaining a balanced view that carefully dissects the hype from the solid science. Contains Comprehensive Monographs of Herbs Useful for Skin Care & Diseases Authored by a panel of experts in cell physiology, phytochemistry, ethnopharmacology, applied botany, ethnobotany, and cosmetic science, the book begins with background in skin anatomy and physiology and also the classification, mechanisms of action, and application of herbal compounds. It provides monographs complete with therapeutic properties, specific action and dermatologic properties, toxicities, pictures, and references. The book also addresses the complexities of green biodiversity, including not only higher plants, but also mushrooms, algae, lichens, and bacteria - each chosen for their importance in traditional use, potential for innovation, or recent introduction to market. Includes a Vivid Color Insert with Photographs of Botanical Species Herbal Principles in Cosmetics: Properties and Mechanisms of Action is one of the few books devoted to the mechanisms of action of herbal compounds based on scientific analysis, making it an exceptionally valuable reference for pharmacologists, natural product chemists, skin physiologists, and dermatologists.
Conference Paper
Oral administration of green tea or caffeine to hairless SKH-1 mice for 2 weeks stimulated UV-induced increases in apoptotic sunburn cells in the epidermis, and a similar effect was observed when caffeine was applied topically immediately after UV. In mice pretreated with UV for 22 weeks (high-risk mice without tumors), topical applications of caffeine 5 days a week for 18 weeks with no further UV treatment inhibited carcinogenesis and stimulated apoptosis in the tumors. Oral administration of green or black tea to UV-pretreated high-risk mice for 23 weeks inhibited skin tumorigenesis, decreased the size of the parametrial fat pads and decreased the thickness of the dermal fat layer away from tumors and directly under tumors. Administration of the decaffeinated teas had little or no effect on these parameters and adding caffeine to the decaffeinated teas restored their inhibitory effects. Administration of caffeine alone also inhibited carcinogenesis and decreased the size of the parametrial fat pads and the thickness of the dermal fat layer. Using data from individual mice and linear regression analysis, we found a highly significant positive correlation between the thickness of the dermal fat layer away from tumors and the number of tumors per mouse. (C) 2002 Lippincott Williams Wilkins.
Various studies have considered the impact of different physico-chemical drug characteristics, skin thickness, or formulation on the absorption from the skin surface to underlying tissues or to the systemic circulation, but they rarely discuss the influence of drug concentration on the permeation flux of molecules. This research therefore aimed at studying the influence of drug concentration in a caffeine formulation. For this study, three same base gels were used at 1, 3 and 5% of caffeine to evaluate the effect of concentration on in vitro release through synthetic membrane and on ex vivo permeation of caffeine through human skin. No correlation was found between transfer through synthetic membrane and that observed through the skin. This shows that the diffusion flux of caffeine permeation does not depend on the concentration of the formulation but rather on the quantity of formulation applied. This is evidenced by the fact that the lowest lag time (Tlag) and higher absorption rates were obtained with gel at 1% of caffeine applied at 1mg/cm2.
Cellulite is a physiological condition that presents etiologic plurality. Caffeine and its derivatives are used in anticellulite cosmetics due to their lipolytic activity on fatty cells. Siloxanetriol alginate caffeine (SAC) is a silanol derived from organic silicon. Radicals primarily from SAC are caffeine and the mannuronic acid. This study aims to analyze the effects of caffeine and siloxanetriol alginate caffeine on fatty tissue by histological evaluation. Formulations were developed with caffeine, caffeine + sodium benzoate or SAC and were applied topically for 21 days on Wistar female mice. The study regarded the histological aspects by determination of diameter and number of fatty cells with a light microscope. Emulsion with caffeine caused a reduction of 17% on the diameter of the fatty cells compared with the control. The emulsion with caffeine + sodium benzoate did not cause alterations on cell diameter. Emulsion with SAC provoked reduction on fatty cell diameters of 16%. No significant alterations were observed on the diameter of the fatty cells treated with gels, although it was noticed that gel with SAC promoted a reduction of 26% on the number of fatty cells. Emulsion with SAC was considered more indicated to promote the lipolytic action on fatty tissue, acting as a complement to treat cellulite. When sodium benzoate was added to the preparations, it inhibited the caffeine efficiency. Gel was not an adequate vehicle to be incorporated with caffeine and SAC.
IFSCC Magazine, 12 (4) 359–363 (2009) Synopsis Caffeine is an effective slimming agent used for topical administration or in cosmetic products. The formulation must be such that caffeine reaches the adipocytes in the hypodermis. Biodegradable caffeine‐loaded microspheres were evaluated for the transport of caffeine to its site of action for 24 h and upto 72 h. The mean diameter of the microspheres was 2.8 μm and their caffeine loading was 2.3 mg g ‐1 of particles. The permeation of caffeine from microspheres applied in aqueous suspension or from solution was evaluated through in vitro diffusion measurements with static Franz cells ( n = 6) over 24 h or 72 h. The first experiments carried out on full‐thickness skin without hypodermis showed that after 24 h the total amount of caffeine was twice as high from microspheres as from aqueous solution (22.6% vs. 9.99%). The results suggested that microspheres could easily penetrate through the skin and accumulate in the receptor compartment, ensuring continuous caffeine release. When the hypodermis was retained, microsphere penetration was only slightly decreased. After 72 hours of exposure the receptor fluid contained 15.3% free caffeine and 27.8% encapsulated fraction. The hypodermis hindered solution permeation, and therefore the free caffeine content was lower. Permeation of microspheres was not stopped by the presence of hypodermis.
In the present study, the ability of a shampoo formulation containing caffeine as well as the fluorescent dye fluorescein to penetrate into hair follicles was investigated by in vivo laser scanning microscopy. A contact time of two minutes between the shampoo and the skin surface was sufficient for the formulation to penetrate deeply into the hair follicles and to remain there for up to 48 hours, even after washing. As hair follicles are surrounded by a close network of capillaries, dendritic cells and stem cells, they represent an important target for drug delivery. The results of the present study demonstrated that in vivo laser scanning microscopy is an efficient tool for the investigation of the dermatopharmacokinetics of topically applied molecules and their penetration pathways, as the method yields space- and timeresolved measurements. (© 2007 by Astro Ltd., Published exclusively by WILEY-VCH Verlag GmbH & Co. KGaA)
In previous in vitro investigations, it was demonstrated that caffeine is able to stimulate the hair growth. Therefore, a penetration of caffeine into the hair follicle is necessary. In the present study, in vivo laser scanning microscopy (LSM) was used to investigate the penetration and storage of a caffeine containing shampoo into the hair follicles. It was shown that a 2-min contact time of the shampoo with the skin was enough to accumulate significant parts of the shampoo in the hair follicles. A penetration of the shampoo up to a depth of approx. 200 μm could be detected, which represents the detection limit of the LSM. At this depth, the close network of the blood capillaries surrounding the hair follicles commences. Even after 24 h, the substance was still detectable in the hair follicles. This demonstrates the long-term reservoir function of the hair follicles for topically applied substances such as caffeine.
Delivery systems for caffeine have been designed for two different purposes: (1) enhancing drug permeation through the skin for systemic delivery and (2) accumulating drug reservoir in the skin for local delivery. Caffeine exhibited concentration-dependent growth inhibition of normal and psoriatic human fibroblasts, as well as 3T3 mouse fibroblasts. High flux of caffeine through the skin was obtained from an aqueous solution containing an enhancing mixture of 20% Transcutol and 10% oleic acid. The presence of the enhancers resulted in caffeine flux 40 times greater than in their absence. The high flux of caffeine through the skin in vitro which was obtained using the enhancing composition was shown to be parallel to increased serum concentrations of drug in rats in vivo. Application of caffeine in aqueous solution containing enhancing mixture resulted in high serum concentrations of 50–60 after 1 h, which remained high for at least 12 h following. The greatest caffeine accumulation in the skin was measured from small liposomal vesicles, 2260 , this being 3 times greater than from aqueous solution containing enhancers, the system which exhibited the second largest accumulation of drug in the skin. Using quantitative skin autoradiography, it was found that after 24 h, the greatest concentration of caffeine (280 tissue) was localized in the epidermis and the lowest amount (50 tissue) in the dermis. In addition, a relatively high concentration of caffeine was found in the appendages.