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Hyaluronic
Acid Knowledge |
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Hyaluronan's Story Time |
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This is what
I am! |
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I am also in
your home |
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Everywhere in
your body |
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How I work in
your body |
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Could Hyaluronan Be an
Anti-Aging Remedy? |
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Anti-inflammatory effects of
hyaluronan in arthritis therapy: Not just for viscosity |
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I am also in
your home |
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Believe it or not, HA(Hyaluronic Acid Foods,
Foods Hyaluronic Acid) is throughout our
bodies. It is also in foods, cosmetics and
pharmaceuticals, so you probably have had more contact
with it than you may think. This site will unveil the
secret of HA(Hyaluronic Acid Food grade) and you will learn about this
little-known but useful material more deeply than ever.
I am also in your home
HA(Hyaluronic Acid Food gradeㄛ
Hyaluronic Acid Foods,Foods Hyaluronic Acid) is in health food products, beauty
products, cosmetics, quasi-drug additives and
pharmaceuticals. In recent times, H-A has
drawn peoples＊ attention in particular to its water
retention properties and viscoelasticity, which are
ideal for cosmetics and pharmaceutical use.
Cosmetics, Quasi-drugs
 Why
do you think a baby's skin is so supple and resilient?
It＊s because it contains large quantities of H-A.
HA(Hyaluronic Acid Food grade) plays a key role in body
moisturizing lotions, skin creams and bathwater
additives with its excellent water retention properties.
Its use stretches even to mouthwashes and eyewashes.
Pharmaceuticals and Medical Devices (Prescription /
OTC drugs)
Highly purified HA(Hyaluronic Acid Food gradeㄛ
Hyaluronic Acid Foods,Foods Hyaluronic Acid) is used in
pharmaceutical products, such as joint function
improving agents, ophthalmic surgical aids, surgical
aids for endoscopic mucosal resection and eye-drops.
These applications make good use of the water retention,
viscoelasticity and various other properties of
HAㄗHyaluronic Acid Foods,Foods Hyaluronic Acidㄘ. |
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http://www.seikagaku.co.jp/english/ha/index.html |
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Everywhere in
your body |
HA(Hyaluronic Acid Food gradeㄛ
Hyaluronic Acid FoodsㄛFoods Hyaluronic Acid) is found throughout our body, and is
essential for our body to function properly. Each body
part has different optimal Hyaluronan
concentrations. The HA(Hyaluronic Acid Food gradeㄛHyaluronic Acid Foods,
Foods Hyaluronic Acid) -richest parts are
umbilical cord, joint fluid, vitreous body and skin.
1.Eyes
The vitreous body is the clear gelatinous fluid that
fills the area inside the eyeball, behind the lens. It
contains large amounts of HA(Hyaluronic Acid Food gradeㄛ
Hyaluronic Acid FoodsㄛFoods Hyaluronic Acid) and plays a
role in the maintenance of the eyeball's round shape.
2.Skin
The skin is broadly composed of three layers (from the
outside): the epidermis (surface skin), dermis (inner
skin) and subcutaneous tissue (tissue under the skin).
The dermis is about 10 times thicker than the epidermis,
and contains large amounts of HA, which
plays a role in preventing the skin from drying out.
3.Joints
Joints contain fluid that is composed of large
quantities of HA. HA(Hyaluronic Acid Food gradeㄛ
Hyaluronic Acid Foods,Foods Hyaluronic Acid) allows
joints to move smoothly.
Body loses HA with age
The concentration of HA in the body
decreases with aging. It has been reported that the
concentration in skin starts to decrease in the late
40＊s.
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This is what
I am! |
The name HA(Hyaluronic Acid Food gradeㄛ
Hyaluronic Acid Foods,Foods Hyaluronic Acid) is getting more familiar these
days, because many industries have become aware of its
usefulness. But, do you know why＃?
In this section, we will tell you about the unique
properties of HA, which you have not have
known before.
Excellent hydrating properties
A gram of HA(Hyaluronic Acid Food grade) is capable of hydrating 2
to 6 liters of water.
(Quote: Akasaka H, et, al, FRAGRANCE JOURNAL:1986, 78,
42)
Jelly, viscous and elastic substance
An aqueous solution of HA(Hyaluronic Acid Food grade) has no color or
odor. HA(Hyaluronic Acid Food grade) is a viscoelastic
 substance,
meaning that it has very high viscosity and elasticity
(the ability to return to its original shape)
characteristics. The elasticity of HA
varies depending on its concentration and molecular
weight. At high concentrations and molecular weight, HA behaves like a gel. |
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How I work in
your body |
HA(Hyaluronic Acid Food gradeㄛHyaluronic Acid Foods,
Foods Hyaluronic Acid) plays various roles.
Roles in our bodies HA(Hyaluronic Acid Food gradeㄛHyaluronic Acid Foods,Foods Hyaluronic Acid) fills the spaces
between cells, protecting them by retaining water and
serving as a cushion.
﹞Skin
HA is found abundantly in dermis, helping
skin retain its moisture.
Skin with high Hyaluronan content
The skin remains hydrated and the surface is supple when
the skin contains adequate concentrations of HA.
Skin with low Hyaluronan content
The skin loses its elasticity and the surface becomes
dry, because moisture is lost as HA(Hyaluronic Acid Foods,Foods Hyaluronic Acid)
concentrations decrease.
﹞Joints
 Joint
fluid and articular cartilage contain HA at
high concentration. It serves as a lubricant (preventing
bone-to-bone friction) and as a cushion. This function
allows our joints to move smoothly.
﹛﹞Eyes
The vitreous body contains high concentrations of
HA(Hyaluronic Acid Foods,Foods Hyaluronic Acid), where it provides cushioning and plays
a role in the maintenance of the shape of the eyeball.
Benefits Hyaluronan brings for health and
well-being
1.Joint Function Improvement
A common medical treatment uses Hyaluronan as a
joint function improving agent .Hyaluronan(Hyaluronic Acid Food grade) is injected into joints to treat
patients suffering from knee osteoarthritis, periarthritis of the shoulder*1 (also known as frozen
shoulder syndrome), and knee pain from rheumatoid
arthritis*2. Hyaluronan has been reported to have
anti-inflammatory and pain relieving effects in such
uses.
*1:Applicable in some countries
*2:Applicable in Japan
2.Ophthalmic Surgical Aid
An ophthalmic surgical aid made of Hyaluronan(Hyaluronic Acid Food grade) is
used during cataract surgery and penetrating keratoplasty. The viscosity of helps
protect easily damaged cells and is used to secure
sufficient intraocular space during surgery. |
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Hyaluronan's Story Time |
1. How did "Hyaluronan" get its name?
Hyaluronan(Hyaluronic Acid Food gradeㄛ
Hyaluronic Acid Foods,Foods Hyaluronic Acid) was first isolated from the bovine
vitreous body in 1934 by Dr. Karl Meyer, a professor at
Columbia University in the US. The name ※Hyaluronan§ is derived from ※hyaloid§, which means vitreous
body in Greek, and uronic acid, which is found in large
quantities in the vitreous body. Since 1986, the word "hyaluronan"
has also been used by the international nomenclature of
polysaccharides.
2. How does ※Hyaluronan§ form?
Hyaluronan(Hyaluronic Acid Foods,Foods Hyaluronic Acid) is a linear polysaccharide. It has a
repetitive structural unit composed of the disaccharides
N-Acetyl-D-Glucosamine and D-glucuronic acid. Hyaluronan in our bodies generally exists as a high molecular
weight of several million times, and has not been shown
to have structural differences in different animal
species.
3. An Injured Racehorse Sheds Light on a Medical Use
of Intra-Articular Hyaluronan Injection.
The development of Hyaluronan as an intra-articular
injection started with a racehorse. We cannot explain
※how intra-articular Hyaluronan(Hyaluronic Acid Foods,Foods Hyaluronic Acid) was developed§
without the story of an injured racehorse. The racehorse
was on the verge of retirement, due to inflamed joints
caused by a lot of hard racing. Amazingly, following
Hyaluronan injection to its inflamed knees, the
horse returned to racing, and even won! That event
encouraged researchers to drive for the development of
Hyaluronan injectables for human treatment. |
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http://www.seikagaku.co.jp/english/ha/ha04.html |
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Could Hyaluronan Be an
Anti-Aging Remedy? |
The Secret Ingredient
Dr. Toyosuke Komori, the town doctor who has studied and
written books on longevity in Yuzuri Hara, believes
these locally grown starches help stimulate the body's
natural creation of a substance called Hyaluronan,
or Hyaluronan(Hyaluronic Acid Foods,Foods Hyaluronic Acid), which aging bodies typically lose. This may ward
off the aging process by helping the cells of the body
thrive and retain moisture, keeping joints lubricated,
protecting the retina in eyes and keeping skin smooth
and elastic.
"I have never seen anyone suffer from skin cancer here,"
he says. "I have seen a woman in her 90s with spotless
skin."
One of Japan's leading pharmaceutical companies began
researching and developing a pill supplement containing
Hyaluronan. The company tested the pills on 1,000
people, and said roughly half reported smoother skin,
less fatigue and better eyesight.
In the United States, Hyaluronan has been used for
years in eye surgery as a shock absorber to protect the
retina, and has been proven effective in lubricating
arthritic joints.
Synvisc, for example, a Food and Drug
Administration-approved product used to treat
osteoarthritis, works by injecting Hyaluronan(Hyaluronic Acid Food grade), or Hyaluronan, which acts as a shock absorber and
lubricant.
Dr. Irving Raphael, a Syracuse, N.Y., orthopedist who
specializes in sports medicine, explains that these
injections coat the surface of the joint to decrease
friction, which allows the joint to move more smoothly
and cuts down pain.
"When I prescribe it," he says, "I simply tell my
patients I'm going to give them a lube job."
But, he warns, before prescribing it, he always asks if
the patient is allergic to chicken or eggs. That's
because Hyaluronan is extracted from chicken combs. The mohawk
crown on a chicken's head is washed, sliced and
purified.
Western Skeptics
While Hyaluronan(Hyaluronic Acid Food gradeㄛ
Hyaluronic Acid Foods,Foods Hyaluronic Acid) has proven useful in orthopedics
and opthalmology, many Western experts are skeptical
that swallowing it in a pill could actually help prolong
one's life.
"I cannot today imagine any possible benefit," says Dr.
Endre Balazs, a leading expert on H-A.
"The only way it acts, as far as I can see, as an
anti-aging remedy," adds Raphael, "is because if you're
not limping, and your joints feel better, you feel
younger."
But Hyaluronan(Hyaluronic Acid Food gradeㄛ
Hyaluronic Acid Foods,Foods Hyaluronic Acid) has been shown to have wound-healing and
tissue-reconstruction applications, and some cosmetic
companies tout it as an effective ingredient in
moisturizers that can soften facial lines, leaving skin
elastic and firm. One company even claims it may be the
latest development in treating hair loss. |
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http://www.appliedhealth.com/ABC_News_HA.html |
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Anti-inflammatory effects of
hyaluronan in arthritis therapy: Not just for viscosity |
Abstract:
Hyaluronan(Hyaluronic Acid Food gradeㄛ
Hyaluronic Acid Foods,Foods Hyaluronic Acid)hasbeenwidelyusedforviscosupplementationofdiseasedor
agedarticularjoints.However,recentinvestigationshaverevealedtheactiveanti-inflammatory
or chondroprotective effect of , suggesting its
potential role in attenuation of joint damage. In
particular, interactions between and other
inflammatory mediators are attracting inter-est. This
review summarizes several aspects of recent
investigations of the anti-inflammatory effects of
Hyaluronan(Hyaluronic Acid Foods,Foods Hyaluronic Acid) in
arthritis. Keywords: hyaluronan, inflammation,
chondroprotection
Introduction
Intra-articular administration of Hyaluronan(Hyaluronic Acid Food grade) is a widely applied treatment for
osteoarthritis (OA) (reviewed by Simon and Strand).1
Although Hyaluronan injection provides relief from pain, albeit
transiently, its mechanism of action has not been fully
clarified. In a recent recommendation on the management
of hip and knee OA by the Osteoarthritis Research
Society International (OARSI),2 the strength of
recommendation(SOR)ofintra-articularH-Awascalculatedtoberelativelylow(64%), whereasthatofnonsteroidalanti-inflammatorydrugs(NSAIDs)fororaladministration
as analgesics was 92%每93%.
TheeffectofH-AinOAhasoftenbeenattributedtoitspotentialuseinviscosupple-mentation,
ie, supplementation of viscosity; however, the benefits
of Hyaluronan(Hyaluronic Acid Foods,Foods Hyaluronic Acid) from ※some other action and not by its
biomechanical properties§ is also suggested (reviewed by Neustadt and colleagues).3 More specifically, a direct
effect of against inflammation or cartilage
degradation in OA has also been suggested.
InadditiontoitsuseinOA,intra-articularinjectionof
Hyaluronan
hasbeenusedinpatients
with inflammatory arthritis such as rheumatoid arthritis
(RA). In some reports, it is indicated that H-A has
beneficial effects on inflammatory arthritis.4每6
This study briefly reviews the recent findings related
to the function of HyaluronanㄗHyaluronic Acid Foods,
Foods Hyaluronic Acidㄘ, focusing on its reported effects
in chondrocytes, not only in supplementing viscosity,
but also as a
potentialanti-inflammatoryanti-arthriticagent.Sinceitiswell-knownthatoligosaccharide
hyaluronan is inversely involved in inflammation,7
whenever is mentioned in this paper, it should be
understood that the reference is to high molecular
weight hyaluronan.
Biochemistry of HA
Hyaluronan is a polysaccharide composed of
repeating disaccharide units, ie, 1,4-glucuronic acid (GlcUA)
and 1,3-N-acetylglucosamine (GlcNAC).
Masuko et al Dovepress
to the group of glycosaminoglycans, but unlike
chondroitin sulfate or keratan sulfate, H-A is not
sulfated. H-A is synthe-sized by bioactivity of
hyaluronan synthase, which has been reported to
have three isoforms in humans.8
H-A is widely distributed but mainly localized to the extracellular matrix and body fluid. It contributes to
the
viscoelasticityofthefluidandelasticityinconnectivetissues,
which absorb mechanical stress, for example, between
cartilage and cartilage surfaces.3
In addition to this property of providing
viscoelasticity, recent investigations have continued to
reveal the variety of
actionsof
Hyaluronan(Hyaluronic Acid Foods,Foods Hyaluronic Acid)oncartilage.Forexample,innormaldiarthrodial
joints, Hyaluronan not only works as a mechanical/physical
barrier, but also has anti-inflammatory and analgesic
functions.3 As for pain suppression, it has been shown
that Hyaluronan attenuates prostaglandin-or bradykinin-induced
pain in experimental OA animals.9,10
Hyaluronan binds to the signal-transducing receptor molecules
CD44 and receptor for H-A-mediated motility (reviewedbyTaylorandcolleagues).11 Inthisregard,CD44is
the primary receptor of Hyaluronan, and has also been found to
bind withothermatrixcomponents,includingcollagen,chondroi-tinsulphate,andosteopontin.11每13 Bindingofthecomponents to CD44 leads to modulation of
cellular functions;14每16 for example, Hyaluronan(Hyaluronic Acid Food grade) is reported to
inhibit proteoglycan degradation and anti-Fas-induced
apoptosis of chondrocytes through CD44 expressed on the
cells.17,18
HA suppresses inflammatory
responses in articular joints
HA suppresses MMPs and ADAMTS
In inflammatory or degenerative joints, cartilage matrix
is degraded by the action of an array of proteinases. In
particular, the families of matrix metalloproteinases (MMP)
andadisintegrinandmetalloproteinasewiththrombospondin
motifs (ADAMTS) are mainly responsible for cartilage
deg-radation. More specifically, the collagenases (MMP-1
and MMP-13) and stromelysin-1 (MMP-3) play a pivotal
role in
collagendegradation,whereastheaggrecanases(ADAMTS)
induce aggrecan degradation. These proteinases are often
inducedbyinflammatorystimuli,suchasinterleukin-1(IL-1)
or tumor necrosis factor-汐(TNF-汐), which are activated
by inflammation or mechanical or physical stress in
joints.19,20 Subsequently, in an inflamed joint,
cartilage exposed to the induced ADAMTS-4 and ADAMTS-5
would release
Hyaluronan(Hyaluronic Acid Food gradeㄛHyaluronic
Acid Foods,Foods
Hyaluronic Acid), indicating deterioration of matrix
integrity;21 this loss of Hyaluronan from the cartilage matrix
is thought to result in the progression of cartilage
degradation. On the other hand, it has been demonstrated
that Hyaluronan(Hyaluronic Acid Food gradecan enhance synthesis of chondroitin sulfate and
proteoglycans,22,23 and reduce the production and
activity of MMPs and ADAMTS.5,24,25
IL-1 is considered to be the dominant catabolic cytokine
present in the inflamed articular joints. In this
regard, is reported to counteract the catabolic
process induced by IL-1. For example, Fioravanti and
colleagues stimulated human
chondrocytesunderhydrostaticpressureandshowedthat MW
500每730 kDa abrogates a decrease in proteoglycan and an
increase in nitric oxide (NO) levels, both induced by
IL-1.InastudybyKarnaandcolleagues,500每730kDa was
found to counteract the effect of IL-1, as inhibited
IL-1-induced downregulation of type II collagen mRNA
expression.26 Julovi and colleagues27 used 800-kDa
Hyaluronan(Hyaluronic Acid Food gradeㄛ
Hyaluronic Acid Foods,Foods Hyaluronic Acid) to
assess the inhibitory effect of Hyaluronan on IL-1汕-induced MMPs
in cartilage and found that the 800-kDa penetrated
cartilage tissue, localized in the pericellular matrix
around chondrocytes, and bound with CD44 on chondrocytes,
lead-ing to the suppression of IL-1汕-stimulated MMP
production
bychondrocytes.Inthiscontext,wefoundthat 800kDa and
1900 kDa suppressed IL-1-induced MMP-1 production both
at protein and mRNA levels in cultured human chon-drocytes,
and this effect was cancelled by treatment with
anti-CD44 antibody.
Plasmin/plasminogen system and HA
Fibrinolysis is one of the major pathological changes
occur-ring in arthritic joints, in which the plasminogen
system is known to play a key role.
Dovepress Anti-inflammatory effects of hyaluronan in
arthritis
activator (PA) and plasminogen activator inhibitor (PAI)
determines the direction in which plasminogen is
activated into plasmin, which in turn further promotes
fibrinolysis by activating proteinases, including
gelatinases and other MMPs. PA occurs in two forms:
urokinase-type PA (uPA) and tissue-type PA (tPA).
It has been suggested that hyaluronan modulates the PA
system in articular joints. For example, Nonaka and
colleagues30 reported that suppressed the secretion
of u-PA and PAI-1 from OA synovial fibroblasts. Further,
it was found that the receptor for u-PA (u-PAR) was
expressed in the synovium in both OA and RA and that the
expression was attenuated by treatment with H-A.30 These
results sug-gested that Hyaluronan(Hyaluronic Acid Food gradeㄛ
Hyaluronic Acid Foods,Foods Hyaluronic Acid) could suppress fibrinolytic
activity mediated by the uPA and uPAR systems. More
recently, Hsieh et al measured the levels of MMP-2,
MMP-9, u-PA, and PAI-1 in a series of chondral, meniscal,
and synovial cultures of early OA after treatment with
or without three products with different molecular
weights (MW), and demonstrated that all of the
products could decrease the secretion of MMP-2 and
MMP-9. They suggested that Hyaluronan with high MW might be more
effective in inhibiting MMP-2, MMP-9, u-PA, and PAI-1
expression.31 Further investigation on the crosstalk
between PA/PAI and would provide important clues to
the protection of cartilage degradation by these proteinases.
Hyaluronan and cyclooxygenase
Acidic NSAIDs are a major subset of anti-inflammatory
drugs that inhibit the activity of cyclooxygenase (COX),
leading to suppression of prostaglandins and
leukotrienes in inflamed tissue. In this regard,
interaction has been demonstrated between Hyaluronan(Hyaluronic Acid Food gradeㄛ
Hyaluronic Acid Foods,Foods Hyaluronic Acid) or its
fragment and COX-2 expression in a variety of
cells.32每35 Several studies showed upregulation of COX-2
expression . For example, 200-kDa was reported
to increase the expression of glomerular COX-2 in rat
renal glomerular cells34 and in human vascular
endothelial cells,36 respectively. The effect of
Hyaluronan(Hyaluronic Acid Foods,Foods Hyaluronic Acid) has
been reported to be mimicked by an engagement of CD44 .35,36 Further, Stuhlmeier reported
prostaglandin E2(PGE2) as a potent activator of H-AS1 in
IL-1-treated type-B-synoviocytes.37 In that study, the
author tested a series of eicosanoids and found that
PGE2, and to a lesser extent, PGI2 and thromboxane A2
analogues activated H-AS1 expression in synoviocytes
after IL-1 treatment, whereas the lipoxygenase product
leukotriene B4 had no effect on H-AS1 induction.
Therefore, Hyaluronan(Hyaluronic Acid Foods,Foods Hyaluronic Acid) may upregulate COX-2, causing the
activated COX-2 to induce PGE2, which would then
activate H-AS1 through a positive feedback mechanism
(Figure 1). Conversely, Mitsui and colleagues
demonstrated an inhibitory effect of Hyaluronan(HA,Hyaluronate,Hyaluronan) on the
expression of COX-2 mRNA in IL-1-stimulated subacro-mial
synovial fibroblasts.33 In that study, however,
Hyaluronan with
a molecular weight of 90 ℅104 was used; therefore, the
different effect of Hyaluronan(Hyaluronic Acid Food gradeㄛ
Hyaluronic Acid Foods,Foods Hyaluronic Acid) might have been due to the dif-ference
in the molecular weight. In addition, Kinugasa and
colleagues40 reported that inhibition of COX-2 using a
COX inhibitor or COX-2 antisense oligonucleotide in a
tumor cell line resulted in downregulation of CD44
expression.38
Collectively, the H-AS/H-A system and COX/PG system may
have a regulatory network via CD44, which would be
regulated differently by each Hyaluronate component present in
each cell type, and further modulated by the presence of
inflammatory cytokines and mediators (Figure 1). Still,
inconsistency among studies concerning the interaction
between Hyaluronan(Hyaluronic Acid Food gradeㄛ
Hyaluronic Acid Foods,Foods
Hyaluronic Acid) and COX/PG may also, at least in part, be due
to the expression or activation of H-AS isoforms
(H-AS1-3), the expression pattern of prostanoid
receptors, or the amount of concomitant stimuli by other
inflammatory mediators such as IL-1. For example,
isoforms of H-AS or EP recep-tors are expressed and
function differentially among tissues and cells.8,39
Elucidation of the interaction between Hyaluronan and COX
systems in articular chondrocytes would give important
information about the clinical application of
Hyaluronate with
simultaneous clinical use of NSAIDs, and may clarify the
possible beneficial effects of HyaluronateㄗHyaluronic Acid Foods,Foods Hyaluronic Acidㄘ with larger molecular
weight in this regard. |
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