2. Normal Cartilage
Avascular, Alymphatic and Aneural tissue.
Smooth and resilient.
Allows shearing and compressive forces to be
dissipated uniformly across the joint.
3. Normal Articular Cartilage
Normal articular cartilage is composed of chondrocytes
that occupy approximately 5% of the tissue volume, and
the extracellular matrix, which composes the remaining
95% of the tissue.
The chondrocytes secrete and maintain the matrix; the
matrix in turn supplies the chondrocytes with an
environment conducive to their continued existence in
the face of a high level of mechanical stress.
Because of its role in chondrocyte support, and because
it physically forms such a large percentage of cartilage,
the importance of the matrix in joint function cannot
be overstated.
4. .
Chondrocytes are responsible for metabolism of
ECM.
They are embedded in ECM and do not touch one
another, unlike in other tissues in the body.
Chondrocytes depend on diffusion for nutrients
and therefore the thickness of cartilage is
limited.
Extracellular matrix is a highly hydrated
combination of proteoglycans and non-
collagenous proteins immobilized within
collagen network that is anchored to bone.
6. Structure of Normal Cartilage
Divided into 4 morphologically distinct zones:
Superficial: flattened chondrocytes.
High collagen-to-proteoglycan ratio and high
water content.
Collagen fibrils form thin sheet parallel to
articular surface giving the superficial zone
an extremely high tensile stiffness.
Restricts loss of interstitial fluid,
encouraging pressure of fluid.
7. Structure of Normal Cartilage
Transitional zone:
Small spherical chondrocytes.
Higher proteoglycan and lower water content than
superficial zone.
Collagen fibrils bend to form arcades.
8. Structure of Normal Cartilage
Radial Zone:
Occupies 90% of the column of articular
cartilage.
Proteoglycan content highest in upper radial
zone.
Collagen oriented perpendicular to bone
providing anchorage to underlying calcified
matrix.
Chondrocytes are largest and most synthetically
active in this zone.
9. Structure of Normal Cartilage
Calcified zone:
Articular cartilage is attached to the subchondral
bone via a thin layer of calcified cartilage.
During injury and OA, the mineralization front
advances causing cartilage to thin.
10. Function of Normal Cartilage
Articular cartilage is a white, smooth tissue which
covers the ends of bones in joints.
It enables bones of a joint to easily glide over one
another with very little friction.
This establishes easy movement.
Many areas of the body can contain this kind of
cartilage.
Joints between the bones, knee, elbow, and rib cage are
some typical locations.
Cartilage is a connective tissue that is flexible. Some of
the main types include fibrous, elastic, and hyaline.
11. Characteristic features of cartilage
Cartilage has no blood vessels or lymphatics and the nutrition of
the cells diffuses through the matrix. This explains the slowness of
healing process in cartilages.
Cartilage has no nerves and therefore it is insensitive.
Cartilage is surrounded by a fibrous membrane known as the
perichondrium. This perichondrium is similar to the periosteum in
structure and function. The articular cartilage has no
perichondrium and thus its regeneration after injury is inadequate
because the perichondrium plays a major role in regeneration of
the cartilage.
When a cartilage calcifies the chondrocytes die and the cartilage
is replaced by bone like tissue.
Calcium salts are not present in cartilage matrix. Instead it has
flexible material known as chondroitin which provides flexibility
to it.
12. Types of cartilage
There are3types of cartilage
Fibrous cartilage
Hyaline cartilage
Elastic cartilage
13.
14. OA – Articular Cartilage
Articular cartilage is the main tissue affected
OA results in:
Increased tissue swelling.
Change in color.
Cartilage fibrillation.
Cartilage erosion down to subchondral bone
15. OA – Articular Cartilage
The cartilage damage causes chondrocyte cloning in
an attempt to restore articular surface (Normal adult
chondrocytes are fully differentiated and do not proliferate)
(A) Normal articular cartilage (B) Osteoarthritic cartilage
16. Cytokines in OA
It is believed that cytokines and growth factors play
an important role in the pathophysiology of OA.
Pro inflammatory cytokines are believed to play a
pivotal role in the initiation and development of the
disease process.
Anti inflammatory cytokines are found in increased
levels in OA synovial fluid.
18. Anti-inflammatory cytokines
Are spontaneously made in synovium and cartilage
and increased in OA.
Likely the body’s attempt to reduce the damage
being produced by proinflammatory cytokines, these
two processes are not balanced in OA.
20. TGC is a topical gel for application onto joints. Through Lynk Biotech’s
proprietary Transdermal Delivery Technology, a high concentration of
glucosamine sulphate salt (10% w/w) is able to penetrate through the
skin directly to affected joints.
What is glucosamine?
Glucosamine is one of the primary building blocks of cartilage and is
essential for maintenance of healthy cartilage.
It also helps in the stimulation of synovial fluid production, which
lubricates and cushions our joints. It is considered one of the safest and
most effective supplements for the maintenance of healthy joints.
As we grow older, our body loses the capacity to produce sufficient
glucosamine, causing thinning of cartilage and eventually
degeneration of joints.
What is TGC (Transdermal
Glucosamine Cream)
21. TGC contains a higher concentration (up to 10% w/w)
of glucosamine sulphate salt than any other topical
glucosamine product available in the market.
The higher concentration of glucosamine in TGC is
enabled by our unique proprietary Transdermal
Delivery Technology.
Through this technology, water-soluble glucosamine
is encapsulated in active lipovesicular carriers that
transport glucosamine through the skin layer and
reaches the blood directly.
TGC is proven to deliver glucosamine effectively to
blood and synovial fluid of joints.
What makes TGC different from
other joint cream?
22. When glucosamine is consumed orally, it goes
through the gastrointestinal tract and liver first-pass,
where it is rapidly metabolized, resulting in only a
small proportion of glucosamine reaching the blood.
This proportion of glucosamine is then circulated
throughout the entire body, resulting in ultimately
an even smaller proportion of glucosamine reaching
joints where it is needed the most. Also, oral
consumption of glucosamine in high dosage may
result in gastrointestinal distress.
What makes TGC different from
glucosamine taken orally?
23. In contrast, TGC enables glucosamine to be delivered
through the skin directly into the specific joint where
it is needed. Lynk Biotech has conducted both animal and
human studies to demonstrate that TGC provides the
body with a high and sustained level of glucosamine
in the blood.
.
24. Yes, you may continue taking oral glucosamine if you
wish to. However, we urge you to try using TGC only,
so as to discover its benefits as compared to
consuming glucosamine orally.
can I apply TGC while consuming
glucosamine orally?
25. Objective: To evaluate the efficacy and safety of a new transdermal
formulation of glucosamine in the treatment of osteoarthritis
(OA).
Method:
Forty four (44) patients with mild to moderate OA attending 16
different outpatient clinics in Singapore were recruited into the
4‐week study.
Three criteria were used to quantify the severity of disease
activity evaluated before and after treatment with one gram (3
times daily) of transdermal glucosamine (TG) cream formulation
viz: Ritchie articular index (RAI), functional disability assessment
[Doctor’s Evaluation of Health status (DEH)] and arthritis
self‐efficacy scale [Patient’s Assessment Questionnaire (PAQ)].
OA&Glucosamine Sulfate
26. Results:
After four weeks, UTG treatment was observed to improved RAI pain
score from the baseline (day 0) in all demographic group and further
enhanced functional abilities.
Overall, 59% of the patients had a good opinion rating for this
transdermal formulation and showed beneficial effects.
Efficacy appeared to be related to the site of arthritis with 100% of
patients having arthritis of the shoulders reporting beneficial effects of
UTGtherapy as opposed to 75% of patients with ankle, wrist and elbow
OA and 58% of knee OA respectively.
Additionally, compliance to treatment was observed to be over 95% and
there were no reports of adverse reactions and no skin irritations were
observed at any time point.
Conclusion:
UrahTransdermal Glucosamine Cream significantly alleviated pain in
arthritic joints when applied over four weeks suggesting an
improvement in the quality of life.
This results support further clinical trial into the use of transdermal route
of administration of glucosamine.
.
27. We did a randomized, double-blind placebo controlled trial, in
which 212 patients with knee osteoarthritis were randomly
assigned 1,500 mg sulphate oral glucosamine or placebo once daily
for 3 years.
Weight bearing, anteroposterior radiographs of each knee in full
extension were taken at enrolment and after 1 and 3 years.
Mean joint-space width of the medial compartment of the
tibiofemoral join was assessed by digital image analysis, whereas
minimum joint-space width .
i.e , at the narrowest point – was measured by visual inspection
with a magnifying lens.
Symptoms were scored by the western Ontario and McMaster
Universities (WOMAC) osteoarthritis index.
Long-Term Effects of Glucosamine Sulphate on OA
progression
28. The 106 patients on placebo had a progressive joint-space
narrowing, with a mean joint-space loss after 3 years of -0.31 mm
(95% CI -0.48 to -0.13).
There was no significant joint-space loss in the 106 patients on
glucosamine sulphate: -0.06 mm (-0.22 to -0.09).
Similar results were reported with minimum joint-space
narrowing. As assessed by WOMAC scores, symptoms worsened
slightly in patients on placebo compared with the improvement
observed after treatment with glucosamine sulphate.
There were no differences in safely or reasons for early
withdrawal between the treatment and placebo groups.
INTERPRETATION
The long-term combined structure-modifying and symptom-
modifying effects of glucosamine sulphate suggest that it could
be a disease modifying agent in osteoarthritis.
FINDINGS
30. Transdermal profile of Glucosamine Cream in healthy
human volunteers. Human volunteers were given a single
dose of 10 g of Glucosamine Cream(equivalent to 1,000 mg
glucosamine sulphate salt) on their legs around the knee
cap areas.
Blood samples were collected from fore arm at pre-dose (0
hr), 0.5, 1, 2, 3, 4, 6 and 8 hrs post-dose. Plasma glucosamine
levels were determined by C18 reversed phase LC/MS/MS.
.
31. Chondroitin sulfate (CS) is one of the natural
glycosaminglycans (GAG) composed of the alternating
sugars D-glucuronic acid (GlcA) and N-acetyl-D-
galactosamine (GalNAc).
It is an important component of the extracellular matrix
(ECM).
CS is the most frequent GAG in the aggrecan molecule of
the cartilage.
Due to the negative charge of CS, it is responsible for the
water retention of the cartilage, which is important for
pressure resistance.
Chondroitin Sulfate & OA
32. Many clinical studies tested chondroitin sulfate together with
glucosamine. The results suggest that both components may enhance
each other’s efficacy. This synergistic effect was also proposed by
various in vivo and in vitro studies.
CS increases the hyaluronan production by human synovial cells, which
has a beneficial effect on maintaining viscosity in the synovial fluid.
It has been shown that CS stimulates the chondrocyte metabolism,
leading to the synthesis of collagen and proteoglycan, the basic
components of new cartilage.
Furthermore, CS inhibits the enzymes leukocyte elastase and
hyaluronidase, which are found in high concentration in the synovial
fluid of patients with rheumatic diseases.
CS also increases the production of hyaluronic acid by synovial cells,
which subsequently improves the viscosity and the synovial fluid levels.
In general, CS inhibits cartilage destruction processes and stimulates the
anabolic processes involved in new cartilage formation.
In addition, CS, when added to chondrocyte cultures, produces a dose-
dependent increase in cell proliferation.
Study
33. The glucosamine and chondroitin sulfate combination suppresses
IL-1-induced gene expression of iNOS, COX-2, mPGEs, and NF-κB in
cartilage explants.
This leads to reduced production of NO and PGE2, two mediators
responsible for the cell death of chondrocytes and inflammatory
reactions.
There are several ways by which glucosamine or chondroitin
sulfate reduce synthesis of the COX-2 enzyme.
Inhibition of the IL-1 beta induced NF-κB pathway by glucosamine
sulfate results in reduced synthesis of the COX-2 enzyme .
Another manner in which glucosamine hydrochloride inhibits COX-
2 activity is the prevention of COX-2 co-translational N-
glycosylation and the facilitation of COX-2 protein turnover.
How Can Glucosamine Sulfate & Chondroitin Sulfate
Modulate Inflammation Processes and Oxidative Stress
Involved in Osteoarthritis?
34. CS alone diminishes the nuclear translocation of NF-κB, which
reduces the formation of pro inflammatory cytokines IL-1beta
and TNF-alpha and pro inflammatory enzymes such as
cyclooxygenase 2 (COX-2) and nitric oxide synthase-2 (NOS-2).
In addition to their anti-inflammatory action, glucosamine and
chondroitin sulfate exhibit an antioxidant action which leads to
a significant reduction in iNOS expression and activity.
This is one explanation why glucosamine and chondroitin
reduce the otherwise NO-induced cell death of chondrocytes.
In comparison to glucosamine and CS, hyaluronic acid exerted a
very minor anti-inflammatory and anti apoptotic effect, while it
significantly reduced NO levels.
.
35. Active constituent
The major constituent in eucalyptus leaves is a volatile oil
known as eucalyptol (1,8-cineol).
The leaf oil should contain approximately 70–85%
eucalyptol.
Further more p-cymene, alpha-pinenes, limonene,
camphene.
Eucalyptus oil is similar to menthol by acting on
receptors.
Eucalyptus oil
36. Twelve agents (including taxifolin, rhamnetin, rhamnazin, quercetin,
and eriodictyol) isolated from the stem bark of Eucalyptus globulus
were shown to have antioxidant capabilities. The listed agents had
greater antioxidant activity than vitamin E .(Yun et al, 2000).
Eucalyptus contains substances related to menthol, and has a warming
effect on the skin and muscles.
This could result in a pain-relieving effect on sore muscles.
During muscle and joint pains, massaging eucalyptus oil on the skin
surface helps in getting relief from the pain.
The volatile eucalyptus oil is analgesic and anti inflammatory in nature.
Therefore it is often recommended to patients suffering from
rheumatism, sprained ligaments and tendons, stiff muscles, aches,
fibrosis and even nerve pain.
Antioxidant Effects
37. In spite of the morphological features typical of activated macrophages, and
of the increased phagocytic ability acquired by EO-treated or pre-treated
MDMs, the release in the extracellular medium of pro-inflammatory and
immune-modulating cytokines was significantly lower compared to that
recorded for LPS treatment alone (Fig. 4).
This effect is particularly evident for the pro-inflammatory cytokines
conspicuously produced by MDMs under LPS stimulation, such as IL-4, IL-6
and TNF-α.
In absence of LPS stimulation, EO activated macrophages produced very low
levels, comparable to the untreated control, of IL-4, IL-6 and TNF-α .
Moreover, in accordance with the anti-inflammatory properties ascribed to
EO, pre-treatment with EO 24h before the addition of LPS to cell culture was
able to significantly decrease the LPS-induced cytokines production .
No significant effect on the production of the other immune-modulating
cytokines tested (IL-2, IL10 and IFNγ) was recorded for both EO or LPS
treatments.
Effect of Eucalyptus oil on production of pro-inflammatory
and immune-modulating cytokines by human MDMs
38. We also investigated whether the observed differences in LPS- or EO-induced
internalization and cytokine production were associated with differences in
the cytoskeletal elements that mediate phagocytosis.
In particular, we verified if the phagocytic ability of LPS- or EO- stimulated
MDMs required integrity of the microtubular network.
To this purpose, control cells and macrophages, pre-treated with LPS or EO,
were treated with the microtubule-destabilizing agent nocodazole and the
phagocytic ability was tested after fluorescent beads administration.
It showed that, after damage of the microtubular network by nocodazole
treatment, while controls and LPS-stimulated MDMs were still able to
internalize beads, in EO-stimulated cells bead uptake was almost completely
inhibited.
These results clearly suggest that LPS- and EO-induced phagocytosis occur
possibly by means of different mechanisms, since only the EO-stimulated
internalization requires integrity of the microtubule network.
Cytoskeletal elements mediating the Eucalyptus oil
stimulated internalization
39. Abstract
BACKGROUND:
Essential oils are often used in alternative medicine as analgesic and anti-inflammatory remedies. TRPM8 is a
thermosensitive receptor that detects cool temperatures and menthol whereas TRPA1 is a sensor of noxious
cold. Ideally, an effective analgesic compound would activate TRPM8 and inhibit TRPA1.
RESULTS:
We screened essential oils and fragrance chemicals showing a high ratio of human TRPM8-activating ability
versus human TRPA1-activating ability using a Ca2+-imaging method, and identified 1,8-cineole in eucalyptus
oil as particularly effective. Patch-clamp experiments confirmed that 1,8-cineole evoked inward currents in
HEK293T cells expressing human TRPM8, but not human TRPA1. In addition, 1,8-cineole inhibited human TRPA1
currents activated by allyl isothiocyanate, menthol, fulfenamic acid or octanol in a dose-dependent manner.
Furthermore, in vivo sensory irritation tests showed that 1,8-cineole conferred an analgesic effect on sensory
irritation produced by TRPA1 agonists octanol and menthol. Surprisingly, 1,4-cineole, which is structurally
similar and also present in eucalyptus oil, activated both human TRPM8 and human TRPA1.
CONCLUSIONS:
1,8-cineole is a rare natural antagonist of human TRPA1 that has analgesic and anti-inflammatory effects
possibly due to its inhibition of TRPA1.
Takaishi M, Fujita F, Uchida K, Yamamoto S, Sawada Shimizu M, Hatai Uotsu C, Shimizu M, Tominaga
M.Source:Division of Cell Signaling, Okazaki Institute for Integrative Bioscience (National Institute for Physiological Sciences), National
Institutes of Natural Sciences, Okazaki, 444-8787, Japan.
PMID: 23192000 [PubMed - in process] PMCID: PMC3567430
1,8-cineole, a TRPM8 agonist, is a novel natural
antagonist of human TRPA1.
40. MSM is used for its anti-inflammatory and pain-relief properties
while helping in the regeneration of wounded tissues.
MSM (methyl sulfonyl methane) is a sulfur-containing compound
normally found in many of the foods we eat.
It is chemically related to DMSO (dimethyl sulfoxide), a popular
treatment for arthritis. When DMSO is applied on the skin about
15% of it breaks down in the body to form MSM.
Some researchers have suggested that the resulting MSM could
be responsible for the benefits attributed to DMSO.
If so, MSM might be preferable as a treatment, because it does
not cause some of the unpleasant side effects associated with
DMSO treatment, such as body odor.
Methyl Sulfonyl Methane
41. MSM is an amino acid supplement that has been used for years to treat arthritis and
bursitis in humans.
MSM readily donates sulfur to body tissues, and sulfur is needed for tissue health.
In fact, there is evidence that a lack of available sulfur in the connective tissues may
be one of the causes of aging and degenerative diseases such as arthritis.
MSM relieves muscle and joint pain through its ability to inhibit pain impulses along
the C type nerve fibers, enhance blood flow, remove inflammatory compounds in
the tissue and reduce muscle spasm.
It is now readily available in most health stores. MSM is present in many of the
foods we eat, such as eggs, nuts and other fresh foods. Cooking or processing
destroys MSM in food, and taking supplements can increase MSM intake
dramatically.
MSM is quite similar to DMSO in structure and function. DMSO can be helpful when
used topically over arthritic joints, but its unpleasant smell and topical application
make it difficult to use.
Dr. Stanley Jacobs, the DMSO pioneer at the Oregon Health Sciences University, has
been studying DMSO, MSM and other related compounds for over 20 years. His
studies indicate that they are safe to use in all types of arthritis.
.
42. In a double-blind, placebo-controlled study performed in India,
118 people with osteoarthritis of the knee were given one of the
following four treatments: glucosamine (500 mg, 3 times daily),
MSM (500 mg, 3 times daily), a combination of glucosamine and
MSM, or placebo. 16 The study ran for 12 weeks.
The results showed that both MSM and glucosamine improved
arthritis symptoms as compared to placebo, and that the
combination of MSM and glucosamine was more effective than
either one alone.
Benefits were also seen in a 12-week, double-blind, placebo-
controlled trial of 50 people with osteoarthritis, utilizing MSM
at a dose of 3 g twice daily. 18
MSM& glucosamine
43. bilobaGingko
Cartilage has no blood vessels or lymphatics and the nutrition of the cells
diffuses through the matrix. This explains the slowness of healing
process in cartilages.
44. Circulatory Benefits
By increasing circulation to the extremities, ginkgo biloba may help to
treat several painful conditions.
The NIH states that ginkgo biloba may reduce symptoms of claudication, or
leg pain, caused by poor blood flow.
Compounds in ginkgo biloba appear to increase the distance that a person
with peripheral vascular disease can walk before experiencing pain, and it
may also reduce the need for surgery to treat this condition.
Additionally, the NIH regards ginkgo as "possibly effective" as a method
for reducing the number of attacks in people .
http://www.livestrong.com/article/326913-does-ginkgo-biloba-increase-
circulation/#ixzz2MZfmkKq5
So G.B stimulate circulation
45. Abstract
In a randomized placebo controlled single-blind cross-over study
of n = 10 apparently healthy subjects the influence of Ginkgo
biloba (Kaveri) on blood fluidity and cutaneous microcirculation
was studied.
Microcirculation was measured before and every 30 min for 4 h
after administration of Ginkgo biloba; fluidity of blood was
determined before and after 1, 2 and 4 h.
Significant changes in blood pressure or heart rate were found
neither during Ginkgo phase nor placebo phase.
Haematocrit, plasma viscosity, erythrocyte rigidity, thrombocyte
and leukocyte count as well as thrombocyte aggregation and the
number of circulating thrombocyte aggregates were also not
influenced by the Ginkgo nor the placebo solution.
Effect of Ginkgo biloba on fluidity of blood and
peripheral microcirculation in volunteers.
46. In contrast a remarkable influence on the erythrocyte
aggregation was observed: comparing two samples a
significant decrease by 15.6% (p less than 0.001) with regard
to the initial value was observed after 2 h.
The blood flow in the nail fold capillaries also increased
significantly by about 57% (p less than 0.004) 1 h after
administration.
Source
Department of Clinical Haemostasiology and Transfusion Medicine,
University of Saarland, Homburg/Saar, Fed. Rep. of Germany.
PMID: 2383302 [PubMed - indexed for MEDLINE]
.
47. Although oxygen is essential for life, it can have adverse effects
on your body. Unstable oxygen molecules can often be created
during our body's normal break down and use of oxygen or can
form in response to external factors and pollutants.
These unstable molecules, called free radicals, can damage cells
and structures within cells. If the genetic material in cells is
affected and not repaired, it can replicate in new cells,
contributing to cancer and other health problems.
These free radicals may also weaken artery walls, allowing fatty
deposits that can lead to heart disease.
As an antioxidant, ginkgo biloba combats free radicals and
repairs molecular damage.
A great deal of research suggests that antioxidants such as GBE
may play important roles in preventing or delaying heart
disease, cancer and other ills. Antioxidants may even halt the
damage to cells, thereby slowing the effects of aging.
Antioxidant Properties
48. Health Benefits
The enduring popularity of gotu kola has been attributed to active
ingredients known as triterpenes.
One medicinal form, which is an Extract of gotu kola, is sometimes
referred to as TTFCA (total terpenoid fraction of Centella asiatica).
For memory and cognitive function.
For circulation.
For blood vessels and capillaries.
For skin disorders.
For varicose veins.
For nervous system.
For pain and inflammation.
Gotu Kola (Centella)
49. Gotu Kola contains chemicals called triterpines (saponins)
like asiaticoside, madecassoside and madasiatic acid.
Which enhance the formulation of tough, fibrous Protein
known as collagen in bones, cartilage and connective
tissue.
These substances work to promote healthy blood vessels
by strengthening their walls and improving blood flow.
Gotu Kola encourages production of chemical messengers
called neurotransmitters to help with brain function.
Health Benefits
50. In the evaluation of the effects of TTFCA (total triterpenic fraction
of Centella asiatica) microcirculatory alterations associated with
edema in passengers travelling for more than 3 hours found that
ankle swelling (AS) and edema were significantly lower in the
TTFCA-treated group (p<0.025).
The progressive increase in AS, transcutaneous PCO2, and the
decrease in VAR and O2 were linearly associated with flight time (up
to 10 hours), according to “Flight microangiopathy in medium- to
long-distance flights:
R… prevention of edema and microcirculation alterations with
total triterpenic fraction of Centella asiatica”
by Cesarone MR, Incandela L, De Sanctis MT, Belcaro G, Geroulakos G, Griffin M, Lennox A, Di Renzo AD, Cacchio
M, Bucci M(11)
Prevention of edema and microcirculation
:alterations
51. Various studies comparing placebos with gotu kola
as well as various preparations of its prime
constituent showed …. gotu kola is effective in
reducing fluid retention and swelling of the lower
limbs through improved circulation.
A study showed gotu kola effective in improving the
vascular tone of varicose vein sufferers. There was
less leakage from their blood vessels and
improvement in microcirculation.
http:a jumbled box of topics webs .com
THE HERB ON BLOOD VESSELS AND CIRCULATION
52. A 2-month double-blind, placebo-controlled study of 94 people with venous
insufficiency of the lower limb compared the benefits of gotu kola extract at 120 mg
daily and 60 mg daily against a placebo.
The results showed a significant dose-related improvement in the treated groups in
symptoms such as subjective heaviness, discomfort, and edema.
Another 2-month study of double-blind design enrolled 90 people with varicose
veins and compared the benefits of gotu kola at 60 mg and 30 mg daily against
placebo.
The results showed improvements in both treated groups, but greater improvement at
the higher dose.
In one study of people with venous insufficiency, 2 weeks of treatment with gotu
kola extracts was shown to reduce the time necessary for the swelling to disappear.
Another study of double-blind design followed 87 people with varicose veins and
compared the benefits of gotu kola at 60 mg and 30 mg daily against placebo.
The results showed improvements in both treated groups, but greater improvement at
the higher dose.
.
53. In the identification of antioxidant effects of C. asiatica was
exposed to various fermentations: no fermentation (0 min),
partial fermentation (120 min) and full fermentation (24 h).
Total phenolic content (TPC) and ferric-reducing antioxidant
power (FRAP) of C. asiatica, found that C. asiatica herbal teas
should be prepared at 100 °C for 10 min to obtain the optimum
antioxidant capacity.
Multiple brewing steps in C. asiatica herbal tea are encouraged
due to the certain amount of antioxidant obtained, according to
“Antioxidant capacity and phenolic composition of fermented
Centella asiatica herbal teas”
By Ariffin F, Heong Chew S, Bhupinder K, Karim AA, Huda N.(7)
Antioxidant capacity
54. The chemical composition and biological activity of clove
essential oil, Eugenia caryophyllata .
The essential oil extracted from the dried flower buds of
clove, Eugenia caryophyllata L.
Is used as a topical application to relieve pain , natural
analgaesic and to promote healing .
The main constituents of the essential oil are
phenylpropanoids such as carvacrol, thymol, eugenol and
cinnamaldehyde.
Clove essential oil possesses anti inflammatory, antioxidant
and anaesthetic properties.
Clove Oil
55. Biological properties of clove have been reported.
This work was aimed to investigate the effect in vivo of a water-
soluble part of hydroalcoholic extract of clove on pro-inflammatory
cytokines (IL-1beta and IL-6) production by macrophages of BALB/c
mice.
The action of the essential oil of clove on the production of these
cytokines macrophages was also investigated in vitro.
Treatment of mice with water extract of clove was found to inhibit
macrophages to produce both IL-1beta and IL-6.
The essential oil of clove also inhibited the production of these
cytokines in vitro.
Eugenol was found to be the major component of the clove extract
and essential oil, and is the causative agent of cytokine inhibition.
Taken together, these data suggest an anti-inflammatory action of
this oil.
Rodrigues TG, Fernandes A Jr, Sousa JP, Bastos JK, Sforcin JM.
In vitro and in vivo effects of clove on pro-inflammatory
cytokines production by macrophages.
57. Camphor
Is a stimulant, rubefacient & antipruritic . When in combination
with other ingredient like menthol, it becomes ideal for
neuralgia and other painful areas.
Provide symptomatic relief for mild to moderate muscular and
joint aches and pains, muscle cramps, shoulder aches and stiff
neck
For the temporary relief of pain associated with rheumatism,
arthritis, neuralgia, sprains and strains of joints and muscles,
lumbago and fibrositis.
Its counterirritant action is due to vasoconstriction which leads
to the activation of reflex mechanisms resulting in improved
local circulation.
Campher & Menthol
58. Camphor is used exclusively because of its local effects. When
rubbed on the skin, it acts as a rubefacient and causes localized
vasodilatation (mediated by way of an axon reflex), which gives
feelings of comfort and warmth.
As an anti-pruritic gent, when applied gently on the skin, it may
create a feeling of coolness, and a mild, local anaesthetic effect,
which may be followed by numbness.
Cinnamomum Camphora extracts display free radical scavenging
activities.
Ref: In vitro anti-inflammatory and anti-oxidative effects of
Cinnamomum Camphora extracts-Department of Pharmacology,
College of Medicine, Cheju National University, Ara-1 dong, Jeju 690-
756, South Korea School of Biotechnology and Bioengineering,
Kangwon National University, Hyoja-2-dong, Chuncheon 200-701, South
Korea.
.
59. Menthol
It is a terpene compound that is well known for its cold or
heat sensations as well as its antinociceptive and
counterirritant properties
It dilates the blood vessels causing a sensation of coldness,
followed by an analgesic effect.
Menthol also acts as a penetration enhancer, increasing
the penetration of componants when applied on the skin,
to give a faster onset of action.
.
60. It is utilized to soothe the effects of muscle soreness,
and even joint pain .
This could play acrucial role in sideline treatment of
soft tissue injuries during an athletic event .
If an athlete becomes injured, immediate and
effective treatment must be applied to help sustain
their performance capabilities and prevent further
injuries.
.
61. It is now understood that pain is sensed when an effector stimulates
somatosensory receptors. Nociceptors, or pain receptors, trigger an
action potential that stimulates the body to make adjustments either
via the spinal cord, or the upper CNS.
This action potential is caused by depolarization of the nerve cell body
through an influx of sodium ions via voltage-operated sodium channels
Research has shown that the possible anti nociceptive effects of
menthol could be due to the blocking of these sodium channels.
Human skeletal muscle tissue was sampled, and electric stimulus was
applied after tissue was exposed to menthol.
At various application strengths, inactivated sodium channels were
measured to determine the effect on depolarization.
It was demonstrated that the menthol acted as a block of the alpha
subunit of voltage gated sodium channels, therefore causing
hyperpolarization of the nervous membrane and a block in the signal
of pain transduction .
Effect of Menthol on Pain Starting
62. Another study demonstrates the anti nociceptive effects
of menthol by placing mice on a hotplate and determining
pain threshold via observation of painfully stimulated
behavior.
This study suggests that the temporary pain relief from
menthol was as effective as morphine for the hot plate
test .
It is suggested that menthol selectively activates central
K-opioid receptors, which led to this increase in pain
threshold.
Anti nociceptive effects of menthol by
63. Menthol has many other noted effects as well, such as temperature
sensations, which are a display of thermoreceptor excitation.
Menthol generates feelings of cold via the transient receptor potential
family of ion channels or (TRP's). TRP's are found throughout the body,
but TRPM8, found mainly within thermosensitive neurons, is known to
be commonly effected by menthol.
Utilization of calcium imaging techniques has demonstrated that upon
the application of menthol to cloned TRPM8 cells, a heavy intracellular
influx of calcium ions caused depolarization due to the opening of non-
selective calcium permeable cation channels .
This nervous transduction leads to the thermo-sensation that is
recognized from menthol application.
However, menthol is not a direct effector of this calcium channel
stimulation.Phosphatidylinositol 4,5 bisphosphate or PI(4,5)P2 is a
compound that is thought to activate TRPM8 channels, as well as other
calcium cation channels throughout the body.
Cooling effect
64. Rohacs et al has demonstrated that application of menthol
causes a direct sensitization of TRPM8 to the effects of PI(4,5)P2
.
This increase in sensitization is what leads to the excitation
properties of thermo sensation via menthol application.
Under certain circumstances, menthol exacerbates cold
response to the point of innocuous cold nociception, typically
referred to as cold allodynia .
It has been demonstrated that menthol propagates painful cold
stimuli by attenuating the actions of A-delta sensory fibers.
A-delta fibers are responsible for painless cold transmission and
their inhibitory effects on C nociceptor fibers.
With menthol present, A-delta fibers become inactive, and
Cnociceptors transmit cold pain.
.
65. Many studies report that many terpene compounds, such as
menthol, are extremely efficient at penetrating human skin,
including the dermal and epidermal layers.
Terpenes are compounds that are typically derived from
essential plant oils, making them rather lipophilic, which allows
for easypenetration of cellular membranes.
A range of 10 to 100 fold increases in skin permeation have been
observed with the use of topical terpene products.
Menthol, in specific, has been show to be effective at skin
penetration.
Martin et al. demonstrate that menthol can actually be
measured in the bloodstream (19.0 ± 5.4 ng/mL) after topical
application, and retains a half life of approximately 4.7 hours.
The penetration effects of topicalmenthol suggest that it may
even alter intracellular mechanisms of muscle cells.
penetration Enhancer
66. Moisturizer
The primary use of glycerin for the skin is as a moisturizer for dry, rough or scaly
skin. Various studies, such as one conducted in 2002 on patients with eczema in
Sweden, have clearly demonstrated that glycerin has humectant properties,
drawing water into the outer layer of the skin.
Irritants
It's been known in scientific circles for years that glycerol protects skin against irritation. In a
study published in the journal Dermatology in 1998, researchers pretreated skin with several
irritating substances and then applied glycerol to the area under an air-tight and water-tight
dressing. The glycerol staved off any negative effects from the irritations, provided a
significant improvement of the protective barrier function in the skin and caused skin cells to
regenerate.
Bruising and Swelling
Glycerin also helps promote skin regeneration in skin that is bruised and swollen. In a double-
blind, placebo-controlled clinical study, a product containing glycerin provided a reduction in
the severity and duration of bruising with just one application in 65 percent of the patients in
the study.
Glycerin
67. Anti-Oxidant effect
Vitamin C is one of the more powerful and well-known antioxidants.
Just as exposing a cut apple to air causes it to quickly turn brown, cells
of the body can also suffer damage when exposed to oxygen, a process
known as oxidation.
Oxidation causes aging of the skin as well as all other organs and
tissues of the body.
Vitamin C, as a free-radical fighter, helps ward off wrinkles and many
illnesses linked to oxidation, including arthritis, heart disease, and
cancer.
stimulates collagen synthesis, and to a lesser extent the synthesis of
aggrecan. Proteoglycan synthesis is increased in chondrocyte cultures.
An animal study showed that vitamin C has a protective effect on knee
cartilage.
The effect of chondrocyte protection could be mediated by its
antioxidant capacity.
Vit C & vit C Acetate
68. Decreases oxidative stress
The BALANCE Between Pro-Oxidants and Antioxidants
Pro-Oxidants
((||(Reactive Oxygen Species
Free Radicals)
Antioxidants
Ascorbic Acid
OXIDATIVE STRESS
Cell & Tissue Damage
Protection / Tissue Repair
Antioxidants
Cell / Tissue Damage
Oxidants
69. vitamin C are required for collagen synthesis.
Hydroxyproline, an amino acid, is vital for the stability of
collagen, and vitamin C assists in the production of
hydroxyproline.
Conversely, a deficiency in vitamin C halts production of
hydroxyproline, and subsequently the body cannot create
collagen.
Collagen synthesis&Vit C
70. Vitamin C reduces the amount of histamine in the blood. that block
your body from releasing histamines, a substance that produces an
inflammatory response in your body.
Read more: http://www.livestrong.com/article/article/156597-natural-
substitutes-for-antihistamines/#ixzz2MlByAcdJ
An article from the August 1992 "Journal of the American Dietetic
Association" found that 2 g of ascorbic acid decreased histamine levels
by 40 percent. An article from the April 1992 "Journal of the American
College of Nutrition" also found that 2 g of ascorbic acid decreased
histamine levels by 38 percent, and those levels did not change for four
hours.
How Vitamin C Works as an Antihistamine
In the March 2011 "Journal of Evidence-Based Complementary &
Alternative Medicine," researchers reported that Vitamin C works as an
antihistamine by destroying the molecular structure of the imidole ring
of the histamine molecule, thereby decreasing the amount of
histamine in the blood.
effectAntihistamine
71. Vitamin C functions as an anti-inflammatory, and helps the
body fight inflammatory diseases, including arthritis,
fibromyalgia, and chronic fatigue.
A multitude of other conditions may be improved vitamin
C, including bronchitis, bruises, canker sores, diabetes,
gingivitis, glaucoma, infertility, joint pain, rashes,
shingles, sore throat, sprains, sunburn, and scurvy (a
disease caused by vitamin C deficiency).
Because vitamin C helps the body absorb iron, it is also
useful in treating iron deficiency and anemia.
Anti-inflammatory effect
72. For a study published in 2006, 18 healthy men took either
a placebo or three grams of vitamin C in supplement form
each day for two weeks.
Next, all participants performed 70 elbow extensions,
then continued taking either the placebo or vitamin C
supplements for four days.
Study results showed that vitamin C reduced muscle
soreness, but had little effect on loss of muscle function.
Zainuddin Z, Newton M, Sacco P, Nosaka K. "Effects of massage on delayed-onset muscle
soreness, swelling, and recovery of muscle function." J Athl Train. 2005 40(3):174-80.
Reduce muscle aches
74. o Mobiease …… Extra strength.
o Mobiease …… fast penetrating the skin and help reduce pain.
o Mobiease …… deep cooling.
o Mobiease …… pain relief.
o Mobiease …… Improves patient comfort.
o Mobiease …… Relieve muscle pain and joint stiffness.
o Mobiease …… Cool To Warm Sensation.
o Mobiease …… Relax Muscle Prior to and After Activity.
o Mobiease …… Increased Flexibility.
o Mobiease …… Time Delivery, Released Relief For Hours.
The Natural Solution forMuscle and Joint
Recovery
75. o You are older than 65. “A lot of elderly patients can’t take
oral NSAIDs because they have stomach or heart risk
factors, and they can’t take narcotic analgesics because they
could become so drowsy they could fall and break a bone.
o You want to avoid pills. Some people with OA who want to
avoid systemic side effects seek compounding pharmacies,
so that they can have their favorite pain killer made into a
topical formula.
o If you have arthritis in just one or two joints, you may not
need to expose yourself to the risks of oral non-steroidal
anti-inflammatory drugs (NSAIDs) – such as ulcers; stomach
upset; or potential heart, kidney or liver problems – in order
to achieve some relief.
.