Prostanoïds, cyclo-oxygenase products of
arachidonic acid, belong to the mediators of acute inflammation and
they are also suggested to be involved in the pathogenesis of
rheumatoid arthritis.
On the other hand, prostanoids (mainly PGE2)
have been reported to have anti-inflammatory properties in some forms
of experimental inflammation. Furthermore, leukotrienes (mainly LTB4),
5 lipoxygenase products of arachidonic acid, are also suggested to act
as mediators in inflammation diseases such as rheumatoid arthritis.
(The therapeutic action of non-steroidal anti-inflammatory drugs can
partly be explained by their inhibitory effects on prostanoids
biosynthe-sis).
8
Note on the Assay
There’s different methods of analysis
- Method
of the European Pharmacopea : HPLC of the harpagoside “as harpagoside”.
The most precise. That’s the one we use. Some also use the total peaks
as harpagoside, which gives higher results.
- Method of harpagoside by UV. It’s at least double of the HPLC, and more usually 2.5 times more. We also check it.
- Method UV of total iridoides : we do not do it since it’s far from real harpagoside.
For
instance, our products named IridoForce™ 40.20 brings min. 20%
Harpagoside by HPLC, and min. 40% Harpagoside by UV (and usually
45-50%). Our IridoForce™ 5.2 brings 5-7% by UV and 2.5% by HPLC
Harpagoside is the primary iridoïd glycoside.
Iridoid were not considered previously as a particularly important
pharmacologically active class of compounds. More recently, extensive
investigations into their biological activity in general and their
potential pharmacological activity in particular, have revealed that
iridoids exhibit a wide range of bioactivity.
2
Action
on eicosanoïd synthesis : Devil’s claw extracts and its marker
substances harpagoside and harpagide were shown to exert
anti-inflammatory effects by interacting with the eicosanoid synthesis.
The observations made by Loew et al. strongly indicated a close
relation between serum harpagoside levels and the inhibition of
leukotriene biosynthesis.
9
Action on cyclo-oxygenase and NO synthetase :
Some preliminary evidence suggest that harpagoside inhibits both
arachidonic metabolism path-ways : the cyclo-oxygenase (COX) and
lipoxygenase inflammatory pathways. Devil’s claw seems to inhibit COX-2
but not COX-1, and nitric oxide synthetase, a modular of inflammation.
2,10 Recent studies on IridoForce™ (high titled Harpagosides) proved a great inhibition of COX-2.
It
has been demonstrated that Harpagophytum procumbens extract produces a
dose dependent inhibition of both the prostaglandin and leukotriene
pathways of arachidonic acid metabolism.
11
Action on Cys-LT synthesis
: It is currently ac-cepted that, according to initial exploratory in
vitro data, harpagoside seems to be an effective constituent of the
Cys-LT synthesis.
1Action on TNFα liberation : In addition of these effects on COX and/or the lipoxy-genase in the arachidonic acid metabolism
6,12,13,
it has been shown that devil’s claw extracts inhibit inflammatory
processes mainly by preventing the release of Tumor Necrosis Factor
alpha (TNF-α)
8,14,15,16, an important cytokine which is
increased in inflammatory diseases, such as rheumatoid arthritis (Fox,
2000).
17 The anti-inflammatory effect may also be due to increased
synthesis and release of cytokine tumor necrosis factor (TNF)-alpha by
compounds other than harpagoside.
Pharmacokinetics
: Harpagoside, currently consid-ered as one of the major
pharmacologically active principle, has been reported by Van Haelen,
1983 to have a resorption and a bioavailability after oral intake
(therapeutic dosage) of about 50% for the carnivorous.
The maximum concentration of harpagoside in plasma after oral intake is dose-dependent.
9.
Efficient dosage
:Harpagoside dosage is here mentioned as analysed by HPLC. Other common
methods based on UV easily gives 2 to 2,5 times more harpagoside.
ESCOP
monography recommends the following dosages
18 : Osteoarthritis : 2-5
g/day of root pow-der (ie. about 12-30 mg Harpagoside) or an equivalent
dosage of an aqueous or hydroalco-holic extract (1-3 g extract per day)
during 2 to 3 months. Low back pain : from 4,5 g/day of a dry extract,
corresponding to 30mg/day harpagoside. According to Chrubasik et al.,
1999, the products containing a daily dosage of at 30-50 mg
iri-doidglycosides, calculated as harpagoside, provided the best
results, which happens to be of ethanolic extraction
19. A
treatment with extract containing more harpagoside was more effective
than in terms of number of pain free patients but not in terms of
improvement of the pain compo-nent of the Arhus score.
20,21
IridoForce™ is recommended at 10 to 40mg har-pagoside per day
[up to 40mg within the European Community—dossier PL 1151/1] which
means 50-200mg of IridoForce™ 40.20 per day. Usual uses is 20 mg
Harpagoside / day [Stand alone Formula] with mention of a possible
double dose to reach 40mg in case of severe pains or problems, and
5-20mg Harpagoside if combined with other effective components.
References