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Systematic
review of the nutritional supplement Perna Canaliculus (green-lipped
mussel) in the treatment of osteoarthritis 1/25/2008
S. Brien,
P. Prescott, B. Coghlan, N. Bashir and G. Lewith
From the
Department of Primary Care, University of Southampton, Aldermoor
Health Centre, Aldermoor Close, Southampton, Hampshire, SO16
5ST and School of Mathematics, University of Southampton, University
Road, Southampton, Hampshire SO17 1BJ, UK
Complementary
treatments for osteoarthritis (OA) are sought by patients for
symptomatic relief and to avoid the iatrogenic effects of non-steroidal
anti-inflammatories. This systematic review evaluates the efficacy
of the nutritional supplement Perna Canaliculus (green-lipped
mussel, GLM) in the treatment of OA and substantially adds to
previous work by focussing solely on GLM use in OA as well providing
a re-analysis of the original trial data. Randomized or quasirandomized
controlled trials (comparative, placebo-controlled or crossover)
were considered for inclusion from Cochrane Library, Medline,
Embase, Amed, Cinahl, Scopus and NeLH databases where adults
with OA of any joint were randomized to receive either GLM vs.
placebo, no additional intervention (usual care), or an active
intervention. The methodological quality of the trials was assessed
using the JADAD scale. Four RCTs were included, three placebo
controlled, the fourth a comparative trial of GLM lipid extract
vs. stabilized powder extract. No RCTs comparing GLM to conventional
treatment were identified. All four studies assessed GLM as
an adjunctive treatment to conventional medication for a clinically
relevant time in mild to moderate OA. All trials reported clinical
benefits in the GLM treatment group but the findings from two
studies cannot be included in this review because of possible
un-blinding and inappropriate statistical analysis. The data
from the two more rigorous trials, in conjunction with our re-analysis
of original data suggests that GLM may be superior to placebo
for the treatment of mild to moderate OA. As a credible biological
mechanism exists for this treatment, further rigorous investigations
are required to assess efficacy and optimal dosage.
Novel
anti-inflammatory omega-3 PUFAs from the New Zealand green-lipped
mussel, Perna canaliculus 8/1/2007
Comp Biochem
Physiol B Biochem Mol Biol. 2007 Aug;147(4):645-56. Epub 2007
Apr 14
Treschow
AP, Hodges LD, Wright PF, Wynne PM, Kalafatis N, Macrides TA.
Natural Products Research Group, School of Medical Sciences,
RMIT University, Bundoora, Victoria, 3083, Australia.
The present
study has identified in the marine mollusc, Perna canaliculus,
an homologous series of novel omega 3 polyunsaturated fatty
acids (omega-3 PUFA) with significant antiinflammatory (AI)
activity. The free fatty acid (FFA) class was isolated from
a supercritical-CO2 lipid extract of the tartaric acid-stabilised
freeze-dried mussel powder by normal phase chromatography, followed
by reversed-phase high performance liquid chromatography (RP-HPLC).
The RP-HPLC involved separation based on carbon numbers, followed
by argentation-HPLC (Ag-HPLC) of the methyl esters based on
degree of unsaturation. Identification of the FFA components
was performed using gas chromatography (GC) with flame ionisation
detection, and individual structures were assigned by GC-mass
spectroscopy (GC-MS). Inhibition of leukotriene production by
stimulated human neutrophils was used as an in vitro screening
method to test the AI activity of the purified PUFAs. A structurally
related family of omega-3 PUFAs was identified in the most bioactive
fractions, which included C18:4, C19:4, C20:4, and C21:5 PUFA.
The C20:4 was the predominant PUFA in the extract, and was a
structural isomer of arachidonic acid (AA). The novel compounds
may be biologically significant as AI agents, as a result of
their in vitro inhibition of lipoxygenase products of the AA
pathway.
Immunomodulation
of murine collagen-induced arthritis by N, N-dimethylglycine
and a preparation of Perna canaliculus 6/11/2007
BMC Complement
Altern Med. 2007 Jun 11;7:20
Lawson BR,
Belkowski SM, Whitesides JF, Davis P, Lawson JW. Department
of Biological Sciences, Clemson University, Clemson, SC, USA.
BACKGROUND:
Rheumatoid arthritis (RA) and its accepted animal model, murine
collageninduced arthritis (CIA), are classic autoimmune inflammatory
diseases which require proinflammatory cytokine production for
pathogenesis. We and others have previously used N, Ndimethylglycine
(DMG) and extracts from the New Zealand green-lipped mussel
Perna canaliculus (Perna) as potent immunomodulators to modify
ongoing immune and/or inflammatory responses. METHODS: In our
initial studies, we treated lipopolysaccahride (LPS) stimulated
THP-1 monocytes in vitro with increasing concentrations of Perna
extract or DMG. Additionally, we treated rat peripheral blood
neutrophils with increasing concentrations of Perna extract
and measured superoxide burst. In subsequent in vivo experiments,
CIA was induced by administration of type II collagen; rats
were prophylactically treated with either Perna or DMG, and
then followed for disease severity. Finally, to test whether
Perna and/or DMG could block or inhibit an ongoing pathologic
disease process, we induced CIA in mice and treated them therapeutically
with either of the two immunomodulators. RESULTS: Following
LPS stimulation of THP-1 monocytes, we observed dose-dependent
reductions in TNF-alpha and IL-12p40 production in Perna treated
cultures. DMG treatment, however, showed significant increases
in both of these cytokines in the range of 0.001-1 microM. We
also demonstrate that in vitro neutrophil superoxide burst activity
is dose-dependently reduced in the presence of Perna. Significant
reductions in disease incidence, onset, and severity of CIA
in rats were noted following prophylactic treatment with either
of the two immunomodulators. More importantly, amelioration
of mouse CIA was observed following therapeutic administration
of Perna. In contrast, DMG appeared to have little effect in
mice and may act in a species-specific manner. CONCLUSION: These
data suggest that Perna, and perhaps DMG, may be useful supplements
to the treatment of RA in humans.
In vitro
modulation of inflammatory cytokine and IgG levels by extracts
of Perna canaliculus 1/13/2006
BMC Complement
Altern Med. 2006 Jan 13;6:1
Mani S, Lawson
JW. Department of Microbiology and Molecular Medicine, Clemson
University, Clemson, SC 29634, USA.
BACKGROUND:
Inflammation is a predominant characteristic of autoimmune
diseases which is characterized by the increased expression
of pro-inflammatory cytokines. Soon to be published work from
our laboratory has shown that ingestion of Perna canaliculus
prevents the development of autoimmune diseases such as Systemic
Lupus Erythematosus and rheumatoid arthritis in laboratory
animals. The current paper attempts to illustrate how Perna
can alleviate inflammation by modulating inflammatory cytokines,
cyclooxygenase enzymes and Immunoglobulin-G (IgG) levels.
METHODS: In the present study, hydrochloric acid [HCl] and
Tween-20 were used to develop extracts of Perna. These extracts
were assayed for protein content. Increasing concentrations
of these extracts were then tested in cell culture for modulation
of inflammatory cytokine, cyclooxygenase enzymes and IgG levels.
Parallel tests were run using an available glycogen extract
of Perna as a comparison to our in-house laboratory preparations.
RESULTS: Tween-20 Perna extracts were found to be more stable
and less toxic in cell culture than HCl digest of Perna. They
also assayed higher in protein content that HCl extracts.
Although both extracts inhibited IgG production in V2E9 hybridomas,
Tween-20 extracts were more consistent in IgG suppression
than HCl extracts. Overall Tween-20 extracts effectively decreased
levels of TNF-alpha, IL-1, IL-2 and IL-6 as observed using
cytokine bioassays. Twenty micrograms of Tween-20 Perna extracts
induced such significant decreases in inflammatory cytokine
production that when tested on sensitive cell lines, they
very nearly abolished the decrease in viability induced by
these cytokines. Tween-20 extracts effectively inhibited both
COX-1 and COX-2 cyclooxygenase activity. As a comparison,
the glycogen extract also demonstrated a similar though weaker
effect on COX-1 and COX-2 enzymes. The active components of
both extracts (Tween-20 and glycogen) were observed to possess
molecular weights above 100 kDa. Although the anti-cytokine
activity of the Tween-20 extract was destroyed by Proteinase-
K treatment, the anti-COX-1 and anti-COX-2 activity of both
the extracts were not sensitive to protease treatment. CONCLUSION:
We have successfully demonstrated modulation in the levels
of inflammatory cytokines, cyclooxygenase enzymes and immunoglobulins
by our in-house laboratory preparations of Perna canaliculus,
whereby suggesting an immunomodulatory role of Perna canaliculus
in regulating inflammation.
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