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      Pain Controlling and Cytokine-regulating Effects of Lyprinol, a Lipid Extract of Perna Canaliculus, in a Rat Adjuvant-induced Arthritis Model

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          Abstract

          Using an adjuvant-induced arthritis rat model, we investigated the effects of a lipid extract of Perna canaliculus (Lyprinol®) on pain. Radiological examinations, as well as levels of pro- and anti-inflammatory (AI) cytokines, were measured aiming to provide independent objective data to the pain controlling investigation. We confirmed the ability of Lyprinol® to control pain at the initial phase of its administration; with similar efficacy to that observed with Naproxen. The pain scores slowly increased again in the group of rats treated with Lyprinol® after day 9–14. The Naproxen-treated rats remained pain-free while treated. Both Naproxen and Lyprinol® decreased the levels of the pro-inflammatory cytokines TNF-α and IFN-γ, and increased that of IL-10. Extra-virgin olive oil was ineffective on cytokine secretion. Rats treated with Lyprinol® were apparently cured after 1 year. This study confirms the AI efficacy of this lipid extract of P. canaliculus, its initial analgesic effect, its perfect tolerance and its long-term healing properties.

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          Controlling pathological pain by adenovirally driven spinal production of the anti-inflammatory cytokine, interleukin-10.

          Kirk Johnson, C E Sloane, Sai-Lin He … (2005)
          Gene therapy for the control of pain has, to date, targeted neurons. However, recent evidence supports that spinal cord glia are critical to the creation and maintenance of pain facilitation through the release of proinflammatory cytokines. Because of the ability of interleukin-10 (IL-10) to suppress proinflammatory cytokines, we tested whether an adenoviral vector encoding human IL-10 (AD-h-IL10) would block and reverse pain facilitation. Three pain models were examined, all of which are mediated by spinal pro-inflammatory cytokines. Acute intrathecal administration of rat IL-10 protein itself briefly reversed chronic constriction injury-induced mechanical allodynia and thermal hyperalgesia. The transient reversal caused by IL-10 protein paralleled the half-life of human IL-10 protein in the intrathecal space (t(1/2) approximately 2 h). IL-10 gene therapy both prevented and reversed thermal hyperalgesia and mechanical allodynia, without affecting basal responses to thermal or mechanical stimuli. Extra-territorial, as well as territorial, pain changes were reversed by this treatment. Intrathecal AD-h-IL10 injected over lumbosacral spinal cord led to elevated lumbosacral cerebrospinal fluid (CSF) levels of human IL-10, with far less human IL-10 observed in cervical CSF. In keeping with IL-10's known anti-inflammatory actions, AD-h-IL10 lowered CSF levels of IL-1, relative to control AD. These studies support that this gene therapy approach provides an alternative to neuronally focused drug and gene therapies for clinical pain control.
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            Anti-inflammatory activity of a lipid fraction (lyprinol) from the NZ green-lipped mussel.

            N Kalafatis, Jonathan W Betts, Gwilym Haynes … (1996)
            A lipid-rich extract, preparared by supercritical fluid extraction of fresh stabilized mussel powder (Lyprinol), showed significant anti-inflammatory (AI) activity given therapeutically and prophylactically po to Wistar and Dark Agouti rats developing either (a) adjuvant-induced polyarthritis or (b) collagen(II)-induced autoallergic arthritis, with ED(50) /=25 mg/kg or various therapeutic oils (flaxseed, evening primrose, fish)>/=1800 mg/kg given orally. Lyprinol showed little or no activity in acute irritation assays (carrageenan, kaolin, histamine) indicating it is not mimicking rapid-acting NSAIDs.Incorporating Lyprinol into arthritigenic adjuvants composed of heat-killed Mycobacterium. tuberculosis suspended in olive oil or squalane, effectively prevented arthritis development at a dose of 5 mg/rat. By contrast, 'dummy adjuvants' prepared with Mycobacterium tuberculosis and flaxseed, evening primrose or fish oils were still arthritigenic in Dark Agouti rats (doses of oil=90 mg/rat).Lyprinol subfractions inhibited leukotriene-B(4) biosynthesis by stimulated human polymorphonuclear leukocytes in vitro, and prostaglandin-E(2) production by activated human macrophages in vitro. Much of this AI activity was associated with polyunsaturated fatty acids and natural antoxidants (carotenoids, etc.).In contrast to NSAIDs, Lyprinol is non-gastrotoxic in disease-stressed rats at 300 mg/kg po and does not seem to affect platelet aggregation (human, rat). These data show Lyprinol to be a reproducible, relatively stable, source of bioactive lipids with much greater potency than plant/marine oils currently used as nutritional supplements to ameliorate signs of inflammation.
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              Treatment of asthma with lipid extract of New Zealand green-lipped mussel: a randomised clinical trial.

              A Abulimity, G Fedoseev, O Krasnoschekova … (2002)
              Asthma is a chronic inflammatory disease of the airways mediated, at least in part, by leukotrienes and other lipid mediators. Experimental studies have shown that lipid extract of New Zealand green-lipped mussel, Perna canaliculus, is effective in inhibiting 5'-lipoxygenase and cyclo-oxygenase pathways responsible for production of eicosanoids, including leukotrienes and prostaglandins. The aim of this study was to assess its effect on symptoms, peak expiratory flow (PEF) and hydrogen peroxide (H2O2) in expired breath condensate as a marker of airway inflammation in patients with steroid-naïve atopic asthma in a double-blind randomised, placebo-controlled clinical trial. Forty six patients with atopic asthma received two capsules of lipid extract (Lyprinol) or placebo b.i.d for 8 weeks. Each capsule of lipid extract contained 50 mg omega-3 polyunsaturated fatty acids and 100 mg olive oil, whereas placebo capsules contained only 150 mg olive oil. There was a significant decrease in daytime wheeze, the concentration of exhaled H2O2 and an increase in morning PEF in the lipid extract group compared to the placebo group. There were no significant side-effects. The authors conclude that lipid extract of New Zealand green-lipped mussel may have some beneficial effect in patients with atopic asthma.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Evid Based Complement Alternat Med
                Journal ID (publisher-id): ecam
                Journal ID (hwp): ecam
                Title: Evidence-based Complementary and Alternative Medicine : eCAM
                Publisher: Oxford University Press
                ISSN (Print): 1741-427X
                ISSN (Electronic): 1741-4288
                Publication date (Print): June 2009
                Publication date (Electronic): 26 September 2007
                Publication date PMC-release: 26 September 2007
                Volume: 6
                Issue: 2
                Pages: 239-245
                Affiliations
                1State Key Laboratory of Chinese Medicine and Molecular Pharmacology, Shenzhen and Department of Applied Biology and Chemical Technology and 2Department of Health Technology and Informatics, Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong SAR, China
                Author notes
                For reprints and all correspondence: Prof. Samuel C. L. Lo, Dept. of Applied Biology & Chemical Technology, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong SAR, China. Tel: +(852) 34008669; Fax: +(852) 23649932; E-mail: bcsamlo@ 123456inet.polyu.edu.hk
                Article
                Publisher ID: nem100
                DOI: 10.1093/ecam/nem100
                PMC ID: 2686621
                PubMed ID: 18955235
                SO-VID: 51dd3c5b-8e0b-44fa-a7ba-199db0a66466
                Copyright © © 2007 The Author(s).
                License:

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Date received : 9 November 2006
                Date accepted : 10 July 2007
                Categories
                Subject: Original Articles - Basic Science

                ScienceOpen disciplines: Complementary & Alternative medicine
                Keywords: lyprinol®,inflammatory cytokines,adjuvant-induced arthritis,nzglm, pain score
                Data availability:
                ScienceOpen disciplines: Complementary & Alternative medicine
                Keywords: lyprinol®, inflammatory cytokines, adjuvant-induced arthritis, nzglm, pain score

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