A lipid extract of
Perna canaliculus
(New Zealand green-lipped mussel) has reportedly displayed anti-inflammatory effects in animal models and in human controlled studies. However, the anti-inflammatory lipid components have not been investigated in detail due to the instability of the lipid extract, which has made the identification of the distinct active components a formidable task. Considering the instability of the active component, we carefully fractionated a lipid extract of
Perna canaliculus
(Lyprinol) and detected furan fatty acids (F-acids). These naturally but rarely detected fatty acids show potent radical-scavenging ability and are essential constituents of plants and algae. Based on these data, it has been proposed that F-acids could be potential antioxidants, which may contribute to the protective properties of fish and fish oil diets against chronic inflammatory diseases. However, to date, in vivo data to support the hypothesis have not been obtained, presumably due to the limited availability of F-acids. To confirm the in vivo anti-inflammatory effect of F-acids in comparison with that of eicosapentaenoic acid (EPA), we developed a semisynthetic preparation and examined its anti-inflammatory activity in a rat model of adjuvant-induced arthritis. Indeed, the F-acid ethyl ester exhibited more potent anti-inflammatory activity than that of the EPA ethyl ester. We report on the in vivo activity of F-acids, confirming that the lipid extract of the green-lipped mussel includes an unstable fatty acid that is more effective than EPA.
Matrix metalloproteinase-7 (MMP-7) has emerged as a protein
playing
important roles in both physiological and pathophysiological processes.
Despite the growing interest in MMP-7 as a potential therapeutic target
for diseases including cancer and fibrosis, potent and selective MMP-7
inhibitors have yet to be identified. Compound 1, previously
reported by Edman and co-workers, binds to the S1′ subsite
of MMP-7, exhibiting moderate inhibitory activity and selectivity.
To achieve both higher inhibitory activity and selectivity, we conceived
hybridizing 1 with short peptides. The initially designed
compound 6, which was a hybrid molecule between 1 and a tripeptide (Ala-Leu-Met) derived from an MMP-2-inhibitory
peptide (APP-IP), showed enhanced MMP-7-inhibitory activity. Subsequent
optimization of the peptide moiety led to the development of compound 18 with remarkable potency for MMP-7 and selectivity over
other MMP subtypes.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.