Abstract
Over the last few decade Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) are the drugs of choice for treating numerous inflammatory diseases including rheumatoid arthritis. The NSAIDs produces anti-inflammatory activity via inhibiting cyclooxygenase enzyme, responsible for the conversation of arachidonic acid to prostaglandins. Likewise, cyclooxegenase-2 inhibitors (COX-2) selectively inhibit the COX-2 enzyme and produces significant anti-inflammatory, analgesic, and anti-pyretic activity without producing COX-1 associated gastrointestinal and renal side effects. In last two decades numerous selective COX-2 inhibitors (COXIBs) have been developed and approved for various inflammatory conditions. However, data from clinical trials have suggested that the prolong use of COX-2 inhibitors are also associated with life threatening cardiovascular side effects including ischemic heart failure and myocardial infection. In these scenario secondary metabolites from natural product offers a great hope for the development of novel anti-inflammatory compounds. Although majority of the natural product based compounds exhibit more selectively toward COX-1. However, the data suggest that slight structural modification can be helpful in developing COX-2 selective secondary metabolites with comparative efficacy and limited side effects. This review is an effort to highlight the secondary metabolites from terrestrial and marine source with significant COX-2 and COX-2 mediated PGE2 inhibitory activity, since it is anticipated that isolates with ability to inhibit COX-2 mediated PGE2 production would be useful in suppressing the inflammation and its classical sign and symptoms. Moreover, this review has highlighted the potential lead compounds including berberine, kaurenoic acid, α-cyperone, curcumin, and zedoarondiol for further development with the help of structure–activity relationship (SAR) studies and their current status.
Highlights
Inflammation is a tightly regulated immune-protective response to combat xenobiotic invasion, mechanical, chemical, and thermal injury (Nathan, 2002; Barton, 2008)
The results suggests that the up regulation of cyclooxegenase-2 inhibitors (COX-2) mRNA and COX-2 derived and PGE2 production was observed carrageenan induced paw edema, no significant change was observed in COX-1 mRNA
The results suggested that rutaecarpine (2) able to inhibit COX-1 and COX2 mediated PGD2 production in bone marrow derived mast cells (BMMC) at a concentration dependent manner with an IC50 value of 0.28 and 8.7 μM, respectively
Summary
Reviewed by: Lihong Chen, Dalian Medical University, China Carlo Riccardi, University of Perugia, Italy. Data from clinical trials have suggested that the prolong use of COX-2 inhibitors are associated with life threatening cardiovascular side effects including ischemic heart failure and myocardial infection. In these scenario secondary metabolites from natural product offers a great hope for the development of novel anti-inflammatory compounds. This review is an effort to highlight the secondary metabolites from terrestrial and marine source with significant COX-2 and COX-2 mediated PGE2 inhibitory activity, since it is anticipated that isolates with ability to inhibit COX-2 mediated PGE2 production would be useful in suppressing the inflammation and its classical sign and symptoms.
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