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

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Summary

Raging the War Against Inflammation With Natural Products

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.

INTRODUCTION
CYCLOOXYGENASE PATHWAY
MECHANISM OF ACTION OF CYCLOOXYGENASE PATHWAY
ROLE OF CYCLOOXYGENASE IN
Pain and Inflammation
Autoimmune Diseases
Allergic Diseases
Fatty Acids
Miscellaneous Compounds
Findings
CONCLUSION
Full Text
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