Tetra- and Pentacyclic Triterpene Acids from the Ancient Anti-inflammatory Remedy Frankincense as Inhibitors of Microsomal Prostaglandin E2 Synthase-1

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• 作者：Moritz Verhoff ; Stefanie Seitz ; Michael Paul ; Stefan M. Noha ; Johann Jauch ; Daniela Schuster ; Oliver Werz
• 刊名：Journal of Natural Products
• 出版年：2014
• 出版时间：June 27, 2014
• 年：2014
• 卷：77
• 期：6
• 页码：1445-1451
• 全文大小：386K
• ISSN：1520-6025

文摘

The microsomal prostaglandin E₂ synthase (mPGES)-1 is the terminal enzyme in the biosynthesis of prostaglandin (PG)E₂ from cyclooxygenase (COX)-derived PGH₂. We previously found that mPGES-1 is inhibited by boswellic acids (IC₅₀ = 3鈥?0 渭M), which are bioactive triterpene acids present in the anti-inflammatory remedy frankincense. Here we show that besides boswellic acids, additional known triterpene acids (i.e., tircuallic, lupeolic, and roburic acids) isolated from frankincense suppress mPGES-1 with increased potencies. In particular, 3伪-acetoxy-8,24-dienetirucallic acid (6) and 3伪-acetoxy-7,24-dienetirucallic acid (10) inhibited mPGES-1 activity in a cell-free assay with IC₅₀ = 0.4 渭M, each. Structure鈥揳ctivity relationship studies and docking simulations revealed concrete structure-related interactions with mPGES-1 and its cosubstrate glutathione. COX-1 and -2 were hardly affected by the triterpene acids (IC₅₀ > 10 渭M). Given the crucial role of mPGES-1 in inflammation and the abundance of highly active triterpene acids in frankincence extracts, our findings provide further evidence of the anti-inflammatory potential of frankincense preparations and reveal novel, potent bioactivities of tirucallic acids, roburic acids, and lupeolic acids.