Munronia pinnata (Wall.) Theob.: Unveiling phytochemistry and dual inhibition of 5-lipoxygenase and microsomal prostaglandin E₂ synthase (mPGES)-1

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• 作者：Mayuri Napagoda ; Jana Gerstmeier ; Andreas Koeberle ; S ; ra Wesely ; Sven Popella ; Sybille Lorenz ; Kerstin Scheubert ; Sebastian B枚cker ; Ale拧 Svato拧 ; Oliver Werz
• 关键词：Munronia pinnata ; Inflammation ; 5-Lipoxygenase ; Radical scavenger ; Microsomal prostaglandin E2 synthase-1 ; Mass spectrometry
• 刊名：Journal of Ethnopharmacology
• 出版年：3 February, 2014
• 年：2014
• 卷：151
• 期：2
• 页码：882-890
• 全文大小：640 K

文摘

Ethnopharmacological relevance

Preparations from Munronia pinnata (Wall.) Theob. are extensively used in traditional medicine in Sri Lanka for the treatment of inflammatory conditions. However, neither the pharmacological features nor the phytochemistry of this plant are explored in order to understand and rationalize the reported ethnobotanical significance. As 5-lipoxygenase (5-LO) and microsomal prostaglandin E₂ synthase (mPGES)-1 are crucial enzymes in inflammatory disorders, we evaluated their inhibition by M. pinnata extracts and studied the chemical profile of the plant for the identification of relevant constituents.

Materials and methods

Cell-free and cell-based assays were employed in order to investigate the suppression of 5-LO and mPGES-1 activity. Cell viability, radical scavenger activities, and inhibition of reactive oxygen species formation (ROS) in neutrophils were studied to assess cytotoxic and antioxidant effects. Gas and liquid chromatography coupled to mass spectrometric analysis enabled the characterization of secondary metabolites.

Results

The n-hexane extract of M. pinnata efficiently suppressed 5-LO activity in stimulated human neutrophils (IC₅₀ =8.7 碌g/ml) and potently inhibited isolated human recombinant 5-LO (IC₅₀ =0.48 碌g/ml) and mPGES-1 (IC₅₀ =1.0 碌g/ml). In contrast, no significant radical scavenging activity or suppression of ROS formation was observed, and neutrophil viability was unaffected. The phytochemistry of the plant was unveiled for the first time and phytosterols, fatty acids, sesquiterpenes and several other types of secondary metabolites were identified.

Conclusions

Together, potent inhibition of 5-LO and mPGES-1 activity, without concomitant antioxidant activity and cytotoxic effects, rationalizes the ethnopharmacological use of M. pinnata as anti-inflammatory remedy. Detailed chromatographic/mass spectrometric analysis reveals discrete chemical structures of relevant constituents.