Nasturtium (Indian cress, Tropaeolum majus nanum) dually blocks the COX and LOX pathway in primary human immune cells

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• 作者：Hoai Thi Thu Tran^a ; ^c ; Melinda-Rita Má ; rton^a ; Corinna Herz^a ; ^c ; Ronald Maul^b ; Susanne Baldermann^b ; Monika Schreiner^b ; Evelyn Lamy^a ; ^c ; ^{evelyn.lamy@uniklinik-freiburg.de" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Nasturtium ; Isothiocyanates ; Anti-inflammatory effect in primary human PBMC ; Cyclooxygenase-2 ; PGE2 ; LTB4
• 刊名：Phytomedicine
• 出版年：2016
• 出版时间：1 June 2016
• 年：2016
• 卷：23
• 期：6
• 页码：611-620
• 全文大小：1474 K

文摘

Nasturtium (Indian cress, Tropaeolum majus) is known for its pharmacological value in the treatment of bacterial infections of the upper air tract and urinary bladder. However, scientific data on the anti-inflammatory potency in human-derived cells is missing.

Purpose

The aim of this study was to investigate the potential of nasturtium to inhibit the lipopolysaccharide (LPS) induced inflammatory response in primary human cells of the immune system.

Study design

The anti-inflammatory activities of nasturtium and its fractions were evaluated via regulation of arachidonic acid (AA) pathway and MAPK kinase cascade. Fraction H4 which was responsible for the anti-inflammatory effects was further characterized.

Methods

Human peripheral blood mononuclear cells (PBMC) were either treated with plant extracts or fractions thereof, stimulated with LPS and/or N-formyl-methionyl-leucyl-phenylalanine (fMLP) and analysed for COX and LOX, release of prostaglandin PGE₂, leukotriene LTB₄, TNF-alpha and ERK signaling pathway activation. The plant extracts were separated into four fractions by HPLC; fraction H4 was subjected to UHPLC-ToF/MS analysis to identify potential bioactive compounds.

Results

We found that aqueous extracts of nasturtium did exert strong concentration dependent suppression of LPS-triggered TNF-alpha release and COX pathway signaling, including PGE2 synthesis. Whereas COX-1 protein expression was not impacted, LPS-triggered COX-2 protein expression was concentration dependently blocked by the plant extract but not COX-2 enzyme activity. These findings suggest a mechanism of action for the plant extract which is different from non-steroidal anti-inflammatory drugs (NSAIDs). Moreover, the plant extract blocked leukotriene LTB4 release, the major end product of the 5-LOX pathway from PBMC. Down-regulation of ERK1/2 and c-Jun activation preceded COX-2 suppression upon plant extract treatment in the presence of LPS. Using HPLC separation of the aqueous extract followed by metabolomic analysis we could limit the number of relevant bioactive compounds in the extract to about 50.

Conclusions

This study provides a rationale for the anti-inflammatory efficacy of nasturtium observed in man and gives first insight into the underlying molecular mechanisms.