Nasturtium (Indian cress, Tropaeolum majus nanum) dually blocks the COX and LOX pathway in primary human immune cells
Background: 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 PG[E.sub.2], leukotriene LT[B.sub.4], 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 PG[E.sub.2] 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.
Anti-inflammatory effect in primary human
Nasturtium (Indian cress, Tropaeolum majus) is a herbal plant from the order Brassicales, that meets the German "Commission E" standards of herbal medicines in 1978 (Blumenthal 1998). It is known for its anti-bacterial, anti-fungal and anti-viral characteristics and consequently used in pharmacological remedies for the treatment of acute sinusitis, bronchitis and urinary tract infection (Conrad et al. 2006; Goos et al. 2006). This plant contains benzyl glucosinolate (benzyl-GLS) at high amounts and there are some reports which attribute the biological effect of the plant to its enzyme mediated hydrolysis product, namely benzyl isothiocyanate (BITC). This is because for BITC, anti-bacterial as well as anti-inflammatory effects were already described (Aires et al. 2009; Dufour et al. 2012; Lee et al. 2009). But besides GLS, nasturtium contains a variety of bioactive compounds which are also known for their anti-inflammatory potency, including flavonoids, carotenoids and other polyphenolics (Butnariu and Bostan 2011). However, so far no scientific data are available which either demonstrate the anti-inflammatory potency of nasturtium in a human cell...