Rosmarinic Acid in Prunella vulgaris Ethanol Extract Inhibits Lipopolysaccharide-Induced Prostaglandin E2 and Nitric Oxide in RAW 264.7 Mouse Macrophages

Abstract

Prunella vulgaris has been used therapeutically for inflammation-related conditions for centuries, but systematic studies of its anti-inflammatory activity are lacking and no specific active components have been identified. In this study, water and ethanol extracts of four P. vulgaris accessions were applied to RAW 264.7 mouse macrophages, and the ethanol extracts significantly inhibited lipopolysaccharide (LPS)-stimulated prostaglandin E2 (PGE2) and nitric oxide (NO) production at 30 μg/mL without affecting cell viability. Extracts from different accessions of P. vulgaris were screened for anti-inflammatory activity to identify accessions with the greatest activity. The inhibition of PGE2 and NO production by selected extracts was dose-dependent, with significant effects seen at concentrations as low as 10 μg/mL. Fractionation of ethanol extracts from the active accession, Ames 27664, suggested fractions 3 and 5 as possible major contributors to the overall activity. Rosmarinic acid (RA) content inP. vulgaris was found to independently inhibit inflammatory response, but it only partially explained the extracts' activity. LPS-induced cyclooxygenase-2 (COX-2) and nitric oxide synthase (iNOS) protein expression were both attenuated by P. vulgaris ethanol extracts, whereas RA inhibited only COX-2 expression. Prunella vulgaris has been used therapeutically for inflammation-related conditions for centuries, but systematic studies of its anti-inflammatory activity are lacking and no specific active components have been identified. In this study, water and ethanol extracts of four P. vulgaris accessions were applied to RAW 264.7 mouse macrophages, and the ethanol extracts significantly inhibited lipopolysaccharide (LPS)-stimulated prostaglandin E2 (PGE2) and nitric oxide (NO) production at 30 μg/mL without affecting cell viability. Extracts from different accessions of P. vulgaris were screened for anti-inflammatory activity to identify accessions with the greatest activity. The inhibition of PGE2 and NO production by selected extracts was dose-dependent, with significant effects seen at concentrations as low as 10 μg/mL. Fractionation of ethanol extracts from the active accession, Ames 27664, suggested fractions 3 and 5 as possible major contributors to the overall activity. Rosmarinic acid (RA) content in P. vulgaris was found to independently inhibit inflammatory response, but it only partially explained the extracts' activity. LPS-induced cyclooxygenase-2 (COX-2) and nitric oxide synthase (iNOS) protein expression were both attenuated by P. vulgaris ethanol extracts, whereas RA inhibited only COX-2 expression.

Validation of determination of plasma metabolites derived from thyme bioactive compounds by improved liquid chromatography coupled to tandem mass spectrometry

“…Among these compounds, rosmarinic acid (RA) is one of the most important anti-oxidative polyphenols in thyme and is also widely found in Lamiaceae herbs [5]. In addition to its potent antioxidant activity [6], many beneficial properties, including anti-inflammation [7], anti-mutagenicity [8] and prevention of Alzheimer's disease [9], have been attributed to rosmarinic acid. There are also large amounts of monoterpenes in thyme and their pharmacological properties have recently been reviewed, they are especially considered promising agents for the prevention or treatment of cardiovascular diseases [10].…”

Phenolic compounds and total antioxidant activity determination in rosemary and oregano extracts and its use in cheese spread

“…Many beneficial functionalities of rosmarinic acid, which include anti-inflammation (HUANG et al, 2009), anti-mutagenicity (FURTADO et al, 2008), prevention of Alzheimer's disease (HAMAGUCHI et al, 2009), apoptosis induction of colorectal cancer cells (XAVIER et al, 2009), etc., have been recently reported in addition to its potent antioxidant activity.…”

The Anti-Inflammatory and Vasodilating Effects of Three Selected Dietary Organic Sulfur Compounds from Allium Species

“…Meanwhile, the three OSC at a concentration of 500 µM decreased COX-2 protein expression, although there was no significant difference between DADS, DMDS, and the cells treated with LPS alone ( p > 0.05) (Figure 3B). Many studies have shown that the production of PGE 2 and NO by macrophages, upon LPS induction, is mediated by the toll-like receptor 4 (TLR-4) and the subsequent nuclear factor-kB (NF-kB) downstream activation, which results in the expression of COX-2 and iNOS [26]. Therefore, the inhibition of signal transduction for the iNOS and COX-2 gene expression and the direct inhibition of iNOS and COX-2 expression are the main pathways for inhibiting the production of NO and PGE 2 [27].…”