The contribution of phenolic acids to the anti-inflammatory activity of mushrooms: Screening in phenolic extracts, individual parent molecules and synthesized glucuronated and methylated derivatives

Oludemi Taofiq,Ricardo C Calhelha,Sandrina Heleno,Lillian Barros,Anabela Martins,Celestino Santos-Buelga,Maria João R.P Queiroz,Isabel C.F.R Ferreira

doi:10.1016/j.foodres.2015.07.044

Abstract

In the present study, the ethanolic extracts of fourteen edible mushrooms were investigated for their anti-inflammatory potential in LPS (lipopolysaccharide) activated RAW 264.7 macrophages. Furthermore the extracts were chemically characterized in terms of phenolic acids and related compounds. The identified molecules (p-hydroxybenzoic, p-coumaric and cinnamic acids) and their glucuronated and methylated derivatives obtained by chemical synthesis were also evaluated for the same bioactivity, in order to establish structure–activity relationships and to comprehend the effects of in vivo metabolism reactions in the activity of the compounds. The extracts of Pleurotus ostreatus, Macrolepiota procera, Boletus impolitus and Agaricus bisporus revealed the strongest anti-inflammatory potential (EC50 values 96±1 to 190±6μg/mL), and also the highest concentration of cinnamic acid (656 to 156μg/g), which was also the individual compound with the highest anti-inflammatory activity. The derivatives of p-coumaric acid revealed the strongest properties, specially the derivative methylated in the carboxylic group (CoA-M1) that exhibited similar activity to the one showed by dexamethasone used as anti-inflammatory standard; by contrast, the derivatives of p-hydroxybenzoic revealed the lowest inhibition of NO production. All in all, whereas the conjugation reactions change the chemical structure of phenolic acids and may increase or decrease their activity, the glucuronated and methylated derivatives of the studied compounds are still displaying anti-inflammatory activity.

Highlights

Inflammation is considered to be part of the complex biological response to remove injury or harmful stimuli such as pathogens, damaged cells, or irritation and this is a central feature of many pathophysiological conditions such as atherosclerosis, obesity, metabolic syndrome, diabetes (Pradhan, 2007) and even several types of cancers (Moro et al, 2012).When cells are exposed to immune stimulants, the pro-inflammatory cells, such as macrophages, monocytes, or other host cells, start to produce cytokines and other mediators, which initiate the inflammation process
Ethanolic extracts were prepared from fourteen different edible mushroom species: Agaricus bisporus, A. bisporus Portobello, Amanita caesaria, Boletus aereus, B. edulis, B. flagrans, B
The phenolic composition of the mushrooms seems to be characterised by the presence of phenolic acids, being cinnamic acid the major compound in most cases

Summary

Introduction

Inflammation is considered to be part of the complex biological response to remove injury or harmful stimuli such as pathogens, damaged cells, or irritation and this is a central feature of many pathophysiological conditions such as atherosclerosis, obesity, metabolic syndrome, diabetes (Pradhan, 2007) and even several types of cancers (Moro et al, 2012).When cells are exposed to immune stimulants, the pro-inflammatory cells, such as macrophages, monocytes, or other host cells, start to produce cytokines and other mediators, which initiate the inflammation process. Among the various inflammatory mediators, the most common are interleukins (IL-1β, IL-6, IL-8), tumour necrosis factor (TNF-α), nuclear factor-κB cyclooxygenase-2 (COX-2), prostaglandin E2 (PGE2), 5-lipooxygenase (5-LOX), and inducible nitric oxide synthase (iNOS) that leads to the production of reactive nitrogen species such as nitric oxide (NO). Overproduction of these inflammatory mediators leads to different kinds of cell damage (Kanwar, Kanwar, Burrow, & Baratchi, 2009). Many studies have shown that the long-term administration of NSAIDs has the potential for significant side effects on the gastrointestinal tract with numerous harmful effects such as mucosal lesions, bleeding, peptic ulcers, and intestinal perforation (Dugowson & Gnanashanmugam, 2006)

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