Anti-inflammatory activity of mushrooms extracts, identified phenolic acids and their possible metabolites

Mushrooms are rich sources of many bioactive compounds, such as phenolic acids, that play an important role in the organism, acting as antioxidants, antitumors, antimicrobials, immunomodulators, among others. However, their anti-inflammatory activity has not been deeply studied. In the present study, the ethanolic extracts of fourteen edible mushroom species were firstly characterized in terms of phenolic acids and related compounds by HPLC-PDA, followed by the study of the anti-inflammatory activity of those extracts and corresponding identified compounds, by using LPS (lipopolysaccharide) activated RAW 264.7 macrophages and measuring the inhibition in NO production. Furthermore, methylated and glucuronated derivatives of the identified compounds (p-hydroxybenzoic, p-coumaric and cinnamic acids) were synthesised and evaluated for the same bioactivity to understand the contribution of these compounds for the overall activity of the extracts, and to establish structure-activity relationships. Pleurotus ostreatus, Macrolepiota procera, Boletus impolitus and Agaricus bisporus revealed the strongest anti-inflammatory potential, presenting also the highest concentration in cinnamic acid, which was also the individual compound displaying the highest activity. The derivative compounds of p-coumaric acid revealed the strongest properties, especially the compound CoA-M1 (presenting an ester instead of the carboxylic group), that exhibited a very similar activity to the one showed by dexamethasone, used as anti-inflammatory standard. On the contrary, p-hydroxybenzoic acid derivatives revealed the lowest activity. Overall, the conjugation reactions change the chemical structure of phenolic acids and may increase or decrease their activity; nevertheless, the glucuronated and methylated derivatives of the studied compounds are still displaying anti-inflammatory activity.