Ganoderma pfeifferi and Ganoderma applanatum as inhibitors of eicosanoids biosynthesis

Abstract

Ganoderma pfeifferi and G. applanatum are fungi from Ganodermataceae family, considered to be functional foods, due to significant anticancer, antimicrobial, antioxidant, hepatoprotective, immunopotentiating and hypoglycemic activity. This paper describes examination of anti-inflammatory activity of G. pfeifferi CHCl3 extract and G. applanatum EtOH extract using ex vivo method, based on determination of inhibition of inflammatory mediators production. Five eicosanoids were monitored. The levels of PGE2, PGF2α, 12-HHT, and TXB2 were used to evaluate the level of cyclooxigenase (COX) pathway inhibition. The COX enzyme has a critical role in inflammation processes, induction of pain and high body temperature. On the other hand, 12-lipooxygenase (12-LOX) has a major role in tumor cells proliferation and growth, and in allergic reactions and autoimmune diseases. The level of LOX inhibition was evaluated by monitoring inhibition of 12-HETE production. The inflammation was induced in human platelets using calcium ionofore A23184 (calcimicine). Highly sensitive LC-MS/MS technique was used for metabolites quantification. The inhibition of metabolites production was calculated, and IC50 values were determined from inhibition curves. In all examined extracts, dose-dependent inhibition of eicosanoids biosynthesis was observed. For G. pfeifferi, IC50 was 2.12 mg/mL for 12-HHT production, 1.16 mg/mL for 12-HETE, and 1.00 mg/mL for TXB2, while IC50 value for PGE2 metabolite was not reached in the examined concentration range. For G. applanatum, IC50 was 0.565 mg/mL for 12-HHT, 1.17 mg/mL for 12-HETE, 4.61 mg/mL for PGE2, and 0.406 mg/mL for TXB2 production. IC50 values for PGF2α metabolite could not be calculated due to its absence in control samples; however, experimental data also confirmed that extracts do not stimulate PGF2α synthesis. Low IC50 values prove high inhibitory potential of the extracts towards the COX and LOX pathway, and confirm their potential as functional foods.