Inhibition of inflammatory mediators and reactive oxygen and nitrogen species by some depsidones and diaryl ether derivatives isolated from Corynespora cassiicola, an endophytic fungus of Gongronema latifolium leaves

摘要

In this study, some depsidones and diaryl ether derivatives isolated from Corynespora cassicola, a fungi endophyte of Gongronema latifolium, were assessed for their anti-inflammatory potentials. The isolated metabolites corynesidone A (1), corynesidone C (2), corynesidone D (3) and corynether A (4) were screened for their effects on tumour necrosis factor-α (TNF-α), inducible nitric oxide (iNO), and reactive oxygen species (ROS) and reactive nitrogen species (RNS) production by stimulated RAW264.7 macrophages. Concentration of 1, 2, 3 and 4 up to 100μM did not remarkably affect the viability of treated macrophages. The compounds were found to cause a concentration-dependent decrease in lipopolysaccharide-induced TNF-α and iNO in RAW264.7 cells. Pre-treatment with 100μM of 1, 2, 3 and 4 suppressed iNO by as much as 96.28%, 95.71%, 78.14% and 73.28%; with IC50 of 8.16, 9.49, 15.29 and 26.52μM, respectively. Similarly, pre-treatment with 100μM of 1, 2, 3 and 4 caused an inhibition of 99.17%, 99.59%, 95.02% and 74.07% in the formation of iNO production, respectively, with IC50 of 1.88, 3.99, 7.48 and 37.22μM. Treatment of with compounds 1-4 (10, 30 and 100&M) followed by stimulation with phorbol 12-myristate 13-acetate (1&M) caused significant (p<0.05) suppression of ROS/RNS-evoked chemiluminescence of luminol by as much as 100.96±1.88%, 98.59±1.38%, 87.35±1.41% and 79.22±0.30%, respectively at 100&M. The depsidone derivatives (1-4) showed more potent inhibition of TNF-α and NO production and better scavenging ROS/RNS than the diaryl ether derivative (4). These chemical scaffolds can serve as suitable lead molecules for further development into novel anti-inflammatory and/or anti-cancer agents.