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

Abstract

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 100 μM 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 100 μM 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 26.52 μM, respectively. Similarly, pre-treatment with 100 μM 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 37.22 μM. Treatment of with compounds 1–4 (10, 30 and 100 µM) followed by stimulation with phorbol 12-myristate 13-acetate (1 µM) 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 µM. 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.

• Anti-inflammatory
• Corynespora cassiicola
• depsidone
• diaryl ether
• endophytic fungi
• Gongronema latifolium
• iNO
• ROS/RNS
• TNF-α

Acknowledgements

The authors are grateful to the Alexander von Humboldt Foundation for the postdoctoral fellowship sponsorship to Dr F. B. C. Okoye and to the Fulbright African Research Scholar Program (ARSP) for the postdoctoral fellowship award to Dr C. S. Nworu.