Cytoprotective Activity of p-Terphenyl Polyketides and Flavuside B from Marine-Derived Fungi against Oxidative Stress in Neuro-2a Cells.

Ekaterina A Yurchenko,Elena V Girich,Dmitry L Aminin,Anton N Yurchenko,Ekaterina A Chingizova,Valery V Mikhailov,Evgeny A Pislyagin,Ekaterina S Menchinskaya

doi:10.3390/molecules26123618

Abstract

The influence of p-terphenyl polyketides 1–3 from Aspergillus candidus KMM 4676 and cerebroside flavuside B (4) from Penicillium islandicum (=Talaromyces islandicus) against the effect of neurotoxins, rotenone and paraquat, on Neuro-2a cell viability by MTT and LDH release assays and intracellular ROS level, as well as DPPH radical scavenging activity, was investigated. Pre-incubation with compounds significantly diminished the ROS level in rotenone- and paraquat-treated cells. It was shown that the investigated polyketides 1–3 significantly increased the viability of rotenone- and paraquat-treated cells in two of the used assays but they affected only the viability of paraquat-treated cells in the LDH release assay. Flavuside B statistically increased the viability of paraquat-treated cells in both MTT and LDH release assays, however, it increased the viability of rotenone-treated cells in the LDH release assay. Structure–activity relationships for p-terphenyl derivatives, as well as possible mechanisms of cytoprotective action of all studied compounds, were discussed.

Highlights

Marine-derived fungi are a known source of antioxidants [1]
The isoflavonoid rotenone is widely used in agricultural production as a pesticide
As a part of this study, we investigated the influence of p-terphenyl polyketides 1–3 from Aspergillus candidus KMM 4676 [14,15] and cerebroside flavuside B (4) (Figure 1)

Summary

Introduction

Marine-derived fungi are a known source of antioxidants [1]. They produce secondary metabolites which can directly scavenge reactive oxygen species [2] as well as activate theKeap1/Nrf2/ARE antioxidant cellular machinery [3] and as a result upregulate antioxidant enzymes’ expression [4]. Marine-derived fungi are a known source of antioxidants [1]. They produce secondary metabolites which can directly scavenge reactive oxygen species [2] as well as activate the. Keap1/Nrf2/ARE antioxidant cellular machinery [3] and as a result upregulate antioxidant enzymes’ expression [4]. Both these direct and indirect natural antioxidants from marinederived fungi protect the cells from oxidative stress (OS) induced damage. Despite the protective measures applied, cases of illness and death from the toxic effects of paraquat are not uncommon [5]. It was believed that rotenone is not toxic to humans, in detailed studies, exposure to rotenone caused various toxic effects [6,7]

Methods

Results

Conclusion