Neuroprotective Effect of Tricyclic Pyridine Alkaloids from Fusarium lateritium SSF2, against Glutamate-Induced Oxidative Stress and Apoptosis in the HT22 Hippocampal Neuronal Cell Line

Abstract

Excessive glutamate damages neuronal cells via the accumulation of intracellular reactive oxygen species (ROS), calcium ion (Ca2+) influx, depolarization of mitochondrial membrane potential, and apoptosis, which may result in the development of chronic neurodegenerative diseases. In this study, we evaluated the effects of 4,6′-anhydrooxysporidinone isolated from endophytic fungus Fusarium lateritium SSF2 on glutamate-induced cytotoxicity, accumulation of intracellular ROS, increases in superoxide anion production, Ca2+, depolarization of mitochondrial membrane potential, and apoptotic cell death in hippocampal HT22 cells. 2′,7′-Dichlorofluorescin diacetate (H2DCFDA) staining was used to determine the intracellular reactive oxygen species concentration and dihydroethidine (DHE) staining was used to determine the superoxide radical. Expression of the nuclear factor-erythroid-2–related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) was analyzed by Western blot. Fluo-4 staining was used to determine the intracellular Ca2+ levels. In order to explore mitochondrial membrane potential, tetramethylrhodamine methyl ester (TMRM) staining was used. Apoptotic cell death was evaluated using Annexin-V/propidium iodide (PI) staining and TUNEL staining. Expression of the cytochrome c release and cleaved caspase-9, -3 was analyzed by Western blot. Here, we were able to isolate 4,6′-anhydrooxysporidinone from endophytic fungus, Fusarium lateritium SSF2, which was shown to protect HT22 cells from glutamate-induced cytotoxicity, accumulation of intracellular ROS, increases in superoxide anion production, Ca2+, and depolarization of mitochondrial membrane potential. In addition, 4,6′-anhydrooxysporidinone enhanced the expressions of Nrf2 and HO-1. It also inhibited the apoptotic cell death through the inhibition of cytochrome c release and cleaved caspase-9, -3 in glutamate-treated HT22 cells. Therefore, our results provide ample evidence of the neuroprotective properties of 4,6′-anhydrooxysporidinone.

4,6′-Anhydrooxysporidinone from Fusarium lateritium SSF2 Induces Autophagic and Apoptosis Cell Death in MCF-7 Breast Cancer Cells

“…The effect is mediated via the inhibition of glutamate-induced oxidative stress and apoptosis. In this study, low concentrations of 2.5 and 5 µM SSF2-2 were effective [17]. The anticancer effects of compounds isolated from F. lateritium SSF2 have not been explored to date.…”

Protective Effect of NGR1 against Glutamate-Induced Cytotoxicity in HT22 Hippocampal Neuronal Cells by Upregulating the SIRT1/Wnt/β-Catenin Pathway

“…Neurons are the functional unit of the nervous system [ 21 – 23 ]. The oxidative stress induced by glutamate will trigger the changes in the structure and function of the neurons and cause the death of neurons [ 14 , 24 ]. Earlier studies showed that plant extracts and compounds with strong antioxidant activity protected glutamate-induced neuronal death [ 4 , 25 ].…”

The Neuroprotective Potential of Endophytic Fungi and Proposed Molecular Mechanism: A Current Update

“…Lee et al [ 75 ] isolated tricyclic pyridine alkaloids including (1) 6-deoxyoysporidinone (SSF2-1), (2) 4,6′-anhydrooxysproridinone (SSF2-2), and (3) sambutoxin (SSF2-3) from Fusarium lateritium (SSF2). Furthermore, SSF2-1, SSF2-2, and SSF2-3 were evaluated for their protective effects against glutamate-induced HT22 cell death.…”

“…The compound SSF2-2 showed the significant protective effects against HT22 cells from cytotoxicity induced by glutamate, it reduces the intracellular accumulation of ROS, increases in superoxide anion production, Ca 2+ influx, and depolarization of mitochondrial membrane potential. Additionally, the compound SSF2-2 increased the expression of Nrf2 and HO −1 pathways, whereas inhibited the apoptotic cell death via inhibition of cytochrome c and cleaved caspase-9, -3 in glutamate-induced HT22 cells [ 75 ]. Choi and co-workers, isolated and identified six neuroprotective bioactive compounds present in an endophytic fungi Fusarium solani JS-0169 collected from the leaves of Morus alba [ 76 ].…”