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Mar Drugs
2013 May 03;115:1440-55. doi: 10.3390/md11051440.
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Neuritogenic and neuroprotective effects of polar steroids from the Far East starfishes Patiria pectinifera and Distolasterias nipon.
Palyanova NV
,
Pankova TM
,
Starostina MV
,
Kicha AA
,
Ivanchina NV
,
Stonik VA
.
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The neuritogenic and neuroprotective activities of six starfish polar steroids, asterosaponin Р₁, (25S)-5α-cholestane-3β,4β,6α,7α,8,15α,16β,26-octaol, and (25S)-5α-cholestane-3β,6α,7α,8,15α,16β,26-heptaol (1-3) from the starfish Patiria pectinifera and distolasterosides D₁-D₃ (4-6) from the starfish Distolasterias nipon were analyzed using the mouse neuroblastoma (NB) C-1300 cell line and an organotypic rat hippocampal slice culture (OHSC). All of these compounds enhanced neurite outgrowth in NB cells. Dose-dependent responses to compounds 1-3 were observed within the concentration range of 10-100 nM, and dose-dependent responses to glycosides 4-6 were observed at concentrations of 1-50 nM. All the tested substances exhibited notable synergistic effects with trace amounts of nerve growth factor (NGF, 1 ng/mL) or brain-derived neurotrophic factor (BDNF, 0.1 ng/mL). Using NB cells and OHSCs, it was shown for the first time that starfish steroids 1-6 act as neuroprotectors against oxygen-glucose deprivation (OGD) by increasing the number of surviving cells. Altogether, these results suggest that neurotrophin-like neuritogenic and neuroprotective activities are most likely common properties of starfish polyhydroxysteroids and the related glycosides, although the magnitude of the effect depended on the particular compound structure.
Figure 2. Neuritogenic activity of starfish steroids from P. pectinifera in NB C-1300 cells. (A) Images of control and steroid-treated cultures. Treatment with compounds PP1, PP2 or PP3 (1–3) at concentration of 100 nM for 4 days; (B) Dose-dependent neuritogenic effects of compounds PP1, PP2, and PP3 (1–3). The data are presented as the mean values ± SEM from representative experiments. * p ≤ 0.05.
Figure 3. Neuritogenic activity of starfish steroids from D. nipon in NB C-1300 cells. (A) Images of control and steroid-treated cultures. Treatment with compounds D1, D2 or D3 (4–6) at concentration of 50 nM for 4 days; (B) Dose-dependent neuritogenic effects of compounds D1, D2, and D3 (4–6). The data are presented as the mean values ± SEM from representative experiments. * p ≤ 0.05.
Figure 4. Synergistic effects of neurotrophins and starfish steroids on cell differentiation in NB C-1300 cells. (A,B) Effects of compounds from P. pectinifera and NGF (A) or BDNF (B). (C,D) Effects of compounds from D. nipon and NGF (C) or BDNF (D). The data are presented as the mean values ± SEM from representative experiments. * p ≤ 0.05.
Figure 5. Starfish steroids protect NB C-1300 cells from oxygen-glucose deprivation (OGD). Cultures were maintained in oxygen- and glucose-free medium for 20 h, and the cell viability at 24 h after OGD was determined by counting the cells including trypan blue dye as the percentage of total cells. Starfish steroids were added twice to the cultures at the indicated concentrations for the OGD period and for 24 h after OGD. The data are presented as the mean values ± SEM from representative experiments performed in triplicate. * p < 0.05. (A) Compounds PP1, PP2, and PP3 (1–3) failed to increase cell viability at the concentration of 25 nM; (B) Protective effects of compounds PP1, PP2, and PP3 (1–3) at the concentration of 50 nM; (C) Protective effects of compounds D1, D2, and D3 (4–6) at the concentration of 50 nM.
Figure 6. Effect of starfish steroids on cell damage induced by OGD in organotypic hippocampal slice cultures. (A) Representative confocal images of control slices and slices stained with propidium iodide (PI) 24 h after exposure to OGD. Starfish steroids were added to OHSCs for 24 h prior to and for 24 h after OGD; (B) Quantitative assay of cell damage 24 h after exposure to OGD. Five independent experiments were carried out. The data are presented as the mean values ± SEM. *—a significant difference from exposure to 35 min OGD, p ≤ 0.05.
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