Two new steroid glycosides, linckosides L1 (1) and L2 (2), were isolated, along with the previously known echinasteroside C (3) from the ethanolic extract of the Vietnamese blue starfish, Linckia laevigata. The structures of the new compounds were elucidated by spectroscopic methods (mainly 2D NMR) and chemical transformations. Lifetime observations and analyses of silver impregnated preparations on the culture of neuroblastoma C-1300 cells showed that glycosides 1, 2, and 3 are capable of inducing neuronal differentiation similar to that of neurotrophins and of enhancing substantially the neuritogenic activity of NGF.

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.

Two new steroid glycosides: distolasteroside D6, (24S)-24-O-(beta-D-xylopyranosyl)-5alpha-cholestane-3beta,6alpha,8,15beta,16beta,24-hexaol, and distolasteroside D7. (22E,24R)-24-O-(beta-D-xylopyranosyl)-5alpha-cholest-22-ene-3beta,6alpha,8,15beta,24-pentaol were isolated along with the previously known distolasterosides D1, D2, and D3, echinasteroside C, and (25S)-5alpha-cholestane-3beta,4beta,6alpha,7alpha,8,15alpha,16beta,26-octaol from the Far Eastern starfish Distolasterias nipon. The structures of new compounds were elucidated by NMR spectroscopy and MALDI TOF mass spectrometry. Like neurotrophins, distolasterosides D1, D2, and D3 were shown to induce neuroblast differentiation in a mouse neuroblastoma C 1300 cell culture.

Aging is the major risk factor of the most common (∼95% of cases) sporadic Alzheimer's disease (AD). Accumulating data indicate middle age as a critical period for the relevant pathological processes, however, the question of when AD starts to develop remains open. It has been reported only recently that in the early postnatal period-when brain development is completing-preconditions for a decrease in cognitive abilities and for accelerated aging can form. Here, we hypothesized that specific features of early postnatal brain development may be considered some of the prerequisites of AD development at an advanced age. To test this hypothesis, we used OXYS rats, which are a suitable model of sporadic AD. The duration of gestation, litter size, and weight at birth were lower in OXYS rats compared to control Wistar rats. The shortened duration of gestation may result in developmental retardation. Indeed, we noted decreased locomotor activity and increased anxiety in OXYS rats already at a young age: possible signs of altered brain development. We demonstrated retardation of the peak of postnatal neurogenesis in the hippocampal dentate gyrus of OXYS rats. Delayed neuronal maturation led to alterations of mossy-fiber formation: a shortened suprapyramidal bundle and longer infrapyramidal bundle, less pronounced fasciculation of granule cells' axons, and smaller size and irregular shape of nuclei in the CA3 pyramidal layer. These changes were accompanied by altered astrocytic migration. The observed features of early development may be considered some of the risk factors of the AD-like pathology that manifests itself in OXYS rats late in life.