Linlin Yin

Ginsenoside Rg1 attenuates tau phosphorylation in SK-N-SH induced by Aβ‐stimulated THP-1 supernatant and the involvement of p38 pathway activation

AIM In the present study we aimed to investigate the neuroprotective effect of ginsenoside Rg1 (GRg1) on neuronal damage examined in an adopted in vitro inflammatory neurodegeneration model and the involvement of p38 MAPK signal pathway. MAIN METHODS The supernatant from Aβ(1-40)-stimulated THP-1 monocytes was used as culture medium for SK-N-SH neuroblastoma cells which was used as target neuronal cells. The cell viability of SK-N-SH cells was assessed by detecting lactate dehydrogenase (LDH) leakage; the content of pro-inflammatory cytokine was measured by radioimmunoassay; the expressions of tau phosphorylation, p-38 and synaptophysin (SYN) were evaluated by western blot assay. The microtubule associated protein-2 (MAP-2) expression was confirmed by immunostaining. KEY FINDINGS Our results showed that incubation of the supernatant from Aβ(1-40)-stimulated THP-1 cells with SK-N-SH neuroblastoma cells for 24h significantly increased LDH leakage, tau and p-38 phosphorylation in SK-N-SH cells with increased interleukin (IL)-1β release into the supernatant of THP-1 cells. Pretreatment of THP-1 cells with GRg1 (50, 100 and 150μM) for 30min before Aβ(1-40)-stimulation inhibited THP-1 cell-mediated Aβ neurotoxicity towards SK-N-SH neuroblastoma and also decreased IL-1β release into THP-1 supernatant dose-dependently. An inhibitor of p38 MAPK, SB203580, had the same effect. SIGNIFICANCE These results suggested that activation of the p38 cell signal pathway may be involved in monocyte-mediated Aβ neurotoxicity towards SK-N-SH cells. Data obtained from this study demonstrated that GRg1 represented a potential treatment strategy for Alzheimers disease (AD).

Involvement of JAK/STAT signaling in the effect of cornel iridoid glycoside on experimental autoimmune encephalomyelitis amelioration in rats

In the present study, we investigated the therapeutic benefit of cornel iridoid glycoside (CIG), the main component extracted from Cornus officinalis, in experimental autoimmune encephalomyelitis (EAE) rats. CIG was intragastrically administered daily after EAE initiation for 20days and reduced disease severity, incidence, disease onset and ongoing paralysis. Histopathological staining showed that CIG could reduce T cell entry to the central nervous system and microglia activation, increased brain-derived neurotrophic factor (BDNF) expression and mature oligodendrocytes, and decreased oligodendrocyte progenitor cells (OPCs). Also, CIG treatment inhibited brain JAK/STAT1/3 and reduced proinflammatory cytokines. CIG might be a novel potential therapeutic agent for multiple sclerosis (MS).

Ginsenoside Rg1 prevents SK-N-SH neuroblastoma cell apoptosis induced by supernatant from Aβ1–40-stimulated THP-1 monocytes

Excessive accumulation of amyloid-β (Aβ) has been proposed as a pivotal event in Alzheimers disease (AD) pathogenesis. Possible mechanisms underlying Aβ-induced neurotoxicity include inflammation and apoptosis. Here, the protective effect of ginsenoside Rg1 (GRg1) on neuronal damage was examined in an in vitro inflammatory neurodegeneration model. Supernatant from Aβ(1-40)-stimulated THP-1 monocytes was added to SK-N-SH neuroblastoma cell culture medium. Incubation of SK-N-SH cells with cell-free supernatant from Aβ(1-40) (125nM)-treated THP-1 monocytes for 24 h significantly increased lactate dehydrogenase (LDH) release, cell apoptosis, Bax and caspase-3 expression in SK-N-SH cells. However, pretreating THP-1 monocytes with GRg1 (50, 100 or 150 μM) for 30 min markedly reduced IL-1β, IL-8 and TNF-α levels in Aβ(1-40)-stimulated supernatant. LDH release, cell apoptosis, Bax and caspase-3 expression in SK-N-SH cells were significantly decreased when cultured with cell-free supernatant from Aβ(1-40)-stimulated THP-1 monocytes that were pretreated with GRg1. The results suggest that Aβ(1-40)-induced neuronal injury and apoptosis may be mediated by inflammatory monocyte reactions, and GRg1 exerts a protective effect against Aβ(1-40)-induced neuronal injury and apoptosis, likely through its anti-inflammatory mechanism.

Autophagy-related gene16L2, a potential serum biomarker of multiple sclerosis evaluated by bead-based proteomic technology

Multiple sclerosis (MS) is an autoimmune disease characterized by neuroinflammation and demyelination that are mediated by T cells. The prolonged survival of autoreactive T cells acts as a primary event to trigger an inflammatory cascade that mediates myelin loss and clinical relapse in MS. Recently, T cell survival has been shown to be modulated by the autophagy-related gene (Atg). In the present study, we performed bead fractionation/matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry analyses using serum from 54 MS patients and 55 healthy controls. Eleven peptides were significantly different between the two groups with one being identified as a fragment of Atg16L2. Then the decreased levels of Atg16L2 peptides in MS patients were validated by immunoblotting and real-time PCR. As the Atg12-Atg5·Atg16 multimeric complex plays an essential role in autophagy, our results suggest that Atg16L2 may play an important role in autophagy of T cells and serve as a potential biomarker to predict clinical relapse of MS.

White Matter Abnormalities in Two Different Subtypes of Amnestic Mild Cognitive Impairment

White matter (WM) degeneration has been found during the course of cognitive decline in both Alzheimers disease (AD) and amnestic mild cognitive impairment (aMCI), however, it is unclear whether there are different WM microstructural abnormalities between two subtypes of aMCI, including single domain aMCI (aMCI-s) and multiple domain aMCI (aMCI-m). Thirty-two patients of aMCI single-domain (aMCI-s), twenty-three patients of aMCI multiple-domain (aMCI-m) and twenty-three healthy normal controls (NC) participated in this study. Neuropsychological measures and diffusion tensor imaging (DTI) data were acquired from each subject and tract-based spatial statistics (TBSS) was implemented. It was found that both aMCI groups showed significantly reduced fractional anisotropy (FA) in the right superior longitudinal fasciculus (SLF) than NC. It was also identified that, as compared to aMCI-m, aMCI-s showed significantly decreased FA in the left SLF, left uncinate fasciculus (UF) and left inferior longitudinal fasciculus (ILF), while significantly increased FA in the left anterior thalamic radiation (ATR). The correlation analysis showed that FA values in the regions with group difference were significantly correlated with cognitive functions as measured by Boston naming test and trail making test. These results suggested that the variations of aMCI may be differentiated by FA indexes and DTI may help to understand why specific signs and symptoms occur in patients.

Icariin enhances remyelination process after acute demyelination induced by cuprizone exposure

Pathology are still progressive and cumulative in the remission course of relapsing-remitting MS (RRMS), thus drug treatment during the remission period may play a great role for the regeneration of the myelin sheath. C57BL/6 mice were fed with cuprizone (CPZ, 0.2% w/w) for 5 weeks to induce acute demyelination and oligodendrocytes degeneration, after which CPZ was withdrawn to allow recovery. Icariin (ICA, 6.25, 12.5 and 25mg/kg/day), vehicle (0.5% sodium carboxymethyl cellulose solution) or water was administrated orally to mice for 1 week after CPZ withdrawal. Luxol-fast blue (LFB), immunohistochemical or immunofluorescence staining was used to detect morphological and biological changes in the brains. CPZ administration for 5 weeks resulted in completely demyelination and remyelination occurred when CPZ was withdrawn. ICA treatment during the recovery period for 1 week significantly improved myelin restoration, enhanced NF200-positive axons repair, increased the number of APC+/Olig2+ mature oligodendrocytes and prevented neuron-derived neurotrophic factor such as nerve growth factor (NGF) loss. Our results demonstrated that ICA treatment during the recovery period promotes remyelination and axon rewrapped, at least, in part, by promoting oligodendrogenesis and neurotrophic factor production.

Preventing the BDNF and NGF loss involved in the effects of cornel iridoid glycoside on attenuation of experimental autoimmune encephalomyelitis in mice

The present study was designed to investigate the beneficial effects of cornel iridoid glycoside (CIG), a main component extract from Cornus officinalis, on neurotrophin expression in mouse experimental autoimmune encephalomyelitis (EAE), a classical model of multiple sclerosis (MS). After EAE initiation, CIG was intragastrically administered daily for 32 days and reduced disease severity. Histopathological staining and western blotting both showed that CIG could prevent brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) loss in the spinal cord of EAE mice. In conclusion, our findings indicated that CIG treatment suppressed disease severity of EAE partially through blocking downregulation of neurotrophic factor expression such as BDNF and NGF, suggesting that CIG may have beneficial effects for the treatment of demyelinating diseases such as MS.

Association between Plasma Leptin and Estrogen in Female Patients of Amnestic Mild Cognitive Impairment.

Increasing evidences suggested the association between leptin and cognitive functions. Estrogen is an important factor that regulates the production and metabolism of leptin. However, little is known about the relationship between leptin and estrogen in mild cognitive impairment (MCI). Plasma levels of leptin, total estradiol, and β-amyloid protein (Aβ) were measured in a total of 23 female amnestic MCI (aMCI) patients and 19 female cognitively normal controls. This study showed that female aMCI patients had lower plasma levels of leptin and higher levels of estradiol compared to female normal controls. Leptin and estradiol levels were not correlated with cognitive performances or plasma Aβ levels in either aMCI patients or normal controls. There was a significant negative correlation between leptin and estrogen in female aMCI patients (r = −0.633, p = 0.002) but not in female normal controls. The potential mechanisms of this disease-stage-specific association between leptin and estrogen need further investigations.