Ginsenoside Rb1 attenuates okadaic acid-induced Tau protein hyperphosphorylation in rat hippocampal neurons / 生理学报

The present study was aimed to investigate the effects of ginsenoside Rb1 on okadaic acid (OA)-induced Tau hyperphosphorylation in hippocampal neurons of Sparague-Dawley rat and to explore its possible mechanism. Animals were randomly divided into four groups. Group 1 received dimethysulphoxide (DMSO) injection (vehicle group), group 2 only received OA injection (OA group), group 3 was pretreated with Rb1 and then received OA injection (Rb1 pretreatment group), and the group 4 was an intact control group. The animals in group 3 were injected intraperitoneally with various doses of Rb1 at 5, 10, and 20 mg/kg (once a day for 14 d). On the thirteen day of pretreatment, animals in Rb1 pretreatment group as well as animals in OA group received a bolus injection of 0.483 microg of OA (1.5 microl of solution in DMSO) at right dorsal aspect of hippocampus to induce Tau hyperphosphrylation. The brains were harvested one day after the last treatment. In all groups, the morphology of neurofibrils, phosphorylation of Tau protein, and the activity of phosphatase 2A (PP2A) were investigated. In OA group, the Bielschowski's assay revealed darkened and uneven neurofibrils staining in the hippocampus. The immunohistochemistry results showed a significant increase in Thr(231) phosphorylation of Tau protein in OA group relative to the control group (P<0.01). OA injection also markedly decreased PP2A activity (P<0.01). Western blot confirmed Thr(231) phosphorylation of Tau protein and it also detected phosphorylation of Ser(396) of Tau protein. The animals with Rb1 pretreatment displayed even staining of neurofibrils and normal pattern of fiber organization. Rb1 pretreatment also attenuated Thr(231) and Ser(396) hyperphosphorylations of Tau protein, and restored PP2A activity compared to the OA group (P<0.01). These results indicate that OA-induced hyperphosphorylation of Tau protein in rat hippocampal neurons can be attenuated by the pretreatment of ginsenoside Rb1. These data also implicate that Rb1 has potential neuroprotective effects on Tau-related neuropathology.

Ginsenoside Rbl attenuates beta-amyloid peptide25-35 -induced tau hyperphosphorylation in cortical neurons / 药学学报

<p><b>AIM</b>To explore the effect and the possible mechanism of ginsenoside Rb1 on beta-amyloid peptide (beta-AP)(25-35) -induced tau protein hyperphosphorylation in cortical neurons.</p><p><b>METHODS</b>Western blotting and immunocytochemical staining were used to detect tau phosphorylation level, total tau and glycogen synthase kinase-3beta (GSK-3beta) in cortical neurons.</p><p><b>RESULTS</b>After exposure to beta-AP(25-35) (20 micromol x L(-1)) for 12 h, the levels of tau protein phosphorylation in the sites of Ser 396, Ser 199/202, Thr 231 and total tau were raised. Meanwhile, the expression of GSK-3beta also increased. Pretreatment with ginsenoside Rbl or lithium chloride, a specific inhibitor of GSK-3beta, markedly reduced beta-AP(25-35)-induced tau hyperphosphorylation and the expression of GSK-3beta.</p><p><b>CONCLUSION</b>Ginsenoside Rb1 can attenuate beta AP(25-35)-induced tau protein hyperphosphorylation in cortical neurons by inhibiting the expression of GSK-3beta.</p>