Tiaobu Xinshen Recipe () Improved Mild Cognitive Impairment of Alzheimer's Disease Patients with Xin (Heart) and Shen (Kidney) Deficiency.

OBJECTIVE: To observe the intervention effects of Tiaobu Xinshen Recipe (, TXR) on patients with mild cognitive impairment caused by Alzheimer's disease (MCI-AD). METHODS: Totally 88 MCI-AD patients with syndrome of Xin (Heart) and Shen (Kidney) deficiency were assigned to the experimental group (47 cases, treated with TXR) and the control group (41 cases, treated with donepezil hydrochloride) using a random number table. Final recruited qualified patients were 44 cases in the experimental group and 39 cases in the control group. The therapeutic course was 12 weeks. Neuropsychological scales [mini mental state examination (MMSE) and Montreal cognitive assessment (MoCA)], and Chinese medicine (CM) dementia syndromes scales were performed in all patients, and results were compared between groups or intra-group before and after treatment. RESULTS: MMSE and MoCA scores of the two groups were increased after treatment compared with those before treatment (P<0.05). But there was no statistical difference in MMSE or MOCA scores after treatment between the two groups (P>0.05). CM dementia syndrome score was significantly decreased after treatment in the experimental group compared with the control group (P<0.01). Visual spatial and executive function scores and delayed recall scores of the two groups were increased compared with those before treatment (P<0.01). CONCLUSION: TXR could effectively improve cognitive impairment of MCI-AD patients with syndrome of Xin and Shen deficiency.

Neuroprotective role of tripchlorolide on inflammatory neurotoxicity induced by lipopolysaccharide-activated microglia.

A large body of evidence has suggested a strong association between neuroinflammation and the pathogenesis of many neurodegenerative diseases. Therefore, it is a good target for therapeutic treatment. So far, studies have proven anti-inflammatory herbal medicine and its constituents to be effective in slowing down the neurodegenerative process. The present study tested tripchlorolide, an extract of Tripterygium wilfordii Hook F (TWHF), as a novel agent to suppress inflammatory process in microglia. It showed this novel agent to be cytotoxic at a dose of 20-40 nM to primary microglia and BV-2 microglial cells but not to primary cortical neurons and Neuro-2A cells in vitro. Moreover, tripchlorolide protected primary cortical neurons and Neuro-2A cells from neuroinflammatory toxicity induced by the conditioned media from lipopolysaccharide (LPS)-stimulated microglia, which resulted in a significant decrease in their cell survival. The changes of the inflammatory mediators in this process were further investigated. In the LPS-stimulated microglia, the production of tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), nitric oxide (NO), prostaglandin E(2) (PGE(2)), and intracellular superoxide anion (SOA) was markedly attenuated by tripchlorolide at a dose of 1.25-10 nM in a dose-dependent manner. Furthermore, the production of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) was also significantly inhibited by tripchlorolide in both mRNA and protein levels. These results suggest that tripchlorolide can protect neuronal cells via a mechanism involving inhibition of inflammatory responses of microglia to pathological stimulations. Therefore, it is potentially a highly effective therapeutic agent in treating neuroninflammatory diseases.

[JNK/p38 MAPK involves in ginsenoside Rb1 attenuating beta-amyloid peptide (25-35) -induced tau protein hyperphosphorylation in embryo rat cortical neurons].

To explore the effect of ginsenoside Rb1 on JNK/p38 MAPK in the process of beta-amyloid peptide (25-35) -induced tau protein hyperphosphorylation, Western blotting and immunocytochemical stain were performed to observe the tau protein phosphorylation and the expression of JNK/p38 MAPK. The level of tau protein phosphorylation in the sites of Ser396 , Ser199/202 and Thr205 increased after rat cortical neurons exposed to 20 micromol x L(-1) Abeta25-35, meanwhile the level of JNK/p38 MAPK also increased after Abeta25-35 treatment for 12 h. Pretreatment with several doses of ginsenoside Rbl markedly attenuated tau protein hyperphosphorylation and the expression of JNK/p38 MAPK. Ginsenoside Rbl markedly attenuated tau protein hyperphosphorylation through JNK/p38 MAPK pathway.

[Ginsenoside Rb1 attenuates beta-amyloid peptide(25-35) -induced hyperphosphorylation of tau protein through CDK5 signal pathway].

This study is to explore the effect of ginsenoside Rb1 on the process of beta-amyloid peptide(25-35) (Abeta(25-35)) -induced hyperphosphorylation of tau protein, and on the level of cyclin-dependent kinase 5 activator, p25/p35. Western blotting and/or immunocytochemical staining were used to detect the levels of phosphorylation of tau protein at the sites of Thr205, Ser396, Ser404 in hippocampal neurons, cdk5 and p25/p35. After exposure to Abeta(25-35) (20 micromol x L(-1)) for 12 h, the levels of tau protein phosphorylation at the sites of Thr205, Ser396, Ser404 were enhanced, the level of p25 was increased, but the level of protein cdk5 was not changed markedly. Pretreatment with ginsenoside Rb1 reduced Abeta(25-35) -induced hyperphosphorylation of tau protein and decreased the lever of p25, but had no effect on cdk5. Ginsenoside Rb1 can attenuate Abeta(25-35) -induced hyperphosphorylation of tau protein through CDK5 signal pathway.

[Ginsenoside Rbl attenuates beta-amyloid peptide25-35 -induced tau hyperphosphorylation in cortical neurons].

AIM: 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. METHODS: Western blotting and immunocytochemical staining were used to detect tau phosphorylation level, total tau and glycogen synthase kinase-3beta (GSK-3beta) in cortical neurons. RESULTS: 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. CONCLUSION: Ginsenoside Rb1 can attenuate beta AP(25-35)-induced tau protein hyperphosphorylation in cortical neurons by inhibiting the expression of GSK-3beta.