Drug-Loaded Nanoparticles from 'Ershiwuwei Shanhu' Pill Induced Cellular Swelling of SH-SY5Y Neuroblastoma Cells.

Drug-loaded nanoparticles from 'Ershiwuwei Shanhu' Pill (ESP) inducing cellular swelling of the SH-SY5Y neuroblastoma cells were investigated. Electron microscope was used to observe nanoparticles existing in the freeze-dried supernatant of 'Ershiwuwei Shanhu' Pill. Drug-free nanoparticles were obtained from the solution of drug-loaded nanoparticles via dialysis. The size and zeta potential of two kinds of nanoparticles were tested by granularmetric analysis and surface charge analysis. Results showed that nanoparticles could penetrate into cellular nucleus and caused cell swelling. CCK8 analysis implied that low concentration of drug-free nanoparticles from 'Ershiwuwei Shanhu' Pill can induce cell proliferation of the SH-SY5Y neuroblastoma cells, while drug-loaded nanoparticles can reduce cell viability through NF-κB pathway. Drug-loaded nanoparticles existed in 'Ershiwuwei Shanhu' pill might play a vital role during pharmacotherapy, which served as nanocarriers in delivering drugs into cells.

Rannasangpei Is a Therapeutic Agent in the Treatment of Vascular Dementia.

Rannasangpei (RSNP) is used as a therapeutic agent in the treatment of cardiovascular diseases, neurological disorders, and neurodegeneration in China; however, its potential use in the treatment of vascular dementia (VD) was unclear. In this study, our aim was to examine the neuroprotective effect of RSNP in a VD rat model, which was induced by permanent bilateral common carotid artery occlusion (2VO). Four-week administration with two doses of RSNP was investigated in our study. Severe cognitive deficit in the VD model, which was confirmed in Morris water maze (MWM) test, was significantly restored by the administration of RSNP. ELISA revealed that the treatments with both doses of RSNP could reinstate the cholinergic activity in the VD animals by elevating the production of choline acetyltransferase (ChAT) and reducing the acetylcholinesterase (AChE); the treatment of RSNP could also reboot the level of superoxide dismutase (SOD) and decrease malondialdehyde (MDA). Moreover, Western blot and quantitative PCR (Q-PCR) results indicated that the RSNP could suppress the apoptosis in the hippocampus of the VD animals by increasing the expression ratio of B-cell lymphoma-2 (Bcl-2) to Bcl-2-associated X protein (Bax). These results suggested that RSNP might be a therapeutic agent in the treatment of vascular dementia in the future.

Lower Prevalence of Alzheimer's Disease among Tibetans: Association with Religious and Genetic Factors.

BACKGROUND: The prevalence of dementia differs among racial groups, the highest prevalence being in Latin America (8.5%) compared to sub-Saharan African regions (2-4%). The most common type of dementia is Alzheimer's disease (AD). OBJECTIVE: To estimate the prevalence of AD in the Qinghai-Tibet plateau and to investigate the related factors. METHODS: This was a cross-sectional, multistage cluster sampling design survey. Data was collected from May 2014 to September 2014 from 4,060 Tibetan aged >60 years. Participants underwent clinical examinations and neuropsychological evaluations. MALDI-TOF was used to test the genotypes of CLU, TFAM, TP53INP1, IGHV1-67, CR1, ApoE, and BIN1. Logistic regression models were used to ascertain the associations with AD. RESULTS: The prevalence of AD among Tibetan individuals aged >60 years was 1.33% (95% CI: 0.98-1.69). The CLU haplotypes AA+GA (odds ratio (OR) = 4.483; 95% CI: 1.069-18.792) of rs2279590 was correlated with AD. The CLU haplotypes GG+GC (OR = 0.184; 95% CI: 0.038-0.888) of rs9331888 and kowtow (OR = 0.203; 95% CI 0.046-0.896) were negatively correlated with AD. CONCLUSION: A low prevalence of AD was found in Tibetans from the Qinghai-Tibet plateau. Multivariate analysis might suggest that regular "mind-body" religious meditative activities may be negatively associated with AD in this population, as well as the CLU genotype at rs9331888.

Therapeutic efficacy of classic Tibetan formulas combined at different hours in resisting cerebral ischemia.

The study focused on the therapeutic efficacy of Tibetan medicines on cerebral ischemia. The combined medication methods and administration habits in clinic for more than 10 years were simulated. Three typical Tibetan medicines, i.e., 25-Herb Shanhu pill, Wishful-Treasure pill and 20-Herb Chenxiang pill, were administered to the animal model of permanent middle cerebral artery occlusion in the morning, noon and evening, respectively. On the second day after the final administration, the activity of serum oxidative stress marker SOD and the content of MDA were evaluated. Infarct volumes were quantified through TTC staining. Inflammatory reaction maker NF-kappaB p65 gene and apoptosis. makers Bax and Cyct were selected to study the molecular mechanism of combined herbs with the immunohistochemistry technique. According to the result, the respective combination of 25-Herb Shanhu pill, Wishful-Treasure pill and 20-Herb Chenxiang pill in the morning, noon and evening showed unique advantages in reducing the damage of oxidative stress, infarct volumes, encephaledema caused by ischemia, inflammatory factor aggregation and inhibiting apoptosis, with consistent therapeutic efficacies in clinic.

Identification and analysis of absorbed components and their metabolites in rat plasma and tissues after oral administration of 'Ershiwuwei Shanhu' pill extracts by UPLC-DAD/Q-TOF-MS.

ETHNOPHARMACOLOGICAL RELEVANCE: 'Ershiwuwei Shanhu' pill (ESP), a classical and famous prescription of traditional Tibetan medicine, has a long history of empirical clinical use for the treatment of cerebrovascular and neurological diseases, but the absence of scientific evidence for its effect restricted its clinical application and further development. MATERIALS AND METHODS: The methodology of plasma pharmacochemistry was adopted to analyze the potentially bioactive components in ESP extracts. A method based on UPLC-DAD/Q-TOF-MS was established to identify herb components in ESP extracts and analyze the absorbed components of ESP and their metabolites in rat plasma, brain, heart, liver and kidney samples after oral administration of ESP extracts. RESULTS: A total of 61 herb components were detected and identified in ESP extracts, while 35 absorbed components-including 19 prototype compounds and 16 metabolites-were discovered as potentially bioactive components in rat plasma and tissues by comparative analysis of the UV and MS chromatograms of ESP extracts, blank biosamples and dosed biosamples. CONCLUSIONS: The potentially bioactive components of ESP extracts identified from rat plasma and tissues provide useful information for further study of the pharmacology and mechanism of action of ESP.

[Advance in studies on traditional Chinese medicine on Abeta's scavenging effect].

Aggregation and accumulation of beta-amyloid peptide (Abeta) in brain tissues contribute to the pathogenesis of Alzheimer's disease. Therefore, the promotion of Abeta clearance is one of the key targets for preventing and treatment Alzheimer's disease. Studies proved that some traditional Chinese medicine (TCM) compounds and extracts could impact the activity of degrading enzyme in amyloid peptide, the transport of hemato encephalic barrier and the phagocytosis of microglial cells, promote Abeta clearance, and improve learning and memory of animal models with Alzheimer's disease. In this review, we made an summary for the relations between Abeta and Alzheimer's disease, the Abeta clearance mechanism and the clearance effect of traditional Chinese medicines.

Meta-analysis of the relationship between the Metholenetetrahydrofolate reductase C677T genetic polymorphism, folate intake and esophageal cancer.

OBJECTIVE: To evaluate the effect of the methylenetetrahydrofolate reductase C677T genetic polymorphism (MTHFR C677T) and folate intake on the risk of esophageal cancer. METHODS: A total of 17 studies (3,277 cases and 4,661 controls) regarding MTHFR C677T and 6 studies (1,817 cases and 7,678 controls) regarding folate intake published between 2001 and 2011 were identified through researching MEDLINE, EMBASE and the Chinese Biomedical Database. The data of the last search was February 2011. A meta-analysis was performed to obtain summary estimated odd ratios and 95% confidence intervals of folate intake and MTHFR C677T for esophageal cancer. RESULTS: A significant association was seen between MTHFR 677 CT [adjusted OR (95% CI)=1.55(1.28-1.88)] and TT [crude OR (95% CI)=1.63(1.24-2.15)] genotypes and esophageal cancer. Folate intake was seen to have a preventive effect on esophageal cancer [OR (95% CI)=0.60(0.50-0.70)]. Non-drinkers with MTHFR 677 CT and TT showed light esophageal cancer risk, and higher esophageal cancer risk was found among smokers. Also, the MTHFR 677 CT and TT genotypes were associated with light esophageal cancer risk in non-drinkers and a higher risk in drinkers. The meta-regression analysis showed the effect of MTHFR 677 CT and TT increased with the level of alcohol and tobacco consumption. The MTHFR 677 TT genotype showed a decreased risk of esophageal cancer in the high folate intake group. CONCLUSION: MTHFR 677CT/TT increase the risk of esophageal cancer, and the effects are greatly modified by alcohol, tobacco and folate intake. Folate intake was seen to have a preventive effect on developing esophageal cancer.