Celery Abstracts 2

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N-butylidenephthalide attenuates Alzheimer's disease-like cytopathy in Down syndrome induced pluripotent stem cell-derived neurons.
            (Chang et al., 2015) Download
Down syndrome (DS) patients with early-onset dementia share similar neurodegenerative features with Alzheimer's disease (AD). To recapitulate the AD cell model, DS induced pluripotent stem cells (DS-iPSCs), reprogrammed from mesenchymal stem cells in amniotic fluid, were directed toward a neuronal lineage. Neuroepithelial precursor cells with high purity and forebrain characteristics were robustly generated on day 10 (D10) of differentiation. Accumulated amyloid deposits, Tau protein hyperphosphorylation and Tau intracellular redistribution emerged rapidly in DS neurons within 45 days but not in normal embryonic stem cell-derived neurons. N-butylidenephthalide (Bdph), a major phthalide ingredient of Angelica sinensis, was emulsified by pluronic F127 to reduce its cellular toxicity and promote canonical Wnt signaling. Interestingly, we found that F127-Bdph showed significant therapeutic effects in reducing secreted Aβ40 deposits, the total Tau level and the hyperphosphorylated status of Tau in DS neurons. Taken together, DS-iPSC derived neural cells can serve as an ideal cellular model of DS and AD and have potential for high-throughput screening of candidate drugs. We also suggest that Bdph may benefit DS or AD treatment by scavenging Aβ aggregates and neurofibrillary tangles.

Ninety-day administration of dl-3-n-butylphthalide for acute ischemic stroke: a randomized, double-blind trial.
            (Cui et al., 2013) Download
BACKGROUND:  Dl-3-n-butylphthalide (NBP), first isolated from the seeds of celery, showed efficacy in animal models of stroke. This study was a clinical trial to assess the efficacy and safety of NBP with a continuous dose regimen among patients with acute ischemic stroke. METHODS:  A randomized, double-blind, double-dummy trial enrolled 573 patients within 48 hours of onset of ischemic stroke in China. Patients were randomly assigned to receive a 14-day infusion of NBP followed by an NBP capsule, a 14-day infusion of NBP followed by aspirin, or a 14-day infusion of ozagrel followed by aspirin. The efficacy measures were Barthel index score and the modified Rankin scale (mRS) at day 90. Differences among the three groups on mRS were compared using χ(2) test of proportions (with two-sided α = 0.05) and Logistic regression analysis was conducted to take the baseline National Institutes of Health Stroke Scale (NIHSS) score into consideration. RESULTS:  Among the 535 subjects included in the efficacy analysis, 90-day treatment with NBP was associated with a significantly favorable outcome than 14-day treatment with ozagrel as measured by mRS (P < 0.001). No significant difference was found among the three groups on Barthel index at day 90. The rate of adverse events was similar among the three groups. CONCLUSIONS:  The 90-day treatment with NBP could improve outcomes at the third month after stroke. The NBP treatment (both intravenous and oral) is safe (ChiCTR-TRC-09000483).

A Pilot Study to Evaluate the Antihypertensive Effect of a Celery Extract in Mild to Moderate Hypertensive Patients
            (Madhavi et al., 2013) Download
Objective: To evaluate the efficacy of a standardized extract of celery seed, 150 mg/d, supplying 85% 3-n-butylphthalide (3nB) in mild to moderate hypertensive patients. Study Design: A single-arm study of 30 mild to moderate hypertensive patients given the test medication following a 7-day wash out period. The primary clinical assessment was the effect on blood pressure at week 3 and week 6. Secondary measures were fasting blood levels of total cholesterol, LDL cholesterol, HDL cholesterol, VLDL cholesterol, free fatty acids, and serum electrolytes (ie, sodium, potassium, calcium). Results: There was statistically significant decrease in both systolic blood pressure (SBP) and diastolic blood pressure (DBP) at week 3 and week 6 compared to baseline. The change at week 6 for the SBP was 8.2 mmHg (SD=3.6, P<0.005) and for the DBP was 8.5 mmHG (SD=2.9, P<0.005). Conclusions: The results from this pilot study suggest that celery seed extract may have clinically relevant blood pressure–lowering effects, indicating that additional clinical research is warranted.

Protective effects of dl-3n-butylphthalide against diffuse brain injury.
            (Zhao et al., 2013) Download
Dl-3n-butylphthalide can effectively treat cerebral ischemia; however, the mechanisms underlying the effects of dl-3n-butylphthalide on microcirculation disorders following diffuse brain injury remain unclear. In this study, models of diffuse brain injury were established in Sprague-Dawley rats with the vertical impact method. Dl-3n-butylphthalide at 80 and 160 mg/kg was given via intraperitoneal injection immediately after diffuse brain injury. Ultrastructural changes in the cerebral cortex were observed using electron microscopy. Cerebral blood flow was measured by laser Doppler flowmetry, vascular density was marked by tannic acid-ferric chloride staining, vascular permeability was es-timated by the Evans blue method, brain water content was measured using the dry-wet method, and rat behavior was measured by motor function and sensory function tests. At 6, 24, 48, and 72 hours after administration of dl-3n-butylphthalide, reduced cerebral ultrastructure damage, creased vascular density and cerebral blood flow, and improved motor and sensory functions were observed. Our findings demonstrate that dl-3n-butylphthalide may have protective effects against diffuse brain injury by ameliorating microcirculation disorder and reducing blood-brain barrier age and cerebral edema.


References

Chang, CY, et al. (2015), ‘N-butylidenephthalide attenuates Alzheimer’s disease-like cytopathy in Down syndrome induced pluripotent stem cell-derived neurons.’, Sci Rep, 5 8744. PubMedID: 25735452
Cui, LY, et al. (2013), ‘Ninety-day administration of dl-3-n-butylphthalide for acute ischemic stroke: a randomized, double-blind trial.’, Chin Med J (Engl), 126 (18), 3405-10. PubMedID: 24034079
Madhavi, D., et al. (2013), ‘A Pilot Study to Evaluate the Antihypertensive Effect of a Celery Extract in Mild to Moderate Hypertensive Patients’, Natural Medicine J, 5 (4), PubMedID:
Zhao, Y, et al. (2013), ‘Protective effects of dl-3n-butylphthalide against diffuse brain injury.’, Neural Regen Res, 8 (28), 2615-24. PubMedID: 25206572