Celery Abstracts 1

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Vasorelaxant activity of extracts obtained from Apium graveolens: possible source for vasorelaxant molecules isolation with potential antihypertensive effect.
            (Jorge et al., 2013) Download
OBJECTIVE: To investigate vasorelaxant effect of organic extracts from Apium graveolens (A. graveolens) which is a part of a group of plants subjected to pharmacological and phytochemical study with the purpose of offering it as an ideal source for obtaining lead compounds for designing new therapeutic agents with potential vasorelaxant and antihypertensive effects. METHODS: An ex vivo method was employed to assess the vasorelaxant activity. This consisted of using rat aortic rings with and without endothelium precontracted with norepinephrine. RESULTS: All extracts caused concentration-dependent relaxation in precontracted aortic rings with and without endothelium; the most active extracts were Dichloromethane and Ethyl Acetate extracts from A. graveolens. These results suggested that secondary metabolites responsible for the vasorelaxant activity belong to a group of compounds of medium polarity. Also, our evidence showed that effect induced by dichloromethane and ethyl acetate extracts from A. graveolens is mediated probably by calcium antagonism. CONCLUSIONS: A. graveolens represents an ideal source for obtaining lead compounds for designing new therapeutic agents with potential vasorelaxant and antihypertensive effects.

Antihypertensive effect of celery seed on rat blood pressure in chronic administration.
            (Moghadam et al., 2013) Download
This study investigated the effects of different celery (Apium graveolens) seed extracts on blood pressure (BP) in normotensive and deoxycorticosterone acetate-induced hypertensive rats. The hexanic, methanolic, and aqueous-ethanolic extracts were administered intraperitoneally and their effects on BP and heart rate (HR) were evaluated in comparison with spirnolactone as a diuretic and positive control. Also, the amount of n-butylphthalide (NBP), as an antihypertensive constituent, in each extract was determined by HPLC. The results indicated that all extracts decreased BP and increased the HR in hypertensive rats, but had no effect on normotensive rats. The data showed that administration of 300 mg/kg of hexanic, methanolic, and aqueous-ethanolic (20/80, v/v) extracts of the celery seed caused 38, 24, and 23 mmHg reduction in BP and 60, 25, and 27 beats per minute increase in the HR, respectively. Also, the HPLC analysis data revealed that the content of NBP in the hexanic extract was 3.7 and 4 times greater than methanolic and aqueous-ethanolic extracts. It can be concluded that celery seed extracts have antihypertensive properties, which appears to be attributable to the actions of its active hydrophobic constitutes such as NBP and can be considered as an antihypertensive agent in chronic treatment of elevated BP.

Antiplatelet and antithrombotic activity of L-3-n-butylphthalide in rats.
            (Peng et al., 2004) Download
3-n-butylphthalide (NBP) is a potentially beneficial drug for the treatment of ischemic stroke with multiple actions on different pathophysiological processes. In the present study, the effect of l-, d-, and dl-NBP was investigated on ADP-, collagen-, and AA-induced platelet aggregation. l-NBP was the most potent among l-, d-, and dl-NBP. At higher concentration the effect of dl-NBP on platelet aggregation was greater than that of l- or d-NBP alone. The ex vivo antiaggregatory activity of l-NBP 100mg/kg declined gradually after 2 hours, but a considerable antiplatelet activity was still observed 4h after l-NBP administration. NBP was given orally and resulted in a dose-dependent inhibition of thrombus formation. Of the two isomers, l-NBP was the most potent. It significantly protected mice from a mixture of collagen and epinephrine induced thromboembolic death. When 100 mg/kg of l-NBP were administered orally to rats, the bleeding time increased 2.1-fold compared with the control group. At the same dose, ex vivo platelet aggregation induced by ADP, collagen, and AA was inhibited by l-NBP and the antithrombotic effects of the compound were also observed. Thus, NBP exerts oral anti-platelet and anti-thrombotic efficacy without perturbing systemic hemostasis in rats. l-NBP is more potent than d- and dl-NBP as antiplatelet agent.

l-3-n-Butylphthalide improves cognitive impairment induced by chronic cerebral hypoperfusion in rats.
            (Peng et al., 2007) Download
3-n-Butylphthalide (NBP) may be beneficial for the treatment of ischemic stroke with multiple actions on different pathophysiological processes. In the present study, we investigated the effect of NBP isomers on learning and memory impairment induced by chronic cerebral hypoperfusion in rats. Male Wistar rats were orally administered 10 and 30 mg/kg l-, d-, or dl-NBP daily for 23 days after bilateral permanent occlusion of the common carotid arteries. Rats receiving 10 mg/kg l-NBP performed significantly better in tests for spatial learning and memory, and they had attenuated cerebral pathology, including neuronal damage, white matter rarefaction, and glial activation compared with controls. Furthermore, 10 mg/kg l-NBP-treated rats had significantly higher choline acetyltransferase activity, decreased cortical lipid peroxide, and reduced hippocampal superoxide dismutase activity, compared with vehicle controls. However, d- and dl-NBP did not show significant beneficial effects. The present findings demonstrate that the beneficial effects of l-NBP on hypoperfusion-induced cognitive deficits may be due to preventing neuropathological alterations, inhibiting oxidative damage and increasing acetylcholine synthesis. Our results strongly suggest that l-NBP has therapeutic potential for the treatment of dementia caused by decreased cerebral blood flow.

L-3-n-butylphthalide improves cognitive impairment and reduces amyloid-beta in a transgenic model of Alzheimer's disease.
            (Peng et al., 2010) Download
Alzheimer's disease (AD) is an age-related, progressive neurodegenerative disorder that occurs gradually and results in memory, behavior, and personality changes. L-3-n-butylphthalide (L-NBP), an extract from seeds of Apium graveolens Linn (Chinese celery), has been demonstrated to have neuroprotective effects on ischemic, vascular dementia, and amyloid-beta (Abeta)-infused animal models. In the current study, we examined the effects of L-NBP on learning and memory in a triple-transgenic AD mouse model (3xTg-AD) that develops both plaques and tangles with aging, as well as cognitive deficits. Ten-month-old 3xTg-AD mice were given 15 mg/kg L-NBP by oral gavage for 18 weeks. L-NBP treatment significantly improved learning deficits, as well as long-term spatial memory, compared with vehicle control treatment. L-NBP treatment significantly reduced total cerebral Abeta plaque deposition and lowered Abeta levels in brain homogenates but had no effect on fibrillar Abeta plaques, suggesting preferential removal of diffuse Abeta deposits. Furthermore, we found that L-NBP markedly enhanced soluble amyloid precursor protein secretion (alphaAPPs), alpha-secretase, and PKCalpha expression but had no effect on steady-state full-length APP. Thus, L-NBP may direct APP processing toward a non-amyloidogenic pathway and preclude Abeta formation in the 3xTg-AD mice. The effect of l-NBP on regulating APP processing was further confirmed in neuroblastoma SK-N-SH cells overexpressing wild-type human APP(695) (SK-N-SH APPwt). L-NBP treatment in 3xTg-AD mice also reduced glial activation and oxidative stress compared with control treatment. L-NBP shows promising preclinical potential as a multitarget drug for the prevention and/or treatment of Alzheimer's disease.


 

L-3-n-butylphthalide reduces tau phosphorylation and improves cognitive deficits in AbetaPP/PS1-Alzheimer's transgenic mice.
            (Peng et al., 2012) Download
L-3-n-butylphthalide (L-NBP), an extract from seeds of Apium graveolens Linn (Chinese celery), has been shown to have neuroprotective effects on cerebral ischemic, vascular dementia and amyloid-beta (Abeta)-induced animal models by inhibiting oxidative injury, neuronal apoptosis and glial activation, regulating amyloid-beta protein precursor (AbetaPP) processing and reducing Abeta generation. The aim of the present study was to examine the effect of L-NBP on learning and memory in AbetaPP and presenilin 1 (PS1) double-transgenic AD mouse model (AbetaPP/PS1) and the mechanisms of L-NBP in reducing Abeta accumulation and tau phosphorylation. Twelve-month old AbetaPP/PS1 mice were given 15 mg/kg L-NBP by oral gavage for 3 months. L-NBP treatment significantly improved the spatial learning and memory deficits compared to the vehicle-treated AbetaPP/PS1 mice, whereas L-NBP treatment had no effect on cerebral Abeta plaque deposition and Abeta levels in brain homogenates. However, we found an L-NBP-induced reduction of tau hyperphosphorylation at Ser199, Thr205, Ser396, and Ser404 sites in AbetaPP/PS1 mice. Additionally, the expressions of cyclin-dependent kinase and glycogen synthase kinase 3beta, the most important kinases involved in tau phosphorylation, were markedly decreased by L-NBP treatment. The effects of L-NBP on decreasing tau phosphorylation and kinases activations were further confirmed in neuroblastoma SK-N-SH cells overexpressing wild-type human AbetaPP695 (SK-N-SH AbetaPPwt). L-NBP shows promising candidate of multi-target neuronal protective agent for the treatment of Alzheimer's disease.

Comparison of Two Old Phytochemicals versus Two Newly Researched Plant-Derived Compounds: Potential for Brain and Other Relevant Ailments.
            (Wang et al., 2014) Download
Among hundreds of formulae of Chinese herbal prescriptions and recently extracted active components from the herbs, some of which had demonstrated their functions on nervous system. For the last decade or more, Gingko biloba and Polygala tenuifolia were widely studied for their beneficial effects against damage to the brain. Two compounds extracted from Apium graveolens and Rhizoma coptidis, butylphthalide and berberine, respectively, received much attention recently as potential neuroprotective agents. In this review, the two traditionally used herbs and the two relatively new compounds will be discussed with regard to their potential advantages in alleviating brain and other relevant ailments.


2-(1-Hydroxypentyl)-benzoate increases cerebral blood flow and reduces infarct volume in rats model of transient focal cerebral ischemia.
            (Zhang et al., 2006) Download
2-(1-Hydroxypentyl)-benzoate (dl-PHPB), a derivate of 3-n-butylphthalide (dl-NBP), is a novel drug candidate used for treatment of cerebral ischemia. The goal of the present study was to investigate the effects of dl-PHPB on infarct volume, neurological function, and cerebral blood flow (CBF) in transient focal cerebral ischemia. Therefore, an animal model of 2-h middle cerebral artery occlusion (MCAO) followed by 24-h reperfusion was used. Rats received dl-PHPB (1.3, 3.9, or 12.9 mg/kg) intravenously 10 min after the onset of MCAO. Compared with the vehicle control group (37.4%), infarct volume in dl-PHPB-treated groups was reduced significantly and dose-dependently to 25.4, 17.4, and 13.7%, respectively. The changes in neurological deficient were also observed in neurobehavioral test in a dose-dependent manner, and the neuronal score was improved significantly from the vehicle control of 3.2 to 2.7, 2.1, and 1.8, respectively. At the highest dose, the potency of dl-PHPB was similar to those of dl-NBP. CBF was quantified by using laser-Doppler flowmetry. During the ischemia, the regional CBF values of dl-PHPB groups were significantly higher than that of vehicle group. In addition, our study showed that dl-PHPB converted into dl-NBP very quickly in blood in vitro. Approximately 70% of dl-PHPB converted into dl-NBP in 5 min when dl-PHPB was added into plasma at final concentrations of 6, 30, and 60 mug/ml. This result demonstrated that the neuronal protection effects of dl-PHPB were mainly induced by dl-NBP, an active compound converted from its precursor, dl-PHPB. In conclusion, dl-PHPB can reduce infarct volume and improve neurobehavioral deficits in a rat model of transient MCAO. Those effects may partially be due to an increase in CBF by the active metabolite (dl-NBP) of dl-PHPB. Therefore, our results suggest that dl-PHPB may be useful for treatment of ischemia stroke.

 


 

References

Jorge, VG, et al. (2013), ‘Vasorelaxant activity of extracts obtained from Apium graveolens: possible source for vasorelaxant molecules isolation with potential antihypertensive effect.’, Asian Pac J Trop Biomed, 3 (10), 776-79. PubMedID: 24075341
Moghadam, MH, M Imenshahidi, and SA Mohajeri (2013), ‘Antihypertensive effect of celery seed on rat blood pressure in chronic administration.’, J Med Food, 16 (6), 558-63. PubMedID: 23735001
Peng, Y, et al. (2004), ‘Antiplatelet and antithrombotic activity of L-3-n-butylphthalide in rats.’, J Cardiovasc Pharmacol, 43 (6), 876-81. PubMedID: 15167282
Peng, Y, et al. (2007), ‘l-3-n-Butylphthalide improves cognitive impairment induced by chronic cerebral hypoperfusion in rats.’, J Pharmacol Exp Ther, 321 (3), 902-10. PubMedID: 17374747
Peng, Y, et al. (2010), ‘L-3-n-butylphthalide improves cognitive impairment and reduces amyloid-beta in a transgenic model of Alzheimer’s disease.’, J Neurosci, 30 (24), 8180-89. PubMedID: 20554868
Peng, Y, et al. (2012), ‘L-3-n-butylphthalide reduces tau phosphorylation and improves cognitive deficits in AbetaPP/PS1-Alzheimer’s transgenic mice.’, J Alzheimers Dis, 29 (2), 379-91. PubMedID: 22233765
Wang, CM, W Liang, and DT Yew (2014), ‘Comparison of Two Old Phytochemicals versus Two Newly Researched Plant-Derived Compounds: Potential for Brain and Other Relevant Ailments.’, Evid Based Complement Alternat Med, 2014 682717. PubMedID: 24949079
Zhang, Y, et al. (2006), ‘2-(1-Hydroxypentyl)-benzoate increases cerebral blood flow and reduces infarct volume in rats model of transient focal cerebral ischemia.’, J Pharmacol Exp Ther, 317 (3), 973-79. PubMedID: 16527903