Safety evaluation and biochemical efficacy of celery seed extract (Apium Graveolens) capsules in hypertensive patients: a randomized, triple-blind, placebo-controlled, cross-over, clinical trial.

The present study was conducted to evaluate the safety of celery seed extract (Apium graveolens), as a medicinal herb with active ingredients such as 3-n-butylphthalide (NBP), in hypertensive patients. This study was a randomized, triple-blind, placebo-controlled, cross-over clinical trial. Hypertensive patients (51 participants) received 4 celery seed capsules (a total of 1.34 g extract per day) or 4 placebo capsules per day for 4 weeks as a supplement to their usual medication regimen. The results indicated that the celery seed capsule not only was safe for hypertensive patients but also caused a reduction in BP, FBS, and lipid profile values. Also, it had beneficial effects on kidney and liver functions. No significant change was observed in blood cells and serum electrolytes (p > 0.05). The mean reduction in BUN and SCr were 3.43 and 0.075 mg/dL, and in SGPT and SGOT were 4.08 and 3.03 U/L, respectively (p < 0.05). FBS reduced from 108.53 to 97.96 mg/dL after 4 weeks of celery administration (p < 0.01). The decrease in TC, TG, LDL, and increase in HDL were 16.37, 16.22, 11.84, and 2.52 mg/dL, respectively (p < 0.001). According to the promising results of this clinical trial, celery seed extract can be considered a safe supplement for hypertensive patients. The study is limited by the small sample size; therefore, larger randomized trials are required.

Preparation, evaluation, and application of dummy molecularly imprinted polymer for analysis of hesperidin in lime juice.

Lime juice as the most commonly used natural source production can be characterized using determination of flavonoids contents such as hesperidin. So, development of analyzing methods for checking the quality and healthiness of lime juices is necessary. In this study, we aimed to set up a selective solid phase extraction method using dummy molecularly imprinting approach for extraction and separation of hesperidin in lime juice to check the quality of commercial lime juice products of Mashhad city market. The imprinted polymers were synthesized by hesperitin as dummy template due to the hesperitin solubility in the wide range of porogenic solvents. The specificity extent of synthesized polymers toward hesperidin was tested and optimum one was used as adsorbent in solid-phase extraction cartridge. The dummy molecularly imprinted polymer with high adsorption capacity for hesperidin (dissociation constant 0.12 µM) was successfully used for extraction and clean-up of hesperidin in the lime juice matrix prior to analysis by high-performance liquid chromatography. The analysis of hesperidin was done in the range of 0.312-50 µg/mL with detection limit of 0.05 µg/mL. This technique was successfully set up to remove the interfering compounds for analysis of hesperidin in commercial lime juice products.

Effects of rutin on acrylamide-induced neurotoxicity.

BACKGROUND: Rutin is an important flavonoid that is consumed in the daily diet. The cytoprotective effects of rutin, including antioxidative, and neuroprotective have been shown in several studies. Neurotoxic effects of acrylamide (ACR) have been established in humans and animals. In this study, the protective effects of rutin in prevention and treatment of neural toxicity of ACR were studied. RESULTS: Rutin significantly reduced cell death induced by ACR (5.46 mM) in time- and dose-dependent manners. Rutin treatment decreased the ACR-induced cytotoxicity significantly in comparison to control (P <0.01, P < 0.001). Rutin (100 and 200 mg/kg) could prevent decrease of body weight in rats. In combination treatments with rutin (50, 100 and 200 mg/kg), vitamin E (200 mg/kg) and ACR, gait abnormalities significantly decreased in a dose-dependent manner (P < 0.01 and P < 0.001). The level of malondialdehyde significantly decreased in the brain tissue of rats in both preventive and therapeutic groups that received rutin (100 and 200 mg/kg). CONCLUSION: It seems that rutin could be effective in reducing neurotoxicity and the neuroprotective effect of it might be mediated via antioxidant activity.

Effects of saffron (Crocus sativus L.) and its active constituent, crocin, on recognition and spatial memory after chronic cerebral hypoperfusion in rats.

Cerebral ischemia produces brain damage and related behavioral deficits such as memory. In this study, a rat model of chronic cerebral hypoperfusion was used to determine whether saffron extract and crocin, which are potent antioxidants and free radical scavengers, can reduce vascular cognitive impairment. Male adult Wistar rats were administered different doses of an aqueous solution of crocin or hydroalcohol extract of saffron intraperitoneally (i.p.) 5 days after permanent occlusion of the common carotid arteries. Spatial learning and memory were assessed in training trials, 7-11 days after common carotid artery ligation using the Morris water maze. The results showed that the escape latency time was significantly reduced from 24.64 s in the control group to 8.77 and 10.47 s by crocin (25 mg/kg) and saffron extract (250 mg/kg). The traveled distance to find the platform was also changed from 772 cm in the control group to 251 and 294 cm in the crocin (25 mg/kg) and saffron extract (250 mg/kg) groups. The percentages of time spent in the target quadrant, in comparison with the control group (24.16%), increased to 34.25% in the crocin (25 mg/kg) and 34.85% in the saffron extract (250 mg/kg) group. This study suggests that saffron extract and crocin improve spatial cognitive abilities following chronic cerebral hypoperfusion and that these effects may be related to the antioxidant effects of these compounds.

Neuroprotective and memory enhancing effects of auraptene in a rat model of vascular dementia: Experimental study and histopathological evaluation.

Vascular dementia and Alzheimer disease are most common type of dementia. These diseases have been associated with cognitive decline and affected personal behavioral activities. Moreover, the pattern of cerebral blood flow in mild cognitive disorder has appeared as a predictive indication for the development into Alzheimer's disease. Permanent, bilateral occlusion of the common carotid arteries (2VO) is a standard animal model to study vascular dementia and chronic cerebral hypoperfusion. In present study neuroprotective and memory enhancing effects of auraptene (AUR), a citrus coumarin, were studied in 2VO rats. Different doses (25, 8 & 4mg/kg) of AUR were administered orally. The spatial memory performance was tested with Morris water maze after 2VO induction. Biochemical experiments and histopathological evaluations were also applied to investigate the neuroprotective effect of AUR in brain tissue. In comparison with 2VO group, AUR could significantly decrease the scape latency time in treated rats. Also AUR increased the percentage of time spent and traveled pathway in target quadrant on final trial test day. All behavioral results were confirmed by biochemical and histopathological data. Biochemical data indicated that AUR could decrease malondialdehyde (MDA), as lipid peroxidation indicator, and increase glutathione (GSH) content in cortex and hippocampus tissues. Histopathological data showed that AUR could protect cerebrocortical and hippocampus neurons against ischemia. This study demonstrated the memory enhancing effect and neuroprotective activity of AUR after induction of brain ischemia in a rat model of vascular dementia.

Crocin restores hypotensive effect of subchronic administration of diazinon in rats.

OBJECTIVE(S): In this study, the effects of crocin against subchronic toxicity of diazinon (DZN) on systolic blood pressure (SBP) and heart rate (HR) were evaluated in rats. MATERIALS AND METHODS: Rats were equally divided into 7 groups; control (corn oil), DZN (15 mg/kg), crocin (each group received 12.5, 25 or 50 mg/kg crocin plus DZN), vitamin E (200 IU/kg plus DZN) and crocin (50 mg/kg) treated groups. Rats were given DZN via gavage once a day for 4 weeks. Vitamin E (three times per week) and crocin (once a day) were intraperitoneally injected to rats for 4 weeks. Plasma cholinesterase activity (Elman method), malondealdehyde (MDA) levels in the aortic tissue (Thiobarbituric acid reactive substances or TBARS method); SBP and HR (tail cuff method) were evaluated at the end of 4th week. RESULTS: A significant decrease in cholinesterase activity was observed in DZN group (P< 0.001). Crocin did not show any effects on cholinesterase activity. DZN increased MDA levels in aortic tissue (P< 0.001) in comparison with control group. Crocin and vitamin E plus DZN decreased MDA elevation induced by DZN in aortic tissue. DZN significantly reduced SBP (P< 0.01) and increased HR (P< 0.001) in comparison with control. Concurrent administration of crocin and DZN, improved the reduction of SBP and the elevation of HR induced by DZN in rat. Crocin alone did not have any effect on SBP and HR. CONCLUSION: This study showed that concurrent administration of crocin and DZN could restore the effects of subchronic DZN administration on SBP and HR in rats.

Crocetin attenuates spatial learning dysfunction and hippocampal injury in a model of vascular dementia.

Chronic cerebral hypoperfusion produces brain ischemia and is associated with related memory impairment. In this study, we prepared crocetin from crocin (the main water soluble pigment in saffron stigmas) in an acidic hydrolysis and its purity was evaluated using spectrophotometry, thin layer chromatography (TLC) and high performance liquid chromatography (HPLC). The memory enhancing effect of crocetin was then studied in a rat model of chronic cerebral hypoperfusion. Different doses of crocetin were administered intraperitoneally (i.p.). The spatial learning and memory function were tested using Morris water maze, after permanent occlusion of common carotids. Finally, the animals were euthanatized in CO2 chamber and histopathological changes in cerebral cortex and hippocampus were investigated. The results indicated that the escape latency time significantly decreased in crocetin treated rats, in comparison with control animals. Also, the percentage of time spent and traveled distance in target quadrant on final test trial day increased in crocetin 8 mg/kg group, compared to control group, while no difference was observed between groups in swimming speed. All behavioral results were confirmed by histopathological analysis. According to our data, crocetin (8 mg/kg) could properly protect cerebrocortical and hippocampus neurons against ischemia. In conclusion, treatment with crocetin could effectively prevent neuropathological alterations in hippocampus thereby resulting in improvement of spatial learning memory in rats after chronic cerebral hypoperfusion.