Findings and previous studies
The current study aims to evaluate the safety of celery seed extract
capsules, as a drug supplement, in hypertensive patients, in a
randomized, triple-blind, placebo-controlled, cross-over clinical trial.
The results of the present study showed that celery seed extract
capsules (1.34 g per day for 4-weeks) not only are safe for hypertensive
patients but also could improve some clinical, biochemical, and
hematological parameters. The variations were in normal ranges which
could be important clinically. The hypotensive effect of celery and NBP
were studied in some research [12, 30]. Also, some studies have
reported hypolipidemic and hypoglycemic properties of celery and NBP in
animal models and clinical trials [24, 26, 31, 32]. Based on Tables
1 and 2, the two groups had no significant difference at the beginning
of the clinical trial in terms of demographic characteristics, FBS,
lipid profile, and BP parameters (P>0.05). Furthermore, no
significant differences were seen in terms of dietary intake within and
between the groups during the study (P>0.05). The
cross-over study was applied to minimize the underlying and confounding
factors which can affect the results in the clinical trial. In this
study, celery seed extract capsules (1.34g extract per day for 4-weeks)
decreased BP parameters; SBP, DBP, MAP, and PP (P<0.001). The
mean reduction in SBP and DBP were 11.08 and 6.54 mmHg, respectively,
during celery therapy (P<0.001). In a study by Moghadamet al. , the chronic effect of celery seed extract on hypertension
was demonstrated in hypertensive and normotensive male rats. It has been
reported that celery seed extract reduced BP, which is ascribed to its
vasodilatory and diuretic effects [12]. Moreover, a significant
reduction in BP, due to NBP administration, was observed in the chronic
kidney disease model against hypertensive nephropathy using
spontaneously hypertensive rats [30]. In another study, the
hypotensive effects of NBP were reported in vivo model which
significantly decreased BP [33]. In the present clinical study,
celery capsules had no significant effect on blood cells including WBC,
RBC, platelet, and their indices in comparison with placebo treatment
(P>0.05). All blood cells factors were in the normal range
clinically. The results of another study by Masar et al. on male
rats indicated a significant increase in RBC, PCV, and Hb concentration
in the celery groups (P>0.05), while the results of WBC
count showed non-significant differences (P<0.05) compared to
control group [34]. Khuon et al. reported that the oral
administration of aqueous extract of celery (200 mg/kg for 2 weeks)
significantly increased WBC, RBC and Hb (P<0.01) in rats
subjected to the hematotoxicity induced by carbon tetrachloride. No
significant increase or decrease were also observed in MCV, MCHC and
Lymph (P>0.05) [35]. In another work, alcoholic extract
of celery leaves (10 mg/kg) in birds caused a significant increase in
RBC, Hb, and PCV with no significant change in WBC [36]. This
increase may be attributed to the release of erythropoietin from the
kidneys, which stimulates hematopoiesis [36]. Moreover, celery seed
could improve kidney function by decreasing BUN and SCr in hypertensive
patients (P<0.05). The mean reduction in BUN and SCr were 3.43
and 0.08 mg/dL, respectively. These changes are in the normal range
clinically. Some important serum electrolytes including Na, K, Ca, and P
were not affected during celery seed extract consumption
(P>0.05). Celery extract contains flavonoids with
inhibitory effect on oxidative stress in different tissues such as the
kidney. Flavonoids increase antioxidant activity and synthesis of
glutathione s-transferase. They also trap ROS by donating hydrogen atoms
to free radicals and thereby produce non-reactive free radicals. This
effect can improve kidney function [37]. In a study, oral
administration of ethanolic extract of celery at a dose of 1000 mg/kg
protected kidney harm in the kidney ischemia/ reperfusion injury rat
model [38]. The protective effect of celery extract may be due to
the content of phthalide and apiin glycosides as anti-inflammatory
compounds [39, 40]. Regarding the effect on liver function, in the
present work, SGOT and SGPT significantly reduced during 4-weeks celery
treatment (P<0.05) while ALP had no change after celery
administration (P>0.05). The mean reduction for SGOT and
SGPT were 4.08 and 3.03 U/L which are in the normal range clinically.
Celery stimulates the healthy and normal functioning of the liver
[41]. Celery root and leaf juices enhance antioxidative capacity
i.e. decrease glutathione content and the antioxidative capacity in
liver homogenate [42]. Celery seed is effective in liver injuries,
caused by a single dose of paracetamol, in rats. Celery has the
protective effect against thioacetamide medications [43]. In another
study in Wistar rats, celery seed had an inhibitive effect on liver
carcinoma [44]. Another study showed a reduction in the release of
AST and ALT enzymes into the blood and the ingredients of celery
stabilize liver cell membranes [45]. In another study biochemical
analysis of serum liver enzymes and blood, lipids showed that celery
reduces ALT, AST, and ALP [46]. In the present study, celery therapy
could significantly reduce FBS after 4-weeks of administration in
hypertensive patients (P<0.01). The mean reduction in FBS was
10.48 mg/dL. In a 12 days study by Yusni et al. celery capsules
(250 mg, three times per day) effectively decreased the glucose levels
of blood [31]. In addition, it has been achieved that celery seed
extract reduced serum glucose levels and induction of insulin release
from pancreatic islets [24]. In another experiment, it was reported
that celery seed extract decreased glucose levels in rats. Compared to
the negative control group, the concentrations of alanine
aminotransferase and aspartate aminotransferase were decreased in the
diabetic animals [26]. Another research showed that hepatic
glucose‐6‐phosphatase and serum glucose levels decreased in the
alloxan‐induced diabetic mice model. Also, in comparison with the
control group, concentrations of serum insulin were increased
significantly [47]. Furthermore, NBP demonstrated the
neuroprotective property by increasing vascular endothelial growth
factor expression and inhibiting caspase‐3‐mediated apoptosis [48].
In our clinical research, celery seed extract capsules were found to
have antihyperlipidemic properties and have the potential for decreasing
serum lipid profile in hypertensive patients (P<0.001). Celery
treatment reduced TC, TG, LDL, and increased HDL as 16.37, 16.22, 11.84,
and 2.52 mg/dL, respectively. Moreover, the ratio of LDL: HDL and TC:
HDL were significantly decreased after treatment with celery
(P<0.01). In the 8-weeks study, rats were fed a high‐fat diet
to induce hyperlipidemia. Celery has a significant effect on reducing
TC, TG and LDL concentrations [49]. In other studies, celery caused
a reduction in serum levels of LDL, LDL:HDL ratio, TC and TG
[50-53]. In a 12-week study, celery seed extract reduced the liver
lipids and serum lipid profile [54]. Moreover, aqueous and ethanolic
extracts of celery seeds showed hypolipidemic bioactivity, and
decreasing in LDL concentration in hamsters [55].