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 (Moghadam et al., 2013; Zhu et al., 2015). Also, some studies have reported hypolipidemic and hypoglycemic properties of celery and NBP in animal models and clinical trials (Illes, 2021; Niaz, 2013; Tashakori-Sabzevar, Ramezani, et al., 2016; Yusni et al., 2018). 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 Moghadam et 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 (Moghadam et al., 2013). 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 (Zhu et al., 2015). In another study, the hypotensive effects of NBP were reported in vivo model which significantly decreased BP (Tsi and Tan, 1997). 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 (Al-Kurdy, 2016). 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) (Khuon, 2012). 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 (Al–Gnami, 2014). This increase may be attributed to the release of erythropoietin from the kidneys, which stimulates hematopoiesis (Al–Gnami, 2014). 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 (Kang et al., 2016). 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 (Afifah et al., 2019). The protective effect of celery extract may be due to the content of phthalide and apiin glycosides as anti-inflammatory compounds (Mencherini et al., 2007; Zhu et al., 2017). 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 (Kolarovic et al., 2010). Celery root and leaf juices enhance antioxidative capacity i.e. decrease glutathione content and the antioxidative capacity in liver homogenate (Kolarovic et al., 2009). Celery seed is effective in liver injuries, caused by a single dose of paracetamol, in rats. Celery has the protective effect against thioacetamide medications (Hamza and Amin, 2007). In another study in Wistar rats, celery seed had an inhibitive effect on liver carcinoma (Singh and Handa, 1995). 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 (Taher et al., 2007). In another study biochemical analysis of serum liver enzymes and blood, lipids showed that celery reduces ALT, AST, and ALP (Abd El-Mageed, 2011). 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 (Yusni et al., 2018). In addition, it has been achieved that celery seed extract reduced serum glucose levels and induction of insulin release from pancreatic islets (Niaz, 2013). 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 (Tashakori-Sabzevar, Ramezani, et al., 2016). 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 (Panda and Kar, 2007). Furthermore, NBP demonstrated the neuroprotective property by increasing vascular endothelial growth factor expression and inhibiting caspase‐3‐mediated apoptosis (Zhang et al., 2010). 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 (Tsi et al., 1995). In other studies, celery caused a reduction in serum levels of LDL, LDL:HDL ratio, TC and TG (Cheng et al., 2010; Iyer and Patil, 2011; Kooti, Ghasemiboroon, et al., 2014; Kooti, Mansori, et al., 2014). In a 12-week study, celery seed extract reduced the liver lipids and serum lipid profile (Ahmed and Sayedda, 2012). Moreover, aqueous and ethanolic extracts of celery seeds showed hypolipidemic bioactivity, and decreasing in LDL concentration in hamsters (Lin et al., 2011).