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Abstract

The metabolic syndrome (MetS) is a cluster of multiple conditions that includes hypertension, dyslipidemia, abdominal obesity, and hyperglycemia disorders. Most studies revealed that the MetS is accompanied with an increased risk for cardiovascular disease, Type 2 diabetes mellitus, and insulin resistance. It can be said that, in treating or preventing the MetS and its components, lifestyle adjustment and weight loss have a vital role. According to various studies, among natural compounds, celery (Apium graveolens) is one of the most important sources of phytochemicals such as phenolic acids, flavones, flavonols, and antioxidants such as vitamin C, beta‐carotene (Provitamin A), and manganese. These antioxidants have a role in decreasing the oxidative damage. The phytochemicals in celery decrease the activity of proinflammatory cytokines and prevent inflammation. Also, flavonoids in celery suppress cardiovascular inflammation. Oxidative stress and inflammation in the blood stream are the main risk factors in increasing cardiovascular disease, especially atherosclerosis. Celery phthalides leads to expanding of smooth muscle in the blood vessels and lower blood pressure. As a result, the most active ingredients in celery (A. graveolens (have shown hypolipidemic, antidiabetic, and hypotensive properties. In this review, we summarized the mechanisms underlying the protective effects of celery components on insulin action, glucose, lipid metabolism, and blood pressure.

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... Treatment with celery improved behavioral changes and oxidative stress parameters (Chonpathompikunlert et al. 2018). Celery seeds contain several active ingredients such as phthalides, luteolin, d-limonene, apigenin, and linalool (Hedayati et al. 2019). Ye et al. (2018) have shown that 3-n-butylphthalide (NBP) is the main component of celery seed extract. ...
... There are different active ingredients such as phthalides, apigenin, and d-limonene in celery seeds. It can be beneficial to survey studies which were reported the efficacy of these components on cerebral and mental properties (Hedayati et al. 2019;Tashakori-Sabzevar et al. 2016a, b). The NBP, as a phthalide, is reported to have anti-anxiety and anti-depressive effects. ...
... medicine (Hedayati et al. 2019;Moghadam et al. 2013;Tashakori-Sabzevar et al. 2016b). Some studies have reported that patients with HTN awareness have an increased risk of anxiety disorders (Hamer et al. 2010;Wei et al. 2003). ...
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Background: Anxiety and depression are crucial public health issues, affecting the rising in hospitalizations and death. Anxiety and depression can worsen hypertension and vice versa. Objective: The current study has investigated the effects of celery seed extract, as a drug supplement, with the active ingredient of 3-n-butylphthalide, on mental problems primarily anxiety and secondary depression in hypertensive patients. Design: The current study was a randomized, triple-blind, placebo-controlled, cross-over, 4-week clinical trial with a 4-week washout period. Fifty hypertensive patients received 4 placebo or celery seed extract capsules (1.34 g per day) for 4 weeks as a supplement to their usual medication regimen. The blood pressure parameters were assessed using 24-h ambulatory blood pressure monitoring device. Anxiety and depression and their wide range of symptoms were evaluated using Beck anxiety and depression inventories (BAI and BDI). Results: In the celery treatment step, the mean reduction in BAI and BDI scores were 6.78 (P < 0.001) and 3.63 (P < 0.01), respectively. Some symptoms of anxiety including unable to relax, nervousness, numbness, dizziness, flushed face, sweating, and breathing difficulty were significantly improved by celery consumption (P < 0.001). Celery could decrease symptoms of depression such as sadness, crying, loss of energy, insomnia, irritability, fatigue, loss of interest in sex, and punishment feeling (P < 0.01). The mean reduction in blood pressure parameters was also significant during celery therapy (P < 0.001). Conclusions: The psychometric properties of anxiety and depression were investigated and the results were promising. The results indicated the anti-anxiety and anti-depressive properties of celery seed extract as a supplement in hypertensive patients. Clinical trial registration: Registry name: Iranian Registry of Clinical Trials (IRCT), Registration number: IRCT20130418013058N8, Registration link: https://www.irct.ir/trial/30021 . The study was carried out between 2018-09-21 and 2020-07-20.
... The phthalides present in celery results in expanding of smooth muscle in the blood vessels which helps in decreasing the blood pressure. Moreover, the antioxidative and anti-inflammatory properties of phthalides provide additional protection against cardiovascular diseases, especially atherosclerosis (Hedayati et al., 2019). ...
... Celery seeds contain several essential phytochemicals like phenolic acids, flavones, flavonols, and antioxidants, beta-carotene and manganese. Thus, they contribute to overall immunity mainly by acting as antioxidative and antiinflammatory agent (Hedayati et al., 2019). A. graveolens seeds showed a protective effect against LDLinduced injury of macrophages by decreasing the secretion of cytokine TNF-α and interleukin (IL)-6 and suppressing the production of NF-κB, p65 and notch1 protein expressions (Si et al., 2015). ...
Article
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The ancient world practically depended on herbal sources of medicines to treat common as well as chronic diseases. Till now, over 80% population in the developing and under developed countries depend on plant materials for the same. Many claims have been justified about the efficacy of modern medicines; it is interesting to know that most of them are derived from plants. The common herbs and spices are exploited by the existing herbal branches of medicines to prepare potential drugs. Occasionally, it also uses rare species of medicinal plants, native to specific climate or region. The screening of new and rare plant species is required to improve the scope of pharmacological alternatives. However, the common herbs and spices provide a more practical, productive as well as a feasible source of medicine. Hence, the current review describes the medicinal benefits of black cumin (Nigella sativa L.) and celery (Apium graveolens L.) seeds, and chicory (Cichorium intybus L.) roots. They are not only commonly available but are loaded with essential nutrients that promote overall health and boosts immunity.
... Compared to other parts of the plant, celery seeds have more effective ingredients (Moghadam et al. 2013;Popović et al. 2006). The celery seeds contain various active ingredients, including luteolin, d-limonene, phthalides, apigenin, hesperidin, linalool, and quercetin (Hedayati et al. 2019;Priecina and Karklina 2014;Tashakori-Sabzevar et al. 2016a, b). The pharmacological mechanisms of these active ingredients are discovered and reported in previous studies (Anjos et al. 2013;Dianat et al. 2015;Su et al. 2015;Triyono et al. 2018). ...
... Other ingredients in celery seed extract such as luteolin, d-limonene, phthalides, apigenin, hesperidin, linalool, and quercetin were not measured in the final extract. Thus, the extract and capsules were standardized based on NBP content (Hedayati et al. 2019;Priecina and Karklina 2014;Tashakori-Sabzevar et al. 2016a, b). Figure 1 represents chromatograms of standard methanolic solution of NBP (10 g/mL) and celery seed capsule powder (1000 μg/mL). ...
Article
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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.
... Celery phthalides lead to smooth muscle expansion in the blood vessels and lower blood pressure [16]. Additionally, it is used in dieting and weight loss programs [17]. Its leaves, roots, and seeds are used as food, seasoning in a daily diet, and as natural medicinal remedies around the world. ...
Article
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Background Non-alcoholic fatty liver disease (NAFLD) is a condition resulting from fat aggregates in liver cells and is associated with metabolic syndrome, obesity, and oxidative stress. The present work was designed to investigate the role of celery and curcumin against high-fructose–high-fat (HFHF) diet-induced NAFLD in rats. Thirty male rats were classified into five groups: GP 1 : control group (rats were fed a normal control diet), GP 2 : HFHF group as a positive control (rats were fed a HFHF diet) for 20 weeks, GP 3 : HFHF + sily group, GP 4 : HFHF + celery group, and GP 5 : HFHF + cur group (rats in 3, 4, and 5 were treated as in the HFHF group for 16 weeks, then combined treatment daily by gavage for 4 weeks with either silymarin (as a reference drug, 50 mg/kg bw) or celery (300 mg/kg bw) or curcumin (200 mg/kg bw), respectively. The progression of NAFLD was evaluated by estimating tissue serum liver enzymes, glycemic profile, lipid profile, oxidative stress markers in liver tissue, and histopathological examination. Moreover, DNA fragmentation and the released lysosomal enzymes (acid phosphatase, β-galactosidase, and N -acetyl-B-glucosaminidase) were estimated. Results Our results showed that HFHF administration for 16 weeks caused liver enzymes elevation, hyperglycemia, and hyperlipidemia. Furthermore, increased hepatic MDA levels along with a decline in GSH levels were observed in the HFHF group as compared to the control group. The results were confirmed by a histopathological study, which showed pathological changes in the HFHF group. DNA fragmentation was also observed, and the lysosomal enzyme activities were increased. On the other hand, oral supplementation of celery and cur improved all these changes compared with positive control groups and HFHF + sily (as a reference drug). Moreover, celery, as well as curcumin co-treatment, reduced HFHF-enhanced DNA fragmentation and inhibited elevated lysosomal enzymes. The celery combined treatment showed the most pronounced ameliorative impact, even more than silymarin did. Conclusion Our findings suggest that celery and curcumin consumption may exhibit ameliorative impacts against NALFD progression, while celery showed more ameliorative effect in all parameters .
... Celery (Apium graveolens L.), a plant of the Apiaceae family, is a leaf vegetable that originated from the Mediterranean and the Middle East and is cultivated globally. The consumption of celery is increasingly popular due to its vitamin and nutrient content and is especially beneficial for the suppression of inflammation, which is associated with multiple diseases [1]. Among the various celery parts, especially the leaves and stems, differences in chemical compositions were previously noted [2], which may have implications for their anti-inflammatory properties. ...
Article
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The present work demonstrated and compared the anti-inflammatory effects of celery leaf (CLE) and stem (CSE) extracts. LC-MS-based metabolomics were an effective approach to achieve the biomarker identification and pathway elucidation associated with the reduction in inflammatory responses. The celery extracts suppressed LPS-induced NO production in RAW 264.7 cells, and CLE was five times more effective than CSE. Distinct differences were revealed between the control and celery-treated samples among the 24 characteristic metabolites that were identified. In celery-treated LPS cells, reversals of intracellular (citrulline, proline, creatine) and extracellular (citrulline, lysine) metabolites revealed that the therapeutic outcomes were closely linked to arginine metabolism. Reversals of metabolites when treated with CLE (aspartate, proline) indicated targeted effects on the TCA and urea cycles, while, in the case of CSE (histidine, glucose), the glycolysis and the pentose phosphate pathways were implicated. Subsequently, apigenin and bergapten in CLE were identified as potential biomarkers mediating the anti-inflammatory response.
... Common herbal remedies for the treatment of T2DM among Latinx individuals include prickly pear cactus, aloe vera, celery, and chayote [69]. The efficacy of these herbal remedies has been shown, but with uncertain implications for clinical practice; for example, while prickly pear cactus has been shown to reduce serum glucose and insulin levels, likely due to its high fiber contents and hypoglycemic properties [70], aloe vera has shown to slightly improve glycemic control, but with great heterogeneity across studies [71], substances like celery have mostly shown promise for hyperglycemia control in rat models [72]. One study found that while nearly 70% of Latinx patients used herbal remedies, a majority reported that they did not disclose their use of herbal remedies to providers [69]. ...
Article
Type 2 diabetes mellitus (T2DM) affects a large number of the American population. When compared to their representation in the general American population, a disproportionate number of Latinx individuals are affected. Within the Latinx American population, T2DM prevalence rates vary among individuals based on their country of origin. Deaths from T2DM among Latinx American population are also more compared to other ethnicities. This disparity underlines the importance of understanding the cultural considerations of T2DM disease presentation and management in Latinx communities, including risk factors, socioeconomic variables, and other social determinants of health such as access to care. There are various modifiable and non-modifiable risk factors for the development of T2DM, regardless of race. Staple foods in the diet of Latinx American communities, such as tortillas, rice, and beans, can cause spikes in blood sugar levels and can lead to obesity, which predisposes patients to develop T2DM. Latinx American populations suffer from lower access to healthcare than the general population due to many reasons, including language proficiency, immigration status, socioeconomic status, and level of acculturation. This study utilized the format of a commentary, while incorporating elements of a scoping review for data collection, to further explore these disparities and their impact on these populations. Understanding the cultural beliefs of Latinx individuals and how these beliefs contribute to the perceived development of T2DM is essential to properly treat these unique populations. Despite high rates of T2DM affecting Latinx individuals, non-adherence to prescribed diabetes medications is high among these populations. Interventions in the form of culturally tailored preventative education, in addition to active T2DM management, are necessary to combat the toll of this disease on Latinx Americans. Generic interventional techniques and methods should be replaced entirely by those that acknowledge, highlight, and utilize the sociocultural characteristics of Latinx Americans.
... Recent studies have indicated a broad spectrum of pharmacological activities of anise, such as antibacterial (25), antidiabetic, and hypolipidemic (26) effects. Celery has been shown to effectively prevent cardiovascular diseases, lower blood pressure, and strengthen the heart (27). ...
Article
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Background: Polycystic ovary syndrome (PCOS) is a complex endocrine disorder associated with irregular menstrual cycles, hyperandrogenism, obesity, and reduced fertility. Objectives: The present study aimed to formulate herbal syrup based on Iranian traditional medicine (ITM) and evaluate its effect on the letrozole-induced PCOS model in female rats. Methods: The herbal syrup contains anise, fennel, and celery seed extracts. Five different formulations were made with different percentages of additive components. Quality control and stability tests were performed on the selected formulation. During the in vivo step, 6 groups of rats were evaluated: The control group (received carboxymethyl cellulose 1% as a vehicle) and the other 5 groups (received letrozole 1 mg/kg orally for 21 days). During 21 days, daily vaginal smears were examined to detect irregularities of the estrous cycle. After induction of PCOS, rats were orally administered with herbal syrup (1, 2, 4 mL/kg) or metformin (200 mg/kg) for 28 days. Moreover, body and ovarian weights, serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol, progesterone, and testosterone were measured. Finally, ovarian tissues were isolated for histological examination. Results: The best formulation of the syrup contained the plant extract (totally 10%), sugar (50%), sodium benzoate (0.1%), and potassium sorbate (0.1%). Body weight was significantly increased in all groups compared to the control group, and after treatment, a significant weight reduction was seen in the metformin and 1-mL/kg dose group. Following PCOS induction, ovary weight was significantly increased, while after treatment, it showed a significant decrease. After 21 days of letrozole administration, induction of PCOS was confirmed by the irregularities in estrous cycles and an increase in testosterone and LH levels. After treatments with the syrup, LH levels significantly decreased in all groups (P < 0.05), and serum testosterone and FSH levels significantly decreased in the 2-mL/kg dose group compared to the PCOS group (P < 0.05). Estradiol and progesterone levels significantly increased in the treatment groups in a dose-dependent manner. Histological studies of metformin and herbal syrup groups exhibited normal follicular development with fewer and smaller cystic follicles compared to the PCOS group. Conclusions: The herbal syrup made from anise, fennel, and celery seed extracts improved serum levels of sex hormones, recovered the ovarian morphology in PCOS-induced rats, and can be a good candidate for further clinical trials.
... Celery is also used as a spice and its extracts have been used in herbal medicine. It has a possible gonadotropic effect -androgenic, a relaxing effect on the myometrium, an increased effect on libido, but no effect on lactation is expressed (Hedayati et al. 2019). ...
Article
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Introduction : Fibrocystic breast disease, commonly called fibrocystic breasts or fibrocystic change, is a benign (noncancerous) condition, which is the most common pathology in women of reproductive age. Treatment of fibrocystic breast disease and concomitant pathologies can involve using herbs. Materials and Methods : To make an analysis of literary sources on the development of fibrocystic breast disease in the pathogenesis of diseases of the female reproductive system (clinical human (75%) and animal studies (25%)) were published in the period of 2017–2021. Results and discussion : The diversity of plants in the world is a promising ground for therapeutic improvisation, allowing for an individual approach to each patient, but, most importantly, creates possibilities for maneuvering in the event of ineffectiveness of any means. In some situations, herbal medicine is not only possible or permissible, but strictly mandatory, and is essentially the only effective therapeutic method, which is relatively safe provided the correct selection of combinations and control by a doctor who applies a certain method of phytotherapy, especially given a duration of treatment. The need for a deeper study is long overdue for the pharmacological capabilities of various plant raw materials in the treatment of not only this pathology, but others as well. Conclusion : The development of phytotherapy should be based primarily on scientific developments, but this area can not be considered the prerogative of only phytotherapists, as herbal medicines should be in the arsenal of doctors of all specialties.
... At the same time, celery contains a vast array of secondary metabolites that with properties of anti-oxidative damage, antiin ammation, and anti-diabetes [7]. Due to global warming and irregular rain fall, both celery production and quality are negatively affected by drought stress [8]. ...
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Background Water shortage caused by global warming seriously affects the yield and quality of vegetable crop. β-carotene, the lipid-soluble natural product with important pharmacological value, is abundant in celery. Transcription factor MYB family extensively disperses in plants and plays regulatory roles in carotenoid metabolism and water scarcity response. Results Here, AgMYB5 gene encoding 196 amino acids was amplified from celery cv. ‘Jinnanshiqin’. In celery, the expression of AgMYB5 exhibited transactivation activity, tissue specificity, and drought-condition responsiveness. Further analysis proved that ectopic expression of the AgMYB5 increased β-carotene content and promoted drought resistance in transgenic Arabidopsis thaliana. Moreover, AgMYB5 expression promoted β-carotene biosynthesis by triggering the expression of AtCRTISO and AtLCYB, which in turn increased antioxidant enzyme activities, and led to the decreased contents of H2O2 and MDA, and the inhibition of O²⁻ generation. Meanwhile, β-carotene accumulation promoted endogenous ABA biosynthesis of the transgenic Arabidopsis plants overexpression AgMYB5 gene, which resulted in ABA-induced stomatal closing and delayed water loss rate. In addition, ectopic expression of AgMYB5 increased expression levels of AtERD1, AtP5CS1, AtRD22, and AtRD29. Conclusions The findings indicated that AgMYB5 up-regulated β-carotene biosynthesis and drought resistance of Arabidopsis.
... As a result, the most active components of celery (A. graveolens) show hypolipidemic, antidiabetic and hypotensive properties [26]. Due to the rich and varied content of phenolic compounds, minerals and vitamins, celery has antioxidant and antibacterial properties, as well as a number of other prohealth activities [27]. ...
Article
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Introduction: As overweight and obesity have become a disease of civilization, more and more people try to accelerate weight reduction in various ways. One of the methods used is the use of dietary supplements. Methods: 30 overweight or obese people took part in the study. At the beginning and at the end of the study, each participant was measured and weighed on a professional Tanita DC-360 body composition analyzer. The age in both groups was similar - the average was about 37 years old, height and weight in the group of men was greater. The subjects used the dietary supplement for 6 weeks. At that time, they did not take any other dietary supplements, followed the diet as before, did not consume caffeine and did not undertake any physical activity at that time. Results: There were significant differences in the results between men and women for the field of physical. Women had a significantly higher result, which means that they were more susceptible to the effects of supplements. Individuals who achieved a weight loss score significantly higher for the field of physical. It also turned out that although weight loss and the absence of gastrointestinal problems during supplementation were observed in both groups, they occurred in a greater amount in women than in men, and the differences these were statistically significant. Higher effectiveness among women may be the result of differences in the functioning of the endocrine system, although it is certainly worth taking a closer look at this issue. 40% of respondents did not notice any weight loss while taking supplementation. Conclusions: Plant-based supplements reduce body weight and metabolism, and may also alleviate gastrointestinal discomfort. In addition, they improve digestion in general, increase vitality and, to a small extent, may contribute to the improvement of the immune system.
Article
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In the present work, the antihypertensive effects of celery seed extract (Apium graveolens) with active ingredients, such as 3‐n‐butylphthalide, were studied as a drug supplement in the treatment of hypertension. This study was a randomized, triple‐blind, placebo‐controlled, cross‐over clinical trial. Fifty‐two patients were divided into two groups (celery and placebo) and completed the two‐step clinical trial. Four celery seed extract capsules (totally 1.34 g per day) or 4 placebo capsules per day were administered to the patients during a 4‐week clinical trial. The blood pressure was assessed using a 24‐hr ambulatory blood pressure monitoring method. In celery group, systolic blood pressure changed from 141.2 ± 5.91 to 130.0 ± 4.38 mmHg (p < .001) while diastolic blood pressure changed from 92.2 ± 5.74 to 84.2 ± 4.87 mmHg (p < .001). Moreover, the mean arterial blood pressure changed from 108.5 ± 5.76 to 99.5 ± 4.66 mmHg (p < .001), and pulse pressure decreased from 49.0 ± 6.21 to 45.8 ± 6.01 mmHg (p < .01). However, no significant changes were observed in placebo group in terms of the above‐mentioned parameters (p > .05). Furthermore, no significant side effect was reported in the celery group, compared to the placebo group (p > .05). The results were promising and indicated the therapeutic effects of celery seed extract as a supplement in the management of hypertension.
Article
For the first time, this research introduces a new analytical method specialized for the analysis of some pesticides in celery and tomato juices based on MIL-88B(Fe) which is matrix-effectless (relative recoveries in the range of 95-103 %) and highly linear (r²=0.998-0.999). Achieving low limits of detection (0.24-0.53 µg L⁻¹) and quantification (0.79-1.75 µg L⁻¹) in this method is also amazing. Moreover, the wide linearity of the method (1.75-1000 µg L⁻¹), high enrichment factors (277-379), and reasonable extraction recoveries (55-75%) are the highlights of the developed method. Initially, the sorbent was synthesized using an autoclave-based approach. Then the resulted sorbent was subjected to Fourier transform infrared spectrophotometry, X-ray diffraction, energy-dispersive X-ray, scanning electron microscopy, and nitrogen adsorption/desorption analyses to infer the accuracy of the obtained phase. Subsequently, it was subjected to the studied juices for the analysis of the surveyed pesticides. In dispersive micro solid phase extraction, which is for the adsorption of the analytes on the sorbent and performing the cleanup step to reduce the matrix effect, the sorbent was dispersed in the solution of analytes and after the accomplishment of the adsorption, the analytes were desorbed using acetonitrile. In dispersive liquid-liquid microextraction, which was done for the aim of preconcentration, the acetonitrile phase (eluate) was mixed with µL-level of carbon tetrachloride and injected into deionized water. After centrifugation an aliquot of it was injected into a gas chromatograph equipped with a flame ionization detector. According to the gas chromatography-mass spectrometry analyses, haloxyfop-R-methyl with a concentration of 23±2 µg L⁻¹ was detected in tomato juice. It is confessed that confident safety assessment analysis of celery and tomato juices is available using the introduced highly-reliable analytical method.
Preprint
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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 1.34g 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 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.
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Disturbances in the prooxidant–antioxidant balance can occur in metabolic syndrome. Here, we present a protocol for the setup of a clinical trial of metabolic syndrome patients treated with berberine, a dietary phytochemical of the Berberis vulgaris plant, or placebo. The main aim is to obtain a quick and real-time assessment on the overall redox state based on measurement of the prooxidant–antioxidant balance.KeywordsMetabolic syndromeProoxidant–antioxidant balanceReactive oxygen speciesNatural productsBarberry
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Apium graveolens (celery) has various roles both in the food and medicine sectors. It grows very well in the tropical and subtropical areas of Africa and Asia, including Indonesia. This Apiaceae member contains a number of phytoconstituents, and geographical origin is known to significantly determine the type and concentration of phytochemicals in plant material. This study was carried out to validate and develop thin layer chromatography (TLC)-based fingerprinting combined with chemometrics, i.e., Principal Component Analysis (PCA) and Cluster Analysis (CA), to evaluate the quality of celery harvested from thirteen different geographical origins in Indonesia. The mobile phase was first optimized with a simplex axial design, resulting in 2-propanol, toluene, and dichloromethane (1:6:1) as the optimum mobile phase for a stable and precise TLC system in the celery sample analysis. When analyzed with chemometrics, the TLC-fingerprints could discriminate celeries from various origins. The PCA score plot of the first two principal components (PCs) and CA clearly distinguished the samples’ properties and classified them into four clusters. Samples grouped into one cluster were concluded to have comparable quality, while those in different clusters had different qualities.
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The archipelagic country of Indonesia is inhabited by 300 ethnic groups, including the indigenous people of Tengger. Based on the reported list of medicinal plants used by the Tengger community, we have reviewed each of them for their phytochemical constituents and pharmacological activities. Out of a total of 41 medicinal plants used by the Tengerrese people, 33 species were studied for their phytochemical and pharmacological properties. More than 554 phytochemicals with diverse molecular structures belonging to different chemical classes including flavonoids, terpenoids, saponins and volatiles were identified from these studied 34 medicinal plants. Many of these medicinal plants and their compounds have been tested for various pharmacological activities including anti-inflammatory, antimicrobial, wound healing, headache, antimalarial and hypertension. Five popularly used medicinal plants by the healers were Garcinia mangostana, Apium graveolens, Cayratia clematidea, Drymocallis arguta and Elaeocarpus longifolius. Only A. graviolens were previously studied, with the outcomes supporting the pharmacological claims to treat hypertension. Few unexplored medicinal plants are Physalis lagascae, Piper amplum, Rosa tomentosa and Tagetes tenuifolia, and they present great potential for biodiscovery and drug lead identification.
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Obesity is one of the world's largest health problems, and 3-N-butylphthalide (NBP), a bioactive compound in celery, has been used in dieting and weight management programs. In this study, NBP prevented high-fat-diet-induced weight gain, reduced the food efficiency ratio, altered the blood biochemical profile, and reduced the obesity-related index. NBP reduced adiposity, white fat depots, liver weight, and hepatic steatosis in obese mice. NBP ameliorated the diabetic state by decreasing glucose levels and improving glucose and insulin tolerance. NBP increased uncoupling protein-1 expression in white adipose tissue and upregulated thermogenesis by enhancing mitochondrial respiration. NBP inhibited white adipocyte development by prohibiting lipid accumulation in human adipose-derived stem cells. NBP increased free fatty acid uptake and the oxygen consumption rate in beige adipocytes. Our results suggest that NBP could be used as functional natural supplement against obesity and its associated disorders.
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Celery (Apium graveolens Linn, Family: Apiaceae) is a common edible herb used as a spice in the traditional medicine of several nations since time immemorial. The whole plant is extensively used in cooking as soups and salads. A. graveolens has various pharmacological properties such as anticancer, anti-obesity, anti-hepatotoxic, and antihypertensive agents. Hence, it is of interest to document the in vitro cytotoxic, antioxidant, and antimicrobial activity of A. graveolens. The plants were collected in the local market, shade dried, and different parts of the plants were extracted with 70% ethanol using a cold maceration process. Antioxidant tests were performed based on the various radical scavenging methods. Antimicrobial activity and MIC were completed using the respective cup-plate and two-fold serial dilution method. In vitro cytotoxic studies were achieved by the MTT; Sulphorhodamine B assayed total cell protein content. DLA and ESC cells determined the short-term toxicity. The leaf extract exhibited significant antioxidant properties against NO, DPPH, ABTS, LPO, and HPO methods. Thus, potential inhibition against Gram-positive, Gram-negative, and fungal strains within the MIC ranges of 250-500 μg/ml was observed. All the extracts of the plant presented in the study revealed greater cytotoxicity effects against five respective cancer cell lines, L6, Vero, BRL 3A, A-549, L929, and L-929 with the ranging of 443-168.5 μg/ml. Thus, we show that A. graveolens possess a potential cytotoxic, antioxidant, and antimicrobial activity.
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Celery (Apium graveolens L. var dulce) is a widely cultivated vegetable which is popularly consumed due to its nutrient content and contains bioactive metabolites with positive effects on human physiology. In this study, ¹H NMR spectroscopy coupled with multivariate statistical analyses was used to distinguish celery stem and leaf samples from different geographical origins. Principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA) were employed to investigate the differences between celery extracts from three geographical origins: Australia, Taiwan and China. Sugars, amino acids and organic acids were found to contribute significantly to the differentiation between origins, with mannitol identified as an important discriminating metabolite. It was demonstrated that NMR-based metabolomics is an effective approach for establishing reliable metabolomic fingerprints and profiles, enabling the identification of metabolite biomarkers for the possible discrimination of geographical origin.
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The impact of sumac supplementation was not previously examined in patients with metabolic syndrome (MetS). So, we investigated the influence of sumac supplementation on insulin resistance, inflammation, oxidative stress, and antioxidant markers in adults with MetS. The current study was a single‐center, triple‐blind, randomized, placebo‐controlled crossover clinical trial that was conducted on 47 patients with MetS. Participants were randomly divided into two groups of intervention and control in the first phase. They received capsules containing 500 mg sumac or placebo (lactose) twice a day, after lunch and dinner, for 6 weeks. After a 2‐week washout period, the subjects crossed over to the alternate arm. In both arms, fasting venous blood samples were obtained at baseline and at the sixth week of the intervention to determine glycemic status, high‐sensitivity C‐reactive protein (hs‐CRP), malondialdehyde (MDA), total antioxidant capacity (TAC), and antioxidant enzymes activity. The mean (±SD) age, weight, and body mass index of participants were respectively 58.7 ± 5.83 years, 79.9 ± 14.35 kg, and 31.6 ± 4.6 kg/m2; 80.9% of subjects were females (n = 38). Based on per‐protocol analyses, the serum fasting insulin concentration was unexpectedly decreased in the placebo group (change in sumac vs. control: 0.95 ± 3.9 vs. −1.17 ± 3.9 mU/L; p = 0.04). Sumac supplementation, compared to control, has marginally enhanced catalase activity (change in sumac vs. control: 2.91 ± 9.5 vs. −1.07 ± 9.1 nmol/min/ml; p = 0.06). This supplementation has also increased serum TAC and the activity of superoxide dismutase, but these changes were not significant. This intervention did not affect other insulin resistance, inflammatory, or oxidative stress markers. We found that 1 g/day sumac consumption for 6 weeks, as adjuvant therapy, could improve the antioxidant defense system in adults with MetS but did not affect insulin resistance, inflammation, or oxidative stress.
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Background:To investigate the effect of Apium graveolen L. (Celery seeds) on blood glucose and insulin concentrations in streptozotocin (STZ) induced diabetic rats. Methods: Forty Sprague Dawely rats weighing from 180 to 250 grams were randomly divided into four experimental groupsA,B,C &D, each containing ten (10) rats. Diabetes was induced by intraperitoneal administration of STZ (60mg/kg) in groups B,C&D,while group A served as normal control. The experimental animals became diabetic within 48 to 72 hours after administration of STZ.,Group B rats were taken as diabetic control. Alcoholic extract of Celery seeds, the test drug was administered (400mg/kg) orally to experimental gruop,C,while group D received standard drug glibenclamide.induced diabetic rats for six weeks. Normal control groupA& diabetic control B received only normal saline solution orally. Blood samples were collected from experimental groups after 43 days,24 hours of the last dose. ANOVA and Tukey HSD (Honestly Significant Difference) test applied to all groups. Results: The results show Celery seeds extract treatment caused a statistically significant decrease in the elevated serum glucose levels and increase in the serum insulin concentrations in test group C as compared to group B . Conclusion: Findings of present study provide evidence for traditional use of apium. graveolen in the control of diabetes. Key Words: Streptozotocin , Apium graveolen .
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Objectives: To analyze the effect of celery leaf extract on blood glucose and plasma insulin levels in elderly pre-diabetics. Methods: This study was conducted between March and November 2014 at the Faculty of Medicine, Syiah Kuala University, Banda Aceh, Indonesia. A quasi-experimental pretest-posttest with a control group was conducted with elderly pre-diabetic volunteers. The subjects included 16 elderly pre-diabetics older than 60 (6 males and 10 females). The subjects were randomly divided into 2 groups: a control group (placebo-treated) and a treatment group (celery-treated). The treatment consisted of celery leaf extract capsules at the dose of 250 mg, 3 times per day (morning, afternoon and evening), 30 minutes before a meal, for 12 days. Data analysis was performed using the t-test (p less than 0.05). Results: There was a significant decrease in pre-prandial plasma glucose levels (p=0.01) and post-prandial plasma glucose levels (p=0.00), but no significant increase in plasma insulin levels (p=0.15) after celery leaf treatment in elderly pre-diabetics. Conclusion: Celery was effective at reducing blood glucose levels, but there was a lack of association between blood glucose levels and plasma insulin levels in elderly pre-diabetics.
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Luteolin is a falconoid compound that is present in various types of plants and possesses remarkable potential as a chemopreventive agent. However, the poor aqueous solubility of luteolin limits its clinical application. In the present study, an approach towards chemoprevention was explored using liposomes to deliver luteolin, and the antitumor efficacy was investigated in colorectal carcinoma. The present findings demonstrated that luteolin was efficiently encapsulated into liposomes with an encapsulation efficiency as high as 90%. The particle size of the liposomal luteolin (Lipo‑Lut) and ζ‑potential were optimized. In vitro studies demonstrated that, Lipo‑Lut had a significant inhibitory effect on the growth on the CT26 colorectal carcinoma cell line compared with free luteolin (Free‑Lut). The in vivo study indicated that Lipo‑Lut could achieve superior antitumor effects against CT26 tumor compared with luteolin alone. The present results suggested that liposome delivery of luteolin improved solubility, bioavailability and may have potential applications in chemoprevention in clinical settings.
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This work was carried out to exploit the feasibility of microemulsion combining apigenin/hydroxypropyl-β-cyclodextrin (API/HP-β-CD) complex as the carrier for improving the solubility of API, a bioactive flavonoid with various pharmacological activities. The API/HP-β-CD complex in solid state was prepared by solvent-freeze-drying method and characterized by FT-IR, PXRD and 1H NMR. To further increase the solubility of API, the complex of HP-β-CD with food-grade cosurfactant-free microemulsion was constructed. The aqueous solubility of API significantly increases in the HP-β-CD/Microemulsion complex, via solubilizing dominantly into the “palisade” layer, minor outer phase and inner core. The HP-β-CD modified microemulsion improves the cumulative percentage of API released. Moreover, API loaded in microemulsions with HP-β-CD had a higher antioxidant activity than that without HP-β-CD.
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Celery (Apium graveolens L., Apiaceae) is one of the popular aromatic vegetables and part of the daily diet around the world. In this study, aqueous-ethanolic and hexane extracts of celery seed were prepared and the amount of n-butylphthalide, as an active component, was determined in each extract. Then the effects of hexanic extract on systolic, diastolic, mean arterial blood pressure and heart rate were evaluated in an invasive rat model. The vasodilatory effect and possible mechanisms of above mentioned extracts on aorta ring were also measured. High performance liquid chromatography analysis revealed that hexanic extract contains significantly higher amounts of n-butylphthalide, compared to aqueous-ethanolic extract. The results indicated that hexanic extract significantly decreased the systolic, diastolic, mean arterial blood pressure and heart rate in normotensive and hypertensive rats. Our data revealed that celery seed extract exerts its hypotensive effects through its bradycardic and vasodilatory properties. Moreover, the active components in celery seed extracts could induce their vasodilatory properties through Ca2+ channel blocking activity in endothelial and non-endothelial pathways and particularly by interference with the extra or intracellular calcium.
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PPARγ is the molecular target of the thiazolidinedione drugs to treat type II diabetes. However, TZD drugs have some side effects including cardiovascular failure, liver toxicity, bone fractures and potential carcinogenesis, which have greatly limited their clinical use. Here, we find apigenin, a flavonoid molecule abundant in various fruits and vegetables, can control macrophage fate to inhibit inflammation and metabolic syndrome without causing some side effects as TZD drugs. Further study indicates that apigenin can target PPARγ with a range of beneficial effects and may represent a lead compound for developing new therapies against metabolic disorders. PPARγ has emerged as a master regulator of macrophage polarization and is the molecular target of the thiazolidinedione drugs. Here we show that apigenin binds and activates PPARγ by acting as a modulator. Activation of PPARγ by apigenin blocks p65 translocation into nuclei through inhibition of p65/PPARγ complex translocation into nuclei, thereby decreasing NF-κB activation and favoringM2 macrophage polarization. In HFD and ob/ob mice, apigenin significantly reverses M1 macrophage into M2 and reduces the infiltration of inflammatory cells in liver and adipose tissues, as well as decreases the levels of pro-inflammatory cytokines, thereby alleviating inflammation. Strikingly, apigenin reduces liver and muscular steatosis, decreases the levels of ALT, AST, TC and TG, improving glucose resistance obviously. Unlike rosiglitazone, apigenin does not cause significant weight gain, osteoporosis etal. Our findings identify apigenin as a modulator of PPARγ and a potential lead compound for treatment of metabolic disorders.
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Objectives . Preliminary researches showed that luteolin was used to treat hypertension. However, it is still unclear whether luteolin has effect on the hypertensive complication such as vascular remodeling. The present study was designed to investigate the effect of luteolin on the hypertensive vascular remodeling and its molecular mechanism. Method and Results . We evaluated the effect of luteolin on aorta thickening of hypertension in spontaneous hypertensive rats (SHRs) and found that luteolin could significantly decrease the blood pressure and media thickness of aorta in vivo . Luteolin could inhibit angiotensin II- (Ang II-) induced proliferation and migration of vascular smooth muscle cells (VSMCs). Dichlorofluorescein diacetate (DCFH-DA) staining result showed that luteolin reduced Ang II-stimulated ROS production in VSMCs. Furthermore, western blot and gelatin zymography results showed that luteolin treatment leaded to a decrease in ERK1/2, p-ERK1/2, p-p38, MMP2, and proliferating cell nuclear antigen (PCNA) protein level. Conclusion . These data support that luteolin can ameliorate hypertensive vascular remodeling by inhibiting the proliferation and migration of Ang II-induced VSMCs. Its mechanism is mediated by the regulation of MAPK signaling pathway and the production of ROS.
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The potent of n-butanol extract of celery (Apium graveolens) seed in ameliorating the lipid peroxidation and antioxidant status were investigated in streptozotocin-induced diabetic rats. Thirty two mature male rats were assigned to four groups, non-diabetic control and three diabetic groups. Diabetes was induced by single injection with streptozotocin (60 mg/kg b.w., i.p.). Rats ≥ 200 mg/dl of blood glucose were used as diabetic. Diabetic groups (D, B, and I) were drenched with drinking water, n-butanol extract (60 mg/kg, b.w.), or injected with insulin (4 IU/animal), respectively for 21 days. On day 22, body weight gain was registered and male rats were sacrificed. Blood and liver subcellular fluid was obtained to assess blood glucose level and subcellular activity of Alanine aminotranferease (ALT), Aspartate aminotransferase (AST), catalase, Super oxide dismutase (SOD), Glutathione (GSH)-transferase and-reductase, and assessment of Malondialdehyde (MDA) and glutathione concentrations. Diabetic rats (D) showed marked increased blood glucose, decreased weight gain, increased activity of ALT, SOD, CAT, GSH-transferase, decreased GSH-reductase and normal AST. N-butanol extract of celery seed (B) or insulin (I) therapy moderated blood glucose within normal range, enhanced body weight gain and normalized the activities of all antioxidant enzymes. In conclusion, n-butanol extract of celery seed have potent role in ameliorating stressful complications accompanied by diabetes mellitus.
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Background and aims: Medicinal plants are used in traditional medicine to treat many diseases. Celery (Apium graveolens) is a native medicinal plant to Europe. This plant has a very wide range of usage and cultivation. The wild type was found in countries such as Algeria, the Caucasus, Iran, India and America. However, due to increasing value and the special place of the plant in the new pharmaceutical industry, it is necessary to recognize the potential in the field of manufacturing and processing. This article presents morphological characteristics, vegetation compounds and evaluation of the therapeutic properties of this valuable medicinal plant. Methods: The information of this review article have been gathered from accessible journals in databases such as Web of Science, PubMed, Scopus, Embase, SID and Iran Medex. The search terms were "Celery" and "Apium graveolens" that searched in Persian and English books on medicinal plants and traditional medicine, as well as reputable sites mentioned. Results: Various studies have shown that Celery plays a role in prevention of cardiovascular disease, lowering blood glucose and serum lipid, decrease blood pressure and strengthener the heart. This herb has anti- bacterial, anti-fungal and anti- inflammatory effects. Also, a powerful antioxidant property has been attributed to compounds such as apigenin, apiein, vitamins A and C. Conclusion: Celery widely used in pharmaceutical, food and ornamental industries, that causes its significant commercial value. Various combinations and numerous medicinal properties of seeds, leaves and stems, cause the need further and more research about the other useful and unknown properties of celery.
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Hypertension is one of the most common diseases of the modern era. This study evaluates the effect of hydro-alcoholic celery leaf extract onsystolic blood pressure (SBP), heart rate (HR) and lipid profile in animals' model of hypertension induced by fructose. Sprague Dawley rats were divided into five groups: 1) control group (free access to tap drinking water), 2) group receiving 200mg/kg celery leaf extract, 3) group receiving fructose 10%, and 4,5) receiving fructose and 100mg/kg or 200mg/kg of extract (n=8). In all groups, before and during the test period, SBP and HR were measured by Power lab system. Lipid profiles were determined by auto analysis. Repeated measurement and one way ANOVA were used for data analysis. P<0.05 was considered statistically significant. The SBP in the fructose group significantly increased compared to control group (P<0.01). SBP, in groups receiving fructose+100mg/kg extract, fructose and receiving 200mg/kg extract, and receiving 200mg/kg of extract, compared to fructose group significantly decreased. Heart rate in any of these groups showed no significant difference. Cholesterol, triglyceride, LDL and VLDL in the fructose group significantly increased; however, these effects significantly decreased in the recipient extract groups. HDL levels in the fructose group showed no difference while in the groups receiving the extract they significantly increased. Celery leaf extract reduces SBP, cholesterol, triglyceride, LDL and VLDL in animal model of fructose-induced hypertension. In conclusion, celery leaf extract with its blood pressure and lipid lowering effects, can be considered as an antihypertensive agent in chronic treatment of elevated SBP.
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The flavonoid luteolin has various pharmacological activities. However, only few studies exist on the in vivo mechanism underlying the actions of luteolin in hepatic steatosis and obesity. The aim of the current study was to elucidate the action of luteolin on obesity and its comorbidity by analyzing its transcriptional and metabolic responses, in particular the luteolin-mediated cross-talk between liver and adipose tissue in diet-induced obese mice. C57BL/6J mice were fed a normal, high-fat, and high-fat + 0.005% (w/w) luteolin diet for 16 weeks. In high-fat-fed mice, luteolin improved hepatic steatosis by suppressing hepatic lipogenesis and lipid absorption. In adipose tissue, luteolin increased PPARγ protein expression to attenuate hepatic lipotoxicity, which may be linked to the improvement circulating fatty acid levels by enhancing fatty acid uptake genes and lipogenic genes and proteins in adipose tissue. Interestingly, luteolin also up-regulated the expression of genes controlling lipolysis and the tricarboxylic acid (TCA) cycle prior to LD formation, thereby reducing adiposity. Moreover, luteolin improved hepatic insulin sensitivity by suppressing SREBP1 expression that modulates Irs2 expression through its negative feedback and gluconeogenesis. Luteolin ameliorates the deleterious effects of diet-induced obesity and its comorbidity via the interplay between liver and adipose tissue. © 2014 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.
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Background and Objectives: Decrease in serum lipids by dietary or pharmacological intervention prevents progression of atherosclerosis and cardiovascular diseases. The aim of this study was to investigate the effects of hydro-alcoholic extract of celery (Apium graveolens) on lipid profile of rats fed a high fat diet. Materials and Methods: In this experimental study, 24 Wistar rats were randomly allocated into four groups. The control group received saline with high-fat diet and treatment groups did hydroalcoholic extract at doses of 100 and 200 mg/kg/BW with high fat diet by gavage over a 30-day period. Afterwards, the serum levels of lipids (triglyceride, cholesterol, LDL, HDL, and VLDL) were determined. The data were analyzed by one-way ANOVA test using SPSS15 software. Results: Hydro-alcoholic extract of celery significantly decreased cholesterol and LDL in treatment groups compared with control group (P≤0.05); but had no significant effects in serum levels of triglyceride, HDL, and VLDL (P>0.05). Conclusions: Probably celery consumption due to the antioxidant properties leads to appropriate changes in serum lipid profiles and reduces them. Therefore it could be useful in the treatment of hyperlipidemia.
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Obesity and hypertension are important risk factors for cardiovascular diseases. The present study investigates the effect of d-limonene on blood pressure, plasma lipids, circulatory lipid peroxidation byproducts and antioxidants status in young male Wistar rats fed a high fat diet (HFD; 42.2% beef tallow) together with Nω-nitro-L-arginine methyl ester (L-NAME; 80mg/L in drinking water) for 8 weeks and subsequently with 2% d-limonene for the final 4 weeks. HFD fed rats showed increased systolic blood pressure, increased concentrations of circulatory lipids and lipid peroxidation byproducts, increased activities of circulatory enzymic antioxidant and decreased concentrations of nonenzymic antioxidant, L-NAME supplementation further increased systolic blood pressure, lipid concentrations, lipid peroxidation byproducts and enzymic antioxidant and decreased nonenzymic antioxidant. Supplementation of 2% d-limonene to HFD and L-NAME treated rats decreased the blood pressure and reverses the changes in lipids, lipid peroxidation byproducts and antioxidant. d-limonene should be considered as a promising lipid lowering agent and antioxidant activities with blood pressure-lowering properties.
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Elevated uric acid causes direct injury to pancreatic β-cells. In this study, we examined the effects of luteolin, an important antioxidant, on uric acid-induced β-cell dysfunction. We first evaluated the effect of luteolin on nitric oxide (NO) formation in uric acid-stimulated Min6 cells using the Griess method. Next, we performed transient transfection and reporter assays to measure transcriptional activity of nuclear factor (NF)-κB. Western blotting assays were also performed to assess the effect of luteolin on the expression of MafA and inducible NO synthase (iNOS) in uric acid-treated cells. Finally, we evaluated the effect of luteolin on uric acid-induced inhibition of glucose-stimulated insulin secretion (GSIS) in Min6 cells and freshly isolated mouse pancreatic islets. We found that luteolin significantly inhibited uric acid-induced NO production, which was well correlated with reduced expression of iNOS mRNA and protein. Furthermore, decreased activity of NF-κB was implicated in inhibition by luteolin of increased iNOS expression induced by uric acid. Besides, luteolin significantly increased MafA expression in Min6 cells exposed to uric acid, which was reversed by overexpression of iNOS. Moreover, luteolin prevented uric acid-induced inhibition of GSIS in both Min6 cells and mouse islets. In conclusion, luteolin protects pancreatic β-cells from uric acid-induced dysfunction and may confer benefit on the protection of pancreatic β-cells in hyperuricemia-associated diabetes.
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Infertility is one of the health problems that will have a negative impact on the individual, social and economic and is seen in 10-15% of couples (1). About 40 % of the issues involved with infertility are due to the man. Male sperm cells count nowadays has decreased dramatically in comparison with those who lived 50 years ago (2). Causes of infertility in men are included: oligozoospermia, immaturity of sperm, sperm deformity, and sperm non-motility. Spermatogenesis takes place within the testes under control of testosterone secreted by the testes and secretory activity of the testes controlled by the hypothalamic-pituitary-testicle axis. Due to adverse effects and side effects of chemical drugs today, the use of traditional medicine, especially herbal therapy is taken into consideration. In traditional medicine, it has been pointed to therapeutic properties of celery. Celery has anti-fungal, anti-bacterial, and anti-cancer properties (3). Also this plant is an appetite stimulant and sexual booster (4). Previous studies have shown that sperm cells are largely vulnerable to oxidative stress but celery is rich in antioxidant compounds such as flavonoids (apiin and apigenin), vitamins E and C that can reduce oxidative stress (5, 6). So, in the present study the protective effect of celery was investigated on the cauda epididymal spermatozoa and testis in rat. A total number of 32 male Wistar rats (weighting 170-220 g) were prepared from animal house central of Ahvaz Jundishapur University of Medical Sciences. Animals were maintained in plastic cages with 12/12 h light/dark cycle at 21±2oC. All experimental animals were carried out in accordance with Ahvaz University Ethical Committee. Hydro-alcoholic extract of celery was prepared by maceration method. The rats were divided into four groups of 8 animals each: control, did not receive anything; vehicle, received propylene glycol; experimental groups, and received hydro-alcoholic extract of celery with doses of 100 and 200 (mg/kg) with solvent of propylene glycol by gavage once every 48 hours for twenty days. At the end of 20th day, rats were scarified under ketamine and xylazine anesthesia then the epididymis and testes were carefully separated. The epididymis was used for sperm count and testes were prepared for morphometric and histologic evaluation. Statistical significance of differences were assessed with one-way ANOVA by SPSS for windows (version 15) followed by LSD test. P
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In this study, a novel carbon nanopowder (CNP) drug carrier was developed to improve the oral bioavailability of apigenin (AP). Solid dispersions (SDs) of AP with CNP were prepared, and their in vitro drug release and in vivo performance were evaluated. The physicochemical properties of the formulations were examined by differential scanning calorimetry, X-ray diffraction, and scanning electron microscopy. Drug release profiles showed that AP dissolution from the CNP-AP system (weight ratio, 6:1) after 60 minutes improved by 275% compared with that of pure AP. Moreover, the pharmacokinetic analysis of SD formulations in rats showed that the AP area under the curve0-t value was 1.83 times higher for the CNP-AP system than for pure AP, indicating that its bioavailability was significantly improved. In addition, compared with pure AP, SDs had a significantly higher peak and shorter time to peak. Preliminary intestinal toxicity tests indicated that there was no significant difference in the tissues of the rats treated with the CNP-AP system, rats treated with the CNP alone, and controls. In conclusion, CNP-based SDs could be used for enhancing the bioavailability of poorly water-soluble drugs while also improving drug safety.
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We investigated the hypotriglyceridemic mechanism of action of linalool, an aromatic monoterpene present in teas and fragrant herbs. Reporter gene and time-resolved fluorescence resonance energy transfer assays demonstrated that linalool is a direct ligand of peroxisome proliferator-activated receptor-α (PPARα). Linalool stimulation reduced cellular lipid accumulation regulating PPARα-responsive genes and significantly induced fatty acid oxidation, and its effects were markedly attenuated by silencing PPARα expression. In mice, the oral administration of linalool for 3 weeks reduced plasma triglyceride concentrations in Western diet-fed C57BL/6J mice (31%, P < 0.05) and human apolipoprotein E2 mice (50%, P < 0.05) and regulated hepatic PPARα target genes. However, no such effects were seen in PPARα-deficient mice. Transcriptome profiling revealed that linalool stimulation rewired global gene expression in lipid-loaded hepatocytes and that the effects of 1 mM linalool were comparable to those of 0.1 mM fenofibrate. Metabolomic analysis of the mouse plasma revealed that the global metabolite profiles were significantly distinguishable between linalool-fed mice and controls. Notably, the concentrations of saturated fatty acids were significantly reduced in linalool-fed mice. These findings suggest that the appropriate intake of a natural aromatic compound could exert beneficial metabolic effects by regulating a cellular nutrient sensor.
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Currently available treatments for Parkinson's disease (PD) do not delay or prevent disease development and progression. DL-3-n-butylphthalide (NBP), isolated from Apium graveolens seeds, alleviates oxidative damage and mitochondrial dysfunction. It has been revealed to reduce the loss of dopamine neurons in pre-clinical PD models, and has been approved for the treatment of ischemic stroke patients. The purpose of the present study was to examine whether NBP has the capacity provide a benefit for PD patients and to slow disease progression. A randomized, controlled trial was performed between September 2014 and December 2016. Pairs of patients matched by age, gender and off-medication Unified PD Rating Scale motor subscale (UPDRS-III) scores, were randomly assigned to an NBP treatment group and a control group. All patients continued their originally prescribed medication regimen and those in the NBP group were administered NBP at 200 mg three times daily for 24 weeks. Primary outcome measures were changes in UPDRS-III, including tremor score and non-tremor score, the Pittsburgh sleep quality index (PSQI) and the PD 39-items questionnaire (PDQ) scores. Assessments were completed by blinded evaluators at baseline and 12, 24 and 48 weeks after randomization. All patients were monitored for adverse events (AEs). A total of 103 patients were enrolled in the present study. The NBP group exhibited significantly greater improvements in the non-tremor, PSQI and PDQ-39 scores than the control group, which generally exhibited no improvement. NBP-associated AEs were uncommon and primarily consisted of mild gastrointestinal symptoms. In conclusion, over the 6-month treatment period, NBP was safe and effective for improving the symptoms and impairing the progression of patients with PD (Trial registry number, ChiCTR1800018892).
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Luteolin is an important flavonoid with low water solubility and oral bioavailability properties, which limit its further clinical applications. In the present study, two new cocrystals of luteolin monohydrate with isoniazid and caffeine have been synthesized successfully using liquid assisted grinding method. Solid characterizations including X-ray diffraction, thermal and spectroscopic analysis were carefully performed to identify the two new cocrystals. Temperature-composition phase diagrams for both cocrystals were plotted through differential scanning calorimetry data. The maximum and minimum extreme values of all the compounds on molecular electrostatic potential surfaces that can be converted into hydrogen driving forces were calculated and illustrated. The luteolin-isoniazid cocrystal presents the solubility (112.3 μg mL⁻¹) about three times better than luteolin monohydrate. In the pharmacokinetic analysis, the integrated AUC0-∞ of luteolin-isoniazid and luteolin-caffeine cocrystals performed 2.7 folds and 1.4 folds respectively more enhancements than luteolin monohydrate.
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Ethnopharmacological relevance: Mexico ranks second in the world for obesity prevalence. In Mexico, obese and overweight subjects commonly seek alternative treatments for weight-loss, including the use of herbal products. Aim of the study: The main objective of this study was to evaluate the prevalence of self-medication with herbal products for weight-loss among overweight and obese subjects residing in four states (Guanajuato, San Luis Potosi, State of Mexico, and Mexico City) from central Mexico. In addition, the factors related to self-medication among patients were studied. Materials and methods: A total of 1404 overweight and obese subjects were interviewed. A chi-square test examined associations between socio-demographic and socio-economic information, and self-medication with herbal products for weight-loss. Results: The prevalence of self-medication was 42.9% among the participants who used herbal products for weight-loss. The female gender was the strongest factor (OR: 2.20 (1.75–2.77) associated with self-medication for weight-loss, followed by a low educational level (elementary and middle school) [OR: 1.80 (1.31–2.44)], and a middle-socioeconomic status [OR: 1.75 (1.21–2.52)]. The main herbal products used for weight-loss were based on: i) green tea, Camellia sinensis (12.7% of frequency), ii) aceitilla, Bidens odorata (6.6%), and iii) soybean, Glycine max (5.3%). In addition, 65% of the respondents considered herbal products ineffective for weight-loss after 6 months of use. Conclusion: Due to the high incidence of overweight and obesity in Mexico, there is a high prevalence (42.9%) of self-medication using natural products for weight-loss, particularly in women from Central Mexico. This study indicates the important need to educate patients about the harmful effects of consuming these products.
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Luteolin (LL) and pinocembrin (PB) are plant-derived flavonoids predominantly found in many fruits and vegetables showing several biological effects, especially an antioxidant activity. However, the low water solubility of these two compounds limits their use in many pharmaceutical applications. Beta-cyclodextrin (βCD) and its derivatives (e.g., methylated (M) and hydroxypropylated (HP) βCDs) have been extensively used to enhance the stability and solubility of many hydrophobic guest molecules through an encapsulation process into the lipophilic inner cavity. In the present study, the dynamics behavior and the stability of inclusion complexes of two flavonoids LL and PB with βCDs were studied using all-atom molecular dynamics simulations and MM/PB(GB)SA free energy calculations. The obtained results showed that the van der Waals driven encapsulation of LL and PB could adapt the structure of the βCDs to become more stable conformers via an enhanced intramolecular hydrogen bond formation on the secondary rim. The structural data and free energy results demonstrated that the phenyl orientation was the preferred binding mode for LL and PB inclusion complexations. In addition, βCD derivatives, especially HPβCDs, could significantly enhance the stability of both flavonoids better than natural βCD.
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Luteolin (3,4,5,7-tetrahydroxyflavone), a type of flavonoid found in medicinal herbs and vegetables, has been of great interest due to its anti-oxidative, anti-inflammatory, and anti-carcinogenic effects. Despite these beneficial biological properties, the ease with which luteolin forms molecular crystals in conventional aqueous formulations has hampered much wider applications. In this study, we introduce an oil-in-water (O/W) nanoemulsion vehicle system for enhanced follicular delivery of luteolin. The luteolin-loaded nanoemulsion, which had an average hydrodynamic size of approximately 290 nm, was produced by the assembly of poly(ethylene oxide)-block-poly(ε-caprolactone) and lecithin at the O/W interface. The luteolin-loaded nanoemulsion showed outstanding stability against drop coalescence and aggregation. This was confirmed from the slight drop size increase after repeated freeze-thaw cycling and long-term storage. Moreover, in vivo hair growth evaluation demonstrated that the luteolin-loaded nanoemulsions fabricated in this study possessed the hair growth-promotion activity, which is comparable with the case of using a luteolin solution in an organic solvent.
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Background Phenolic compounds¹ are one of the main interested nutraceuticals in the food and pharmaceutical industries. The application of phenolics is limited due to their low bioavailability, low solubility, low stability, and un-targeted release. These limitations could be overcome by novel ‘‘lipid-based nano-encapsulation technologies’’ capable of appropriated and targeted delivery functions into foods. Scope and approach In this review, preparation, application, and characterization of lipid-based nanocarriers for phenolics have been considered and discussed including nano-emulsions, nano-scale phospholipids, and nanostructured lipid carriers. The bioavailability of nano-encapsulated phenolic products and capability of them to produce functional foods have been considered as well. Key findings and conclusions In the food and nutraceutical industries, the main aims of loading phenolics into nanocarriers are masking their undesirable flavor for oral administration, providing high stability and high absorption, and better release in gastrointestinal (GIT) conditions. Compared with micro-sized carriers, nanocapsules based on lipid formulations provide more surface area and have the potential to enhance solubility, improve bioavailability, and ameliorate controlled release of the nano-encapsulated phenolic compounds.
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Apigenin (AP) has many pharmacological activities. AP has poor solubility in some solvents. AP is insoluble in water and slightly soluble in ethanol (1.93 mg/mL). It has limited application and exploitation. Therefore, the liquid antisolvent precipitation (LAP) method was applied to improve the solubility of AP in ethanol by changing its crystal form or producing ultra-fine particles. Then, the inclusion complex of AP with 2-Hydroxypropyl-β-cyclodextrin (HP-β-CD) is prepared using the solvent removal method. The effects of various experimental parameters on the solubility of AP in ethanol were investigated through the single factor design. Under the optimum conditions, the AP-ethanol solution of 6.19 mg/mL was obtained. The inclusion complex of AP with HP-β-CD was obtained by the solvent removal method. The load efficiency (LE) and drug encapsulation efficiency (EE) of the inclusion complex of AP with HP-β-CD were 13.98% ± 0.14% and 97.86% ± 1.07%, respectively. SEM, FTIR, (1)HNMR, XRD, DSC, and TG were used to analyze the characteristics of the inclusion complex of AP with HP-β-CD. These results showed that the inclusion complex has significantly different characteristics with AP. In addition, the dissolution rate and solubility of the inclusion complex were approximately 15.24 and 68.7 times higher than AP in artificial gastric juice, and was separately 10.4 times and 40.05 times higher than AP in artificial intestinal juice. The bioavailability of inclusion complex increased 3.97 times compared with AP.
Article
The aim of this study was to develop a novel mix micelles system composing of two biocompatible copolymers of Soluplus? and Pluronic F127 to improve the solubility, oral bioavailability of insoluble drug apigenin (AP) as model drug. The AP-loaded mixed micelles (AP-M) were prepared by ethanol thin-film hydration method. The formed optimal formulation of AP-M were provided with small size (178.5?nm) and spherical shape at ratio of 4: 1 (Soluplus?: Pluronic F127), as well as increasing solubility of to 5.61?mg/mL in water which was about 3442-fold compared to that of free AP. The entrapment efficiency and drug loading of AP-M were 95.72% and 5.32% respectively and a sustained release of AP-M was obtained as in vitro release study indicated. Transcellular transport study showed that the cell uptake of AP was increased in Caco-2 cell transport models. The oral bioavailability of AP-M was 4.03-fold of free AP in SD rats, indicating the mixed micelles of Soluplus? and Pluronic F127 is an industrially feasible drug delivery system to promote insoluble drug oral absorption in the gastrointestinal tract.
Article
The apigenin-phospholipid phytosome (APLC) was developed to improve the aqueous solubility, dissolution, in vivo bioavailability, and antioxidant activity of apigenin. The APLC synthesis was guided by a full factorial design strategy, incorporating specific formulation and process variables to deliver an optimized product. The design-optimized formulation was assayed for aqueous solubility, in vitro dissolution, pharmacokinetics, and antioxidant activity. The pharmacological evaluation was carried out by assessing its effects on carbon tetrachloride-induced elevation of liver function marker enzymes in a rat model. The antioxidant activity was assessed by studying its effects on the liver antioxidant marker enzymes. The developed model was validated using the design-optimized levels of formulation and process variables. The physical-chemical characterization confirmed the formation of phytosomes. The optimized formulation demonstrated over 36-fold higher aqueous solubility of apigenin, compared to that of pure apigenin. The formulation also exhibited a significantly higher rate and extent of apigenin release in dissolution studies. The pharmacokinetic analysis revealed a significant enhancement in the oral bioavailability of apigenin from the prepared formulation, compared to pure apigenin. The liver function tests indicated that the prepared phytosome showed a significantly improved restoration of all carbon tetrachloride-elevated rat liver function marker enzymes. The prepared formulation also exhibited antioxidant potential by significantly increasing the levels of glutathione, superoxide dismutase, catalase, and decreasing the levels of lipid peroxidase. The study shows that phospholipid-based phytosome is a promising and viable strategy for improving the delivery of apigenin and similar phytoconstituents with low aqueous solubility.
Article
In this study, an inclusion complex of apigenin (AP)-hydroxypropyl-β-cyclodextrin (HP-β-CD) was prepared via supercritical antisolvent (SAS) method using N, N-dimethylformamide (DMF) as solvent and carbon dioxide as antisolvent. The mole ratio of AP and HP-β-CD (1:1) was established by phase solubility equilibrium experiment. The optimal conditions were determined through single-factor experiments; these conditions included precipitation pressure of 22.5 MPa, precipitation temperature of 50 °C, and AP concentration of 20 mg/ml. The load efficiency and encapsulation efficiency of the AP-HP-β-CD inclusion complex, with a mean particle size of 392.13 ± 7.56 nm, were 13.97% ± 0.17% and 93.22% ± 1.17%, respectively, under the optimal conditions. FTIR, 1H NMR, SEM, XRD, DSC, and TG analyses were also conducted. Results showed that the inclusion complex was formed because of the interaction between AP and HP-β-CD. DMF residue in the inclusion complex was 0.033% lower than the ICH limit for class II solvents. The solubility of the inclusion complex was approximately 152.43 times higher than that of the raw AP. In the in vitro study, the dissolution rate of the AP-HP-β-CD inclusion complex was about 7.60 times higher than that of the raw AP. In the in vivo study, the bioavailability of the inclusion complex increased by 6.45 times compared with that of the raw AP. Hence, the prepared AP-HP-β-CD inclusion complex exhibits potential as a new oral therapeutic agent formulation for clinical applications.
Article
Celery root belongs to a group of plants classified as the umbelliferous family, which contains phytoestrogens. Phytoestrogens are structurally similar to estrogen as they share a pair of hydroxyl groups and phenolic ring, which enables them to bind to estrogen receptors directly, making them a herbal remedy for low estrogen states such as menopause. We present a case of a female patient with depression who was stabilized on venlafaxine and St John's Wort, and who developed a manic episode due to elevated serum venlafaxine levels after she started taking celery extracts for menopausal related issues. We proffer a hypothesis for this unusual occurrence.
Article
Context Linalool (LL) is associated with numerous pharmacological activities. However, its poor solubility usually results in poor bioavailability, and further limited its applications. Objective To reduce volatilization and improve bioavailability of LL, linalool-loaded nanostructured lipid carriers (LL-NLCs) were prepared. Materials and methods LL-NLCs were prepared using high-pressure homogenization method and optimized via response surface methodology-central composite design, followed by characterization, including particle size (PS), zeta potential (ZP), transmission electron microscope (TEM), X-ray diffraction (XRD), differential scanning calorimetry (DSC) and in vitro release study. Rats were administered 300 mg × kg ⁻ ¹ LL with each preparation (LL-NLCs or LL) via oral gavage. Results LL-NLCs had a PS of 52.72 nm with polydispersity index of 0.172, and ZP of –16.0 mV. The encapsulation efficiency and drug loading gave 79.563 and 7.555%, respectively. The cumulative release of LL from free LL reached 51.414% at 180 min, while LL from LL-NLCs was 15.564%. All the pharmacokinetics parameters of LL-NLCs were better than those of LL, including Cmax (from 1915.45 to 2182.45 ng × mL ⁻ ¹), AUC0–t (from 76003.40 to 298948.46 ng × min × mL ⁻ ¹) and relative bioavailability (393.34%). The t1/2, MRT and tmax of LL-NLCs (110.50, 146.66 and 60 min) were also longer than that of LL (44.72, 45.66 and 40 min). Discussion and conclusion LL-NLCs were for the first time prepared and its oral administration in rats thoroughly investigated. LL-NLCs exhibited sustained release effect and increased absorption of LL. Therefore, these findings might provide a potential possibility for clinical application of LL.
Article
We analyzed the physical properties and digestibility of apigenin-loaded emulsions as they passed through a simulated digestion model. As the emulsion passed through the simulated stages of digestion, the particle size and zeta potential of all the samples changed, except for the soybean oil-Tween 80 emulsion, in which zeta potential remained constant, through all stages, indicating that soybean oil-Tween 80 emulsions may have an effect on stability during all stages of digestion. Fluorescence microscopy was used to observe the morphology of the emulsions at each step. The in vivo pharmacokinetics revealed that apigenin-loaded soybean oil-Tween 80 emulsions had a higher oral bioavailability than did the orally administrated apigenin suspensions. These results suggest that W/O/W multiple emulsions formulated with soybean oil and tween 80 have great potential as targeted delivery systems for apigenin, and may enhance in vitro and in vivo bioavailability when they pass through the digestive tract.
Article
Aims: Diabetes mellitus is a major manifestation of metabolic disorder which presents with hyperglycemia (high levels of serum blood sugar). In the present study, we aimed to investigate the effects of celery seed extract on different biochemical factors and histopathological changes in normal and streptozotocin (STZ)-induced diabetic rats. Methods: A total of 35 male Wistar rats were divided into five groups (one normal and four diabetic groups). STZ was injected intraperitoneally to induce diabetes. The effects of hexane extract of celery seed and glibenclamide (as a positive control) were compared. Blood samples were analyzed on days 0, 18, and 33, and histopathological evaluations were performed at the end of the study. Results: Glucose, triglycerides, and cholesterol levels significantly decreased, whereas insulin and high-density lipoprotein (HDL) levels increased in the extract-administered groups, as compared to the negative diabetic control group (P < 0.0001). The concentrations of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in serum of the extract-administered groups were significantly less than the negative control group (P < 0.0001). Histopathological reports revealed significantly less atrophy, necrosis, and inflammation in the rats receiving celery seed extract compared to the negative control group. Conclusions: The results indicated that celery seed extract can be effective in controlling hyperglycemia and hyperlipidemia in diabetic rats, and demonstrated its protective effects against pancreatic toxicity resulting from STZ-induction.
Article
Background: Celery is a vegetable that can also reduce the caloric input of the diet in weight loss issues. Also, Pilates exercise is one of the new training methods that are effective on reducing the weight and body fat. Circulation of Adiponectin concentration increases by exercise and losing the weight. The aim of the present study is to investigate the effect of 8 weeks Pilates training with Celery supplementation on Adiponectin levels and anthropometric indicators in sedentary overweight women. Materials and Methods: Sixty sedentary overweight women (BMI ≥ 25 kg/m2), aged 35 to 45yearsold, were randomly divided into four groups: control, exercise, supplement and exercise + supplement. There were 15 subjects in each group. Anthropometric parameters and Adiponectin levels were measured at the baseline and end of the study. Results: Significant improvements in body weight and Body Mass Index (BMI) were obtained in exercise group. The most changes of Adiponectin levels were observed in exercise, supplement and exercise + supplement groups. Adiponectin levels significantly increased in 3 of the groups, but the highest increase was realized in exercise + supplement group. Conclusion: The results of present study suggest that the Pilates exercise and consumption of Celery had a significant positive effect on Adiponectin concentration leading to reduced body fat. © 2015 Japan Health Sciences University & Japan International Cultural Exchange Foundation.
Article
The phyto-phospholipid complexation technique is a promising approach to improve the bioavailability and efficacy of flavonoids. The objective of this study was to improve the bioavailability and efficacy of luteolin by phospholipid complexation against inflammatory liver damage. The phospholipid complex of luteolin (LPC) was prepared by solvent evaporation accompanied by freeze drying. The physicochemical properties of LPC were investigated by means of spectroscopy, differential scanning calorimetry (DSC) and X-ray diffraction (XRD). Pharmacokinetic parameters in rats were determined and the hepatoprotective potential was assessed against d-galctosamine and lipopolysaccharide (GalN/LPS) induced hepatic damage. LPC showed drug loading of 74.14% and average particle size 147.4 nm. The results of FTIR, thermal and diffraction studies confirmed the formation of complex. The aqueous/n-octanol solubility showed improvements. LPC showed an increase in relative in vivo bioavailability to 535.31% of pure luteolin. The histological and biochemical changes induced by GalN/LPS were significantly ameliorated by LPC. Hepatoprotective effect of LPC was more profound than luteolin with a particle size suitable for passive targeting of inflammatory sites. LPC was successfully formulated under optimized conditions and is an efficient drug delivery system for oral administration of luteolin with enhanced bioavailability and hepatoprotective potential.
Article
In Indonesia Apium graviolens and Orthosiphon stamineus benth have been used to as traditional medicines to lower blood pressure. Since at present time is avaiLable as a combination of those phytopharmaca in the market, therefore, it is necessary to conduct a study to evaLtnte the ffictivity and side effects of those phytopharmaca toward hypertensive subjects. A randomized double blind conftolled trial was conducted at area of Monica - Jakarta in South of Jalarta from July-untiL 29 October 2001 toward mild and moderate hypertensive subjects. The first group (72 subjects) received phytophanmaca (Tensigard® which contains Apium graviolens and Orthosiphon stamineus benth) 3 x 250 mg, whiLe the second grottp (70 subjects) had Amlodipine I x 5 mg. Obseruation were conducted for 12 weelcs, and the parameter observed wère systolic and diastolic blood pressure (SBP and DBP), plasma lipid, blood glucose before and after treatment, and electrolyte with nvo week intervals. The Resuhs revealed that the phytopharmaca treatment for 12 weel<s lowered SBP and DBP equivalent to Amlodipine (SBP 24.72 t 1.63 mm4g vs 26.27 + 2.18 mmHg; P > 0,05; DBP 10.00 t0.96 mmHg vs 9.49 t 1.37 ntmHg; P> 0.05). Phytopharmaca treatment for 12 weel<s did not influence plasma eLectolyte, as well blood glucose Levels. There was not asignificant side effects noted for both phytopharmaca and Amlodipine during the study period. [n conclusion, the trial reveals that the phytophnrmaca lowered systolic and diastolic blood pressure equivalent with Amlodipine among mild and moderate hypertensive subjects. During the study period there was not a significant side effect noted. (Med J Indones 2002; 11: 195-201)Keywords: blood pressure, phytopharmaca, side effect, plasma electrolytes
Article
Luteolin (LU, 5,7,3′,4′-tetrahydroxyflavone) most active compound in Chinese herbal flavones has been acting as a antimicrobial, anti-inflammatory, anti-cancer, and antimutagen. However, its poor bioavailability, hydrophobicity, and pharmacokinetics restrict clinical application. Here in this study, LU-loaded solid lipid nanoparticles have been prepared by hot-microemulsion ultrasonic technique to improve the bioavailability & pharmacokinetics of compound. LU-loaded solid lipid nanoparticle size was confirmed by particle size analyzer with range from 47 to 118 nm, having zepta potential −9.2 mV and polydisperse index 0.247, respectively. Round-shaped SLNPs were obtained by using transmission electron microscope, and encapsulation efficiency 74.80 % was calculated by using HPLC. Both in vitro and vivo studies, LC–MS/MS technique was used for quantification of Luteolin in rat. The T max value of drug with LU–SLNs after the administration was Ten times shorter than pure Luteolin suspension administration. C max value of drug after the administration of LU–SLNs was five times higher than obtained with native drug suspension. Luteolin with SLNs has increased the half-life approximately up to 2 h. Distribution and clearance of drug with SLNs were significantly decreased by 2.16–10.57 fold, respectively. In the end, the relative bioavailability of SLNs has improved about 4.89 compared to Luteolin with SLNs. From this study, it can be concluded that LU–SLNs have not only great potential for improving solubility but also increased the drug concentration in plasma. Furthermore, use of LC–MS/MS for quantification of LU–SLNs in rat plasma is reliable and of therapeutic usefulness, especially for neurodegenerative and cancerous disorders in humans.
Article
Overweight, obesity, and diabetes are the most common disorders in the world. In most diets, carbohydrates are the greatest source of calories. Inhibition of carbohydrate digestion or absorption can decrease calorie intake to promote weight loss and combat obesity. It is also a mechanism for reducing hyperglycemia in diabetic subjects. Before being absorbed by the body, carbohydrates must be broken down into monosaccharides. α-Amylase catalyzes the hydrolysis of α-(1,4)-d-glycosidic linkages of starch and other glucose polymers. Inhibitors of this enzyme can be used in treatment of obesity and diabetes. In diabetic patients, inhibition of α-amylase leads to prohibition starch breaking and results in lower levels of blood glucose. The effects of pseudosaccharides, proteinaceous, and polyphenolic inhibitors have been previously reported. Polyphenolic compounds are widely distributed in plants and fruits and are present in normal diets. These compounds have been shown to possess beneficial effects in diabetes, cardiovascular diseases, atherosclerosis, allergy, inflammation, and osteoporosis. Among polyphenolic compounds, flavonoids are of particular significance: They have been shown to reduce cholesterol synthesis via direct action on HMG-CoA reductase and hydrolyze lipids via inhibition of phosphodiesterase (PDE) and diminution of cAMP breakdown. In recent years, many lines of research have been done on those plants which are being used traditionally as drug plants, and their effects have been surveyed on weight loss and control of blood glucose levels in diabetic patients. In this review, we want to investigate α-amylase inhibitors especially human pancreatic α-amylase (HPA)
Article
Volatiles of leaves, stalks and roots of Tunisian celery (Apium graveolens var. dulce) were extracted either by hydrodistillation or by maceration in organic solvents. After concentration, essential oils and aroma extracts were studied by gas chromatography (GC) and GC–mass spectrometry (GC–MS). A high proportion of essential oils and aroma extracts consisted of phthalides with 74.6–76.6% in leaves, 56.8–74.1% in stalks and 57.7–79.7% in roots. The studied organs were particularly characterized by appreciable levels of terpene hydrocarbons (17.0–31.5%). Also, results showed that stalks were particularly rich in phenols with 8.7% of total volatiles. The main volatile constituents identified in the different extracts were (Z)-3-butylidenephthalide (27.8–38.4% in leaves, 30.5–38.9% in stalks, 30.5–52.0% in roots), 3-butyl-4,5-dihydrophthalide (34.2–41.0% in leaves, 24.1–27.8% in stalks, 12.3–13.2% in roots) and α-thujene (7.9–9.9% in leaves, 7.5–14.0% in stalks, 7.0–12.4% in roots). The three studied organs of A. graveolens (leaves, stalks and roots) could be considered good sources of phthalides known for their anti-inflammatory, anti-tumor and insecticidal properties. Nevertheless, the efficiency in the extraction of these bioactive compounds depends on both the organ and the method used.
Article
The hypolipidemic and antiobesogenic effects of tea intake have been associated with bioactive compounds that regulate peroxisome proliferator-activated receptors (PPARs). This review describes the recent research on two of these compounds, (-)-epigallocatechin gallate (EGCG) and linalool. Catechins (specifically EGCG) are key bioactive compounds found in tea, and a recent study has shown that linalool may also be an active tea compound. These compounds act on lipid metabolism by regulating PPAR subtypes. EGCG inhibits the key adipogenic transcription factor PPARγ while activating PPARα, whereas linalool is a PPARα agonist activating hepatic fatty acid uptake and subsequent oxidation to reduce plasma triglyceride levels. The collective activities of EGCG and linalool in tea may exert hypolipidemic and antiobesogenic effects by regulating PPARs. The research summarized in this review expands our understanding of the biological and physiological mechanisms of the bioactive compounds found in tea.
Article
Hypertension is not only among the common and leading causes of morbidity and mortality in China and the world, but also is the most important modifiable risk factor for life-threatening diseases. Prevalent reasons of hypertension in China involve heredity, obesity, diet with high sodium and low potassium as well as calcium intakes. All modifiable factors cause hypertension is summed up in dietary, especially the loss of functional components from whole grain to polished grain foods for dietary. The functional food with whole grains (germinated brown rice etc.) and functional vegetables (garlic etc.) as well as functional fruits for dietary, especially functional food with high minerals (K,Ca) and low sodium for hypertension prevention in China is necessary, for example barley grass powder.
Article
Previous studies have demonstrated that a natural product of celery seeds, 3‑n‑butylphthalide (NBP), has significant antihypertensive effects that are widely utilized in Chinese traditional medicine. The present study aimed to investigate the effects of NBP on hypertensive nephropathy, as well as the mechanisms underlying this disease in spontaneously hypertensive rats (SHRs). SHRs were treated orally with saline, NBP (15 or 30 mg/kg) or losartan (10 mg/kg) daily for 20 weeks, during which time blood pressure was measured every four weeks. At the end of the 20‑week treatment, blood and urine samples were collected for biochemical analysis, and kidney tissues were obtained for histopathological analysis and immunohistochemistry. Enzyme‑linked immunosorbent assays and western blotting were used to analyze the expression of transforming growth factor (TGF)‑β1 in blood and kidney tissues, respectively. The results showed that NBP effectively attenuated progression of hypertensive nephropathy by decreasing urinary albumin excretion and blood urea nitrogen levels. It significantly decreased blood pressure (although less markedly than losartan) and the incidence of glomerulosclerosis. In addition, it alleviated tubular impairment and significantly decreased oxidative stress, as well as the expression of pro‑inflammatory cytokines and TGF-‑β1 in kidney tissues. In conclusion, the results suggested that NBP may slow the progression of hypertensive nephropathy by a variety of mechanisms.
Article
Hypertension is a major risk factor for myocardial infarction, heart failure, stroke, peripheral arterial disease, and aortic aneurysm, and is a cause of chronic kidney disease. Hypertension is often associated with metabolic abnormalities such as diabetes and dyslipidemia, and the rate of these diseases is increasing nowadays. Recently it has been hypothesized that oxidative stress is a key player in the pathogenesis of hypertension. A reduction in superoxide dismutase and glutathione peroxidase activity has been observed in newly diagnosed and untreated hypertensive subjects, which are inversely correlated with blood pressure. Hydrogen peroxide production is also higher in hypertensive subjects. Furthermore, hypertensive patients have higher lipid hydroperoxide production. Oxidative stress is also markedly increased in hypertensive patients with renovascular disease. If oxidative stress is indeed a cause of hypertension, then, antioxidants should have beneficial effects on hypertension control and reduction of oxidative damage should result in a reduction in blood pressure. Although dietary antioxidants may have beneficial effects on hypertension and cardiovascular risk factors, however, antioxidant supplementation has not been shown consistently to be effective and improvement is not usually seen in blood pressure after treatment with single or combination antioxidant therapy in subjects thought to be at high risk of cardiovascular disease. This matter is the main focus of this paper. A list of medicinal plants that have been reported to be effective in hypertension is also presented.
Article
Mast cells play important roles in diet-induced obesity and diabetes, and some synthetic mast cell stabilizers can improve related metabolic disturbances in mice. Luteolin (LU) is a potent natural mast cell stabilizer. However, a direct correlation between LU and these common metabolic diseases is not established. Male C57BL/6 mice were fed low-fat diet, high-fat diet (HFD), HFD with 0.002 and 0.01% LU for 12 wk, respectively. Dietary LU suppressed HFD-induced body weight gain, fat deposition, and adipocyte hypertrophy. Meanwhile, glucose intolerance and insulin sensitivity was also improved. Interestingly, dietary LU ameliorated angiogenesis and associated cell apoptosis and cathepsin activity in epididymis adipose tissues, which is a critical mechanism that mast cells are involved in diet-induced obesity and diabetes. Further, we showed dietary LU reduced mast cell and macrophage infiltrations and inflammatory cytokine levels in epididymis adipose tissues. Finally, LU inhibited mast cell-derived IL-6 expression, which is a key cytokine that contributes to mast cell-associated metabolic derangements, and protein kinase C activator phorbol myristoyl acetate reversed the inhibitory effects. As a natural flavonoid, low-dose diet supplement of LU ameliorates diet-induced obesity and insulin resistance in mice, suggesting a new therapeutic and interventional approach for these diseases.
Article
Hyperglycemia is a key feature in diabetes. Hyperglycemia has been implicated as a major contributor to several complications of diabetes. High glucose levels induce the release of proinflammatory cytokines. Luteolin is a flavone isolated from celery, green pepper, perilla leaf, and chamomile tea. Luteolin has been reported to possess antimutagenic, antitumorigenic, antioxidant, and anti-inflammatory properties. In this study, we investigated the effects of luteolin on proinflammatory cytokine secretion and its underlying epigenetic regulation in high-glucose-induced human monocytes. Human monocytic (THP-1) cells were cultured under controlled (14.5 mM mannitol), normoglycemic (NG, 5.5 mM glucose), or hyperglycemic (HG, 20 mM glucose) conditions, in the absence or presence of luteolin. Luteolin (3-10 μM) was added for 48 h. While hyperglycemic conditions significantly induced histone acetylation, NF-κB activation, and proinflammatory cytokine (IL-6 and TNF-α) release from THP-1 cells, luteolin suppressed NF-κB activity and cytokine release. Luteolin also significantly reduced CREB-binding protein/p300 (CBP/p300) gene expression, as well as the levels of acetylation and histone acetyltransferase (HAT) activity of the CBP/p300 protein, which is a known NF-κB coactivator. These results suggest that luteolin inhibits HG-induced cytokine production in monocytes, through epigenetic changes involving NF-κB. We therefore suggest that luteolin may be a potential candidate for the treatment and prevention of diabetes and its complications. Copyright © 2014 John Wiley & Sons, Ltd.
Article
Luteolin protects against high glucose (HG)-induced endothelial dysfunction whereas its cytotoxicity has been reported against normal endothelial cells. This study was undertaken to determine luteolin cytoprotective and cytotoxic dose ranges and to elucidate their respective mechanisms. Luteolin prevented HG-induced human umbilical vein endothelial cell (HUVEC) death with an EC50 value of 2.0 ± 0.07 μM. The protective effect of luteolin was associated with decreased intracellular reactive oxygen species (ROS) and Ca2+ (Cai2+) levels and enhanced nitric oxide (NO) production. At high concentrations, luteolin caused HUVEC death in normal glucose (NG) and HG states (LC50 40 ± 2.23 and 38 ± 1.12 μM, respectively), as represented by increased ROS and Cai2+ and decreased NO. Western blots illustrated that exposure to HG increased cyclooxygenase-2 (COX-2) and integrin-linked kinase (ILK) expression. Luteolin at low concentrations suppressed HG-mediated up-regulation of COX-2 but maintained HG-induced over-expression of ILK while at high concentrations significantly increased COX-2 and decreased ILK expression in both HG and NG states. Our data indicated that cytoprotective action of luteolin was manifested with much lower concentrations, by a factor of approximately 20, compared with cytotoxic activity under both normal or glucotoxic conditions. It appears that luteolin exerts its action, in part, by modulating ILK expression which is associated with regulation of COX-2 expression and NO production in endothelial cells. Copyright © 2014 John Wiley & Sons, Ltd.
Article
Metabolic syndrome is a condition of at least three of the cardiovascular risk factors: obesity, excessive visceral fat storage, dyslipidemia, hypertension and hyperglycaemia or Type 2 diabetes. It is a state of insulin resistance, oxidative stress and chronic inflammation. Cardiovascular disease is the highest cause of death globally. Certain dietary components and over 800 plants help prevent or moderate metabolic syndrome by assisting the body homeostasis mechanisms. This review compiles the most current studies on foods that help fight metabolic syndrome and the scientific evidences to support their use. This includes functional fats, digestive enzymes inhibitors, various beverages, different fruits, specific vegetables, grains, legumes, herbs and spices that can reduce cardiovascular disease risk, through several cellular mechanisms.