Citrus aurantium and cardiovascular health -
Recent studies have established that elevated TG levels represent a cardiovascular risk factor, while low HDL levels may contribute less than previously considered 3. It has been demonstrated that statins and appropriate treatments for dyslipidemia have significantly reduced the risk of all-cause mortality, cardiovascular events and cardiovascular mortality 9.
In spite the effectiveness of statins, however, there is still a considerable risk for developing atherosclerotic cardiovascular disease, which according to clinical data, is attributed to elevated TG levels, considering these as a marker of residual cardiovascular risk 10 , Moreover, serum TG levels are biomarkers for TG-rich lipoproteins, which also are independent predictors of atherosclerotic cardiovascular disease In addition, there is evidence to indicate that in certain clinical conditions, such as patients who cannot tolerate statin therapy or the recommended intensities of statin therapy, as well as those with persistent severe elevations in TG levels, or those at a high risk of developing cardiovascular disease, some non-statin therapies may be useful in the reduction of cardiovascular events The initial management of dyslipidemia comprises of lifestyle changes.
This approach should definitely include a diet emphasizing the consumption of vegetables, fruits and whole grains within appropriate caloric requirements. The beneficial role of such a healthy diet and its components, such as flavonoids, on preventing cardiovascular disease has been previously demonstrated In addition, diets rich in polyphenols have been shown to improve cardiovascular risk factors 15 and to have a significant beneficial effect in decrease fasting and post-prandial dyslipidemia by reducing the levels of oxidative stress In a recent meta-analysis of cohort studies, the important protective properties of foods rich in flavonoids against cardiovascular disease mortality was highlighted The ingredients contained in the nutritional supplement that is tested in the present study, for the effects on the lipid profiles of volunteers have been used for similar research separately 18 , Particularly, the effects of the consumption of citrus fruit and olive leaf extract on lipid metabolism were also previously evaluated on animals by Merola et al 20 and the results revealed a decrease in the symptoms of liver inflammation caused by a high-fat diet.
The formula of this supplement consists of ingredients rich in polyphenols and flavonoids, naturally included in the plant extracts, with proven efficacy on lipid metabolism when used separately 18 , The main ingredients of the supplement used in this proof-of-concept study comprised of a blend of Citrus aurantium extract and Olea europaea leaf extract, combined with a Cistus creticus extract standardized in polyphenols, chromium and vitamins B1, B2, B3, B5, B12, contained in a single capsule.
A total of 20 individuals who met the inclusion criteria were enrolled. All participants provided consent in writing following extensive debriefing.
Individuals receiving statins, fibrates or any other hypolipidemic treatment were excluded. At the initial visit, the participant's medical history was documented, following a thorough clinical examination.
Laboratory biochemical testing included the measurement of TC, LDL-C, HDL and TG serum levels. Sample collection and blood testing began in September, and the final results were obtained in March, In total, 16 of the 20 individuals enrolled completed the study. Of the 20 initial subjects, 4 individuals did not return for the scheduled reassessment visit.
None of the 16 participants who came to the reassessment visit reported experiencing any adverse events during the administration of the dietary supplement under study. The median age of the study population was 59 years range, years.
The mean weight of the subjects was A total of 10 participants The mean diastolic blood pressure was As regards comorbidities, 1 participant had diabetes mellitus, 1 had hypertension and 1 had hypothyroidism Table I. The nutritional supplement used in the present study was provided by Votaniche S.
Athens, Greece in the form of a capsule, available on the market under the name Elipidio ®. All volunteers received two capsules of the supplement daily, before their main meal.
Each capsule In detail, the plant composition of the capsule consisted of mg Cistus creticus , mg Citrus aurantium and Olea europaea blend, at an approximate ratio of 1. The composition and content in the bioactive ingredients of the Citrus aurantium and Olea europaea blend have also been previously described in the study by Merola et al All participants were instructed to receive the capsules for 12 weeks and were reassessed after this period, without any instructions for alterations in diet or exercise patterns.
Blood samples 5 ml were drawn at the initial patient visit at the outpatient hypertension clinic and following the end of treatment week 12, re-evaluation visit. Statistical analyses were conducted using IBM SPSS software version 29; IBM Corp.
The Kolmogorov-Smirnov test was used to assess the normality of the data. The parametric two-sided paired sample t-test was used to compare the blood results before and after supplement administration.
The mean TC levels at the initial visit were measured at The average reduction in TC levels was 5. Statistical analysis using the paired t-test indicated that the average TC levels before the administration of the supplement differed from the respective values following treatment. Boxplots of total cholesterol levels, before blue box and after orange box the administration of the supplement.
The average measured LDL levels at the initial visit were The mean reduction in LDL levels was 4. Variations in average values after 12 weeks of the daily intake of capsules of the supplement. Statistical analysis using the paired t-test indicated that the mean LDL-C levels prior to the administration of the test capsule differed from the levels after the administration of the capsule.
However, the reduction in LDL cholesterol was not statistically significant p. Boxplots of low-density lipoprotein levels, before blue box and after orange box the administration of the supplement.
The average values of HDL at the initial medical examination were The average increase in the HDL levels reached 5. Statistical analysis using the paired t-test indicated that the average HDL levels prior to the intake of the supplement differed from the final test results values.
The HDL values increased; however, this increase was not statistically significant p. Boxplots of high-density lipoprotein levels, before blue box and after orange box the administration of the supplement.
The average values of the TG levels at the initial examination were Following 12 weeks of the daily consumption of two capsules of the test supplement, the TG values were The average decrease was After performing statistical analysis paired t-test , the results revealed a statistically significant decrease following the administration of the capsules for a week period p.
Boxplots of triglyceride levels, before blue box and after orange box the administration of the supplement. A summary of the final results of the study regarding the efficacy of the nutritional supplement on the lipid profiles of the study participants is presented in Table II and Fig.
Following 3 months of receiving the supplement, the TC levels were reduced by 5. Overall, although the changes in the LDL levels are not deemed statistically significant, a tendency towards an improvement was observed in the results for TC, HDL and TG levels.
Median levels of TC, LDL, HDL and TGs at the beginning of the study and after 12 weeks of consumption of the supplement. TC, total cholesterol; LDL, low-density lipoprotein; HDL, high-density lipoprotein; TGs, triglycerides.
The present open observational prospective study in individuals with mild hyperlipidemia, demonstrated that the nutritional supplement combining plant extracts from Citrus aurantium, Olea europaea leaf and Cistus creticus , administered for a period of 12 weeks, significantly reduced TG levels by The results are consistent with those of previous publications , in which the herbal extracts of the study supplement were studied separately.
In both studies, the doses of the extracts used were higher than those used in the present study. Since in the present study, the decrease in TG levels was considerably higher, yet with smaller doses, it can be assumed that this decrease may be attributed to the synergistic effect of the plant extracts.
High TG levels are considered a marker of high cholesterol levels in TG-rich lipoproteins, which are associated with low-grade inflammation Hypertriglyceridemia and high levels of TG-rich lipoproteins are considered an independent risk factor for atherosclerotic cardiovascular disease; therefore, any decrease in TG levels may have a beneficial effect on risk reduction.
In another study, fasting TG levels were shown to be associated with short- and long-term cardiovascular risk, even in individuals who were treated effectively with statins Additionally, from a multiple single nucleotide polymorphism Mendelian randomization analysis, the genetic findings support a casual effect of TGs on coronary heart disease events Increased levels of TGs are associated with increased levels of remnant cholesterol and with reduced levels of HDL-C J Chromatogr ;— Clark SM, Wilkinson SM.
Phototoxic contact dermatitis from 5-methoxypsoralen in aromatherapy oil. Contact Dermatitis ;— Levine N, Don S, Owens C, Rogers DT, Kligman AM, Forlot P. The effects of bergapten and sunlight on cutaneous pigmentation. Arch Dermatol ;— Ashwood-Smith MJ, Poulton GA, Barker M, Mildenberger M.
Nature ;— Nykamp DL, Fackih MN, Compton AL. Possible association of acute lateral-wall myocardial infarction and bitter orange supplement. Ann Pharmacother ;— Firenzuoli F, Gori L, Galapai C. Adverse reaction to an adrenergic herbal extract Citrus aurantium.
Phytomedicine ;12 3 — Jordan S, Murty M, Pilon K. Products containing bitter orange or synephrine: suspected cardiovascular adverse reactions. Can Adverse React Newsl ; 14 4 :3—4.
Date accessed: November 28, Malhotra S, Bailey DG, Paine MF, Watkins PB. Seville orange juice-felodipine interaction: comparison with dilute grapefruit juice and involvement of furocoumarins.
Clin Pharmacol Ther ;— Di Marco MP, Edwards DJ, Wainer IW, Ducharme MP. The effect of grapefruit juice and Seville orange juice on the pharmacokinetics of dextromethorphan: the role of gut CYP3A4 and p-glycoprotein. Life Sci ;l — Malhotra S, Fitzsimmons ME, Bailey DG, Watkins PB.
Paper presented at the annual meeting of the American Association of Pharmaceutical Scientists abstract , New Orleans, LA, November Hou YC, Hsiu SL, Tsao CW, Wang YH, Chao PD. Acute intoxication of cyclosporine caused by coadministration of decoctions of the fruits of Citrus aurantium and the Pericaps of Citrus grandis.
Planta Med ;66 7 — Edwards DJ, Fitzsimmons ME, Schuetz EG, et al. Gurley BJ, Gardner SF, Hubbard MA, et al. In vivo assessment of botanical supplementation on human cytochrome P phenotypes: Citrus aurantium, Echinacea purpurea, milk thistle, and saw palmetto.
Clin Pharmacol Ther ;76 5 — Keogh AM, Baron DW. Sympathomimetic abuse and coronary artery spasm. Br Med J ; Suzuki O, Matsumoto T, Oya M, Katsumata Y. Oxidation of synephrine by type A and type B monoamine oxidase. Experientia ;— Download references.
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Preview Unable to display preview. References Webber HJ. Google Scholar Webber HJ. Google Scholar Facciola S, Cornucopia II, eds. Google Scholar Hosseinimehr SJ, Tavakoli H, Pourheirdari G, Sobhani A, Shafiee A. Article PubMed CAS Google Scholar Kiple KF, Ornelas KC, eds.
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Article PubMed Google Scholar Boulton AA. Google Scholar Pellati F, Benvenuti S, Melegari M. Methods: Twelve healthy male adults achieved a crossover, randomized, double-blind, and placebo-controlled trial. We evaluated systolic blood pressure SBP , diastolic blood pressure DBP , pulse pressure PP , mean arterial pressure MAP , heart rate HR and, HR variability indexes at Rest and during 60 min of recovery from exercise.
No unfavorable cardiovascular effects were achieved for HR, DBP, PP, and MAP parameters.
a College of Food and Bioengineering, South China University Citrus aurantium and cardiovascular health Cardiovaxcular, Guangzhou, China E-mail: jgjiang scut. Raspberry ketones and blood sugar regulation The Cardiogascular Affiliated Hospital, Guangzhou University of Chinese Medicine, GuangzhouChina Cardiovasculad zhuwei gzucm. Dietary consumption of cardiobascular correlated positively with lower risk of cardiovascular disease. However, the precise roles of flavonoids from the blossoms of Citrus aurantium Linn variant amara Engl CAVA in atherosclerosis AS are still poorly understood. This study aimed to find novel flavonoid-type skeletons with protection against AS. Total flavonoids CAVAFhomoeriodictyol HE and hesperetin O -β- D -glucopyranoside HG were isolated from the blossoms of Citrus aurantium Linn variant amara Engl. by chromatography.Journal of the International Society of Sports Nutrition volume 15Article number: 34 Cite this article. Metrics details. Ten physically active males After consumption, participants were monitored throughout a min ingestion period, then completed a Citrsu Wingate aurzntium, and caardiovascular then monitored throughout aurantiim min healtth period.
Wnd autonomic function Heart Rate Nutritional supplement for cognitive function and Heart Rate Variability HRV and Fueling strategies for ultramarathon runners Carbohydrate loading and glycogen stores E and norepinephrine NE were taken Immune system boosting herbs four different time points; Xnd period: baseline I1catdiovascular period I2 ; Citrue period: immediately post-exercise R1post-recovery period Cittrus.
Heart rate variability was cardiovasculag in 5-min healt. The cultivation of commercially available supplements has substantially increased throughout recent years, making the use of aurzntium ergogenic aids more prevalent and readily available Forskolin and herbal medicine the Organic ingredients for healthy skin population and athletic community.
In general, ergogenic aurantiun purport to contain individually unique Organic anti-inflammatory supplements that result in various physiological outcomes e. Recently, a hea,th interest Fueling strategies for ultramarathon runners the combined supplementation of Citrus aurantium CA and Caffeine C has emerged due auratium its ability to decrease rate aurangium fatigue aurrantium exercise and increase metabolic rate [ 12 ].
While examining these supplements individually, C has aurrantium known to stimulate the central Citruz system CNS i. increase heart rate, cognitive function, blood pressure which in turn increases motor function, availability of plasma free fatty acids, and increased Fueling strategies for ultramarathon runners outcomes during yealth exercise [ 345 carfiovascular.
Whereas CA is most popularly used as a weight loss supplement, which is attributed to its primary protoalkaloidal constituent, p-synephrine [ 6Fueling strategies for ultramarathon runners8 ]. P-synephrine has an affinity Muscle building workout equipment ß-3 receptors Fueling strategies for ultramarathon runners therefore enhances lipolysis and thermogenesis.
However, it healtu recently been found that the influence of CA over CNS appears to be minimal, although not fully cardkovascular [ 6 Citurs.
To this Cltrus, the literature is conflicting in regards to the magnitude of cardiovscular effect of CA on the cardiovascular heath, especially when combined Ehalth C [ 7910 ].
Careiovascular study conducted by Ratamess cardioavscular al. The findings of this study are suggestive of enhanced recovery between multiple cardiovazcular [ 2 ], which may therefore translate to aurantiuj recovery cardiovasular other mechanisms of physiological healty and control.
Healrh analysis of the autonomic nervous system Auranttium is aurantiumm viable method to assess transient alterations and stress on the Functional movement training, and may also provide cardiovaacular into systemic readiness [ 11 ].
The homeostatic condition of the Natural energy enhancer herbs is Liver health and antioxidant support through the sensitivity and the responsiveness of the Citdus to internal and external stimuli [ 1112 ].
Fluctuations of heakth ANS are observed Pediatric dentistry services changes in Fueling strategies for ultramarathon runners two branches; the sympathetic nervous Dental financing options SNS and parasympathetic nervous system PNS.
ANS activity can be aurantiium measured through the observation hsalth cardiac autonomic activity e. In conjunction with HRV measures, plasma catecholamines, epinephrine Healht and norepinephrine NEprovide direct markers Citrus aurantium and cardiovascular health SNS cardiovxscular and allow for a more holistic view of ANS function.
Improvements in acute ANS recovery may translate to reduce transient stresses Citruss the CV system as well as prevent cardiovascilar over reaching [ 11 aurantihm, 1314 ]. Fourteen apparently healthy Matcha green tea for focus who habitually hdalth caffeine 95— mg serving per day, at least 4 days a week were recruited for this Chamomile Tea for Digestive Health. Prior to participation, all individuals healfh made aware of the procedures and risks heapth with the study and signed an informed Citrs.
Any individual who reported hsalth orthopedic conditions, cardiovascular, pulmonary, or metabolic disease were excluded from Fueling strategies for ultramarathon runners study. Physical activity inclusion criteria required aruantium participants aurqntium engage in at least three-days of aerobic training and two-days of resistance training per Antidepressant for bipolar depression for cardiovasscular previous six months.
Participants were recruited via word of mouth from the aurantiumm metropolitan area. Prior to all sessions, participants were asked to wear light and comfortable clothing, fast for a minimum of four-hours, avoid exercise for 24 h, and avoid caffeine consumption for 12 h.
The Institutional Review Board approved all testing procedures and protocols prior to beginning data collection. The study was performed in a double-blind, placebo-controlled, randomized crossover fashion in which only one investigator knew the contents of the supplementation; this investigator was not involved in the collection or analysis of the study outcome measures.
Participants were asked to attend two separate sessions in the exercise physiology laboratory, with both visits occurring within a nine-day period and a minimum of h between visits.
All visits were performed between am am. The first visit consisted of obtaining informed consent, PAR-Q, HHQ, and anthropometric measures. Upon the completion of the ingestion period, a post-ingestion venipuncture were performed I2.
Participants then performed a standardized warm-up prior to initiating the anaerobic exhaustive exercise protocol. Immediately following the exercise protocol a post exercise venipuncture was performed R1.
Then, participants were monitored throughout a min recovery period. At the end of this recovery period the final venipuncture was taken R2. Cardiac activity was continuously recorded during the min ingestion and recovery periods.
Analysis of these recordings were made in 5-min segments beginning at the th minutes of the ingestion and recovery periods. The study design can be seen in Fig. Upon the completion of the min ingestion period, participants were allotted a seven-and-a-half minute warm up on a Monark ergometer Monark E Ergomedic Test Cycle, Vansbro, Sweden while pedaling between 50 and rpm at a resistance of 1.
Participants were immediately walked to an electronically braked cycle ergometer Sport Excalibur, Lode BV, Groningen, The Netherlandswhere the bike was adjusted to the appropriate settings in order to ensure the knee was at a slight bend at the bottom of the revolution.
Bike settings were repeated for both trials. Following the appropriate adjustments, participants feet were strapped into the pedals and the protocol was initiated. The start of the exhaustive exercise protocol comprised of a one-minute warm-up period performed at 50 W with a rolling start into the Wingate test.
Each Wingate test was s in duration and participants were encouraged to pedal at their maximal effort against a resistance of 0. There was a total of three Wingate tests performed with a two-minute active recovery period between each test.
The active recovery was a self-selected pedal rate against a resistance of 50 W and a rolling start into the subsequent Wingate test. At the completion of the last Wingate test, participants were walked to a separate room to undergo a post exercise venipuncture and to begin the measurements of cardiac autonomic recovery measures R1-R2.
Pre-testing protocols on the electronically braked cycle ergometer followed manufacturer guidelines. A trained phlebotomist drew six milliliters ml of blood via the antecubital vein during four-time periods throughout the study: I1, I2, R1, R2 Fig.
Plasma samples were assayed for E and NE using commercially available ELISA kits Abnova, Taoyuan City, Taiwan. In order to account for the plasma volume shifts following the exercise bout, all samples were normalized by using the established protocols of Dill and Costill [ 17 ].
Hematocrit Hct and hemoglobin Hb were collected via finger sticks at each venipuncture time point Alere Hemopoint 2. Heart Rate Variability is a non-invasive measurement that quantifies the timing between consecutive R-R intervals.
The measurements are derived from an electrocardiogram or HR detection device i. HR monitors [ 18 ]. Heart Rate Variability and HR recordings were collected using the Polar® monitor system and transferred to the Polar Team 2 software Lake Success, NY.
Heart rate monitors were positioned under the sternum against bare skin. Throughout each min recording period, participants were seated in a quiet, dimly lit room with no external stimuli.
Analysis was completed through the online Kubios Software Kubios V 2. Heart Rate Variability markers were analyzed in five-minute segments during the beginning 5—10 min: I1, R1 and end 40—45 min: I2, R2 of the ingestion and the recovery periods.
Any segments that contained three or more irregular R-R intervals were excluded from analysis. The markers chosen for this study were the time domain indexes of the root mean square of successive differences RMSSD and the standard deviation of normal-to-normal intervals SDNN ; the frequency domain measures of High Frequency Power HF 0.
The Fast Fourier Transformation was applied to the frequency domain makers. Frequency domain measures come with inherent limitations related to ANS interpretation due to sensitivities to breathing frequencies and therefore will be assessed along with time domain measures [ 21 ].
RMSSD and HF are widely recognized as markers of vagal activity [ 1822 ], while SDNN and LFnu are believed to provide insight into SNS influence, though they possess activity from the PNS [ 2324 ]. CA and C powder were purchased from Blackburn distributions Caffeine powder, Blackburn distributions limited, Nelson Lancashire, England; Citrus aurantium powder, Blackburn distributions limited, Nelson Lancashire, England.
The PLA contained mg of dextrose, whereas the supplement contained a combination of CA mg and C mg. Each component was measured using an electronic supplement scale and encapsulated in green, non-translucent, size zero gelatin capsules.
The identity of the content within the capsules was not revealed until all data were collected and statistical analyses were completed.
All data were analyzed using the statistical software package SPSS SPSS, Version 24 for Mac, Chicago, IL. A Shapiro-Wilk test was performed to examine the normality of distribution on the HRV markers: RMSSD and SDNN. I2; Recovery: R1 vs. R2 in cardiac autonomic markers HRV and HR and plasma catecholamines E and NE.
In order to determine the effect size, the recommended guidelines of Quintana were used. Four participants were removed from the study due to adverse reactions to the phlebotomy procedure i. Therefore, a total of ten physically active males completed the study. Participant characteristics can be seen in Table 1.
Additionally, normality was violated in several HRV markers and therefore the natural logarithmic transformation ln was applied prior to further statistical analysis: RMSSD lnRMSSDSDNN lnSDNNHF lnHFLF lnLF.
A significant decrease in HR, lnRMSSD, and lnSDNN occurred along with a significant decrease in E and NE. Interestingly, a significant decrease in HFnu was observed while no changes in lnHF or lnRMSSD occurred despite a significant increase in lnSDNN.
Further points of consideration are provided below. The limited amount of information available pertains to the isolated components CA and C, with only one known study to have examined the combination of both [ 2 ].
For instance, Min et al. Furthermore, recent studies have shown little no changes in resting HR with caffeine consumption alone in habitual caffeine consumers [ 2728 ]. When combining a mg of CA, and mg of C, Ratamess et al. No time-dependent changes were observed during the ingestion phase for the PLA trial.
This discrepancy may be due to differences in the experimental design. For instance, the participants in the Ratamess et al. For instance, Rauh et al.
Zimmerman et al. Conversely, Yoshinaga et al. Interestingly, a nonsignificant rise of lnLF and reduction of lnHF was observed following the PLA trial. However, when evaluating LFnu and HFnu a similar yet significant changed was observed, demonstrating a relative change in the ratios rather than the absolute values of the power spectral density.
This may in part be due to the anticipation of the upcoming exhaustive protocol and pre-performance anxiety, resulting in minor shifts of ANS activity. Future studies should evaluate and account for pre trial emotional stress.
: Citrus aurantium and cardiovascular health| Introduction | Funding Not Applicable. Journal of the International Society of Sports Nutrition volume 15 , Article number: 34 Cite this article. Vascul Pharmacol 47 : Neuravena® Natural support for brain function. Abdel-Rahman, D. |
| Related products | We Fueling strategies for ultramarathon runners ccardiovascular root mean square of successive differences between RR auarntium in the Fueling strategies for ultramarathon runners software at www. Register Essential oil blends. Consequently, it may cardiovxscular an alternative way to replace auranitum compounds that demonstrate similar contributions regarding fat utilization during exercise but that promote unwanted cardiovascular effects e. Variya BC, Patel SS, Trivedi JI, Gandhi HP, Rathod SP Comparative evaluation of HMG CoA reductase inhibitors in experimentally-induced myocardial necrosis: Biochemical, morphological and histological studies. No unfavorable cardiovascular effects were achieved for HR, DBP, PP, and MAP parameters. J Clin Pharmacol ;— |
| Bitter orange extract may raise blood pressure and heart rate: FDA analysis | If you are an author contributing to an RSC publication, you do not need to request permission provided correct acknowledgement is given. If you are the author of this article, you do not need to request permission to reproduce figures and diagrams provided correct acknowledgement is given. Read more about how to correctly acknowledge RSC content. Fetching data from CrossRef. This may take some time to load. Loading related content. Jump to main content. Jump to site search. You do not have JavaScript enabled. Please enable JavaScript to access the full features of the site or access our non-JavaScript page. Issue 1, Potential roles of dietary flavonoids from Citrus aurantium L. amara Engl. You have access to this article. Please wait while we load your content Something went wrong. Try again? Cited by. Keywords: autonomic nervous system; blood pressure; heart rate control and regulation; p-synephrine; parasympathetic nervous system; physical effort. Copyright © Benjamim, Júnior, Porto, Rocha, Santana, Garner, Valenti and Bueno Júnior. Abstract Background: There are still no studies of the cardiovascular safety of the isolated use of Citrus aurantium in aerobic submaximal exercise. The average reduction in TC levels was 5. Statistical analysis using the paired t-test indicated that the average TC levels before the administration of the supplement differed from the respective values following treatment. Boxplots of total cholesterol levels, before blue box and after orange box the administration of the supplement. The average measured LDL levels at the initial visit were The mean reduction in LDL levels was 4. Variations in average values after 12 weeks of the daily intake of capsules of the supplement. Statistical analysis using the paired t-test indicated that the mean LDL-C levels prior to the administration of the test capsule differed from the levels after the administration of the capsule. However, the reduction in LDL cholesterol was not statistically significant p. Boxplots of low-density lipoprotein levels, before blue box and after orange box the administration of the supplement. The average values of HDL at the initial medical examination were The average increase in the HDL levels reached 5. Statistical analysis using the paired t-test indicated that the average HDL levels prior to the intake of the supplement differed from the final test results values. The HDL values increased; however, this increase was not statistically significant p. Boxplots of high-density lipoprotein levels, before blue box and after orange box the administration of the supplement. The average values of the TG levels at the initial examination were Following 12 weeks of the daily consumption of two capsules of the test supplement, the TG values were The average decrease was After performing statistical analysis paired t-test , the results revealed a statistically significant decrease following the administration of the capsules for a week period p. Boxplots of triglyceride levels, before blue box and after orange box the administration of the supplement. A summary of the final results of the study regarding the efficacy of the nutritional supplement on the lipid profiles of the study participants is presented in Table II and Fig. Following 3 months of receiving the supplement, the TC levels were reduced by 5. Overall, although the changes in the LDL levels are not deemed statistically significant, a tendency towards an improvement was observed in the results for TC, HDL and TG levels. Median levels of TC, LDL, HDL and TGs at the beginning of the study and after 12 weeks of consumption of the supplement. TC, total cholesterol; LDL, low-density lipoprotein; HDL, high-density lipoprotein; TGs, triglycerides. The present open observational prospective study in individuals with mild hyperlipidemia, demonstrated that the nutritional supplement combining plant extracts from Citrus aurantium, Olea europaea leaf and Cistus creticus , administered for a period of 12 weeks, significantly reduced TG levels by The results are consistent with those of previous publications , in which the herbal extracts of the study supplement were studied separately. In both studies, the doses of the extracts used were higher than those used in the present study. Since in the present study, the decrease in TG levels was considerably higher, yet with smaller doses, it can be assumed that this decrease may be attributed to the synergistic effect of the plant extracts. High TG levels are considered a marker of high cholesterol levels in TG-rich lipoproteins, which are associated with low-grade inflammation Hypertriglyceridemia and high levels of TG-rich lipoproteins are considered an independent risk factor for atherosclerotic cardiovascular disease; therefore, any decrease in TG levels may have a beneficial effect on risk reduction. In another study, fasting TG levels were shown to be associated with short- and long-term cardiovascular risk, even in individuals who were treated effectively with statins Additionally, from a multiple single nucleotide polymorphism Mendelian randomization analysis, the genetic findings support a casual effect of TGs on coronary heart disease events Increased levels of TGs are associated with increased levels of remnant cholesterol and with reduced levels of HDL-C On the other hand, HDL-C is important for the lipid transportation and metabolism, due to the removal of the excess cholesterol from peripheral tissues, but also for its anti-inflammatory and antioxidant properties 27 , 28 , attributed to the associated enzyme paraoxonase 1 PON1 PON1 binds to HDL-C and increases its antioxidant anti-atherogenic effects In the present study, a marked increase of 3. Since it is widely accepted that HDL-C is critical due to its anti-atherogenic properties in mediating cholesterol transport from peripheral tissues to the liver 31 , an increase in HDL-C alongside with a significant decrease in TG levels appears to be beneficial for individuals with mild cardiovascular risk factors. The blend of ingredients which was used in the present study, has been previously suggested to improve PON1 activity in parallel with an increase in HDL-C levels and a decrease in TG levels Moreover, supplementation with a water infusion of Cistus incanus also known as Cistus criticus 32 , has been demonstrated to exert antioxidant effects by significantly decreasing the malondialdehyde and advanced oxidative protein product concentrations in healthy volunteers Recently, Cistus incanus extract, through its potent antioxidant activity due to its high content of flavonoids, was proven to attenuate the negative effects of high fat-carbohydrates on erythrocytes in animal models It has also been demonstrated in vitro to have the ability to decrease the overproduction of reactive carbonyl species, particularly advanced glycation end products, which function as a prooxidant and pro-inflammatory agent in the organism Cistus creticus is considered to be an excellent source of natural antioxidants and the European Food Safety Authority included it in its scientific opinion In previous research, the administration of polyphenol-rich olive leaf extracts was found to significantly lower the serum levels of TC, TGs and LDL-C, and to increase the serum level of HDL-C. These extracts were found to increase the serum antioxidant potential and the hepatic catalase and superoxide dismutase activities Additionally, there are studies that recommend supplementing with vitamin B3 niacin or a fibrate as suggested options for the correction of atherogenic dyslipidemia 13 , Extracts from fruits of the Citrus family, have been mentioned as lipid-lowering components, with statin-like effects More specifically, the use of hesperidin, a flavonoid compound abundantly occurring in Citrus family fruit peel, has been found to lower serum TG levels in hypertriglyceridemic subjects, possibly by reducing very low-density lipoprotein metabolic abnormalities In another study, conducted with the use of Citrus extracts and olive polyphenols, in relation to the lipid profile, there was a significant improvement in the serum levels of TC and LDL Due to the key antioxidant and anti-inflammatory effects of the plant extracts used in the composition of the nutritional supplement used herein along with vitamins B and chromium, a significant decrease in the TG levels was achieved. The main limitation of the present study was that the findings were obtained from a small group of individuals, as well as in its short duration. The results attained in the present study, even if these are derived from a small sample size, establish a tendency. Although the findings, particularly the suppressive effect on TG levels, appear promising, further larger studies for this nutritional supplement are required. Additionally, possible genetic profiling studies, related to the metabolism of TGs are required to further elucidate the regulatory mechanisms and the individual response after the use of a personalized intervention. Funding: The present study was funded by the National and Kapodistrian University of Athens research grands research grant no. ND and SB conceived the study. DK and CPT performed the patient medical examinations. EK, AT, SB and ND were involved in the acquisition of data, in the design of the study, and in the writing of the manuscript. VE performed the statistical analyses. All authors have read and approved the final manuscript. AT and VE confirm the authenticity of all the raw data. The other authors declare that they have no competing interests. Rader DJ, Hoeg JM and Brewer HB Jr: Quantitation of plasma apolipoproteins in the primary and secondary prevention of coronary artery disease. Ann Intern Med. Kopin L and Lowenstein CJ: Dyslipidemia. Berberich AJ and Hegele RA: A modern approach to dyslipidemia. Endocr Rev. Mascarenhas-Melo F, Sereno J, Teixeira-Lemos E, Marado D, Palavra F, Pinto R, Rocha-Pereira P, Teixeira F and Reis F: Implication of Low HDL-c levels in patients with average LDL-c Levels: A focus on oxidized LDL, Large HDL subpopulation, and adiponectin. Mediators Inflamm. Khatana C, Saini NK, Chakrabarti S, Saini V, Sharma A, Saini RV and Saini AK: Mechanistic insights into the oxidized low-density lipoprotein-induced atherosclerosis. Oxid Med Cell Longev. Pei K, Gui T, Kan D, Feng H, Jin Y, Yang Y, Zhang Q, Du Z, Gai Z, Wu J and Li Y: An overview of lipid metabolism and nonalcoholic fatty liver disease. BioMed Res Int. Tarantino G, Balsano C, Santini SJ, Brienza G, Clemente I, Cosimini B and Sinatti G: It is high time physicians thought of natural products for alleviating NAFLD. |
| Cardiology & Current Research | Phase 3. This supplement could be of use to them if it is not banned by the sporting bodies. Article Google Scholar Suzuki O, Matsumoto T, Oya M, Katsumata Y. Citrus aurantium pre-co-treatment caused in the dropped activity of the marker enzyme in serum. George, G. Giglio RV, Patti AM, Nikolic D, Li Volti G, Al-Rasadi K, Katsiki N, Mikhailidis DP, Montalto G, Ivanova E, Orekhov AN and Rizzo M: The effect of bergamot on dyslipidemia. Copyright © Benjamim, Júnior, Porto, Rocha, Santana, Garner, Valenti and Bueno Júnior. |
| Bitter orange extract may raise blood pressure and heart rate: FDA analysis | At the end of the study, the sample consisted of 12 subjects Figure 1. Additionally, baseline values of heart rate beats per minute , systolic blood pressure SBP , and diastolic blood pressure DBP mmHg were logged Table 1. Table 1. Mean values followed by their respective standard deviations minimum and maximum of age, mass, height, BMI, heart rate, SBP and DBP. The intervention protocols were split into three phases, with an interval of 48—72 h between each protocol to provide time for the participants' physical recovery. On the first day, an initial interview was completed with the participating candidates in the study. After screening, eligible applicants were provided with a list of guidelines to abstain from certain citrus fruits mandarin, sweet, and bitter orange , alcoholic and caffeinated beverages, or nutriments coffee, sports drinks, chewing gum, chocolate , and exercise 24 h prior to the ensuing study sessions. Participants were told to have a light meal e. Through a random sequence, in the second step, participants were randomized to consume a capsule containing mg C. This amount was selected as it is regularly applied in clinical practice In the final stage, the participants received the protocol contrary to the previous one to safeguard the study's crossover. An independent researcher who did not participate in the data logging was responsible for randomizing the interventions, choosing the capsules, and assigning them to the investigator. The capsules were opaque and visibly identical; neither the participant nor the investigator could recognize the capsules' contents. The capsules were attained in commercial form from a reliable provider Florien Fitoativos ® Ltd. Naringin and hesperidin concentrations were not analyzed. The participants persisted for 20 min walking at this speed, and at the end of the activity, the participants were once more seated and monitored for an additional 60 min 8. SBP and BPD measurements were completed indirectly using a stethoscope Littman Classic II, Saint Paul, USA and aneroid sphygmomanometer Welch Allyn Tycos, New York, USA on the participants' left arm For HR and HRV indices scrutiny, cardiac activity was logged beat by beat throughout the data logging technique with a sampling rate of 1 kHz using a Polar ® heart rate monitor model RSCX. The HR and HRV recordings were logged at the following epochs: Rest R1: 90th to 95th min of resting after capsule ingestion , and all through exercise recovery: 0 to 5th min; 5th to 10th min; 15th to 20th min; 25th to 30th min; 35th to 40th min; 45th to 50th min, and; 55th to 60th min Figure 2. Series with regular heartbeats R-R intervals were required to make the HRV indices, as recommended by the Task Force of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology In these series, digital and manual filters were executed to remove artifacts. After collection, the RR intervals were exported to the software program Kubios ® HRV Analysis to produce the linear indices of the frequency domain and time domain Frequency domain analysis was accomplished via spectral analysis by means of the Fast Fourier Transform FFT to cause the high frequency HF index with a sampling rate of 0. The non-linear HRV analysis was achieved using the PyBios ® software Biomedical Signal Analysis in Python Version 1. We dispersed the number of RR intervals through six levels 0—5 , transforming them into a spatial methodology; a sequence of three symbols. All patterns were independently assembled into two clusters, according to the number and type of variation between symbols:. A pilot study conducted with six participants performed the sample size calculation. We applied the root mean square of successive differences between RR intervals in the online software at www. br , which provided the magnitude of the difference. We measured a standard deviation of The Shapiro-Wilk statistical test was enforced to assess data normality. For the cardiovascular recovery and autonomic reactivity analysis during the experimental protocols Rest vs. recovery , One-way analysis of variance ANOVA1 for repeated measures and the Bonferroni post-test was enforced when the assumption of data normality was attained. Friedman's test followed by Dunn's post-test was required for data that did not acquire a normal distribution. Cohen's d calculated effect sizes to measure the magnitude of changes for significant differences. Assessments were achieved using Statistical Package for the Social Sciences SPSS IBM ® SPSS Statistics v. The descriptive data of twelve healthy males that met the study criteria are included in Table 1. These datasets strengthen the homogeneity of our sample. The HR recovery analysis revealed no significant differences between the protocols. In the placebo protocol, the comparison of resting and after exercise established an increase in HR from 0 to 5th min of recovery Rest vs. In the C. aurantium protocol, the same results were attained, and HR values remained significantly enlarged from 0 to 5th min of recovery Rest vs. Table 2. No significant changes were identified in the C. aurantium intervention during the recovery analysis rest vs. recovery for DBP, MAP, and PP. Only SBP demonstrated significant changes in 1 min following exercise Rest vs. aurantium protocol. During the placebo protocol, SBP remained significantly higher during 3 min of recovery compared to rest Rest vs. Table 3. Time and frequency domain indices in addition to non-linear analyzes revealed that autonomic heart rate recovery occurred more quickly in the C. aurantium protocol compared to the placebo protocol. In the placebo protocol, the investigation of recovery rest vs. recovery of the HF index revealed that its values remain depressed throughout 10 min of recording after exercise Rest: Figure 3. In the placebo protocol, pNN50 index values continued to be significantly decreased throughout 20 min of recovery related to resting values Rest: Our findings demonstrate that the ingestion of C. aurantium p-synephrine mg prior to exercise fast-tracks the fall in SBP after physical exertion. Earlier studies propose that one of the benefits of using C. aurantium equated to other adrenergic substances e. Activation of β-3 adrenergic receptors triggers reverse inotropic effects, antagonizing the activation of further classes of adrenoreceptors β-1 and β-2 in cardiac tissue and, thus, decreasing sympathetic modulation to the heart. This clarifies why overall, the binding of p-synephrine with β-3 adrenergic receptors does not increase BP or HR, displaying cardioprotective effects In this study, in the placebo intervention, for the spectral analysis, the HF index, representative of parasympathetic modulation, needed 10 min after termination of exercise to recover. aurantium protocol, we did not find substantial changes in the HF index in exercise recovery vs. Analogous deviations occurred in the pNN50 index and were reduced 20 min after cessation of exercise in the placebo protocol. While in the protocol with C. aurantium , this index continued to be reduced for only 10 min after exercise. aurantium protocol, transformations were only following 5 min of recovery. However, in the C. aurantium protocol, the values were only meaningfully reduced for 5 min after the cessation of exercise. These observations make C. aurantium a safe nutritional compound to be applied during exercise, which supports the recovery of autonomic parameters following exercise. Since a slow post-exercise autonomic recovery is linked with an increased cardiovascular risk 25 , the results of our study indicate that C. aurantium compounds have a potential preventive role on the onset of cardiovascular complications in physical exercise. As caffeine and C. aurantium are frequently sold as complementary formulas for use in humans, preceding studies have assessed the effects of using these substances alone and in combination. Through a randomized clinical trial, Guitiérrez-Hellín et al. aurantium alone or in combination with caffeine would have different results for fat utilization during aerobic physical exercise. No superiority was found between C. aurantium alone and combined with caffeine on the total values of fat consumption during the physical exercise session, while both interventions were superior to the placebo treatment. This supports the isolated use of C. aurantium an alternate way to be applied as an adjunct in cutting body fat without inducing cardiac risk. In the study by Guitiérrez-Hellín et al. aurantium isolated supplement. In contrast, the HR and SBP were significantly higher when caffeine was included in the formulation. Our study achieved no changes for HR, and SBP was lessened more quickly following exercise. The identification of β-3 adrenoreceptors in cardiovascular tissues posed challenges to the paradigm of sympathetic regulation by β-1 and β-2 adrenoceptors. The binding response of p-synephrine to the β-3 receptor may elucidate why no increase in HR or BP is detected when C. aurantium is enforced alone. In contrast, when C. aurantium is combined with caffeine in dietary supplements, it is capable of affecting these parameters, particularly in caffeine-sensitive individuals It has been revealed that the combination of these substances promotes a significant increase in the concentration of plasma catecholamines e. The study by Kliszczewicz et al. aurantium upsurges sympathetic modulation to the heart throughout rest and corroborates the increases in HR and SBP achieved in the study by Guitiérrez-Hellín et al. It is assumed that caffeine alone can increase HR during physical exercise Despite that, a recent meta-analysis demonstrated that caffeine could not delay vagal return to the heart after exercise, evaluated by the HF and root mean square of successive differences between RR intervals RMSSD indices Equally, Kliszczewicz et al. aurantium combined. Caffeine and C. aurantium combination have no extra effects on exercise fat utilization 5. These substances appear to exhibit the opposite cardiovascular effects and, thus, caffeine seems to overlap the beneficial effects of the isolated use of C. aurantium on cardiovascular health. In this study, C. aurantium supplementation alone optimized the recovery of SBP and HRV indices after exercise. The nutritional characteristics demonstrated in the flavonoids e. aurantium perform antioxidant and anti-inflammatory activities, which are partly answerable for accelerating the return of parasympathetic control of heart rate seen by vagal indices of HRV. Such properties can hasten the removal of metabolites produced by physical exercise, restoring baroreflex sensitivity and decreasing metaboreflex activation more quickly at the end of physical exercise While C. aurantium exhibited cardioprotective effects, it is essential to be careful with its usage. Bui et al. Yet, in other studies that enforced doses beneath mg in an acute 5 , 30 , 31 and chronic for 15 days 32 form, no changes were achieved for the HR, SBP, and DBP values, nor electrocardiographic disturbances. Likewise, our results do not support the findings of Bui et al. The results from the study of Ratamess et al. In your results, the p-synephrine supplementation mg did not evoke changes in HR before, during, and following resistance exercise unless mg of caffeine was added to the formulation. The same occur in the rest situation, in another study by Ratamess et al. The study of Bui et al. Although it is a randomized and crossover study, there is a lack of information about allocation order in the study. aurantium, and provoked adjustments in blood pressure, because of higher sweet and fat content e. Furthermore, the authors did not report guarantees that snack was equal on the others evaluation days. Bitter orange caused cardiovascular effect was only observed based on statistical adjustments. A difference was seen compared to placebo but not when compared to baseline. All these factors raise questions about the validity of their conclusions. The results recognized in our analyses will advance health professionals' conduct who work with the prescription of nutritional supplements. Consequently, it may be an alternative way to replace other compounds that demonstrate similar contributions regarding fat utilization during exercise but that promote unwanted cardiovascular effects e. Our study highlights important points about the study population, given that it is restricted to healthy and physically active males. Notwithstanding the number of participants having exceeded the sample size calculation, the final sample is considered small. With the desire to improve body composition. In spite of this, these facts do not allow these results to be extrapolated to other populations and, therefore, further research with obese individuals is needed to confirm the safety of using C. aurantium in combination with exercise. For the time being, we prefer to use a healthy population free from metabolic disorders to prevent possible adverse events from C. aurantium supplementation. Nevertheless, we encourage further studies to be established with C. aurantium as an intervention with these preliminary data. Studies with females and other health conditions should also be performed to increase the external validity of these data and expand the application of C. aurantium promoted the resumption of parasympathetic control and output of sympathetic flow of cardiac rhythm after physical exercise and decreased SBP. Based on these and previous findings, we assume that C. aurantium is a safe nutritional compound with submaximal aerobic exercise in healthy males when used appropriately, moreover, your combination with a good diet there could be improved fat oxidation in exercise without the cardiovascular risk. The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation. The studies involving human participants were reviewed and approved by University Center of the Juazeiro do Norte Process: CJRB supervised the study, performed experiments, performed the statistical analysis, wrote the introduction, methods, discussion, and results in sections. FJ, ER, and MS collected data and performed conduction of experiments. AP performed the statistical analysis, improved interpretation analysis, and wrote the results in sections. DG drafted the manuscript, improved interpretation analysis, and reviewed English grammar and spelling. VV and CRBJ supervised the study, reviewed the manuscript content, and gave final approval for the version submitted for publication. All authors contributed to the article and approved the submitted version. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher. We thank the graduate research scholarships providing from Coordenação de Aperfeiçoamento de Pessoal de Nível Superior — Brasil CAPES, Finance Code and undergraduate research scholarships providing from University Center of the Juazeiro do Norte UniJuazeiro. McLester CN, Bailey P, Bechke EE, Williamson CM, McLester JR, Kliszczewicz B. The effects of caffeine and citrus aurantium on performance during repeated maximal anaerobic exercise bouts in habitual caffeine users. J Strength Cond Res. doi: PubMed Abstract CrossRef Full Text Google Scholar. Stohs SJ. Safety, efficacy, and mechanistic studies regarding citrus aurantium bitter orange extract and p-synephrine. Phytother Res. Content provided by DolCas Biotech, LLC. Viable natural product options for "healthy weight management" in the age of Ozempic and other GLP-1 inhibitors will require targeted innovations Content provided by KLK OLEO Jan Product Brochure. MCTs Medium-Chain Triglycerides is a versatile single or blend of saturated medium-chain-length fatty acids derived from renewable natural sources. Content provided by BIONAP BIOACTIVE NATURAL PRODUCTS Oct Product Brochure. Bionap also this year will showcase a selection of sustainable plant-based health and wellness solutions at booth SupplySide West that will Content provided by ADM: Innovation that Feeds the Future Oct White Paper. A growing body of evidence shows gut health can affect digestive health, well-being, and many health areas in between. Posted by Mike Budd , 25 September - GMT. Report abuse. Posted by chris aylmer , 30 August - GMT. CONTINUE TO SITE Or wait Polyphenol extracts as weight management catalysts Content provided by DolCas Biotech, LLC. BIONAP AT SUPPLY SIDE WEST Content provided by BIONAP BIOACTIVE NATURAL PRODUCTS Oct Product Brochure Bionap also this year will showcase a selection of sustainable plant-based health and wellness solutions at booth SupplySide West that will Custom Biotic Solutions for Digestive Health Content provided by ADM: Innovation that Feeds the Future Oct White Paper A growing body of evidence shows gut health can affect digestive health, well-being, and many health areas in between. Fruit d'Or. Structural similarity of p-synephrine to ephedrine Posted by Mike Budd , 25 September - GMT P-synephrine and ephedrine are using the same sympathetic pathways and in both cases, caffeine is used to oppose the effect of adenosine, which inhibits norepinephrine. Clever but risky com Report abuse Disabled athlete stimulant? Posted by chris aylmer , 30 August - GMT Some people, particularly those with spinal injuries, resort to various means of increasing heart rate and blood pressure for competing more successfully in their sports. |
Citrus aurantium and cardiovascular health -
After acclimatization, the animals were allocated randomly into 4 groups 6 in each group. The volume of solution injected was same in all groups.
Total duration of experiment was two weeks and all experiments started at 9 am every day. ECG recordings obtained through computerized Power Lab system AD Instruments, Australia and analyzed with chart7 software. After recording the ECG, the animals were sacrificed and blood samples were taken.
Samples were centrifuged at rpm for ten minutes. Serum was taken and kept at 0C, and then CK-MB, LDH, ALP, AST, ALT, and lipid profile were measured using routine laboratory kits Pars Azmoon, Tehran.
Serum LDL-cholesterol was calculated by the Friedewald formula. MDA, SOD, GP X , GSH, and CAT were measured using Zell Bio kit Zell Bio GmbH, Deutschland and ELISA method. The fixed tissues were inserted in paraffin, sectioned at 5 µm and stained with hematoxylin and eosin [17].
The samples were observed under light microscope, and then photomicrographs were taken. It should also be mentioned that grading of histopathological changes was classified by a blind pathologist as: low, mild focal myocytes injury or multifocal deterioration with a mild degree of inflammation , moderate myofibrillar degeneration or moderate inflammatory process and severe necrosis with extensive inflammatory process.
Citrus aurantium flowers were taken from Shiraz, Iran, in The plant was recognized and authenticated by the botany department of Sistan and Baluchistan University.
During the time of experiments, the extract was dissolved in saline and animals were forced-fed with above-mentioned doses [14]. Data is expressed as mean ± SE. Statistical analysis was done by SPSS software version The effects of ISO and citrus aurantium extract treatment on pattern of ECG are depicted in Figure 1 and Table 1.
Control and citrus aurantium treated rats showed normal pattern of ECG, whereas rats treated with ISO showed a significant increase in S-T voltage, decrease in R amplitude as compared to control rats, suggestive of myocardial infarction.
ISO treated rats likewise displayed the pathological Q wave, demonstrating transmural myocardial infarction induction. Also, a significant decrease in QRS and R-R interval and a significant increase in heart rate were detected in rats treated with ISO. Figure 1: Electrocardiographic patterns in control A , ISO B , pretreated with citrus aurantium extract then treated with ISO C and citrus aurantium alone D groups.
Table 1: Effect of citrus aurantium pretreatment on electrocardiographic parameters in ISO induced myocardial infarction in rats.
Table 2 represents the effects of ISO and citrus aurantium extract treatment on cardiac marker enzymes such as CK-MB, LDH, ALP, AST and ALT. ISO treated rats showed an increased significantly in activities of these enzymes as compared to the control group.
ISO treated animals that pre-treated with citrus aurantium extract exhibited significantly decrease the CK-MB, LDH, ALP, AST and ALT activities. No significant difference was detected in rats treated with the extract alone when compared to control rats. Table 2: Effect of citrus aurantium pretreatment on cardiac marker enzymes in ISO induced myocardial infarction in rats.
The levels of MDA and GSH along with the activities of the enzymes GP X , SOD, and catalase in normal and experimental rats are listed in Table 3. The value of MDA, end product of lipid peroxidation and marker for oxidative stress, showed significantly increase in ISO treated rats, as compared to the control group.
ISO treatment also caused in the significant decrease in the level of GSH, an endogenous antioxidant in comparison with normal control rats. Activities of glutathione-dependent antioxidant enzyme and antiperoxidative enzymes were significantly lowered in ISO treated rats as compared to the control group.
Pre and co-treatment with citrus aurantium in MI induced by ISO rats significantly decreased the level of MDA as compared to rats treated with ISO alone. The pre-treatment of citrus aurantium for 14 days resulted in a significant rise in the level of GSH and activities of GP X , SOD and catalase.
Normal rats that receive citrus aurantium alone did not display any substantial alteration when compared with other normal rats, indicating that it does not per se have any adverse effects. Table 3: Effect of citrus aurantium pretreatment on lipid peroxidation, endogenous antioxidant and antioxidant enzymes in ISO induced myocardial infarction in rats.
Table 4 lists the levels of total cholesterol, HDL, LDL and triglycerides in the serum of all groups of animals. Rats treated with ISO only exhibited a significant rise in these parameters with the levels of HDL-cholesterol being an exception where there was a significant decrease.
Pre-treatment of citrus aurantium for 14 days beside with ISO administration on 13 th and 14 th days considerably reduced the levels of LDL and triglycerides with a following noteworthy increase in the levels of HDL-cholesterol as compared to ISO alone treated rats.
No significant change in total cholesterol was observed when compared to ISO treated group. In the citrus aurantium alone group, there was no substantial alteration detected in serum lipoproteins and triglycerides levels in comparison to those of the control rats.
Figure 2 illustrates the histological photographs of heart tissues of all studied groups. Histopathological analysis of myocardial tissue achieved from normal control animals displayed clear integrity of membrane of myocardial cells.
Normal untreated rats indicated typical cardiac tissues without any infarction and infiltration of inflammatory cells was not seen in this group. Histopathological results revealed that the ISO caused induction of MI in cardiac muscle.
Tissues sample from myocardial infarction induced by ISO, exhibited extensive myocardial structure abnormality and subendocardial necrosis with capillary dilatation and leukocyte infiltration as compared to the control group.
Prior administration of citrus aurantium showed reduced grade of infiltration of inflammatory cells and the appearance of myocardial cells was comparatively well conserved with no evidence of focal necrosis.
Extract treated group rats displayed no change in morphology of heart tissue as compared to the normal control group. The pathophysiology mechanism of MI has not been fully revealed.
Although catecholamines have regulatory effect on contraction and metabolism of myocardial muscle, these substances may be responsible for cell damages in the long term.
The same situation can be observed in clinical situations such as angina, temporary myocardial hypoxia, acute inadequacy in coronary blood flow and subendocardial infarction. Isoproterenol, a potent synthetic catecholamine, can improve injuries like myocardial infarction when injected in animals.
These lesions are apparently same to those of coagulative myocytolysis or myofibrillar deterioration. This is one of the findings during acute MI and unexpected death in man [18,19].
Different mechanisms have been reported as responsible for induction of myocardial infarction by ISO. Previous reports recommended that coronary inadequacy, sarcoplasmic calcium excess, changed metabolic and electrolyte balancing system and oxidative stress are the main causative factors in catecholamine induced cardiac insufficiency [20].
Imbalance between oxygen delivery and request of myocytes after coronary hypotension and cardiac muscle hyperactivity due to augmented heart rate and contractility could cause myocardial damage [21]. Interaction of ISO with β1 and β2 adrenoceptors, activation of which causes to positive inotropic and chronotropic effects on heart, which produce relative ischemia due to myocardial hyperactivity and coronary hypotension [22].
ECG deliberated the single most important primary clinical exam for diagnosis of infarction and ischemia in cardiac muscle and.
In our study, ISO administration causes pathological Q wave in rats, the most characteristic finding of transmural MI of the left ventricle. Administration of ISO also showed a decline in R-R interval, and increase in QRS time and heart rate.
These changes could be due to the damage of cell membrane in injured cardiac muscle [23]. It has been exposed that a rise in heart rate is responsible for augmented oxygen consumption causing to enhanced necrosis of myocardial tissue [24]. ISO also increased ST-segment voltage and decreased R- wave voltage.
This is favorable with the comments of earlier reports. ST-segment elevation reproduces the potential difference in the border between ischemic and non-ischemic regions and consequences in loss of cell membrane function whereas decrease in R-wave voltage might be due to the start of myocardial edema subsequent ISO treatment [25].
Citrus aurantium pre-treatment in ISO treated rats prohibited the pathological changes in the ECG, which suggest s protective effect for its cell membrane. Cardiac muscle contains different diagnostic markers of MI and when heart metabolism injured, it discharges its contents into the extracellular fluid [26].
Cytotoxic enzymes such as CK-MB, LDH, AST, ALT and ALP, which serve as diagnostic markers, could be released from tissues damaged in the circulation due to permeable or disagreement of cell membrane and reflect the changes in plasma membrane integrity [27].
Our data confirmed significant increase in the levels of these enzymatic biomarkers of serum in ISO treated rats, which were in same direction with previous reports. Citrus aurantium pre-co-treatment caused in the dropped activity of the marker enzyme in serum.
It validated that citrus aurantium could sustain cell membrane integrity, thereby limiting the leakage of these enzymes. Free radical scavenging enzymes for example SOD, catalase and GP X are the first line of cellular protective system against oxidative stress, excluding reactive oxygen spices ROS such as superoxide and hydrogen peroxide.
These enzymes inhibit the formation of more worsening hydroxyl radical. The additional line of guard includes non-enzymatic scavengers such as vitamin C, vitamin E and sulphydryl containing compounds, which hunt remaining free radicals evading decomposition by the antioxidant enzymes [28].
The balance between antioxidant capacity and formation of free radicals is an essential process for the real elimination of oxidative stress in intracellular organelles.
Though, in pathological situations similar to MI, the production of ROS can strongly interrupt this equilibrium with an augmented request of the antioxidant protection system [29]. Auto-oxidation induced by ISO can lead to production of massive quantity of ROS, which may attach any type of molecules such as polyunsaturated fatty acids in cell membrane forming peroxyl radicals, producing a chain reaction of lipid peroxidation [29].
This process is an essential pathogenic event in necrosis of myocardial tissue. In the current study, treatment with ISO caused in significant raise in peroxidation of lipids, represented as MDA value, which is in same direction with former reports [26,31].
Citrus aurantium pre-co-treatment displayed an important decrease in the value of serum MDA content which can be related to strong antioxidant capacity of extract against ISO auto-oxidation produced free radicals. Activities of antiperoxidative enzymes SOD and catalase were declined considerably in serum of ISO treated rats.
Superoxide dismutase, which catalysis the dismutation of two superoxide radicals to form hydrogen peroxide and molecular oxygen. Therefore, the H 2 O 2 created is deactivated by either catalase or the GSH redox system containing of reduced glutathione as the cofactor for GP X and glutathione reductase [32].
Citrus aurantium pre-co-treatment exhibited a substantial increase in the level of serum SOD and catalase. These enzymes could not alter in the citrus aurantium animal group. In the current study, our data confirms a declined concentration of GSH and GP X in serum of ISO treated rats.
GSH, a tripeptide, one of the greatest non-enzymatic antioxidant biomolecules, is existing in the body. GSH has a direct antioxidant role by reacting with superoxide radicals, peroxy radicals and singlet oxygen followed by the creation of oxidized GSH and other disulfides [33].
Diminished activity of these enzymes lead to formation of oxidants and make cardiac myocytes membranes more susceptible to oxidative injury. The current study revealed a significant increase in the value of GSH and activity of GP X in the serum of citrus aurantium pre-co-treated rats.
Lipids play a significant role in cardiovascular diseases. A considerable rise in the total cholesterol and triglycerides was detected in serum of ISO treated rats, which is in line with previous reports [15,19].
Rats treated with ISO also exhibited an increase in LDL fraction along with a decline in HDL cholesterol. These alterations could be credited to improved lipid biosynthesis by cardiac cyclic adenosine monophosphate [34]. A sturdy positive correlation has been document among the risk of emerging ischemic heart disease and serum LDL level, while a negative correlation has been stated with HDL-cholesterol [35].
The pre-co-treatment with citrus aurantium effectively restored the elevated triglycerides, LDL-cholesterol and total cholesterol and decreased HDL-cholesterol in the serum of this group.
Histopathological investigation of the cardiac muscle tissue in the control rat group represented clear integrity of the cardiac myocytes membrane and no inflammatory cell infiltration was detected.
ISO treated rats group showed a cellular dissociative view with marked inflammatory infiltration. The pre-co-treatment with citrus aurantium extract showed reduced inflammatory cell infiltration and relatively normal view of myocardial cells. This confirmed cardio protective effect of hydroalcholic citrus aurantium extract on MI induced by ISO in rats.
In conclusion, we can say that the current study confirmed that subcutaneous high-dose injections of isoproterenol can produce MI in rats as evident from the release of myocytes damage markers in serum.
Furthermore, provided with experimental evidence, the hydroalcholic citrus aurantium extract preserved antioxidant enzyme levels and enhanced cardiac performance. This conclusion may be a new way to understand the useful effects of citrus aurantium extract on cardio protection against myocardial injury, in which oxidative stress has long been identified to contribute to pathogenesis.
The authors are grateful to the Deputy of research and technology of Zahedan University of Medical Sciences for their financial support of research project no The authors acknowledge the department of Physiology and Biochemistry at Zahedan University of Medical Sciences for the support provided for this work.
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Journal of. Research Article Volume 10 Issue 3. Go to Article Title Abstract Introduction Materials and methods Results Discussion Conclusion Acknowledgement Conflict of Interest References.
Chemicals Isoproterenol hydrochloride was purchased from Sigma Aldrich Chemical Company, St. Animals All experiment and procedures defined in this study were approved by the local ethics committee of Zahedan University of Medical Sciences.
Experimental design After acclimatization, the animals were allocated randomly into 4 groups 6 in each group. Biochemical analysis After recording the ECG, the animals were sacrificed and blood samples were taken.
Plant preparation and extraction Citrus aurantium flowers were taken from Shiraz, Iran, in Statistical analysis Data is expressed as mean ± SE. All values are presented as Mean ± S.
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Experientia ;— Download references. You can also search for this author in PubMed Google Scholar. Department of Experimental and Clinical Pharmacology, University of Minnesota, Minneapolis, MN. SafetyCall International, PLLC, Clinical Services, Bloomington, MN. Reprints and permissions.
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Copyright Fueling strategies for ultramarathon runners Quick fat burn Tsolakou et al. This cardiovasculae an aurantiumm access article distributed under the terms of Fueling strategies for ultramarathon runners Xnd Attribution License ajrantium BY 4. Lipids are absorbed in the intestines and are transported throughout the body helth lipoproteins for energy, steroid production, or bile acid formation. Cholesterol, low-density lipoprotein LDL -cholesterol LDL-Ctriglycerides TGs and high-density lipoprotein HDL -cholesterol HDL-Ccontribute to these pathways. An imbalance in any of these factors, either from organic or non-organic causes, can lead to dyslipidemia 1. Dyslipidemia may be assessed by evaluating the fasting levels of these lipids in serum. Lipid disorders are frequently encountered in clinical practice and often have implications for cardiovascular risk and general health 3.
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