The researchers said CA might directly suppress adipogenesis of white adipocytes and regulate thermogenesis of brown adipocytes which were both attractive targets of anti-obese strategy.

Adipocyte differentiation or adipogenesis is the process by which pre-adipocytes become adipocytes lipocytes or fat cells. The paper also reported that CA could regulate thermogenesis of brown adipocytes.

According to the researchers, brown fat specialise in energy expenditure to reduce weight gain through thermogenesis heat producing. Also known as sour orange or marmalade orange, CA is available on the market as a beverage and dietary supplement. Show more. Content provided by Gencor May Product Brochure.

ActivAMP® is extracted from an adaptogenic herb, that contains a family of compounds that upregulate alarmins - including sestrins — which activate an CONTINUE TO SITE Or wait A control group was fed a normal diet ND for 12 weeks. Flumazenil, a competitive antagonist of benzodiazepine binding, and the selective 5-HT 1A receptor antagonist WAY were used in the experimental procedures to determine the mechanism of action of the EO.

To exclude false positive results due to motor impairment, the mice were submitted to the rotarod test. Acute treatment with the EO showed no activity in the forced swim test, which is sensitive to antidepressants. A neurochemical evaluation showed no alterations in neurotransmitter levels in the cortex, the striatum, the pons, and the hypothalamus.

Furthermore, no locomotor impairment or signs of toxicity or biochemical changes, except a reduction in cholesterol levels, were observed after treatment with the EO.

Conclusion: This work contributes to a better understanding of the biological activity of C. aurantium EO by characterizing the mechanism of action underlying its anxiolytic-like activity.

Abstract Background: The current treatments for anxiety disorders and depression have multiple adverse effects in addition to a delayed onset of action, which has prompted efforts to find new substances with potential activity in these disorders.

Population studies suggest that limonene may prevent certain cancers, namely colon cancer. However, more rigorous human research is needed An ongoing study is also exploring the use of limonene as a treatment for COVID However, the results are not yet known.

Bear in mind that limonene cannot prevent or cure COVID Another protoalkaloid found in bitter orange is p-octopamine. However, little to no p-octopamine exists in bitter orange extracts.

The leaves of the bitter orange plant are rich in vitamin C , which acts as an antioxidant. Antioxidants are substances that may protect your body from disease by preventing cell damage. They work by deactivating free radicals, which are unstable compounds that damage your cells, increasing inflammation and your disease risk 15 , Protoalkaloids are plant compounds found in bitter orange that have anti-inflammatory and antiviral properties.

They have been shown to be safe for consumption. Many weight loss supplements use bitter orange extracts in combination with other ingredients. However, scientific studies have not thoroughly examined the composition of these supplements to determine which ingredient, if any, supports weight loss.

Notably, p-synephrine has been shown to increase fat breakdown, raise energy expenditure, and mildly suppress appetite , all of which may contribute to reduced weight. Yet, these effects occur at high doses that are discouraged due to the lack of safety information 4 , 8 , Bitter orange and its extracts are used in Traditional Chinese Medicine TCM to treat indigestion, diarrhea, dysentery, and constipation.

In other regions, the fruit is used to treat anxiety and epilepsy 3. Another study noted that the bitter orange compound p-synephrine may improve athletic performance though by increasing total reps and volume load, or your ability to train harder A stimulant is a substance that increases your heart rate and blood pressure 1.

Several sports organizations, such as the National Collegiate Athletic Association NCAA , list synephrine as a stimulant. Furthermore, one study determined that bitter orange juice contains furanocoumarin, a compound that may cause the same medication interactions as grapefruit juice Therefore, people taking decongestants or those who have high blood pressure, an irregular heartbeat, or glaucoma should avoid the juice and fruit of bitter oranges.

Despite numerous studies showing that bitter orange extracts are not stimulants, widespread controversy exists, and the NCAA has listed it as a banned substance. Bitter orange may also interact with certain medications.

Generally, bitter orange extracts in dietary supplements are safe to consume in doses of 50—98 mg per day 1 , One study showed that 40 mg of synephrine combined with mg of caffeine is a safe dose of these combined ingredients 3. In another study, eating a whole bitter orange containing Still, people who are pregnant or breastfeeding should avoid bitter orange due to a lack of safety information 1.

Bitter orange is likely safe in doses ranging from The juice of the bitter orange can be used as a marinade to flavor fish and meat. Bitter orange has several other household uses outside of the kitchen. These include 2 :. Bitter orange is a citrus fruit with several household and industrial uses, ranging from food additives to perfumery.

You may want to avoid this fruit and its extracts if you have high blood pressure, an irregular heartbeat, or glaucoma. Likewise, bitter orange supplements are banned for NCAA athletes. Our experts continually monitor the health and wellness space, and we update our articles when new information becomes available.

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Evaluation of the efficacy of the combination of Citrus aurantium , Cistus creticus and Olea europaea leaf extract on the lipid profiles of individuals with marginally elevated lipid levels Authors: Annia Tsolakou Dimitrios Konstantinidis Vassiliki Economou Stamatis Boulis Evangelia Koutsogiannouli Costas P.

Tsioufis Nikolaos Drakoulis View Affiliations Affiliations: Research Group of Clinical Pharmacology and Pharmacogenomics, Faculty of Pharmacy, School of Health Sciences, National and Kapodistrian University of Athens, Athens, Greece, First Cardiology Clinic, Hippokration Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece, Votaniche S.

A, Athens, Greece. Metrics: Total Views: 0 Spandidos Publications: PMC Statistics: Metrics: Total PDF Downloads: 0 Spandidos Publications: PMC Statistics:.

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Pilc A, Nowak G: GABA-ergic hypotheses of anxiety and depression: Focus on GABA-B receptor. Drugs Today Barc. Hernandez L, Munoz RA, Miro G, Martinez M, Silva-Parra J, Chaves PI: Use of medicinal plants by ambulatory patients in Puerto Rico.

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Leite MP, Fassin-Jr J, Baziloni EMF, Almeida RN, Mattei R, Leite JR: Behavioral effects of essential oil of Citrus aurantium L. inhalation in rats.

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J Pharm Science Res. Download references. We are grateful to Dr. Márcia Ortiz M Marques and Dr. Roselaine Facanali Laboratory of Natural Products — Instituto Agronômico IAC , Campinas, Brazil for the GC-MS analysis of the EO and to Vinícius Bertotti Ribeiro for technical assistance. This work was supported by grants from FAPESP Celso ARA Costa — Proc.

Department of Pharmacology, Institute of Biosciences, Unesp - Univ Estadual Paulista, P. Box , , Botucatu, São Paulo, Brazil.

Department of Pathology, School of Veterinary Medicine and Animal Science, Unesp - Univ Estadual Paulista, Laboratório Clínico Veterinário, , Botucatu, SP, Brazil. Department of Pathology, School of Veterinary Medicine, USP - University of São Paulo, Av.

Orlando Marques de Paiva, 87, São Paulo, SP, Brazil. You can also search for this author in PubMed Google Scholar. Correspondence to Mirtes Costa.

CARAC participated in the design of the study, carried out all the experimental procedures and drafted the manuscript. TCC and BOC participated in experimental protocols and analyzed the behavioral data. RKT made and supervised all biochemical analyzes.

JCF participated in the design of the study and made the neurochemical analyses. MC supervised the entire project, participated in its design and statistical analysis and helped to the final form of the manuscript.

The work was part of the Ph. dissertation of CARAC and the graduation work of TCC and BOC. All of the authors significantly contributed to and have approved the final manuscript. This article is published under license to BioMed Central Ltd.

Reprints and permissions. Costa, C. et al. Citrus aurantium L. essential oil exhibits anxiolytic-like activity mediated by 5-HT 1A -receptors and reduces cholesterol after repeated oral treatment.

BMC Complement Altern Med 13 , 42 Download citation. Received : 11 September Accepted : 11 February Published : 23 February Anyone you share the following link with will be able to read this content:.

Sorry, a shareable link is not currently available for this article. Provided by the Springer Nature SharedIt content-sharing initiative. Skip to main content. Search all BMC articles Search. Download PDF. Research article Open access Published: 23 February Citrus aurantium L. Abstract Background The current treatments for anxiety disorders and depression have multiple adverse effects in addition to a delayed onset of action, which has prompted efforts to find new substances with potential activity in these disorders.

Also known as sour orange or marmalade orange, CA is available on the market as a beverage and dietary supplement. Show more. Content provided by Gencor May Product Brochure. ActivAMP® is extracted from an adaptogenic herb, that contains a family of compounds that upregulate alarmins - including sestrins — which activate an CONTINUE TO SITE Or wait A control group was fed a normal diet ND for 12 weeks.

The researchers said this could suggest CA can regulate the weight of HFD-fed mice. J Cardiol Curr Res 10 2 : DOI: Download PDF.

The citrus aurantium has traditionally been used by the people of Iran. The aim of this study was to evaluate the protective effects of hydroalcholic citrus aurantium extract on electrocardiographic, biochemical and pathological changes after myocardial infarction induced by isoproterenol in rats.

At the end of the experiment, ECG was recorded in lead II. Finally, blood samples were taken and cardiac marker enzymes such as creatine kinase, lactate dehydrogenase, aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase, along with oxidative stress markers such as malondialdehyde, superoxide dismutase, catalase, glutathione reductase, glutathione peroxidase, and lipid profile were determined.

Myocardial infarction induced by isoproterenol produced a significant increase in the heart rate, ST-segment elevation, decrease in R amplitude, and a significant increase in the level of cardiac marker enzymes: LDH, CK-MB, AST, ALT and ALP in serum.

Also, isoproterenol significantly reduced SOD, CAT, GSH, GP X and increased MDA activity, disturbance in lipid profile, and inflammatory process in cardiac myocytes. Pretreatment with citrus aurantium extract for two weeks significantly reduced the effect of isoproterenol on electrocardiographic parameters, cardiac biomarkers, oxidative stress indices, lipid profile and cardiac myocytes injuries.

Results indicated that citrus aurantium extract ameliorates the cardio-toxic effects of isoproterenol through reinforcement of antioxidant defense system and may be of value in treatment of myocardial infarction.

Further studies are required to determine the precise mechanism of the therapeutic effect of the extract. Keywords: Citrus aurantium ; Isoproterenol; Myocardial infarction; Rat. Although clinical care has been amended, public awareness elevated and health innovations are commonly used, Myocardial infarction [1] still remains the prominent cause of death worldwide [1].

According to the World Health Organization WHO , it will be the most important cause of death in the world by the year [2]. MI is one of the usual forms of ischemic heart disease. The principle contributing factor in pathophysiologic condition of myocardial ischemia is disproportion in myocardial oxygen supply and demand.

During myocardial ischemia, a wide range of cellular metabolic errors and structures damage mechanical dysfunction of myocardium by production of free radicals and reactive oxygen species leading to destruction of proteins, nucleic acids, carbohydrates as well as a variety of membrane lipids and subsequent cell deaths [3].

So, by considering the correlation with the pathogenesis of coronary artery diseases, oxidative stress accelerates generation of reactive oxygen species ROS and reduces antioxidant defenses [4]. Isoproterenol, a synthetic β-adrenoceptor agonist, has been found to induce MI in rats as an outcome of disorder in physiological balance between creation of free radicals and the antioxidant defense system [5].

It is the acute form of myocardial necrosis which sources cardiac malfunctions, increased lipid peroxidation, changed activities of cardiac enzymes and antioxidants [6].

Cardiac muscle necrosis induced by ISO, involves membrane permeability changes that produce loss of function and integrity of the cell membrane. Use of ISO drains the energy reserves of myocardial cells and complex biochemical and structural changes producing cell injury, which is preface to necrosis [7].

Citrus aurantium L. is commonly dispersed in tropical and subtropical southeast areas of the world. The dried and immature peels of the citrus fruit are used in traditional herbal medicine [8]. This plant is a native and is commonly used in medicinal plants in Iran.

In traditional Iranian medicine, the flowers of this plant were used for the treatment of neurological disorders such as hysteria, and seizures. In addition, this plant has been known as a sedative-hypnotic, appetizer and palpitation remover. Chemical compounds found in the plant are hydrocarbons, alcohols, some form of acetate, acids and phenols.

Flavonoids are a class of polyphenols that are present in extracts of citrus aurantium flowers [9]. Citrus fruits are a common food source because of their nutrient, flavor, and intrinsic characteristics.

They have long been the basis for usually used traditional medicines in some Asian countries [10]. Amid nutrients of citrus fruits, flavonoids have been more lately documented as having several benefits that contain antioxidant, antimicrobial, anti-inflammatory, and anti-cancer properties [11,12].

The flavonoids extracted from citrus fruit containing c itrus aurantium L. are mostly consisted of hesperidin, naringenin, and nobiletin.

These flavonoids have been stated to have some properties that adjust the inflammatory response and halts carcinogenesis [13]. According to that, since the inflammatory process and antioxidant system involves MI induced by ISO, we hypothesized that this plant extract may have cardio protective effects.

The purpose of this study was to explore the possible antioxidant effect of c itrus aurantium flower extract and cardio protection against MI induced by ISO through electrocardiographic, myocardial marker injury, lipid profile changes as well as peroxidation of lipids, changes in antioxidant system and histopathological parameters.

Isoproterenol hydrochloride was purchased from Sigma Aldrich Chemical Company, St. Louis, MO, USA. Lipid peroxidation product MDA and antioxidant assay kits SOD, GSH, CAT, GP X were bought from Zell Bio Company, Germany.

Other biochemical substances were of analytical grade and purchased from Pars-Azmoon Company, Iran. All experiment and procedures defined in this study were approved by the local ethics committee of Zahedan University of Medical Sciences. Animals were fed with standard pellet diet and water ad libitum.

at 24 h interval for 2 days to experimental myocardial infarction induction [16]. 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.