Potential Effect of Sour Orange Peel Citrus Aurantium Supplementation on Lipid Profile and Liver Function of Albino Rats Fed on High Fat Diet. The present study was carried out to investigate the effects of supplemented high fat diet HFD with two levels 1.

A total of 36 male albino rats weighing 40±5g were used. The rats were divided into two main groups. The second main group 30 rats fed on high fat diet HFD and divided into five subgroup.

The other 4subgroups were fed or HFD supplemented with two levels 1. At the end of experiment, rats were sacrificed and blood samples were collected, then serum was separated, glucose, leptinlevel, lipid profile as well as AST, ALT and ALP enzymes were determined.

In conclusion,the results showed that administration of citrus unripe or ripe sour orange peel at levels 3 or 1. Over weight and obesity are the fifth leading risk for global death. At least 2. Obesity is a significant and increasing public health problem worldwide.

Even through there are several treatments, such as surgery and drugs, there seems to be no efficient treatment without potential side effects. In addition to a lifestyle modification, natural alternatives may provide increased health expectancy.

Several plants possess anti-obesity potential and have been poorlystudied, while others are not even promoted Claudia et al. Polymethoxy flavones the major components of orange peel have been found to have health benefits including anti-inflammatory, anti-carcinogenic, anti-viral anti-oxidant, anti-thrombogenic and anti-atherogenic properties Li et al.

Therefore, the present study was carried out to investigate the effects of supplemented HFD with DURSOP or DRSOP on serum leptin, glucose, lipid profile and liver enzymes of albino rats. Sour orange Citrus aurantium were obtained from El Abour market.

The raw orange ripe and unripe were washed carefully and peel cut into small pieces to be exposed to solar energy at national research center and ground to fine powder. Casein, vitamins,minerals, cellulose, choline chloride were obtained from Elgomhoria Company, Cairo, Egypt.

Kits for biochemical analysis were obtained from Gamma trade Co-for Pharmaceutical and chemicals. Dokki, Egypt. Thirty-six male albino rats of Sprague Dawleystrain 25 days age 40±5 g b. wt were obtained from the laboratory of animal's colony, ministry of health and population, Helwan, Cairo, Egypt.

Rats were housed in individual cages under hygienic laboratory conditions and were fed on basal diet adlibitum for one week for adaptation in the animal house of faculty of Home Economics, HelwanUniversity.

Reeves et al. The salt mixture and vitamin mixture were prepared according to Hegested et al. After a period of adaptation on basal diet, rats were divided into two main groups.

The first main group 6 rats fed on basal diet negative group. Supplementation of diet with dried unripe or ripe dried peel of sour orange was at the expense of starch. Rats of the second main group were divided into five subgroups.

one of them 6 rats was fed on HFD used as a positive control group and the other four subgroups were fed on HFD containing 1. At the end of the experiment period, the rats were starved for 12h and then sacrificed under ether anaesthetized.

Blood samples were collected from hepatic portal vein by the means of fine capillary glass tubes Schermer, Blood samples were received into clean dry centrifuge tube and left to clot at room temperature, then centrifuged for 10 minutes at r.

to separate serum. Serum was careful separated into dry clean Wasserman tubes, using a Pasteur pipette and kept frozen at o C till estimation of some biochemical parameters. Serum samples used for determination of total cholesterol Allain et al.

While serum low- density lipoprotein cholesterol LDL-C and very low-densitylipoproteincholesterol VLDL-C were calculated according to theequation of Friedwald et al. Serum Aspartate Amino Transferase AST and Alaine Amino Transferase ALT Reitman and Frankel, andAlkalinephosphatase ALP Belfield and Goldberg , Statistical analysis:was carried out using SPSS statistical software version 11 SAS.

Effect of sour orange peel citrus aurantium on lipid profile of Albino Rats fed on high fat diet. In this respect Wu et al. Our results revealed that all animals groups which fed on HFD supplemented with 1. Concerning the TG results revealed that groups fed on HFD supplemented with 1.

The phenolic and flavonoids compounds extracted from DURSOP and DRSOP it could be identify 18 fraction, characterizes with high amounts of Naringin, Hespirdin ,Apig 6 rhamnose 8- glucose , Rutin and Quercetrin to be the predominant compounds.

Concerning phenolic compounds resulted in 19 fraction, while DRSOP showed 21 fraction. The predominant phenolic in DRSOP was pyrogallol, whichamounted The predominant phenolic in DURSOP , isoFerulic, Benzoic,Ferulic, catechein, P-OH-benzoic, caffeine and 3.

Therefore, our results revealed that Egyptian sour orange peel have considerable number of healthy compounds namely polyphenols and flavonoids.

Biological results also showed that the supplementation of HFD with DURSOP or DRSOP at levels 3 or 1. In this respect , lee et al.

In this concern kelleya et al. Citrus peel treatment reduced body weight gain and decreasedepididymal fat, mesenteric fat, plasma and hepatic TG levels Karagozlu et al.

Concerning serum lipoprotein cholesterol resultpresented in table 2 showed the effect of HFD supplemented with 1. Our results revealed that all animal groups fed on HFD supplemented with 1. On the other hand result showed that all groups fed on HFD supplemented with 1.

It is known that there is a correlation between lipoprotein cholesterol changes and obesity. In obesity HDL-clevel and elevation of HDL-C is one of the targets for ant-obesity treatment Vozarova et al.

Effect of sour orange peel Citrus aurantium on serum glucose, leptin and liver functions in albino rats fed on high fat diet. Content provided by Horphag Research Feb Clinical Study. New research shows Pycnogenol® French maritime pine bark extract may be effective in managing hyperactivity and impulsivity in children aged six to twelve, CONTINUE TO SITE Or wait Gencor Pacific Limited Content provided by Gencor Oct Product Brochure In a recent clinical trial backing its ingredient Libifem® for improved muscle strength, power, endurance and body composition with a females-only popluation Pycnogenol® May Be Effective for Managing Pediatric ADHD Without Side Effects Content provided by Horphag Research Feb Clinical Study New research shows Pycnogenol® French maritime pine bark extract may be effective in managing hyperactivity and impulsivity in children aged six to twelve, Facebook Twitter Linkedin.

South Korean regulator steps up online inspection against fake ads Daiken Biomedical leverages Japan patent for triple-action formula to strengthen consumer trust and fuel business growth. Oral administration of limonin before D-GalN injection, significantly attenuated markers of hepatic damage elevated liver enzyme activities and total bilirubin and hepatic inflammation TNF-α, infiltration of neutrophils , oxidative stress and expression of TLR-4 but not TLR-2 in D-GalN-treated rats.

Limonin effects were similar in most aspects to that of the lignan silymarin. Limonin exerts protective effects on liver toxicity associated with inflammation and tissue injury via attenuation of inflammation and reduction of oxidative stress.

This is a preview of subscription content, log in via an institution to check access. Rent this article via DeepDyve. Institutional subscriptions. J Viral Hepat — Article CAS PubMed Google Scholar. Chaung SS, Lin CC, Lin J, Yu KH, Hsu YF, Yen MH The hepatoprotective effects of Limonium sinense against carbon tetrachloride and beta-d-galactosamine intoxication in rats.

Phytother Res — Article PubMed Google Scholar. Cotroneo TM, Nemzek-Hamlin JA, Bayliss J, Su GL Lipopolysaccharide binding protein inhibitory peptide alters hepatic inflammatory response post-hemorrhagic shock.

Innate Immun — Decker K, Keppler D Galactosamine induced liver injury. In: Popper H, Schaffner F Eds Progress in liver disseases. Dolganiuc A, Oak S, Kodys K, Golenbock DT, Finberg RW, Kurt-Jones E, Szabo G Hepatitis C core and nonstructural 3 proteins trigger toll-like receptor 2-mediated pathways and inflammatory activation.

Gastroenterology — Duesberg U, von dem Bussche A, Kirschning C, Miyake K, Sauerbruch T, Spengler U Cell activation by synthetic lipopeptides of the hepatitis C virus HCV -core protein is mediated by toll like receptors TLRs 2 and 4. Immunol Lett — Article Google Scholar. Ellman GL Tissue sulfhydryl groups.

Arch Biochem Biophys — El-Mofty SK, Scrutton MC, Serroni A, Nicolini C, Farber JL Early reversible plasma membrane injury in galactosamine-induced liver cell death. Am J Pathol — CAS PubMed Google Scholar. El-Readi MZ, Hamdan D, Farrag N, El-Shazly A, Wink M Inhibition of P-glycoprotein activity by limonin and other secondary metabolites from Citrus species in human colon and leukaemia cell lines.

Eur J Pharmacol — Fan H, Li L, Zhang X, Liu Y, Yang C, Yang Y, Yin J Oxymatrine down regulates TLR4, TLR2, MyD88, and NF-kappa B and protects rat brains against focal ischemia. Mediators Inflamm doi: Article PubMed Central PubMed Google Scholar. J Ethnopharmacol — Hamdan D, El-Readi MZ, Tahrania A, Herrmann F, Kaufmann D, Farrag N, El-Shazly A, Wink M a Secondary metabolites of Ponderosa Lemon Citrus pyriformis and their antioxidant, anti-inflammatory, and cytotoxic activities.

Z Naturforsch C — Hamdan D, El-Readi M, Tahrani A, Herrmann F, Kaufmann D, Farrag N, El-Shazly A, Wink M b Chemical composition and biological activity of Citrus jambhiri Lush. Food Chem — Hartmann P, Haimerl M, Mazagova M, Brenner DA, Schnabl B Toll-like receptor 2-mediated intestinal injury and enteric tumor necrosis factor receptor I contribute to liver fibrosis in mice.

Article CAS PubMed Central PubMed Google Scholar. Huebener P, Schwabe RF Regulation of wound healing and organ fibrosis by toll-like receptors.

Biochim Biophys Acta — Iwata H, Tezuka Y, Kadota S, Hiratsuka A, Watabe T Mechanism-based inactivation of human liver microsomal CYP3A4 by rutaecarpine and limonin from Evodia fruit extract. Drug Metab Pharmacokinet — Keppler DO, Rudigier JF, Bischoff E, Decker KF The trapping of uridine phosphates by D-galactosamine.

D-glucosamine and 2-deoxy-D-galactose. A study on the mechanism of galactosamine hepatitis. Eur J Biochem — Kitazawa T, Tsujimoto T, Kawaratani H, Fujimoto M, Fukui H Expression of Toll-like receptor 4 in various organs in rats with D-galactosamine-induced acute hepatic failure.

J Gastroenterol Hepatol e—e Kitazawa T, Tsujimoto T, Kawaratani H, Fukui H Salvage effect of E, Toll-like receptor 4 antagonist on d-galactosamine and lipopolysaccharide-induced acute liver failure in rats. J Gastroenterol Hepatol — Kolwankar D, Vuppalanchi R, Ethell B, Jones DR, Wrighton SA, Hall SD, Chalasani N Association between nonalcoholic hepatic steatosis and hepatic cytochrome P 3A activity.

Clin Gastroenterol Hepatol — Lam LKT, Zang J, Hasegawa S Citrus limonoid reduction of chemically induced tumorigenesis. Food Technol — CAS Google Scholar. Langeswaran K, Gowtham Kumar S, Revathy R, Balasubramanian MP Attenuation of aflatoxin B1 induced primary hepatocarcinogenesis by a citrus bioactive compound-limonin.

J Pharm Res — Google Scholar. J Pharmacol Sci — Manners GD Citrus limonoids: analysis, bioactivity, and biomedical prospects. J Agric Food Chem — Manners GD, Hasegawa S A new normal phase liquid chromatographic method for the analysis of limonoids in citrus.

The potential of flavonoids in the treatment of non-alcoholic fatty liver disease. Food Sci. There are several subgroups of citrus flavonoids including the polymethoxyflavones PMFs , nobiletin, and tangeretin, which are abundant in citrus fruit peels.

Prevention of obesity and type 2 diabetes with aged citrus peel Chenpi extract. Food Chem. The effects of Nobiletin, Hesperetin, and Letrozole in a combination on the activity and expression of aromatase in breast cancer cells.

A polymethoxy flavonoids-rich Citrus aurantium extract ameliorates ethanol-induced liver injury through modulation of AMPK and Nrf2-related signals in a binge drinking mouse model. The ethanol extract of C.

aurantium peel was purchased from KPLC group Batch No. Kca, Paris, France , and the main flavonoid component was confirmed using HPLC according to Choi et al. for 8 weeks.

Distilled water was used as the vehicle control, and all groups were administered the designated compounds for 8 weeks by oral gavage. After 8 weeks of compound treatment, all mice were euthanized by carbon dioxide asphyxiation, and the blood and liver samples were collected. The liver tissue was carefully dissected, weighed, and subjected to histopathological and Western blot analyses.

Animal experiments were approved by the Ethics Committee of Chungnam National University CNU and proceeded under their guidelines. All stained liver slides were evaluated using a light microscope.

After extraction, cDNA was synthesized using the Primescript first strand cDNA synthesis kit TaKaRa, Shiga, Japan , and the mRNA expression levels of inflammation- and lipogenesis-related genes were analyzed using a real-time PCR LightCycler 96 system Roche, Basel, Switzerland with a SensiMix Plus SYBR kit Quantace, London, U.

The mRNA levels of the target genes were normalized to the GAPDH expression level, and the results were expressed as the fold change relative to the normal control group.

Phosphate buffered saline PBS -washed liver tissue 0. After three washes in Tris-buffered saline plus Tween TBS-T , the primary antibody was adjusted using the Can Get Signal Solution 1 Toyobo, Osaka, Japan at 4°C with the following antibodies: FAS Cell Signaling Technology, MA, U.

of three individual experiments. Effect of the Citrus aurantium Peel Extract CAE on Body Weight Increment and Serum Biochemistry. The mRNA levels for lipid metabolism-related genes and inflammatory cytokines were assessed in fresh tissue using quantitative real-time RT-PCR analysis Fig.

Total RNA was extracted from the liver, and mRNA expression levels were quantified using SYBR Green-based real-time PCR using mouse-specific primers. The protein levels of FAS, p-AMPK, AMPK, and Nrf2 were assessed using Western blot analysis Fig.

Protein levels of FAS, AMPK, and Nrf2 in the liver tissue were assessed using Western-blot analysis. Major HFD-induced histopathological changes in the liver were cytoplasmic ballooning, inflammation, and lipid droplet accumulation.

The increased incidence of metabolic syndrome-associated NAFLD along with the availability of effective therapies used to treat severe chronic viral hepatitis have changed the clinical approach in the treatment of chronic liver disease. Recently, many studies have shown that some active ingredients found in natural materials extracts have proven efficacious in the prevention and treatment of NAFLD.

Animal models of obesity. Antioxidant and hepatoprotective effects of silibinin in a rat model of nonalcoholic steatohepatitis.

Based Compl. Hesperidin, a citrus flavonoid, inhibits bone loss and decreases serum and hepatic lipids in ovariectomized mice. Naringin supplementation lowers plasma lipids and enhances erythrocyte antioxidant enzyme activities in hypercholesterolemic subjects.

Nobiletin attenuates VLDL overproduction, dyslipidemia, and atherosclerosis in mice with diet-induced insulin resistance.

Diabetes , 60 , — In the present study, reduced circulating plasma lipid levels were observed following CAE treatment of HFD-fed mice, which could be the result of decreased lipid synthesis. SREBPs are a family of transcription factors that stimulate gene expression involved in lipid biosynthesis, and the overexpression of lipid metabolism-related transcription factors was reported in the liver from obese patients with NAFLD with increased SREBP-1c and FAS levels as the most representative changes.

A proteolytic pathway that controls the cholesterol content of membranes, cells, and blood. 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. Some argue that orange peels contain important nutrients and should be eaten rather than thrown away.

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Here's why. A Quiz for Teens Are You a Workaholic? How Well Do You Sleep? Health Conditions Discover Plan Connect. Tahrani, Institute of Pharmacy and Molecular Biotechnology, Heidelberg University, Germany for running LC-MS.

Department of Pharmacology and Toxicology, Faculty of Pharmacy, Zagazig University, Zagazig, , Egypt. Department of Pharmacognosy, Faculty of Pharmacy, Zagazig University, Zagazig, , Egypt. Institute of Pharmacy and Molecular Biotechnology, Heidelberg University, Im Neuenheimer Feld , , Heidelberg, Germany.

Department of Pharmacology, Faculty of Pharmacy, University of Zagazig, Zagazig, , Egypt. You can also search for this author in PubMed Google Scholar. Correspondence to Mona F. Reprints and permissions. Mahmoud, M. et al. Hepatoprotective effect of limonin, a natural limonoid from the seed of Citrus aurantium var.

bigaradia , on D-galactosamine-induced liver injury in rats. Naunyn-Schmiedeberg's Arch Pharmacol , — Download citation. Received : 01 July Accepted : 30 October Published : 21 November Issue Date : March Anyone you share the following link with will be able to read this content:.

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Abstract Toll-like receptors have been implicated in inflammation and injury in various tissues and organs including the liver. Access this article Log in via an institution. J Viral Hepat — Article CAS PubMed Google Scholar Chaung SS, Lin CC, Lin J, Yu KH, Hsu YF, Yen MH The hepatoprotective effects of Limonium sinense against carbon tetrachloride and beta-d-galactosamine intoxication in rats.

Phytother Res — Article PubMed Google Scholar Cotroneo TM, Nemzek-Hamlin JA, Bayliss J, Su GL Lipopolysaccharide binding protein inhibitory peptide alters hepatic inflammatory response post-hemorrhagic shock.

Innate Immun — Article CAS PubMed Google Scholar Decker K, Keppler D Galactosamine induced liver injury. Gastroenterology — Article CAS PubMed Google Scholar Duesberg U, von dem Bussche A, Kirschning C, Miyake K, Sauerbruch T, Spengler U Cell activation by synthetic lipopeptides of the hepatitis C virus HCV -core protein is mediated by toll like receptors TLRs 2 and 4.

Immunol Lett —95 Article Google Scholar Ellman GL Tissue sulfhydryl groups. Arch Biochem Biophys —77 Article CAS PubMed Google Scholar El-Mofty SK, Scrutton MC, Serroni A, Nicolini C, Farber JL Early reversible plasma membrane injury in galactosamine-induced liver cell death.

Am J Pathol — CAS PubMed Google Scholar El-Readi MZ, Hamdan D, Farrag N, El-Shazly A, Wink M Inhibition of P-glycoprotein activity by limonin and other secondary metabolites from Citrus species in human colon and leukaemia cell lines. Eur J Pharmacol — Article CAS PubMed Google Scholar Fan H, Li L, Zhang X, Liu Y, Yang C, Yang Y, Yin J Oxymatrine down regulates TLR4, TLR2, MyD88, and NF-kappa B and protects rat brains against focal ischemia.

J Ethnopharmacol — Article PubMed Google Scholar Hamdan D, El-Readi MZ, Tahrania A, Herrmann F, Kaufmann D, Farrag N, El-Shazly A, Wink M a Secondary metabolites of Ponderosa Lemon Citrus pyriformis and their antioxidant, anti-inflammatory, and cytotoxic activities.

Z Naturforsch C — Article CAS PubMed Google Scholar Hamdan D, El-Readi M, Tahrani A, Herrmann F, Kaufmann D, Farrag N, El-Shazly A, Wink M b Chemical composition and biological activity of Citrus jambhiri Lush.

Food Chem — Article CAS PubMed Google Scholar Hartmann P, Haimerl M, Mazagova M, Brenner DA, Schnabl B Toll-like receptor 2-mediated intestinal injury and enteric tumor necrosis factor receptor I contribute to liver fibrosis in mice.

Gastroenterology — Article CAS PubMed Central PubMed Google Scholar Huebener P, Schwabe RF Regulation of wound healing and organ fibrosis by toll-like receptors.

Biochim Biophys Acta — Article CAS PubMed Google Scholar Iwata H, Tezuka Y, Kadota S, Hiratsuka A, Watabe T Mechanism-based inactivation of human liver microsomal CYP3A4 by rutaecarpine and limonin from Evodia fruit extract.

Drug Metab Pharmacokinet —45 Article CAS PubMed Google Scholar Keppler DO, Rudigier JF, Bischoff E, Decker KF The trapping of uridine phosphates by D-galactosamine. Eur J Biochem — Article CAS PubMed Google Scholar Kitazawa T, Tsujimoto T, Kawaratani H, Fujimoto M, Fukui H Expression of Toll-like receptor 4 in various organs in rats with D-galactosamine-induced acute hepatic failure.

J Gastroenterol Hepatol e—e Article CAS PubMed Google Scholar Kitazawa T, Tsujimoto T, Kawaratani H, Fukui H Salvage effect of E, Toll-like receptor 4 antagonist on d-galactosamine and lipopolysaccharide-induced acute liver failure in rats. J Gastroenterol Hepatol — Article CAS PubMed Google Scholar Kolwankar D, Vuppalanchi R, Ethell B, Jones DR, Wrighton SA, Hall SD, Chalasani N Association between nonalcoholic hepatic steatosis and hepatic cytochrome P 3A activity.

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