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How grapefruit beats anaemia (2)

Naringenin belongs to the class of flavonoids called the flavanones. The flavanones are abundant in citrus fruits such as grapefruit (Citrus paradisi) and the oranges (Citrus sinensis).

The role of naringenin and the related citrus flavanone hesperetin in the prevention and treatment of disease has recently received considerable attention, with particular interest in the use of these flavanones as anticancer and antiatherogenic compounds.


The antiseptic and antibacterial properties of unripe Citrus paradisi and Ananas sativus have been equally reported. Antibacterial potency and synergistic effect of crude aqueous and methanolic extracts of parts against multi-drug resistant Salmonella typhi were investigated and compared. Salmonella typhi isolated from patients suffering from typhoid fever was tested against nine plant parts: unripe Carica papaya fruit, Citrus aurantifoliia, Anana sativus, Citrus paradise, etc.


The antibacterial activities of the extracts, individually and in combination were determined using agar diffusion method and the minimum inhibitory concentration (MIC) carried out by agar dilution technique. The plant materials possessed antimicrobial activity with greater efficacy when used synergistically on the test organism.

A high activity of Citrus paradisi (grapefruit) oil to P. larvae with MIC 385.0 mg/L has also been reported. Antibacterial activities of eleven essential oils against Paenibacillus larvae (15 field strains and the reference BCCM / LMG 9820 strain) were studied by the disk diffusion method and the method of serial dilutions in agar. The minimal inhibitory concentration (MIC) of essential oils was determined within one per cent–0.015 per cent v/v.

Citrus essential oils showed the inhibitory effect with MIC ≥ 0.25–0.5 per cent v/v for grapefruit oil. Ethyl acetate extracts from acid less Citrus paradisi inhibited A. fumigatus TISTR 3180 with MIC values of 0.28 mg/ml and MFC values of 0.28 mg/ml, respectively.

Antibacterial activity of some fractions of Citrus paradisi peels extracted with hexane, chloroform, acetone and methanol were evaluated against different bacteria. The alcohol soluble fraction was found to possess maximum activity followed by hexane extract. Extracts were more effective against Gram-positive than Gram-negative bacteria.

The methanolic and ethanolic extracts of these plants were tested for their antimicrobial activity. Results showed that the highest antimicrobial activity was exhibited by the methanolic extracts of Citrus paradisi.

Antibacterial and antifungal activity of ethanolic extract of grapefruit (Citrus paradisi) seed and pulp was examined against 20 bacterial and 10 yeast strains. The level of antimicrobial effects was established using an in vitro agar assay and standard broth dilution susceptibility test. Ethanolic extract exhibited the strongest antimicrobial effect against Salmonella enteritidis (MIC 2.06 per cent m/V).

Other tested bacteria and yeasts were sensitive to extract concentrations ranging from 4.13 per cent to 16.50 per cent (m/V) [23]. The Citrus paradisi and Ficus carica were tested against pathogenic microorganisms; S. aureus, E. coli, K. pneumoniae, B. subtilis, M. luteus and Candida albicans. The extracts tested exhibited good antimicrobial activity against all the clinical isolates when compared with standard. The different extracts showed remarkable inhibitory action against various Gram positive and Gram negative bacteria and two fungal species.

The methanolic, petroleum ether, chloroform, ethyl ether, ethanol extract of Citrus paradisi was screened for its antimicrobial activity. Antimicrobial activity was detected by observing the growth response of different organisms to the methanolic extract. It was generally based on the inhibition of growth of microorganisms which were measured with a desired concentration of the plant extract of Citrus paradisi to be examined with the standard concentration preparation.

Apoptotic activity

The aldehyde compounds of Citrus paradisi essential oil have been reported to induce apoptosis strongly in HL-60 cells.

Anxiolytic and antidepressant

Various extracts petroleum ether, chloroform, methanol and water of the leaves of Citrus paradisi var. Duncan were tested using elevated plus maze (EPM) model and forced swimming test (FST) respectively in Swiss albino mice at different doses of extracts (that is 100, 200 and 400 mg/kg orally).

Studies showed that methanolic extract at the dose of 100 mg/kg of the leaves of Citrus paradise var. Duncan markedly increased the average time spent in the open arms in EPM and methanolic extract at the dose of 400 mg/kg showed a significant decrease in the time spent immobile.

Methanol extract at the dose of 100mg/kg of the leaves of Citrus paradise var. foster markedly increased the average time spent in the open arms in EPM and methanol extract at the dose of 400mg/kg showed a significant decrease in the time spent immobile by mice in FST. The anti-anxiety activity of various extracts viz petroleum ether, chloroform, methanol and water, of the leaves of Citrus paradisi var. star ruby was evaluated using elevated plus maze (EPM) model in Swiss albino mice. Albino mice were treated orally with different doses of the extracts (i.e.100, 200 and 400 mg/kg) and behavior was observed on the EPM. Diazepam (2mg/kg, P.O) was used as a positive control.

Methanol extract at the dose of 100mg/kg of the leaves of Citrus paradisi var. star ruby markedly increased the average time spent in the open arms of the EPM. This effect was comparable to the effect produced by diazepam.


The antioxidant activity of bioactive compounds of grapefruit (Citrus paradisi) has been reported by using four in vitro models. The compounds selected include two limonoids, limonin and limonin 17-β-D-lucopyranoside; eight flavonoids, apigenin, scutelarein, kaempferol, rutin trihydrate, neoheseridin, neoeriocitrin, naringenin and aringin; and a coumarin bergapten. A variety of in vitro including models such as β-carotene, linoleic acid, DPPH, superoxide and hamster low- density lipoprotein were used to measure the antioxidant activity of 11 citrus bioactive compounds.

The above compounds were tested at concentration of 10uM in all four methods. It was found that Limonoids, 17- β -D-lucopyranoside and bergapten inhibited 7 per cent, whereas scutelarein, kaempferol and rutin trihydrate inhibited 51.3 per cent, 47.0 per cent, and 44.4 per cent, respectively, using the β -carotene linoleate model system. Limonoids, 17- β – D-lucopyranoside, scutelarein, kaempferol, neoeriocitrin and rutin trihydrate showed 0.5 per cent, 0.25 per cent, 32.2 per cent, 18.3 per cent, 17.2 per cent, and 12.2 per cent, respectively, free radical scavenging activity using the DPPH method. In the superoxide model, Limonoids, 17- β -D-lucopyranoside and bergapten inhibited the production of superoxide radicals by 2.5 10 per cent, while the flavonoids such as scutelarein, neoeriocitrin and rutin trihydrate, and Neh inhibited superoxide formation by 64.1 per cent, 52.1 per cent, 48.3 per cent, and 37.7 per cent, respectively.

However, 17-β-D-lucopyranoside did not inhibit Low Density Lipo-protein (LDL) oxidation in the hamster LDL model. But, Limonoids and Bergapten offered some protection against LDL oxidation, increasing lag time to 345 min (three-fold) and 160 min (33 per cent increase), respectively, while both Rutin and Neoeriocitrin increased lag time to 2800 min (23-fold).

Scutelarein and kaempferol increased lag time to 2140 min (18-fold) and 1879 min (15.7-fold), respectively. In general, it seems that flavonoids, which contain a chromanol ring system, had stronger antioxidant activity as compared to limonoids and bergapten, which lack the hydroxy groups.

Caffeine metabolism

The effects of grapefruit juice and naringenin on the activity of the human cytochrome P-450 isoform CYP1A2 were evaluated using caffeine as a probe substrate.

In vitro naringenin was a potent competitive inhibitor of caffeine 3- demethylation by human liver microsomes. In vivo grapefruit juice decreased the oral clearance of caffeine by 23 per cent (95 per cent CI: 7 per cent-30 per cent) and prolonged its half-life by 31 per cent (95 per cent CI: 20 per cent-44 per cent) (n = 12). It shows that grapefruit juice and naringenin inhibit CYP1A2 activity in man. However, the small effect on caffeine clearance in vivo suggests that in general the ingestion of grapefruit juice should not cause clinically significant inhibition of the metabolism of other drugs that are substrates of CYPIA2.

Hematopoietic effect

The blood forming effects of (100 per cent methanol seed extract) Citrus paradisi in adult Wistar rats for 30 days was a way of evaluating its traditional use in the treatment of blood deficiencies. Acute oral toxicity study was also conducted using limit dose test of the up and down procedure statistical program (AOT425PgmStat, Version 1.0) at a dose of 2000 mg/kg body weight/oral route.

Results showed significant (p<0.05) progressive and dose dependent elevations in total leukocytes count, lymphocyte differentials, red blood count, hemoglobin concentration, packed cell count, mean corpuscular volume, mean corpuscular haemoglobin, mean corpuscular haemoglobin concentration and platelet count. Reversed effect was recorded for the neutrophil and monocyte differentials which were significantly (p<0.05) decreased in the treated rats.


The capacity of grapefruit juice (GJ) to inhibit the rate of micronucleated polychromatic erythrocytes (MNPE) in mice treated with benzo(a)pyrene (BaP), an environmental contaminant that is biotransformed by Cyp1a1 and is a strong genotoxic agent.

Administration of 4.1, 20.8 and 41.6 ul/g body weight of GJ to BaP-treated mice (340 mg/kg) a significant decrease in the frequency of MNPE at 48 and 72 h compared to BaP-only treated animals. In turn, no prevention of the cytotoxic damage induced by BaP was found. Whether GJ’s antigenotoxic mechanism of action was related to an inhibitory effect on the activity of the Cyp1a1 enzyme. A reduction in microsomal hepatic and intestinal ethoxyresorufin-O-deethylase (EROD) activity of 20 per cent and 44 per cent respectively, was found in mice treated with BaP and GJ compared to BaP-only treated animals.

Furthermore, when EROD inhibition was tested in vitro, a concentration dependent EROD inhibition by grapefruit juice, which reached 85 per cent of the maximum level. Together, these researches suggest that the protective effect of GJ against the genotoxicity of BaP may be related to the inhibition of Cyp1a1 enzyme activity.

Arterial pressure

The coronary vasodilator and hypotensive effects of Citrus paradisi peel extract were assessed in the Langendorff isolated and perfused heart model and in the heart and lung dog preparation. In both models, Citrus paradisi peel extract decreased coronary vascular resistance and mean arterial pressure when compared with control values (60 ± 15 × 107 dyn s cm−5 vs100±10×107 dynscm−5 and90 mmHg vs 130 ± 15 mmHg, respectively).

These decreases in coronary vascular resistance and mean arterial pressure were blocked when isolated and perfused hearts and mongrel dogs were pre-treated with L-NAME. In humans, Citrus paradisi juice decreased diastolic arterial pressure and systolic arterial pressure both in normotensive and hypertensive subjects.

Antidiabetic effect

For this rats were used and divided into five groups. Rats were gavaged at the dose levels of 10ml/kg/day of distilled water, 10ml/kg of body weight/day of dimethyl sulphoxide (DMSO), 100, 300, and 600 mg/kg of body weight/ day of the extract dissolved in 10 ml/kg DMSO, respectively, for 30 days.

On day 31, blood samples obtained were assayed for fasting plasma glucose (FPG), total cholesterol (TC), high density lipoprotein (HDL-c), low density lipoprotein (LDL-c), and very low density lipoprotein (VLDL- c) using standard procedures. Cardiovascular disease risk assessing factors such as obesity or body mass index (BMI), atherogenic index (AI), coronary risk index (CRI) were calculated.

Results showed significant (p<0.05, p<0.001) dose related lowering effects of the extract on FPG, cardiovascular disease risk assessing indices and lipid parameters except HDL-c fraction which was significantly (p<0.05, p<0.001) elevated. The extract also induced significant (p< 0.05) dose related weight loss in the treated rats in the latter 15 days of their treatment. These researches lend support to its therapeutic potentials in the management of suspected type-2 diabetic patients. Other uses

In Sudan, Citrus paradisi internal fruit peel is used to treat for malaria, gastro protective and antiulcer, and this action is attributed to the antioxidant activity of citrus flavonoids found in grapefruit such as naringenin, because this major flavonoid found exhibited the potent antibacterial and anti-helicobacter pylori activity in vitro and was also recently implicated in cytoprotection against injury induced by algal toxins in isolated hepatocytes. Moreover naringenin, the bioactive component showed gastroprotective activity due to increase expression of prostaglandins biosynthesis.

Furthermore, it was shown to exhibit anti-cancer activity against human breast cancers. Therapeutic efficacy of citrus fruits such as red grapes and grapefruits is emphasized by the fact that they contain different classes of polyphenolic flavonoids, which were shown to inhibit platelet aggregation thus decreasing the risk of coronary thrombosis and myocardial infarction. Citrus fruit peel is 1000 times sweeter than sucrose.

Grapefruit drug interactions

Grapefruit can have a number of interactions with drugs, often increasing the effective potency of compounds. Researchers have identified 85 drugs with which grapefruit is known to have an adverse reaction.

Grapefruit contains a number of polyphenolic compounds, including the flavanone naringin, alongside the two furanocoumarins bergamottin and dihydroxybergamottin. These inhibit the drug-metabolizing enzyme isoform CYP3A4 predominantly in the small intestine, but at higher doses also inhibit hepatic CYP3A4. It is via inhibition of this enzyme that grapefruit increases the effects of a variety of drugs by increasing their bioavailability. In particular grapefruit and bitter oranges are known to interact with statins.


Culled from TheGuardian (Nov 2014)




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