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. 2018 Mar 23;18(1):106.
doi: 10.1186/s12906-018-2169-x.

Potentiating and synergistic effect of grapefruit juice on the antioxidant and anti-inflammatory activity of aripiprazole against hydrogen peroxide induced oxidative stress in mice

Seema Zargar  1 , Abdul-Rahman A Al-Majed  2 , Tanveer A Wani  2
Affiliations

Potentiating and synergistic effect of grapefruit juice on the antioxidant and anti-inflammatory activity of aripiprazole against hydrogen peroxide induced oxidative stress in mice

Seema Zargar et al. BMC Complement Altern Med. .

Abstract

Background: Dependence on antipsycotic drugs like aripriprazole (ARI) is increasing at alarming rate, hence, this study was undertaken to support the hypothesis that supplementation of Citrus paradisi (Grapefruit) juice having high concentration of polyphenols might potentiate and synergize the therapeutic effect of ARI, by increasing its bioavailability and inherent antioxidant potential. These benefits together might decrease the daily dosage of the ARI and thus alleviate the possible side effects of drug.

Methods: In this study the antioxidant and anti-inflammatory potential of ARI alone and in combination with GFJ was evaluated for hydrogen peroxide (H2O2) induced oxidative stress in mice. Seventy mice (4 weeks old), were randomly divided into seven groups. Group I: Control; Group II: H2O2 treated; Group III; ARI treated; Group IV GFJ treated; Group V: GFJ and H2O2 treated; Group VI; ARI and H2O2 treated; Group VII; ARI, GFJ and H2O2 treated. Serum levels of alanine aminotransferase (ALT), blood urea nitrogen (BUN), creatinine kinase (CK), creatinine and total protein were measured. Furthermore, pro-inflammatory cytokines Interleukin (IL)-1α, IL-2, IL-10 and tumor necrosis factor-α (TNF-α) concentrations were also measured.

Results: The mice group that was treated with ARI, GFJ or combination of the two showed significant improvement in the H2O2 altered parameters with the combination group showing more significant improvement than the ARI and GFJ alone groups indicating a synergistic and potentiating effect of the antioxidant and anti-inflammatory potential of GFJ on ARI.

Conclusion: Supplementing GFJ to ARI might increase an anti-oxidative potential of ARI due to inherent antioxidant and anti-inflammatory activity of GFJ and thus could alleviate the possible dosage dependent side effects of ARI.

Keywords: Anti-inflammatory; Aripiprazole; Cytokines; Grapefruit juice; Hydrogen peroxide; Oxidative stress.

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Conflict of interest statement

Ethics approval and consent to participate

Animals were maintained in accordance with the recommendations of the ‘Guide for the Care and Use of Laboratory Animals’ approved by institutional animal ethics committee of College of Science, King Saud University, Riyadh, Saudi Arabia. The study protocol was approved (KSU-SE-13-16) by the animal ethics committee, prior to the study.

Consent for publication

Not applicable in this section.

Competing interests

The authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
a; Representative chromatogram of standard drug naringin; b; Representative chromatogram of the 50 μL GFJ injected into HPLC system
Fig. 2
Fig. 2
Effect of grapefruit juice (GFJ) and aripiprazole (ARI) on oxidative stress induced by H2O2 by IL-1α levels. IL-1α concentration is expressed as pg/ml (n = 10); The treated groups were compared to control group. ****P < 0.0001, **P < 0.01, ns: non-significant. #Group I: Control; Group II: H2O2 treated; Group III; ARI treated; Group IV GFJ treated; Group V: GFJ and H2O2 treated; Group VI; ARI and H2O2 treated; Group VII; ARI, GFJ and H2O2 treated
Fig. 3
Fig. 3
Effect of grapefruit juice (GFJ) and aripiprazole (ARI) on oxidative stress induced by H2O2 by IL-2 levels. IL-2 concentration is expressed as pg/ml (n = 10), The treated groups were compared to control group. ****P < 0.0001, **P < 0.01, *P < 0.1, ns: non-significant. #Group I: Control; Group II: H2O2 treated; Group III; ARI treated; Group IV GFJ treated; Group V: GFJ and H2O2 treated; Group VI; ARI and H2O2 treated; Group VII; ARI, GFJ and H2O2 treated
Fig. 4
Fig. 4
Effect of grapefruit juice (GFJ) and aripiprazole (ARI) on oxidative stress induced by H2O2 by IL-10 levels. IL-10 concentration is expressed as pg/ml (n = 10); The treated groups were compared to control group. ****P < 0.0001, *P < 0.1, ns: non-significant. #Group I: Control; Group II: H2O2 treated; Group III; ARI treated; Group IV GFJ treated; Group V: GFJ and H2O2 treated; Group VI; ARI and H2O2 treated; Group VII; ARI, GFJ and H2O2 treated
Fig. 5
Fig. 5
Effect of grapefruit juice (GFJ) and aripiprazole (ARI) on oxidative stress induced by H2O2 by TNF-α levels. TNF-α concentration is expressed as pg/ml (n = 10 The treated groups were compared to control group. ****P < 0.0001, ***P < 0.001, ns: non-significant. #Group I: Control; Group II: H2O2 treated; Group III; ARI treated; Group IV GFJ treated; Group V: GFJ and H2O2 treated; Group VI; ARI and H2O2 treated; Group VII; ARI, GFJ and H2O2 treated
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