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Food Science and Human Wellness 2014, 3(1): 26-35 https://doi.org/10.1016/j.fshw.2014.02.002
Research Article | Open Access | Issue | Published: 28 February 2014

Anti-inflammatory effects of characterized orange peel extracts enriched with bioactive polymethoxyflavones

Show Author's Information Alexander Gosslaua,b( ),  Kuang Yu Chenb,  Chi-Tang Hoc,  Shiming Lic,d
Department of Science, BMCC-City University of New York, New York, NY 10007, United States
Department of Chemistry and Chemical Biology, Rutgers University, Piscataway, NJ 08854-8087, United States
Department of Food Science, Rutgers University, New Brunswick, NJ 08901-8520, United States
College of Chemistry and Chemical Engineering, Huanggang Normal University, Huanggang 438000, China

Peer review under responsibility of Beijing Academy of Food Sciences.

Keywords:
Inflammation, Gene expression, Citrus flavonoids, Edema, Nutrigenomics
Cite this article:
Gosslau A, Chen KY, Ho C-T, et al. Anti-inflammatory effects of characterized orange peel extracts enriched with bioactive polymethoxyflavones. Food Science and Human Wellness, 2014, 3(1): 26-35. https://doi.org/10.1016/j.fshw.2014.02.002
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Abstract Full text About this article

In view of the potential of polymethoxyflavones (PMFs) and hydroxylated PMFs (OH-PMFs) as bioactives against inflammation, we prepared six different orange peel extracts (OPEs). The major compounds of these extracts were characterized and quantified by high performance liquid chromatography (HPLC). Effects on inflammation were analyzed by nutrigenomics using a human cell-based TPA-induced monocyte–macrophage differentiation model employing U-937 cells and inflammatory surrogate genes. Dose response and kinetics analysis of OPEs with different chemical profiles revealed less cytotoxic effects of PMFs as compared to OH-PMFs as demonstrated by the MTT-method. Noteworthy, a comparison of two PMF members such as 3,5,6,7,3′,4′-hexamethoxyflavone (HexaMF) and 3,5,6,7,8,3′,4′-heptamethoxyflavone (HeptaMF) exhibited less cytotoxic effects of HeptaMF as compared to HexaMF. A specific OPE enriched with HeptaMF, PMFs and OH-PMFs at low concentrations (10 μg/mL) significantly down-regulated the expression of a panel of genes involved in inflammatory response, including COX-2, TNF-α, ICAM-1, NFκB, IL-1β, IL-6, and IL-8 with an inflammatory index of −0.55. The strong anti-inflammatory effects were then validated in a mouse carrageenan-induced paw edema model. Oral intake of OPE reduced paw edema significantly in a dose-dependent manner. Importantly, a dosage of 250 mg/kg gave an anti-inflammatory effect comparable to ibuprofen. A preliminary clinical study showed that OPE was well tolerated showing no adverse side effects. In summary, enrichment of phyto extracts such as OPEs with specific polymethoxyflavones as anti-inflammatory bioactives is a promising strategy to find naturally derived extracts that are effective against diseases associated with inflammation.


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About this article

Anti-inflammatory effects of characterized orange peel extracts enriched with bioactive polymethoxyflavones

Show Author's information Alexander Gosslaua,b( ), Kuang Yu Chenb, Chi-Tang Hoc, Shiming Lic,d
Department of Science, BMCC-City University of New York, New York, NY 10007, United States
Department of Chemistry and Chemical Biology, Rutgers University, Piscataway, NJ 08854-8087, United States
Department of Food Science, Rutgers University, New Brunswick, NJ 08901-8520, United States
College of Chemistry and Chemical Engineering, Huanggang Normal University, Huanggang 438000, China

Peer review under responsibility of Beijing Academy of Food Sciences.

Abstract

In view of the potential of polymethoxyflavones (PMFs) and hydroxylated PMFs (OH-PMFs) as bioactives against inflammation, we prepared six different orange peel extracts (OPEs). The major compounds of these extracts were characterized and quantified by high performance liquid chromatography (HPLC). Effects on inflammation were analyzed by nutrigenomics using a human cell-based TPA-induced monocyte–macrophage differentiation model employing U-937 cells and inflammatory surrogate genes. Dose response and kinetics analysis of OPEs with different chemical profiles revealed less cytotoxic effects of PMFs as compared to OH-PMFs as demonstrated by the MTT-method. Noteworthy, a comparison of two PMF members such as 3,5,6,7,3′,4′-hexamethoxyflavone (HexaMF) and 3,5,6,7,8,3′,4′-heptamethoxyflavone (HeptaMF) exhibited less cytotoxic effects of HeptaMF as compared to HexaMF. A specific OPE enriched with HeptaMF, PMFs and OH-PMFs at low concentrations (10 μg/mL) significantly down-regulated the expression of a panel of genes involved in inflammatory response, including COX-2, TNF-α, ICAM-1, NFκB, IL-1β, IL-6, and IL-8 with an inflammatory index of −0.55. The strong anti-inflammatory effects were then validated in a mouse carrageenan-induced paw edema model. Oral intake of OPE reduced paw edema significantly in a dose-dependent manner. Importantly, a dosage of 250 mg/kg gave an anti-inflammatory effect comparable to ibuprofen. A preliminary clinical study showed that OPE was well tolerated showing no adverse side effects. In summary, enrichment of phyto extracts such as OPEs with specific polymethoxyflavones as anti-inflammatory bioactives is a promising strategy to find naturally derived extracts that are effective against diseases associated with inflammation.

Keywords: Inflammation, Gene expression, Citrus flavonoids, Edema, Nutrigenomics

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Received: 27 January 2014
Accepted: 16 February 2014
Published: 28 February 2014
Issue date: March 2014

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© 2014 Beijing Academy of Food Sciences.

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The authors wish to thank WellGen Inc. for support of materials.

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