Exploring the Pharmacokinetics and Gut Microbiota Modulation of Hesperidin and Nobiletin from Mandarin Orange Peel in Experimental Dogs: A Pilot Study

<b>Background/Objectives:</b> Mandarin orange peel (MOP) is recognized for its traditional medicinal properties due to its high flavonoid content. This study aimed to analyze MOP harvested in Japan for specific bioactive compounds and to explore its health applications in dogs, including...

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Main Authors: Jun Nakahigashi, Makoto Kurikami, Satomi Iwai, Sadahiko Iwamoto, Shou Kobayashi, Eiji Kobayashi
Format: Article
Language:English
Published: MDPI AG 2024-12-01
Series:Metabolites
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Online Access:https://www.mdpi.com/2218-1989/15/1/3
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author Jun Nakahigashi
Makoto Kurikami
Satomi Iwai
Sadahiko Iwamoto
Shou Kobayashi
Eiji Kobayashi
author_facet Jun Nakahigashi
Makoto Kurikami
Satomi Iwai
Sadahiko Iwamoto
Shou Kobayashi
Eiji Kobayashi
author_sort Jun Nakahigashi
collection DOAJ
description <b>Background/Objectives:</b> Mandarin orange peel (MOP) is recognized for its traditional medicinal properties due to its high flavonoid content. This study aimed to analyze MOP harvested in Japan for specific bioactive compounds and to explore its health applications in dogs, including effects on gut microbiota and cognitive symptoms. <b>Methods:</b> Flavonoid content (particularly hesperidin and nobiletin) of MOP was measured. High-flavonoid MOP was then incorporated into gelatin cubes. In the time–course blood concentration study, experimental beagle dogs received a single oral dose (4 g). For intestinal microbiota analysis and blood biochemical tests, beagle dogs were administered 1 g twice daily. For the Demonstration Test, older dogs (a 14-year-old female Shiba Inu, a 14-year-old female Miniature Dachshund, and a 19-year-old male Miniature Dachshund) were administered 1 g twice daily. Analysis included microbiota profiling via 16S rDNA sequencing and observational assessment of cognitive indicators in a pilot study involving senior dogs with Alzheimer’s disease. <b>Results:</b> The MOP powder contained 9.3% hesperidin in early-ripening varieties (October harvest) and 6.9% in ripe varieties (December harvest). Nobiletin content was 41 mg/100 g (0.041%) and 35 mg/100 g (0.035%) for the early and late harvests, respectively. Administration of MOP-enriched gelatin cubes reduced <i>Fusobacteriaceae</i> and increased <i>Eggerthellaceae</i>. Cognitive symptoms like howling and counterclockwise turning showed improvement in senior dogs (<i>n</i> = 3). <b>Conclusions:</b> This study provides preliminary support for the potential health benefits of MOP in canine dietary applications, particularly for gut health and cognitive function. Improvement in cognitive symptoms may be due to the anxiolytic effects of mandarin peel.
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spelling doaj-art-0d77dfc922744b788e64266bf078c2a12025-01-24T13:41:07ZengMDPI AGMetabolites2218-19892024-12-01151310.3390/metabo15010003Exploring the Pharmacokinetics and Gut Microbiota Modulation of Hesperidin and Nobiletin from Mandarin Orange Peel in Experimental Dogs: A Pilot StudyJun Nakahigashi0Makoto Kurikami1Satomi Iwai2Sadahiko Iwamoto3Shou Kobayashi4Eiji Kobayashi5Agriculture & Foods Research Center, AIR WATER INC., 1-7, Tsukisamu Higashi 2-jo 16-chome, Toyohira-ku, Sapporo 062-0052, Hokkaido, JapanAgriculture & Foods Research Center, AIR WATER INC., 1-7, Tsukisamu Higashi 2-jo 16-chome, Toyohira-ku, Sapporo 062-0052, Hokkaido, JapanSchool of Veterinary Medicine, Kitasato University, 35-1, Higashi 23, Towada 034-8628, Aomori, JapanDivision of Cardiovascular and Genetic Research, Center for Molecular Medicine, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke-shi 329-0498, Tochigi, JapanKobayashi Regenerative Research Institute, LLC, 1 Chayano-cho, Wakayama-shi 640-8263, Wakayama, JapanSchool of Veterinary Medicine, Kitasato University, 35-1, Higashi 23, Towada 034-8628, Aomori, Japan<b>Background/Objectives:</b> Mandarin orange peel (MOP) is recognized for its traditional medicinal properties due to its high flavonoid content. This study aimed to analyze MOP harvested in Japan for specific bioactive compounds and to explore its health applications in dogs, including effects on gut microbiota and cognitive symptoms. <b>Methods:</b> Flavonoid content (particularly hesperidin and nobiletin) of MOP was measured. High-flavonoid MOP was then incorporated into gelatin cubes. In the time–course blood concentration study, experimental beagle dogs received a single oral dose (4 g). For intestinal microbiota analysis and blood biochemical tests, beagle dogs were administered 1 g twice daily. For the Demonstration Test, older dogs (a 14-year-old female Shiba Inu, a 14-year-old female Miniature Dachshund, and a 19-year-old male Miniature Dachshund) were administered 1 g twice daily. Analysis included microbiota profiling via 16S rDNA sequencing and observational assessment of cognitive indicators in a pilot study involving senior dogs with Alzheimer’s disease. <b>Results:</b> The MOP powder contained 9.3% hesperidin in early-ripening varieties (October harvest) and 6.9% in ripe varieties (December harvest). Nobiletin content was 41 mg/100 g (0.041%) and 35 mg/100 g (0.035%) for the early and late harvests, respectively. Administration of MOP-enriched gelatin cubes reduced <i>Fusobacteriaceae</i> and increased <i>Eggerthellaceae</i>. Cognitive symptoms like howling and counterclockwise turning showed improvement in senior dogs (<i>n</i> = 3). <b>Conclusions:</b> This study provides preliminary support for the potential health benefits of MOP in canine dietary applications, particularly for gut health and cognitive function. Improvement in cognitive symptoms may be due to the anxiolytic effects of mandarin peel.https://www.mdpi.com/2218-1989/15/1/3mandarin orange peelflavonoidshesperidinAlzheimer’s diseasecanine healthgut microbiota
spellingShingle Jun Nakahigashi
Makoto Kurikami
Satomi Iwai
Sadahiko Iwamoto
Shou Kobayashi
Eiji Kobayashi
Exploring the Pharmacokinetics and Gut Microbiota Modulation of Hesperidin and Nobiletin from Mandarin Orange Peel in Experimental Dogs: A Pilot Study
Metabolites
mandarin orange peel
flavonoids
hesperidin
Alzheimer’s disease
canine health
gut microbiota
title Exploring the Pharmacokinetics and Gut Microbiota Modulation of Hesperidin and Nobiletin from Mandarin Orange Peel in Experimental Dogs: A Pilot Study
title_full Exploring the Pharmacokinetics and Gut Microbiota Modulation of Hesperidin and Nobiletin from Mandarin Orange Peel in Experimental Dogs: A Pilot Study
title_fullStr Exploring the Pharmacokinetics and Gut Microbiota Modulation of Hesperidin and Nobiletin from Mandarin Orange Peel in Experimental Dogs: A Pilot Study
title_full_unstemmed Exploring the Pharmacokinetics and Gut Microbiota Modulation of Hesperidin and Nobiletin from Mandarin Orange Peel in Experimental Dogs: A Pilot Study
title_short Exploring the Pharmacokinetics and Gut Microbiota Modulation of Hesperidin and Nobiletin from Mandarin Orange Peel in Experimental Dogs: A Pilot Study
title_sort exploring the pharmacokinetics and gut microbiota modulation of hesperidin and nobiletin from mandarin orange peel in experimental dogs a pilot study
topic mandarin orange peel
flavonoids
hesperidin
Alzheimer’s disease
canine health
gut microbiota
url https://www.mdpi.com/2218-1989/15/1/3
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