Pharmacokinetic variability of 20(S)-protopanaxadiol-type ginsenosides Rb1, rd, and compound K from Korean red ginseng in experimental rodents

Abstract Korean red ginseng (KRG, Panax ginseng C.A. Meyer) contains ginsenosides, which are metabolized into active metabolites with various pharmacological effects. This study assessed the in vivo exposure and accumulation of ginsenosides following single and repeated administration of KRG and its...

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Main Authors: Ji-Soo Jeong, Jeong-Won Kim, Jin-Hwa Kim, Chang-Yeop Kim, Eun-Hye Chung, So-Young Boo, Mario Giorgi, Je-Won Ko, Tae-Won Kim
Format: Article
Language:English
Published: Nature Portfolio 2025-08-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-025-13873-9
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author Ji-Soo Jeong
Jeong-Won Kim
Jin-Hwa Kim
Chang-Yeop Kim
Eun-Hye Chung
So-Young Boo
Mario Giorgi
Je-Won Ko
Tae-Won Kim
author_facet Ji-Soo Jeong
Jeong-Won Kim
Jin-Hwa Kim
Chang-Yeop Kim
Eun-Hye Chung
So-Young Boo
Mario Giorgi
Je-Won Ko
Tae-Won Kim
author_sort Ji-Soo Jeong
collection DOAJ
description Abstract Korean red ginseng (KRG, Panax ginseng C.A. Meyer) contains ginsenosides, which are metabolized into active metabolites with various pharmacological effects. This study assessed the in vivo exposure and accumulation of ginsenosides following single and repeated administration of KRG and its active ingredient, compound K, in experimental rodents. In Study 1, rats received KRG (2 g/kg) orally as a single dose or for 2, 4, and 8 wks. Repeated administration increased the maximum plasma concentrations (Cmax) of ginsenosides Rb1 and Rd compared to a single dose (Rb: 23.9 to 68.3 ng/mL; Rd: 8.5 to 30.8 ng/mL over 8 wks). Compound K was detected at 2.9 and 2.3 ng/mL of Cmax after 4 and 8 wks of continuous KRG administration, with no significant differences. In Study 2, oral administration of compound K (5 or 10 mg/kg) in rats resulted in accumulation factors of 4 and 7, respectively. Study 3 evaluated the oral bioavailability of compound K in mice (intravenous, 2 mg/kg; oral, 10 mg/kg), estimating it at approximately 12%. Additionally, network pharmacology and molecular docking simulation studies supported the clinical potential of compound K against inflammation-related diseases. These findings suggest that for substances like KRG, which undergo in vivo metabolic conversion after administration, repeated KRG administration alters pharmacokinetic profiles and should be taken into consideration in its application.
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spelling doaj-art-d7717ff3cdcd410aade01985d6ec28202025-08-20T03:04:34ZengNature PortfolioScientific Reports2045-23222025-08-0115111310.1038/s41598-025-13873-9Pharmacokinetic variability of 20(S)-protopanaxadiol-type ginsenosides Rb1, rd, and compound K from Korean red ginseng in experimental rodentsJi-Soo Jeong0Jeong-Won Kim1Jin-Hwa Kim2Chang-Yeop Kim3Eun-Hye Chung4So-Young Boo5Mario Giorgi6Je-Won Ko7Tae-Won Kim8College of Veterinary Medicine (BK21 FOUR Program), Chungnam National UniversityCollege of Veterinary Medicine (BK21 FOUR Program), Chungnam National UniversityCollege of Veterinary Medicine (BK21 FOUR Program), Chungnam National UniversityCollege of Veterinary Medicine (BK21 FOUR Program), Chungnam National UniversityCollege of Veterinary Medicine (BK21 FOUR Program), Chungnam National UniversityCollege of Veterinary Medicine (BK21 FOUR Program), Chungnam National UniversityDepartment of Veterinary Sciences, University of PisaCollege of Veterinary Medicine (BK21 FOUR Program), Chungnam National UniversityCollege of Veterinary Medicine (BK21 FOUR Program), Chungnam National UniversityAbstract Korean red ginseng (KRG, Panax ginseng C.A. Meyer) contains ginsenosides, which are metabolized into active metabolites with various pharmacological effects. This study assessed the in vivo exposure and accumulation of ginsenosides following single and repeated administration of KRG and its active ingredient, compound K, in experimental rodents. In Study 1, rats received KRG (2 g/kg) orally as a single dose or for 2, 4, and 8 wks. Repeated administration increased the maximum plasma concentrations (Cmax) of ginsenosides Rb1 and Rd compared to a single dose (Rb: 23.9 to 68.3 ng/mL; Rd: 8.5 to 30.8 ng/mL over 8 wks). Compound K was detected at 2.9 and 2.3 ng/mL of Cmax after 4 and 8 wks of continuous KRG administration, with no significant differences. In Study 2, oral administration of compound K (5 or 10 mg/kg) in rats resulted in accumulation factors of 4 and 7, respectively. Study 3 evaluated the oral bioavailability of compound K in mice (intravenous, 2 mg/kg; oral, 10 mg/kg), estimating it at approximately 12%. Additionally, network pharmacology and molecular docking simulation studies supported the clinical potential of compound K against inflammation-related diseases. These findings suggest that for substances like KRG, which undergo in vivo metabolic conversion after administration, repeated KRG administration alters pharmacokinetic profiles and should be taken into consideration in its application.https://doi.org/10.1038/s41598-025-13873-9PharmacokineticsKorean red ginsengGinsenosideCompound kMetabolic conversion
spellingShingle Ji-Soo Jeong
Jeong-Won Kim
Jin-Hwa Kim
Chang-Yeop Kim
Eun-Hye Chung
So-Young Boo
Mario Giorgi
Je-Won Ko
Tae-Won Kim
Pharmacokinetic variability of 20(S)-protopanaxadiol-type ginsenosides Rb1, rd, and compound K from Korean red ginseng in experimental rodents
Scientific Reports
Pharmacokinetics
Korean red ginseng
Ginsenoside
Compound k
Metabolic conversion
title Pharmacokinetic variability of 20(S)-protopanaxadiol-type ginsenosides Rb1, rd, and compound K from Korean red ginseng in experimental rodents
title_full Pharmacokinetic variability of 20(S)-protopanaxadiol-type ginsenosides Rb1, rd, and compound K from Korean red ginseng in experimental rodents
title_fullStr Pharmacokinetic variability of 20(S)-protopanaxadiol-type ginsenosides Rb1, rd, and compound K from Korean red ginseng in experimental rodents
title_full_unstemmed Pharmacokinetic variability of 20(S)-protopanaxadiol-type ginsenosides Rb1, rd, and compound K from Korean red ginseng in experimental rodents
title_short Pharmacokinetic variability of 20(S)-protopanaxadiol-type ginsenosides Rb1, rd, and compound K from Korean red ginseng in experimental rodents
title_sort pharmacokinetic variability of 20 s protopanaxadiol type ginsenosides rb1 rd and compound k from korean red ginseng in experimental rodents
topic Pharmacokinetics
Korean red ginseng
Ginsenoside
Compound k
Metabolic conversion
url https://doi.org/10.1038/s41598-025-13873-9
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