Pharmacokinetics of ginsenosides following repeated oral administration of red ginseng extract significantly differ betw
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Online ISSN 1976-3786 Print ISSN 0253-6269
RESEARCH ARTICLE
Pharmacokinetics of ginsenosides following repeated oral administration of red ginseng extract significantly differ between species of experimental animals Ji‑Hyeon Jeon1 · Jaehyeok Lee1 · Min‑Koo Choi2 · Im‑Sook Song1
Received: 5 July 2020 / Accepted: 13 November 2020 © The Pharmaceutical Society of Korea 2020
Abstract We aimed to investigate ginsenoside pharmacokinetics in mice and rats following the repeated oral administration of red ginseng extract (RGE) (2 g/kg/day for 7 days). In mouse plasma, seven protopanaxadiol (PPD)type ginsenosides (20(S)-ginsenoside Rb1, Rb2, Rc, Rd, Rg3, 20(S)-compound K, and 20(S)-PPD) and one protopanaxatriol (PPT)-type 20(S)-ginsenoside Re were detected, whereas 20(S)-ginsenoside Rb1, Rb2, Rc, Rd, 20(S)-PPD, and 20(S)-PPT were detected in rat plasma. The tetra- or tri-glycosylated PPD-type ginsenosides Rb1, Rb2, Rc, and Rd, high content ginsenosides in RGE, showed high plasma exposure, a short absorption time ( Tmax), and a long elimination time (T1/2) among the ginsenosides detected in both species. Among the deglycosylated metabolites existing in the feces, 20(S)-compound K and 20(S)-PPD in mice and 20(S)-PPD and 20(S)-PPT in rats were found in the plasma samples. In addition to the differences in the ginsenosides detected in mice and rats, the Tmax and T1/2 of 20(S)-PPD and 20(S)-PPT in rats were greater than those in mice, suggesting the species-dependent difference in the gut metabolism and absorption of ginsenosides in the pathway from 20(S)-ginsenoside Rd to 20(S)-PPD and from 20(S)-ginsenoside Re to 20(S)-PPT. In conclusion, the choice of animal model should be the subject of careful consideration when exploring the pharmacology of RGE with specific focus on the plasma profile of an individual ginsenoside.
* Im‑Sook Song [email protected] 1
College of Pharmacy and Research Institute of Pharmaceutical Sciences, Kyungpook National University, 80 Daehakro, Daegu 41566, Korea
2
College of Pharmacy, Dankook University, Cheon‑an 31116, Korea
Keywords Pharmacokinetics · Ginsenosides · Red ginseng extract · Gut metabolism · Absorption
Introduction Red ginseng extract (RGE) is one of the most popular herbal medicines in many countries, including Korea. RGE is prepared through water extraction at 80–85 °C for 32 h followed by a concentration process under low pressure (60–70 cmHg) at 65 °C. During this process, toxins are removed and new biologically active substances such as ginsenosides are produced (Lee et al. 2015). Ginsenosides are known to stimulate immune function and are effective therapeutic adjuvants for anti-cancer, anti-diabetes, antiinflammation, anti-oxidant, and liver detoxification treatments (Won et al. 2019). Ginsenosides are divided into two categories according to the location of the carbon bonds of the sugar chain: The first category, 20(S)-protopanaxadiol (PPD)-type ginsenosides, are further subdivided into ginsenoside Rb1, ginsenoside Rb2, ginsenoside Rc, ginsenoside Rd, ginse
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