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Int. J. Mol. Sci. 2018, 19(2), 328; https://doi.org/10.3390/ijms19020328

Pharmacokinetic Study of Bioactive Flavonoids in the Traditional Japanese Medicine Keigairengyoto Exerting Antibacterial Effects against Staphylococcus aureus

1
Tsumura Kampo Research Laboratories, Kampo Research & Development Division, Tsumura & Co., Ibaraki 300-1192, Japan
2
Department of Dermatology, Tohoku University Graduate School of Medicine, Miyagi 980-8574, Japan
*
Author to whom correspondence should be addressed.
Received: 15 December 2017 / Revised: 12 January 2018 / Accepted: 22 January 2018 / Published: 23 January 2018
(This article belongs to the Special Issue Bioactive Phenolics and Polyphenols 2018)
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Abstract

Recent studies have demonstrated that flavonoid glucuronides can be deconjugated to the active form aglycone by β-glucuronidase-expressing macrophages. Keigairengyoto (KRT) is a flavonoid-rich traditional Japanese medicine reported to enhance bacterial clearance through immune modulation. Our aims are to examine the pharmacokinetics of KRT flavonoids and to identify active flavonoids contributing to the adjuvant effects of KRT. KRT was evaluated at pharmacokinetic analysis to quantify absorbed flavonoids, and cutaneous infection assay induced in mice by inoculation of Staphylococcus aureus. Preventive or therapeutic KRT administration reduced the number of bacteria in the infection site as well as macroscopic and microscopic lesion scores with efficacies similar to antibiotics. Pharmacokinetic study revealed low plasma levels of flavonoid aglycones after KRT administration; however, plasma concentrations were enhanced markedly by β-glucuronidase treatment, with baicalein the most abundant (Cmax, 1.32 µg/mL). In random screening assays, flavonoids such as bacalein, genistein, and apigenin enhanced bacteria phagocytosis by macrophages. Glucuronide bacalin was converted to aglycone baicalein by incubation with living macrophages, macrophage lysate, or skin homogenate. Taken together, the adjuvant effect of KRT may be due to some blood-absorbed flavonoids which enhance macrophage functions in host defense. Flavonoid-rich KRT may be a beneficial treatment for infectious skin inflammation. View Full-Text
Keywords: Keigairengyoto; bacterial infection; phagocytosis; macrophages; Staphylococcus aureus; flavonoid; pharmacokinetics Keigairengyoto; bacterial infection; phagocytosis; macrophages; Staphylococcus aureus; flavonoid; pharmacokinetics
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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Matsumoto, T.; Kaneko, A.; Koseki, J.; Matsubara, Y.; Aiba, S.; Yamasaki, K. Pharmacokinetic Study of Bioactive Flavonoids in the Traditional Japanese Medicine Keigairengyoto Exerting Antibacterial Effects against Staphylococcus aureus. Int. J. Mol. Sci. 2018, 19, 328.

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