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Effect of Schisandrae Fructus on glycyrrhizin content in Kampo extracts containing Glycyrrhizae Radix used clinically in Japan

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Abstract

Glycyrrhizae Radix is an important crude drug in Japan and is the most frequently prescribed drug in Kampo medicines for the treatment of a wide range of diseases. Glycyrrhizin (GL), the major active ingredient of Glycyrrhizae Radix, has various pharmacological actions but causes adverse effects such as pseudoaldosteronism. In a previous study, the GL content of shoseiryuto was found to be unexpectedly low, and Schisandrae Fructus in shoseiryuto reduced the pH value of the decoction and drastically decreased the extraction efficiency of GL from Glycyrrhizae Radix. In the present study, we investigated the extraction efficiency of GL from Glycyrrhizae Radix in decoctions comprising Glycyrrhizae Radix and five different fruit-derived crude drugs. Among the five fruit-derived crude drugs tested, Schisandrae Fructus markedly decreased both the pH value of the decoction and the extraction efficiency of GL. A comparison of the pH value of the decoction and the GL content of 12 Kampo prescriptions (containing at least Glycyrrhizae Radix and Schisandrae Fructus) showed that the GL content per daily dose was proportional to the compounding amount of Glycyrrhizae Radix, and that the extraction efficiency of GL from Glycyrrhizae Radix was strongly correlated with the pH value of the decoction. In addition, the pH value of the decoction was similar to the pH value documented in interview forms provided by pharmaceutical companies. These results suggested that the GL content in Glycyrrhizae Radix-containing Kampo products can be estimated from both the compounding amounts of Glycyrrhizae Radix and the pH value documented in their interview forms. Knowledge of GL content will help avoid adverse reactions due to Glycyrrhizae Radix.

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References

  1. Notification No. 65 (2001) The Japanese Pharmacopia 16th Ed., “Glycyrrhiza”, Ministry of Health and Welfare, Japan, pp 1649–1650. http://www.mhlw.go.jp/topics/bukyoku/iyaku/yakkyoku/ehglish.html. Accessed 1 Dec 2016

  2. Finney RS, Somers GF (1958) The anti-inflammatory activity of glycyrrhetinic acid and derivatives. J Pharm Pharmacol 10:613–620

    Article  CAS  Google Scholar 

  3. Shibata S (2000) A drug over the millennia: pharmacognosy, chemistry, and pharmacology of licorice. Yakugaku Zasshi 120:849–862

    Article  CAS  Google Scholar 

  4. Baltina LA (2003) Chemical modification of glycyrrhizic acid as a route to new bioactive compounds for medicine. Curr Med Chem 10:155–171

    Article  CAS  Google Scholar 

  5. Raphael TJ, Kuttan G (2003) Effect of naturally occurring triterpenoids glycyrrhizic acid, ursolic acid, oleanolic acid and nomilin on the immune system. Phytomedicine 10:483–489

    Article  CAS  Google Scholar 

  6. Ram A, Mabalirajan U, Das M, Bhattacharya I, Dinda AK, Gangal SV, Ghosh B (2006) Glycyrrhizin alleviates experimental allergic asthma in mice. Int Immunopharmacol 6:1468–1477

    Article  CAS  Google Scholar 

  7. Ma C, Ma Z, Liao XL, Liu J, Fu Q, Ma S (2013) Immunoregulatory effects of glycyrrhizic acid exerts anti-asthmatic effects via modulation of Th1/Th2 cytokines and enhancement of CD4(+)CD25(+)Foxp3 + regulatory T cells in ovalbumin-sensitized mice. J Ethnopharmacol 148:755–762

    Article  CAS  Google Scholar 

  8. Conn JW, Rovner DR, Cohen EL (1968) Licorice-induced pseudoaldosteronism. Hypertension, hypokalemia, aldosteronopenia, and suppressed plasma renin activity. JAMA 205:492–496

    Article  CAS  Google Scholar 

  9. Terasawa K, Bandoh M, Tosa H, Hirate J (1986) Disposition of glycyrrhetic acid and its glycosides in healthy subjects and patients with pseudoaldosteronism. J Pharmacobiodyn 9:98–100

    Article  Google Scholar 

  10. Takeda R, Morimoto S, Uchida K, Nakai T, Miyamoto M, Hashiba T, Yoshimitsu K, Kim KS, Miwa U (1979) Prolonged pseudoaldosteronism induced by glycyrrhizin. Endocrinol Jpn 26:541–547

    Article  CAS  Google Scholar 

  11. Nose M, Tada M, Kojima R, Nagata K, Hisaka S, Masada S, Homma M, Hakamatsuka T (2017) Compariosn of glycyrrhizin content in 25 major kinds of Kampo extracts containing Glycyrrhizae Radix used clinically in Japan. J Nat Med 71:711–722

    Article  CAS  Google Scholar 

  12. Okamura N, Miki H, Orii H, Masaoka Y, Yamashita S, Kobayashi H, Yagi A (1999) Simultaneous high-performance liquid chromatographic determination of puerarin, daidzin, paeoniflorin, liquiritin, cinnamic acid, cinnamaldehyde and glycyrrhizin in Kampo medicines. J Pharm Biomed Anal 19:603–612

    Article  CAS  Google Scholar 

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Acknowledgement

This study was supported by a Health and Labour Sciences Research Grant for ‘Research on Regulatory Science of Pharmaceuticals and Medical Devices’ from the Ministry of Health, Labour and Welfare. We would like to thank Editage (www.editage.jp) for English language editing.

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Correspondence to Mitsuhiko Nose.

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Nose, M., Tada, M., Kato, A. et al. Effect of Schisandrae Fructus on glycyrrhizin content in Kampo extracts containing Glycyrrhizae Radix used clinically in Japan. J Nat Med 73, 834–840 (2019). https://doi.org/10.1007/s11418-019-01325-4

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