Anti-allergic actions and pharmacokinetics of orally administered 18α-glycyrrhetinic acid and 18β-glycyrrhetinic acid in mice

Notification No. 65 (2011) The Japanese Pharmacopoeia, 18th ed. “Glycyrrhiza”, Ministry of Health and Welfare, Japan, pp 1908. https://www.mhlw.go.jp/stf/seisakunitsuite/bunya/0000066530.html Accessed 7 Jan 2025

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

CAS  PubMed  Google Scholar 

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

CAS  PubMed  Google Scholar 

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

CAS  PubMed  Google Scholar 

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

CAS  PubMed  Google Scholar 

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

CAS  PubMed  Google Scholar 

Jitrangsri K, Kamata K, Akiba M, Yajiri Y, Ishibashi M, Tatsuzaki J, Ichikawa T (2022) Is 18α-glycyrrhizin a real natural product? Improved preparation of 18α-glycyrrhizin from 18β-glycyrrhizin as a positive standard for HPLC analysis of licorice extracts. J Nat Med 76:367–378

CAS  PubMed  Google Scholar 

Wang X, Zhu H, Li H, Guo S, Chen B, Liu C, Wang G, Zhou F (2022) Magnesium isoglycyrrhizinate reduces the target-binding amount of cisplatin to mitochondrial DNA and renal injury through SIRT3. Int Mol Sci 23:13093

CAS  Google Scholar 

Jiang W, Xu S, Guo H, Lu L, Liu J, Wang G, Hao K (2020) Magnesium isoglycyrrhizinate prevents the nonalcoholic steatosis via regulating energy homeostasis. J Cell Mol Med 24:7201–7213

CAS  PubMed  PubMed Central  Google Scholar 

Jiang W, Guo H, Su D, Xu H, Gu H, Hao K (2019) Ameliorative effect of magnesium isoglycyrrhizinate on hepatic encephalopathy by epirubicin. Int Immunopharmacol 75:105774

CAS  PubMed  Google Scholar 

Akao T, Hayashi T, Kobashi K, Kanaoka M, Kato H, Kobayashi M (1994) Intestinal bacterial hydrolysis is indispensable to absorption of 18b-glycyrrhetic acid after oral administration of glycyrrhizin in rats. J Pharm Pharmacol 46:135–137

CAS  PubMed  Google Scholar 

Akiyama H, Nose M, Ohtsuki N, Hisaka S, Takiguchi TA, Sugimoto N, Fuchino H, Inui T, Kawano N, Hayashi S, Hishida A, Kudo T, Sugiyama K, Abe Y, Mutsuga M, Kawahara N, Yoshimatsu K (2017) Evaluation of the safety and efficacy of Glycyrrhiza uralensis root extracts produced using artificial hydroponic and artificial hydroponic-field hybrid cultivation systems. J Nat Med 71:265–271

CAS  PubMed  Google Scholar 

Nose M, Tsutsui R, Hisaka S, Akiyama H, Inui T, Kawano N, Hayashi S, Hishida A, Fuchino H, Kudo T, Kawahara N, Yoshimatsu K (2020) Evaluation of the safety and efficacy of Glycyrrhiza uralensis root extracts produced using artificial hydroponic and artificial hydroponic-field hybrid cultivation systems III: anti-allergic effects of hot water extracts on IgE-mediated immediate hypersensitivity in mice. J Nat Med 74:463–466

CAS  PubMed  Google Scholar 

Shin YW, Bae EA, Lee B, Lee SH, Kim JA, Kim YS, Kim DH (2007) In vitro and in vivo antiallergic effects of Glycyrrhiza glabra and its components. Planta Med 73:257–261

CAS  PubMed  Google Scholar 

Horisaka H, Yokawa S, Suzuki R, Emoto R, Maeda R, Furuno T (2025) Suppression of FcεRI-evoked degranulation in RBL-2H3 cells on gelatin methacryloyl hydrogel. Cell Biochem Biophys 83:2481–2488

CAS  PubMed  Google Scholar 

Nose M, Yamanaka K, Hisaka S, Inui T, Kawano N, Hayashi S, Hishida A, Fuchino H, Kawahara N, Yoshimatsu K (2019) Evaluation of the safety and efficacy of Glycyrrhiza uralensis root extracts produced using artificial hydroponic-field hybrid cultivation systems II: comparison of serum concentration of glycyrrhetinic acid serum concentration in mice. J Nat Med 73:661–666

CAS  PubMed  Google Scholar 

Hisaka S, Murase S, Kishi H, Nose M (2021) Immunological validation of the pharmacological and anti-allergic action of glycyrrhetinic acid from Glycyrrhizae radix. Trad Kampo Med 8:148–154

CAS  Google Scholar 

Amagaya S, Sugishita E, Ogihara Y, Ogawa S, Okada K, Aizawa T (1984) Comparative studies of the stereoisomers of glycyrrhetinic acid on anti-inflammatory activities. J Pharm Dyn 7:923–928

CAS  Google Scholar 

Lan X, Olaleye OE, Lu J, Yang W, Du F, Yang J, Cheng C, Shi Y, Wang F, Zeng X, Tian N, Liao P, Yu X, Xu F, Li Y, Wang H, Zhang N, Jia W, Li C (2021) Pharmacokinetics-based identification of pseudoaldosterogenic compounds originating from Glycyrrhiza uralensis roots (Gancao) after dosing LianhuaQingwen capsule. Acta Pharm Sin 42:2155–2172

CAS  Google Scholar 

Sakoda R, Ishiuchi K, Yoshino T, Tsunoo Y, Namiki T, Ogawa-Ochiai K, Minamizawa K, Fukunaga K, Watanabe K, Makino T (2024) 3-epi-18β-glycyrrhetinic acid or its glucuronide, the metabolites of glycyrrhizinic acid with individual differences, correlated with diagnostic marker for licorice-induced pseudoaldosteronism in humans. Drug Metab Dispos 52:1407–1416

CAS  PubMed  Google Scholar 

Malekinejad M, Pashaee MR, Malenkinejad H (2022) 18β-glycyrrhetinic acid altered the intestinal permeability in human Caco-2 monolayer cell model. Eur J Nutr 61:3437–3447

CAS  PubMed  Google Scholar 

Zou Q, Wei P, Li J, Ge ZX, Ouyang P (2009) Simultaneous determination of 18α- and 18β-glycyrrhetinic acid in human plasma by LC-ESI-MA and its application to pharmacokinetics. Biomed Chromatgr 23:54–62

CAS  Google Scholar 

Tian Y, Wang X, Bi Y, Li X, Zhang Y, Yao Y, Zhang M, Xu T, Zhang Y, Gui C, Zhang W, Zhang C, Yu H, Zhang Y (2024) Interactions of oleanane pentacyclic triterpenoids with human organic anion transporting polypeptide 1B1 and 1B3. Toxicol In Vitro 98:105842

CAS  PubMed  Google Scholar 

Wen F, Shi M, Bian J, Zhan H, Gui C (2016) Identification of natural products as modulators of OATP2B1 using LC-MS/MS to quantify OATP-mediated uptake. Pharm Biol 54:293–302

CAS  PubMed  Google Scholar 

Lu T, Liao B, Lin R, Meng C, Huang P, Wang C, Liu F, Xia C (2024) 18β-Glycyrrhetinic acid synergizes with enzalutamide to counteract castration-resistant prostate cancer by inhibiting OATP2B1 uptake of dehydroepiandrosterone sulfate. Eur J Pharmacol 983:176995

CAS  PubMed  Google Scholar 

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