Compendium of the most significant studies with reference to properties, intake, effects.

Carmeli E, Fogelman Y. Antioxidant effect of polyphenolic glabridin on LDL oxidation. Toxicol Ind Health. 2009 May-Jun;25(4-5):321-4. doi: 10.1177/0748233709103034. 

Abstract. This study was conducted to determine the effect of a natural polyphenolic isoflavone antioxidant (Glabridin) on low-density lipoprotein (LDL) oxidation. Determination of the extent of LDL oxidation was done by measuring the formation of Thiobarbituric acid reactive substances (TBARS). After oral administration of licorice-root ethanol extract to healthy subjects for 6 months, the subjects' oxidative stress level as well as plasma LDL oxidation reduced by 20%. We concluded that dietary consumption of glabridin protects LDL from oxidation.

Singh V, Pal A, Darokar MP. Glabridin synergy with norfloxacin induces ROS in multidrug resistant Staphylococcus aureus. J Gen Appl Microbiol. 2021 Dec 31;67(6):269-272. doi: 10.2323/jgam.2021.06.002. 

Abstract. Glabridin (Glb), a polyphenolic flavonoid inhibits the growth of MDRSA (Multidrug resistant S. aureus) 4627 by inducing ROS. Glb in combination with Norfloxacin (Nor) synergistically induced oxidative stress. Increased ROS/RNS levels, in particular, affected macromolecules' (DNA, lipid, protein) integrity and distorted cell morphology. We found correlation between drug-effects and up-/down-regulation of oxidative stress-related as well as MDR genes. These findings could considerably potentiate the dosing routine of Nor in combination with Glb, which holds a promising prospective as a antibacterial agent against S. aureus.

Markina YV, Kirichenko TV, Markin AM, Yudina IY, Starodubova AV, Sobenin IA, Orekhov AN. Atheroprotective Effects of Glycyrrhiza glabra L. Molecules. 2022 Jul 22;27(15):4697. doi: 10.3390/molecules27154697.

Abstract. Cardiovascular diseases associated with atherosclerosis are the major cause of death in developed countries. Early prevention and treatment of atherosclerosis are considered to be an important aspect of the therapy of cardiovascular disease. Preparations based on natural products affect the main pathogenetic steps of atherogenesis, and so represent a perspective for the long-term prevention of atherosclerosis development. Numerous experimental and clinical studies have demonstrated the multiple beneficial effects of licorice and its bioactive compounds-anti-inflammatory, anti-cytokine, antioxidant, anti-atherogenic, and anti-platelet action-which allow us to consider licorice as a promising atheroprotective agent. In this review, we summarized the current knowledge on the licorice anti-atherosclerotic mechanisms of action based on the results of experimental studies, including the results of the in vitro study demonstrating licorice effect on the ability of blood serum to reduce intracellular cholesterol accumulation in cultured macrophages, and presented the results of clinical studies confirming the ameliorating activity of licorice in regard to traditional cardiovascular risk factors as well as the direct anti-atherosclerotic effect of licorice.

Simmler C, Pauli GF, Chen SN. Phytochemistry and biological properties of glabridin. Fitoterapia. 2013 Oct;90:160-84. doi: 10.1016/j.fitote.2013.07.003. 

Abstract. Glabridin, a prenylated isoflavonoid of G. glabra L. roots (European licorice, Fabaceae), has been associated with a wide range of biological properties such as antioxidant, anti-inflammatory, anti-atherogenic, regulation of energy metabolism, estrogenic, neuroprotective, anti-osteoporotic, and skin-whitening. While glabridin is one of the most studied licorice flavonoids, a comprehensive literature survey linked to its numerous bioactivities is unavailable. The present review provides a comprehensive description of glabridin as a key chemical and biological marker of G. glabra, by covering both its phytochemical characterization and reported biological activities. Both glabridin and standardized licorice extracts have significant impact on food, dietary supplements (DSs) and cosmetic markets, as evidenced by the amount of available patents and scientific articles since 1976, when glabridin was first described. Nevertheless, a thorough literature survey also reveals that information about the isolation and chemical characterization of this important marker is scattered and less detailed than expected. Accordingly, the first part of this review gathers and provides all analytical and spectroscopic data required for the comprehensive phytochemical characterization of glabridin. The four most frequently described and most relevant bioactivities of glabridin are its anti-inflammatory, anti-atherogenic, estrogenic-like effects, and its capacity to regulate energy metabolism. While all bioactivities reported for glabridin belong to a wide array of targets, its principal biological properties are likely interconnected. To this end, the current state of the literature suggests that the biological activity of glabridin mainly results from its capacity to down-regulate intracellular reactive oxygen species, bind to antioxidant effectors, and act on estrogen receptors, potentially as a plant-based Selective Estrogen Receptor Modulator (phytoSERM). © 2013.

Seino H, Arai Y, Nagao N, Ozawa N, Hamada K. Efficient Percutaneous Delivery of the Antimelanogenic Agent Glabridin Using Cationic Amphiphilic Chitosan Micelles. PLoS One. 2016 Oct 3;11(10):e0164061. doi: 10.1371/journal.pone.0164061.

Abstract. Partially myristoylated chitosan pyrrolidone carboxylate (PMCP) is a cationic amphiphilic chitosan derivative. Glabridin (Glab) from licorice root extracts is a hydrophobic antimelanogenic agent. Here we assessed the effects of cationic Glab-containing polymeric micelles derived from PMCP (Glab/PMCP-PM) on the ability of Glab to penetrate the skin and inhibit melanogenesis using a human skin model. The amount of Glab absorbed 24 h after the application of Glab/PMCP-PM was approximately four times higher than that of conventional oil-in-water micelles (control) prepared using Tween 60. Further, the release of IL-1α, a mediator of inflammation, was not detected. Treatment with Glab/PMCP-PM significantly increased the inhibition of melanogenesis compared with control. The inhibition of melanogenesis depends upon the enhanced ability of Glab to penetrate the skin, particularly the epidermis. Moreover, the inhibition of melanogenesis and the cationic potential of the Glab/PMCP-PM levels were increased by the cationic phospholipid copolymer. Therefore, Glab/PMCP-PM shows potential as an effective transdermal delivery system for treating skin hyperpigmentation.

Yokota T, Nishio H, Kubota Y, Mizoguchi M. The inhibitory effect of glabridin from licorice extracts on melanogenesis and inflammation. Pigment Cell Res. 1998 Dec;11(6):355-61. doi: 10.1111/j.1600-0749.1998.tb00494.x. 

Abstract. Glabridin is the main ingredient in hydrophobic fraction of licorice extract affecting on skins. In this study, we investigated inhibitory effects of glabridin on melanogenesis and inflammation using cultured B16 murine melanoma cells and guinea pig skins. The results indicated that glabridin inhibits tyrosinase activity of these cells at concentrations of 0.1 to 1.0 microg/ml and had no detectable effect on their DNA synthesis. Combined analysis of SDS-polyacrylamide gel electrophoresis and DOPA staining on the large granule fraction of these cells disclosed that glabridin decreased specifically the activities of T1 and T3 tyrosinase isozymes. It was also shown that UVB-induced pigmentation and erythema in the skins of guinea pigs were inhibited by topical applications of 0.5% glabridin. Anti-inflammatory effects of glabridin in vitro were also shown by its inhibition of superoxide anion productions and cyclooxygenase activities. These data indicated that glabridin is a unique compound possessing more than one function; not only the inhibition of melanogenesis but also the inhibition of inflammation in the skins. By replacing each of hydroxyl groups of glabridin with others, it was revealed that the inhibitory effect of 2'-O-ethyl glabridin was significantly stronger than that of 4'-O-ethyl-glabridin on melanin synthesis in cultured B16 cells at the concentration of 1.0 mg/ml. With replacement of both of two hydroxyl groups, the inhibitory effect was totally lost. Based on these data, we concluded that two hydroxyl groups of glabridin are important for the inhibition of melanin synthesis and that the hydroxyl group at the 4' position of this compound is more closely related to melanin synthesis.

Jirawattanapong, W., Saifah, E., & Patarapanich, C. (2009). Synthesis of glabridin derivatives as tyrosinase inhibitors. Archives of pharmacal research, 32(5), 647-654.

Abstract. A novel 3″,4″-dihydroglabridin was successfully prepared for studying on tyrosinase inhibitory activity. The result demonstrated that 3″,4″-dihydroglabridin exhibited higher activity than glabridin (IC50 value = 11.40 μM), which is probably due to the 4-substituted resorcinol skeleton and the lacking of double bond between carbon atom 3″ and 4″ on its structure giving more conformational flexibily to interact with the enzyme more effectively. In addition, various acylated derivatives were synthesized as glabridin prodrugs. The chemical and enzymatic hydrolysis of prodrugs revealed that the diacetate ester was rapidly hydrolyzed by porcine liver esterase with the half-life of 2.36 minute, while those of the dihexanoate was 14.8 hour. Both of them were sufficiently stable in phosphate buffer, both pH 5.5 and 7.4, at 37°C with more than 15 days half-life.

Gezici, S., & ŞEKEROĞLU, N. (2021). Bioinformatics analyses on molecular pathways and pharmacological properties of Glabridin. International Journal of Agriculture Environment and Food Sciences, 5(4), 628-639.

Abstract. Glabridin, a bioactive compound that originally isolated from the roots of licorice (Glycyrrhiza glabra L., Fam. Fabaceae), has a wide range of pharmacological properties for instance anti-inflammatory, anti-cancer, anti-microbial, anti-viral, anti-osteoporosis, anti-diabetic, anti-atherogenic, neuroprotective, estrogenic, and skin-whitening. Even though, biological activities and pharmacological properties of glabridin have already been determined, molecular signaling pathways, gene targets, and pharmacological properties based on bioinformatics analyses have not been fully elucidated. Thus, in the presented research, network-based bioinformatics approaches were applied to demonstrate targets of glabridin in human genomes and proteomes. The glabridin was input into the ChEBI database, and the targets of its were predicted using DIGEP-Pred, and then, top interacting genes were identified by GeneCards database. Afterward, STRING and KEGG enrichment database were used to construct a protein-protein interaction (PPI) network and molecular targeting pathway network, respectively. A total of 14 genes coding proteins such as UGT1A1, MAPK1, CYP2B6, MMP9, CHKA, CYP3A4, EGFR, PON1, SLC6A4, SRC, EPHX2, TYR, PTK2, and PPIG effected by glabridin were determined by gene set enrichment analysis. Furthermore, multiple pathways including endocrine resistance, bladder cancer, ErbB signaling pathway, VEGF signaling pathway, chemical carcinogenesis, proteoglycans in cancer, relaxin signaling pathway, and estrogen signaling pathway were also identified to be regulated by glabridin. This research showed that glabridin exhibits highly active pharmacological activity as an anti-infective agent, chemopreventive agent, membrane permeability inhibitor, melanin inhibitor, and apoptosis agonist. Taken together, this study is network-based scientific research that will be very useful in elucidating the biological, molecular and pharmacological properties of glabridin for clinical applications in detail.

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