Antibacterial Effects of Glycyrrhetinic Acid and Its Derivatives on Staphylococcus aureus

Abstract

Staphylococcus aureus is a major pathogen in humans and causes serious problems due to antibiotic resistance. We investigated the antimicrobial effect of glycyrrhetinic acid (GRA) and its derivatives against 50 clinical S. aureus strains, including 18 methicillin-resistant strains. The minimum inhibitory concentrations (MICs) of GRA, dipotassium glycyrrhizate, disodium succinoyl glycyrrhetinate (GR-SU), stearyl glycyrrhetinate and glycyrrhetinyl stearate were evaluated against various S. aureus strains. Additionally, we investigated the bactericidal effects of GRA and GR-SU against two specific S. aureus strains. DNA microarray analysis was also performed to clarify the mechanism underlying the antibacterial activity of GR-SU. We detected the antimicrobial activities of five agents against S. aureus strains. GRA and GR-SU showed strong antibacterial activities compared to the other three agents tested. At a higher concentration (above 2x MIC), GRA and GR-SU showed bactericidal activity, whereas at a concentration of 1x MIC, they showed a bacteriostatic effect. Additionally, GRA and GR-SU exhibited a synergistic effect with gentamicin. The expression of a large number of genes (including transporters) and metabolic factors (carbohydrates and amino acids) was altered by the addition of GR-SU, suggesting that the inhibition of these metabolic processes may influence the degree of the requirement for carbohydrates or amino acids. In fact, the requirement for carbohydrates or amino acids was increased in the presence of either GRA or GR-SU. GRA and GR-SU exhibited strong antibacterial activity against several S. aureus strains, including MRSA. This activity may be partly due to the inhibition of several pathways involved in carbohydrate and amino acid metabolism.

Antibacterial activity of disodium succinoyl glycyrrhetinate, a derivative of glycyrrhetinic acid against Streptococcus mutans

“…This hypothesis is consistent with our previous findings concerning S. aureus . Comprehensive analysis of gene expression in S. aureus by DNA microarray analysis showed that GR‐SU treatment alters expression of many genes related to sugar metabolism . Additionally, the minimum concentrations of glucose for growth of S .…”

“…GRA is a major component of licorice extract, which is derived from Leguminosae perennials found in the Mediterranean region, South Russia, central Asia, northern China, and America. GR‐SU, a derivative of GRA, is formed by adding a succinic acid moiety to increase water solubility . GRA has been reported to exhibit anti‐inflammatory, antiallergic, and antipeptic ulcer properties, among others .…”

“…20,21 We have previously reported that glycyrrhetinic acid (GRA) and disodium succinoyl glycyrrhetinate (GR-SU) have antibacterial activity against Staphylococcus aureus, including methicillin-resistant S. aureus. 22 GRA is a major component of licorice extract, which is derived from Leguminosae perennials found in the Mediterranean region, South Russia, central Asia, northern China, and America. GR-SU, a derivative of GRA, is formed by adding a succinic acid moiety to increase water solubility.…”

“…GR-SU, a derivative of GRA, is formed by adding a succinic acid moiety to increase water solubility. 22 GRA has been reported to exhibit anti-inflammatory, antiallergic, and antipeptic ulcer properties, among others. [23][24][25][26] In Japan, a preparation of mono-ammonium glycyrrhizinate (Stronger Neo-Minophagen C) is used to treat chronic hepatitis.…”

18β‐Glycyrrhetinic acid: its core biological properties and dermatological applications

“…Similarly, GA and its derivative, disodium 3‐succinyloxy β‐glycyrrhetinate, improved the action of gentamicin against clinical S. aureus strains. No such effect was observed for the combination of GA with chloramphenicol, ofloxacin or erythromycin . GA and its 30‐piperazine analogue also displayed a synergistic effect when combined with the first‐line anti‐tuberculous drugs isoniazid, rifampicin and streptomycin; they also significantly reduced the MIC values of these drugs against drug‐resistant Mycobacterium bovis .…”