In vitro effectiveness of triterpenoids and their synergistic effect with antibiotics against Staphylococcus aureus strains

Abstract

Objectives:The aim of this study is to evaluate the effect of four triterpenoids such as oleanolic acid, ursolic acid, cycloastragenol, and beta-boswellic acid alone and in combination with antibiotics against Staphylococcus aureus strains.Materials and Methods:Sixteen clinical strains of S. aureus from infected wounds were isolated. Eight were methicillin-sensitive S. aureus (MSSA), and the other eight were methicillin-resistant S. aureus (MRSA). The activity was also seen in reference S. aureus American Type Culture Collection™ strains. The activity of all the triterpenoids and antibiotics against S. aureus was evaluated by broth microdilution method. The effectiveness was judged by comparing the minimum inhibitory concentrations (MICs) of the compounds with antibiotics. The combination of antibiotics with compounds was evaluated by their fractional inhibitory concentrations (FIC).Results:Against both clinical and reference MSSA strains, none of the compounds exhibited comparable activity to antibiotics vancomycin or cefradine except for ursolic acid (MIC 7.8 μg/ml). Against MRSA, all compounds (MIC 16–128 μg/ml) showed lesser activity than vancomycin (MIC 5.8 μg/ml). Among triterpenoid-antibiotic combinations, the most effective were ursolic acid and vancomycin against clinical strain MSSA (FICS 0.17). However, overall, different combinations between triterpenoids and antibiotics showed 95%–46% (P < 0.05) reduction in MICs of antibiotics compared to when antibiotics were used alone. Cefradine, a drug not suitable for treating MRSA (MIC = 45 μg/ml), showed a remarkable decrease in its MIC (87% P< 0.01) when it was used in combination with oleanolic acid or ursolic acid in both clinical and reference strains.Conclusion:The tested triterpenoids are relatively weaker than antibiotics. However, when used in combination with antibiotics, they showed remarkable synergistic effect and thus can help in prolonging the viability of these antibiotics against S. aureus infections. Furthermore, reduction in MIC of cefradine with oleanolic acid indicates their potential use against MRSA.

Effect of Ursolic and Oleanolic Acids on Lipid Membranes: Studies on MRSA and Models of Membranes

“…On both strains (ATCC 33591 and COL), we demonstrated the activity of UA and OA, with MICs ranging from 8–16 mg/L for UA to 16–32 mg/L for OA. These results indicated a strong antibacterial activity against MRSA in agreement with data from other researchers as well [ 5 , 51 , 52 ]. A partial synergistic effect between UA (or OA) and ampicillin was observed with an FIC Index for ampicillin-UA/OA of 0.38/0.31–1 and 0.25/0.31–1 on ATCC and COL strains, respectively.…”

Synergy between Ursolic and Oleanolic Acids from Vitellaria paradoxa Leaf Extract and β-Lactams against Methicillin-Resistant Staphylococcus aureus: In Vitro and In Vivo Activity and Underlying Mechanisms

“…Our results are also limited to the combination of UA and OA with β-lactams. Combinations with other classes of antibiotics have already been described as synergistic for glycopeptides, tetracyclines or macrolides [ 20 , 47 ] or additive for fluoroquinolones against different Staphylococcus aureus strains [ 48 , 49 ]. The mechanism of these interactions has not been elucidated yet but should implicate other mechanisms than those discovered here, though also possibly related to their interaction with membranes.…”

Boswellia serrata Extract as an Antibiofilm Agent against Candida spp.

“…Compared with synthetically prepared molecules, these substances are also effective in eradicating extracellular polymeric structures [46]. Boswellic acids, alone or in combination with antibiotics, can be an example of the search for a positive effect of natural substances [47]. Boswellic acids and their derivatives have anti-inflammatory, anti-cancer, immunomodulatory, anti-asthmatic, antibacterial and anti-rheumatic properties [48] and function as anti-inflammatory agents [49].…”