The Synergistic Effect of Triterpenoids and Flavonoids-New Approaches for Treating Bacterial Infections?

Abstract

Currently, the pharmaceutical industry is well-developed, and a large number of chemotherapeutics are being produced. These include antibacterial substances, which can be used in treating humans and animals suffering from bacterial infections, and as animal growth promoters in the agricultural industry. As a result of the excessive use of antibiotics and emerging resistance amongst bacteria, new antimicrobial drugs are needed. Due to the increasing trend of using natural, ecological, and safe products, there is a special need for novel phytocompounds. The compounds analysed in the present study include two triterpenoids ursolic acid (UA) and oleanolic acid (OA) and the flavonoid dihydromyricetin (DHM). All the compounds displayed antimicrobial activity against Gram-positive (Staphylococcus aureus ATCC 6538, Staphylococcus epidermidis ATCC 12228, and Listeria monocytogenes ATCC 19115) and Gram-negative bacteria (Escherichia coli ATCC 25922, Proteus hauseri ATCC 15442, and Campylobacter jejuni ATCC 33560) without adverse effects on eukaryotic cells. Both the triterpenoids showed the best antibacterial potential against the Gram-positive strains. They showed synergistic activity against all the tested microorganisms, and a bactericidal effect with the combination OA with UA against both Staphylococcus strains. In addition, the synergistic action of DHM, UA, and OA was reported for the first time in this study. Our results also showed that combination with triterpenoids enhanced the antimicrobial potential of DHM.

Keywords: antibacterial activity; cytotoxicity; dihydromyricetin; oleanolic acid; phytocompounds; ursolic acid.

Figure 1

The chemical structures of (A) ursolic acid; (B) oleanoic acid; (C) dihydromyricetin.

Figure 2

Reduction in bacterial growth after ursolic acid treatment and incubation for 24 h. The data represent mean ± SD of the three different experiments performed in triplicate. p-values were determined by one-way analysis of variance (ANOVA), where (*) represents statistically significant results (p ≤ 0.05).

Figure 3

Reduction in bacterial growth after oleanoic acid treatment and incubation for 24 h. The data represent mean ± SD of three different experiments performed in triplicate. p-values were determined by one-way analysis of variance (ANOVA), where (*) represents statistically significant results (p ≤ 0.05).

Figure 4

Reduction in bacterial growth after dihydromyricetin treatment and incubation for 24 h. The data represent mean ± SD of three different experiments performed in triplicate. p-values were determined by ANOVA where (*) represents statistically significant results (p ≤ 0.05).

Figure 5

Synergistic effect of phytocompounds (OA+UA; UA+DHM; OA+DHM) against Gram-positive (S. aureus, S. epidermidis, and L. monocytogenes) and Gram-negative (E. coli, P. hauseri, and C. jejuni) bacteria. The data represent mean ± SD of the three different experiments performed in triplicate. p-values were determined by ANOVA, where (*) represents statistically significant results (p ≤ 0.05).

Figure 6

Viability of human fibroblasts after 24 h incubation with the phytocompounds [20 µg/mL]. The results were expressed as a percentage of viability of the untreated cells. The data represent mean ± SD of the three different experiments performed in triplicate. p-values were determined by ANOVA, where (*) represents statistically significant results (p ≤ 0.05).