Hesperetin—Between the Ability to Diminish Mono- and Polymicrobial Biofilms and Toxicity

Abstract

Hesperetin is the aglycone of citrus flavonoid hesperidin. Due to the limited information regarding hesperetin antimicrobial potential and emerging need for novel antimicrobials, we have studied its antimicrobial activity (microdilution assay), antibiofilm activity with different assays in two models (mono- and polymicrobial biofilm), and toxicity (MTT and brine shrimp lethality assays). Hesperetin inhibited growth of all Candida isolates (minimal inhibitory concentration, MIC, 0.165 mg/mL), while it’s inhibitory potential towards Staphylococcus aureus was lower (MIC 4 mg/mL). Hesperetin (0.165 mg/mL) reduced ability of Candida to form biofilms and moderately reduced exopolysaccharide levels in biofilm matrix. Effect on the eradication of 24 h old C. albicans biofilms was promising at 1.320 mg/mL. Inhibition of staphylococcal biofilm formation required higher concentrations of hesperetin (<50% inhibition with MIC 4 mg/mL). Establishment of polymicrobial C. albicans-S. aureus biofilm was significantly inhibited with the lowest examined hesperetin concentration (1 mg/mL) in crystal violet and CFU assays. Hesperetin toxicity was examined towards MRC-5 fibroblasts (IC50 0.340 mg/mL) and in brine shrimp lethality assay (LC50 > 1 mg/mL). Hesperetin is efficient in combating growth and biofilm formation of Candida species. However, its antibacterial application should be further examined due to the cytotoxic effects provoked in the antibacterial concentrations.

Microbial Transformation of Hesperidin and Biological Evaluation

“…Previous toxicity studies of hesperidin, hesperetin, and naringenin also supported the results. Although there are previous studies of hesperidin toxicity using in vivo animal modeling and other in vivo animal alternative models, to the best of our knowledge, there is no study with the brine shrimp method where a correlation with the results in the literature exists. − …”

Flavonoids: A treasure house of prospective pharmacological potentials

“…Despite the fact that all of these flavonoids have antimicrobial properties, apigenin stood out for having activity against a variety of bacteria and fungi [ 16 ]. Hesperetin, however, has shown extremely significant antifungal action, particularly against the Candida genus [ 124 ]. These chemicals' potent anti-inflammatory effects are primarily attributed to the inhibition of various inflammatory markers, including TNF-α, NF-κB, IL-1β, IL-6, IL-8, and others which are mentioned on these article.…”

“…Another research demonstrated the antimicrobial activity of hesperetin where the compound showed antifungal activity against some Candida fungal strains including C. albicans 10/15, C. albicans 10/15, C. albicans 475/15, C. albicans ATCC 10231, C. parapsilosis ATCC 22019, C. tropicalis ATCC 750, C. krusei H1/16, C. glabrata 4/6/15 with a minimum inhibitory concentration (MIC) of 0.165 mg/mL. Also, the compound exhibited antibacterial activity against S. aureus ATCC 11632 with MIC of 4 mg/mL [ 124 ].…”