Biotransformation of Flavonoids Improves Antimicrobial and Anti-Breast Cancer Activities In Vitro

Abstract

Coarse cereals are rich in flavonoids, which are bioactive substances with a wide range of functions. Biotransformation is considered an emerging approach to methylate flavonoids, displaying prominent regio- and stereoselectivity. In the current study, liquiritigenin, naringenin, and hesperidin flavonoids were biotransformed using O-methyltransferases that were heterologously expressed in Saccharomyces cerevisiae BJ5464-NpgA. Nuclear magnetic resonance (NMR) spectroscopy was used together with high-resolution mass spectroscopy analysis to determine the structures of the resulting methylated transformants, and their antimicrobial and antiproliferation activities were also characterized. Among the five methylated flavonoids obtained, 7-methoxy-liquiritigenin had the strongest inhibitory effect on Candida albicans SC5314 (C. albicans SC5314), Staphylococcus aureus ATCC6538 (S. aureus ATCC6538), and Escherichia coli ATCC25922 (E. coli ATCC25922), which increased 7.65-, 1.49-, and 0.54-fold in comparison to the values of their unmethylated counterparts at 200, 250, and 400 μM, respectively. The results suggest that 3’-methoxyhesperetin showed the best antiproliferative activity against MCF-7 cells with IC50 values of 10.45 ± 0.45 µM, which was an increase of more than 14.35-fold compared to that of hesperetin. These results indicate that methylation enhances the antimicrobial activities and antiproliferative effects of flavonoids. The current study provides an experimental basis for further research on flavonoids as well as flavonoid-containing crops in the development of antimicrobial and anti-breast cancer drugs in addition to supplementary and health foods. The biotransformation method is ideal, as it represents a means for the sustainable production of bioactive flavonoids.

Molecular and Cellular Mechanisms of Propolis and Its Polyphenolic Compounds against Cancer

“…Ma et al [ 170 ] studied the methylation of genes involved in cell cycle control ( p16INK4a or CDKN2A and RASSF1A), and estrogenic transduction ( ER-β or ESR2 ). Hypermethylation of these genes was confirmed in T24 cancer cells, which agrees with other reports on various human cancers [ 169 , 170 , 171 , 172 , 173 , 174 , 175 , 176 , 177 ]. Demethylation of these genes by quercetin restores their transcriptional activity, indicating that p16, RASSF1A, and ER-β are involved in cell growth arrest and apoptosis in T24 cells after quercetin treatment.…”

“…According to [ 39 ] and Hao et al [ 171 ], polyphenols, such as quercetin, resveratrol, chrysin, and citrus flavonoids, have the ability to modify gut microflora and improve an imbalance of intestinal microbiota, thereby promoting gut health. Intestinal polyphenol metabolites are capable of modifying the activity of enzymes important for the detoxification process and inflammation [ 3 , 13 , 49 , 75 , 129 , 170 ].…”

A Comparative Study of Hesperetin, Hesperidin and Hesperidin Glucoside: Antioxidant, Anti-Inflammatory, and Antibacterial Activities In Vitro

“…[ 5 , 6 ]. Hesperidin and hesperetin have been documented to exhibit a wide range of pharmacological properties, including anti-inflammatory, antimicrobial, anticarcinogenic, antithrombotic and anti-viral activity [ 7 , 8 , 9 , 10 , 11 ]. Recently, it has been demonstrated that hesperidin has a beneficial effect on the skin [ 12 ].…”

Production of isoquercitrin from quercetin by biotransformation using Bascillus sp. CSQ10 isolated from Camellia sinensis cultivation soils

“…There is a need to develop efficient methods to produce biologically active compounds, including various glycosylated polyphenolic compounds. In this regard, the biotransformation has been highlighted as an alternative method to produce biological active compounds, and many researchers have contributed their efforts [23]. Biotransformation is the process of converting substrates to products using biological systems.…”

“…However, there is no need to supply these factors for the biotransformation by microorganisms. Compared to chemical synthesis, biotransformation has advantages in that the reaction conditions are simple, safe, and generate less contaminants [23][24][25]. For these reasons, biotransformation has been successfully applied in the large-scale industrial production of biologically active materials for new drugs and cosmetics [26,27].…”