Enhancing the Pharmaceutical Properties of Flavonoids via Methylation and Glycosylation

Methylated flavonoids as anti-seizure agents: Naringenin 4′,7-dimethyl ether attenuates epileptic seizures in zebrafish and mouse models

“…Of interest, methylation of KFL (forming KFD or 4′-O-methyl kaempferol) increased only marginally the activity (as shown in the behavioral test), whereas methylation of NRGs (forming naringenin 7-O-methyl ether (NRG-M), and naringenin 4′,7-dimethyl ether (NRG-DM)), had a clear impact on the outcome. Significantly, it has been observed that methylation of flavonoids dramatically favors their metabolic stability and membrane transport, thereby facilitating absorption and positively affecting their bioavailability (Koirala, 2016;Koirala et al, 2016). In the present study however we were not able to prove any metabolic advantage of the methylated vs the non-methylated compound as any clear metabolic turnover of NRG-DM was lacking (results not shown) and no quantifiable amounts but also no metabolites could be detected in case of NRG.…”

“…As such, dietary flavonoids and chemical derivatives thereof offer a possibly interesting source for ASD and AED chemical discovery work (Jäger and Saaby, 2011;Marder and Paladini, 2002;Singh et al, 2014). Although their pharmaceutical potential is often hampered by metabolic instability and low oral bioavailability, it has been argued that their drug-likeness can be improved via methylation of the free hydroxyl groups, dramatically enhancing the metabolic stability and membrane transport, facilitating absorption and highly increasing the bioavailability (Koirala, 2016;Koirala et al, 2016). Of importance, this methylation also abrogates their chemical anti-oxidant capacity, but leaves the general protective activity of the compounds against oxidative stress intact (Deng et al, 2006).…”

Zebrafish and Flavonoids: Adjuvants against Obesity

“…From these central intermediates, the pathway diverges into several classes of flavonoids which are flavones (e.g., apigenin, and luteolin), flavonols (e.g., quercetin, and kaempferol), flavanones (e.g., naringenin, and hesperetin), isoflavones (e.g., genistein and daidzein), flavanols (e.g., catechin and epicatechin), and anthocyanidins (e.g., pelargonidin, cyanidin, malvidin, and delphinidin) (Figure 4) [72,74]. The bioavailability of flavonoids varies among different subclasses and has been shown to be quite poor in many of them, which has often hindered their pharmaceutical potential [75]. Multiple factors, including their chemical structure and solubility, interaction with endogenous enzymes that modulate certain pathways and the gut microbiota, play a crucial role in determining the absorption and bioavailability of flavonoids [76,77].…”

“…Multiple factors, including their chemical structure and solubility, interaction with endogenous enzymes that modulate certain pathways and the gut microbiota, play a crucial role in determining the absorption and bioavailability of flavonoids [76,77]. In the gastrointestinal tract, dietary flavonoids are enzymatically hydrolyzed by bacterial enzymes to release the aglycones, which are well absorbed in the small intestine com- The bioavailability of flavonoids varies among different subclasses and has been shown to be quite poor in many of them, which has often hindered their pharmaceutical potential [75]. Multiple factors, including their chemical structure and solubility, interaction with endogenous enzymes that modulate certain pathways and the gut microbiota, play a crucial role in determining the absorption and bioavailability of flavonoids [76,77].…”

“…The bioavailability of flavonoids varies among different subclasses and has been shown to be quite poor in many of them, which has often hindered their pharmaceutical potential [ 75 ]. Multiple factors, including their chemical structure and solubility, interaction with endogenous enzymes that modulate certain pathways and the gut microbiota, play a crucial role in determining the absorption and bioavailability of flavonoids [ 76 , 77 ].…”