Pharmacokinetics and Metabolites of 12 Bioactive Polymethoxyflavones in Rat Plasma

Abstract

Polymethoxyflavones (PMFs) are a subgroup of flavonoids possessing various health benefits. 3,5,7,4′-Tetramethoxyflavone (1), 5,6,7,4′-tetramethylflavone (2), 3,7,3′,4′-tetramethoxyflavone (3), 5,7,3′,4′-tetramethoxyflavone (4), 5-hydroxy-3,7,2′,4′-tetramethoxyflavone (5), 3,5,7,2′,4′-pentamethoxyflavone (6), 5-hydroxy-3,7,3′,4′-tetramethoxyflavone (7), 3-hydroxy-5,7,3′,4′-tetramethylflavone (8), 3,5,7,3′,4′-pentamethoxyflavone (9), 5-hydroxy-3,7,3′,4′,5′-pentamethoxyflavone (10), 3-hydroxy-5,7,3′,4′,5′-pentamethoxyflavone (11), and 3,5,7,3′,4′,5′-hexamethoxylflavone (12) were 12 bioactive and available PMFs. The aim of this study was to investigate the pharmacokinetic, metabolite, and antitumor activities as well as the structure–pharmacokinetic–antitumor activity relationships of these 12 PMFs to facilitate further studies of their medicinal potentials. The cytotoxicity of PMFs with a hydroxy group toward HeLa, A549, HepG2, and HCT116 cancer cell lines was generally significantly more potent than that of PMFs without a hydroxy group. Compounds 5, 7, 8, 10, and 11 were all undetectable in rat plasma, while compounds 1–4, 6, 9, and 12 were detectable. Both the number and position of hydroxy and methoxy groups played an important role in modulating PMF pharmacokinetics and metabolites.

Monodemethylated Metabolites of Orally Administered Nobiletin: Identification and Quantitation in Rat Plasma and Tissues

“…Considering these results, the present analytical method realizes simultaneous quantification of all types of MDNobs with high sensitivity. In a recent study on PMF pharmacokinetics in rats, the lowest detectable concentration of demethylated PMFs equaled 10 ng/mL; i.e., was considerably higher than the values obtained herein. Therefore, the developed method is well-suited for quantifying all MDNob isomers in pharmacokinetic studies of Nob.…”

Hydroxylated Tetramethoxyflavone Affects Intestinal Cell Permeability and Inhibits Cytochrome P450 Enzymes

“…Furthermore, the cytotoxicity of PMFs containing a hydroxyl group was significantly higher than PMFs lacking a hydroxyl group when tested against HeLa, A549, HepG2, and HCT116 cancer cell lines. The number and location of hydroxy and methoxy groups in PMF pharmacokinetics and metabolites were critical factors in their modulation [ 21 ]. The bioavailability of a compound is influenced by several factors, such as its solubility, stability, and potential interactions with food or other drugs.…”

Flow injection chemiluminescence determination of ethion and computational investigation of the adsorption process on molecularly imprinted polymerized high internal phase emulsion

“…[ 14–16 ] Another positive feature is the lack of a monochromator, preventing the attenuation of light radiation, [ 17 ] leading to higher sensitivities. [ 18–20 ]…”