Analytical Method Development, Pharmacokinetics, and Pharmacodynamics of Selected Polyphenols
Takemoto, Jody Kyoko
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Novel analytical methods were developed and validated according to the International Conference on Harmonization guidelines using high-performance liquid chromatography (HPLC) with ultraviolet (UV) and/or electrospray ionization (ESI) – mass spectrometry (MS) for the separation, isolation, and detection of sakuranetin, β-glucogallin, gallic acid, oxyresveratrol, and 3’–hydroxypterostilbene in biological matrices. The selected polyphenols were quantified in samples from rice, apples, oranges, grapefruit juice, matico, and/or Indian gooseberry through the application of the developed analytical methods. As these polyphenols are distributed in a variety of botanicals and are widely consumed as plants and nutraceuticals, the pharmacokinetics and pharmacodynamics were studied.These methods were applied to fecal, serum, and urine samples obtained from a rat model to characterize the pharmacokinetics of the selected polyphenols and major metabolites after intravenous or oral administration. The pharmacokinetic parameters of each polyphenol were delineated for the first time. These studies uniformly demonstrated poor bioavailability, rapid metabolism to glucuroconjugates and elimination of the selected polyphenols via renal and non-renal pathways. The clinical pharmacokinetics and attempts to increase bioavailability remain to be evaluated.Effects of sakuranetin, β–glucogallin, gallic acid, oxyresveratrol, and 3’–hydroxypterostilbene in in–vitro and/or in–vivo models of adipogenesis, oxidative stress, inflammation and pain, histone deacetylase / sirtuin 1 modulation, and cell proliferation were examined. In these studies sakuranetin, gallic acid, oxyresveratrol, and 3’–hydroxypterostilbene demonstrated anti’adipogenic properties. All polyphenols studied maintained their ability to scavenge free radicals as anti’oxidants. All of the selected polyphenols were effective in reducing cyclooygenase’1 and’2 activities. Racemic sakuranetin and 3’–hydroxypterostilbene was able to inhibit the synthesis of prostaglandins. β’glucogallin, gallic acid, and 3’–hydroxypterostilbene also demonstrated anti-nociceptive activity. The study of polyphenols may lead to the alternative treatments for inflammation and pain. Although the selected polyphenols were not potent anti’proliferative agents in the cancer cell lines examined as determined using the Alamar blue method, their ability to inhibit histone deacetylase activity was evident. Given their ability to inhibit HDAC the utility of polyphenols as mood stabilizers or anti’epilectics should be studied.