Pharmacokinetic Study of Biotransformation Products from an Anxiolytic Fraction of Tilia americana

Abstract

An anxiolytic fraction of Tilia americana standardized in tiliroside, rutin, quercitrin, quercetin glucoside, and kaempferol was obtained. After oral administration of the fraction, the above-mentioned flavonoids were not detected in plasma over 24 h. However, meta and para hydroxyphenylacetic acid and dihydroxyphenylacetic acid (m-HPAA, p-HPAA and DOPAC) were monitored. These are the biotransformation compounds of the aglycones of kaempferol and quercetin; these aglycones are products of the other flavonoids present in the anxiolytic fraction. The analytical methods (HPLC) for flavonoids and the related compounds (m-HPAA, p-HPAA and DOPAC) were validated, determining the parameters of accuracy, precision, specificity or selectivity, limit of detection, quantification range, and robustness. The pharmacokinetic assay was performed with ICR mice strains, which were given 200 mg/kg of the standardized active fraction. The results of validation of the analytical methods were obtained, allowing it to be established in a validated way that no flavonoids present in the anxiolytic fraction of T. americana were detected in plasma. However, detection and follow up was possible for the serum levels of m-HPAA, p-HPAA, and DOPAC. The three compounds follow a two-compartment model with very similar parameters between m-HPAA and p-HPAA, some being different from the ones characterized in the pharmacokinetics of DOPAC.

Polyherbal Formulation Enhancing Cerebral Slow Waves in Sleeping Rats

“…We performed an open field test to assess the anxiolytic effects of the polyherbal formulation, 17) which would be validated more reliably by other behavioral test batteries, such as the elevated plus-maze test, the light dark test, the zero maze test, and the social interaction test. 18,19) Previous reports demonstrated an anxiolytic effect of linden and tulsi, 4,5) which was not observed in this study. This contradiction may stem from the difference in the extraction method and the administration route.…”

“…4) Thus, our extract was a mixture mainly of water-soluble polar compounds and did not contain purified nonpolar compounds. Moreover, although drugs were orally administered in some previous studies, 4,10) we chose intraperitoneal injection over oral administration to assess the direct effect of herbal extract. Drug effects could vary more widely for oral administration because of the individual differences in digestive systems between animals.…”

“…2) In addition, there are other polyherbal formulations enhancing learning and memory. 3) However, most of these studies have examined the effects of formulations solely in molecular and behavioral experiments. Therefore, it remains almost unknown how polyherbal medicines exert neurophysiological impacts on central activity.…”

“…Of these medicinal herbs, linden and tulsi have anxiolytic effects. [4][5][6] Mulberry and lavandin have antioxidant effects, [7][8][9] while butterfly pea facilitates memory retention. 10) Therefore, we reasoned that their mixture would have a central impact.…”

The research progress on the anxiolytic effect of plant‐derived flavonoids by regulating neurotransmitters

“…But most of them have serious side effects (Murrough et al, 2015). For instance, although BZDs can produce a rapid pharmacological effect to control anxiety symptoms, they should only be used for short periods due to side effects such as drowsiness, falls, confusion, thinking/memory loss, and incoordination (Juárez Ramírez et al, 2017). The development of small‐molecule drugs is also entering a relatively difficult period (C. Wang et al, 2021).…”