Abstract
Herbal medication used in the treatment of sleep disorders and anxiety often contain
extracts of Valeriana officinalis or Passiflora incarnata . Valerenic acid in V. officinalis and apigenin, orientin, and vitexin in P. incarnata are thought to contribute to their therapeutic effect. It was the aim of this study
to test whether these constituents of herbal extracts are interacting with the uptake
of estrone 3-sulfate, pregnenolone sulfate, and dehydroepiandrosterone sulfate mediated
by the uptake transporters organic anion transporting polypeptide 2B1 (OATP2B1) or
organic anion transporting polypeptide 1A2 (OATP1A2). Madin-Darby canine kidney cells
overexpressing OATP2B1 or OATP1A2 were used to determine the influence of the constituents
on the cellular accumulation of the sulfated steroids. Subsequently, competitive counterflow
experiments were applied to test whether identified inhibitors are also substrates
of the transporters. Valerenic
acid only interacted with OATP2B1, whereas apigenin, orientin, and vitexin interacted
with OATP2B1 and OATP1A2. Competitive counterflow revealed that orientin is a substrate
of both transporters, while apigenin was transported by OATP1A2 and vitexin by OATP2B1.
In a next step, commercially available P. incarnata preparations were assessed for their influence on the transporters, revealing inhibition
of transporter-mediated estrone 3-sulfate uptake. HPLC-UV-MS analysis confirmed the
presence of orientin and vitexin in these preparations, thereby suggesting that these
constituents are involved in the interaction. Our data indicate that constituents
of P. incarnata may alter the function of OATP2B1 and OATP1A2, which could affect the uptake of other
compounds relying on uptake mediated by the transporters.
Key words OATP2B1 - OATP1A2 - interaction - sulfated steroids -
Passiflora incarnata
- Passifloraceae -
Valeriana officinalis
- Caprifoliaceae
