There has been interest for some time in chrysin pharmacokinetics because of its purported effects on hormone metabolism and brain function. The intestinal absorption of chrysin is limited due to metabolic transformation in the gastrointestinal system and the presence of an efficient transport system that prevents significant quantities from entering the bloodstream. Such findings raise doubts about chrysin being responsible for any of the pharmacological effects of passion flower extract.
In other studies, four passion flower flavonoids, isovitexin, vitexin, orientin, and homoorientin, were administered orally to rats to examine their metabolism and excretion.16 As the majority of the administered dose of these agents was found in the feces, it appears these flavonoids are not readily absorbed into the systemic circulation. When given alone to rats, the maximum blood levels of vitexin were attained in less than an hour following oral administration, and its serum half-life was approximately two and a half hours. The liver and kidney were the organs with the highest concentrations of this compound. Notably, none was found in the brain. As most of the administered dose of vitexin was recovered in the feces, it was concluded that its absorption is limited following this route of administration. Indeed, it is estimated that only 3% to 4% of an orally administered dose of vitexin makes its way from the gastrointestinal system into the bloodstream. Thus, the bulk of the ingested agent never exits the digestive tract. Of the small fraction that does reach the circulation, the majority is rapidly metabolized in the liver. These findings, especially the absence from the brain, make it appear unlikely that vitexin is responsible for any of the central nervous system effects of passion flower.
With regard to apigenin, studies in rats indicate it is slowly absorbed following oral administration. However, its appearance in blood is limited by the fact that it is metabolized by intestinal bacteria and, once absorbed, rapidly metabolized by the liver. A study with human volunteers revealed that small quantities of apigenin appear in blood following the consumption of parsley. No information is available on whether apigenin appears in the brain when it is consumed orally and, if so, what the concentrations are when it is taken in this manner. Inasmuch as its absorption from the gastrointestinal system is limited, and a significant fraction is metabolized before it can be absorbed, there is little likelihood that the brain concentrations of apigenin are sufficient to induce changes in central nervous system function.
Although luteolin appeared in rat and human blood after it was taken orally, a significant portion was metabolized in the intestine and liver, limiting the amount available for mediating pharmacological effects. While in rats it appears luteolin absorption occurs primarily by passive diffusion, up to one-third of the quantity ingested is excreted in the feces. It is evident, therefore, that only a limited amount of luteolin finds its way into the bloodstream even when it is administered in solvents that would be expected to facilitate its absorption. It is likely that the passage of luteolin from the human gastrointestinal system into blood would be much less than that reported in these laboratory animal studies as the extract formulation used clinically would not be as optimal for its absorption.
As for orientin, very little, if any, of this compound was found in rat brain following its intravenous administration. This indicates that orientin is not sufficiently lipid soluble to cross into the brain even if significant quantities are present in blood. Such a finding suggests that, like the other passion flower flavonoids examined, orientin is not a good candidate as the constituent responsible for central nervous system effects.
Laboratory studies demonstrate that passion flower extract, and some of the individual flavonoids contained in this product, have the potential to influence the response to other drugs. In vitro experiments revealed that this extract can interfere with a transport system that restricts the absorption of drugs used to treat breast cancer. If such an interaction occurs in humans, co-administration of the extract with these chemotherapeutics could enhance their effectiveness. Conversely, these data also indicate that by affecting this efflux transporter system, the passion flower extract could facilitate the absorption of toxic agents that would normally be excreted before gaining entry into the systemic circulation.
There are numerous reports on the ability of chrysin, apigenin, and luteolin to affect the activity of drug metabolizing enzymes. Both enhancement and inhibition of enzyme activity have been reported, depending on the type of in vitro analysis performed and the particular enzyme examined. As such studies are generally conducted in vitro, their relevance to what occurs in humans consuming this supplement is unknown.
These pharmacokinetic data indicate that passion flower flavonoids penetrate poorly into the bloodstream following oral administration. For this reason alone, they are not good candidates as the chemical constituents responsible for the pharmacological effects of passion flower extract. The finding that some of these flavonoids can influence the transport of certain drugs and toxic agents into and out of the gastrointestinal system could be of clinical significance since this does not necessarily require absorption into the systemic circulation. If consumed in sufficient quantities, passion flower extract could very well modify the absorption of other substances as the herb travels down the gastrointestinal tract.
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