Gingko Biloba and Hypericum Peforatum Uses

Gingko Biloba and Hypericum Peforatum Uses1.0 Gingko bilobaGinkgo biloba is an herb removeed from the leaves of the tree. It has been traditionally used for benefit of blood flow (vasodilation), protection of cells from oxidative damage (antioxidation) and enhancement of memory and concentration. The herb is know to induce CYP450 enzymes such(prenominal) as CYP2C9, CYP2C19 and CYP2B, changing the metabolism of several(prenominal) drugs.2 Hence, concomitant intake of some drugs with Ginkgo may give rise to herb-drug interactions which plenty cause serious adverse effect.1.1 Antiepileptic drugsA recent pharmacogenetic study with 18 volunteers revealed significant inductive effect of CYP2C19 by Ginkgo. Omeprazole which has CYP2C9 activity was used as a substrate. The results demonstrated that Ginkgo decreased the AUC of omeprazole by a significant amount. Besides, the plasma concentrations of omeprazole and its metabolite were switch offd by almost 30% when comp ared to controls. F rom the results obtained, it might be deduced that Ginkgo reduces serum concentrations of antiepileptic drugs which are substrates of CYP2C19 resembling phenytoin, phenobarbital and diazepam.3Ginkgo might also induce CYP2B activity. According to study by Kubota et al 2004, Ginkgo was shown to reduce the hypnotic potency of phenobarbital (50 mg/kg) in rats. The maximum plasma concentration and AUC of phenobarbital were reduced by 40% and 20%, respectively. These might be overdue to innovation of CYP2B activity by Ginkgo since phenobarbital is a substrate for CYP2B in rats, leading to the possible herb-drug interaction.3Study also shows that Ginkgo contains a potent neurotoxin, which is a vitamin B6 derivative. It is also known as Ginkgotoxin or 4-O-methopridoxine.2, 3 The neurotoxin is said to be responsible for the seizure activity. It is a competitive antagonist of pyridoxil phosphate which is a coenzyme of the glutamate decarboxylase. Inhibition of this coenzyme inhibits the ga mma aminobutyric acid synthesis. This interaction might hence diminish the effect of antiepileptic drugs.1.2 Anticoagulants medicationOne of the concerns associated with Ginkgo is the increase risk of bleeding. Several cases have been reported when pickings Ginkgo and anticoagulant drugs like aspirin and warfarin simultaneously. The proposed mechanism of bleeding caused by Ginkgo is via the action of ginkgolide B. According to Smith et al. 1996, Ginkgolide B is a character of Ginkgo which acts as a platelet-activating factor (PAF) antagonist. It is reported to displace PAF from its receptor- binding site, thus inhibiting PAF and results in reduced platelet aggregation and eventually bleeding. Nevertheless, some clinical studies have shown that Ginkgo does not decrease PAF-mediated platelet aggregation as well as prothrombin times.4Warfarin is metabolised by CYP2C9 enzymes. An in vitro study by Gaudineau et al. 2004 stated that Ginkgo inhibits CYP450 enzymes, mainly CYP2C9. Hence, i t is possible that this inhibition might lead to increase in warfarin levels and subsequently greater anticoagulant action. However, there are some contradicting studies which reported that Ginkgo induces rather than inhibits hepatic CYP, including (S)-warfarin hydroxylase. It is also reported that bilobalide found in terpene trilactone fraction of Ginkgo is responsible for the induction. This will thus reduce the efficacy of anticoagulants rather than enhancing the anticoagulant action.4It remains unclear whether Ginkgolide B increase bleeding and whether Ginkgo potentiates or decreases the anticoagulant effect of warfarin in vivo. Nevertheless, it is recommended that for patients on warfarin or other anticoagulants therapy to not take ginkgo-containing products due to a possible risk of serious bleeding.2.0 Hypericum Peforatum (St. Johns Wort)St. Johns Wort preparations may interact with medicines either by increasing the rate of their metabolism or increasing levels of neurotrans mitters.2.1 Drugs metabolized by CYP-450St. Johns Wort interferes with metabolism of drugs by inducing some CYP450 enzymes in the liver and gut. For instance, the main enzyme affected is CYP3A4, as well as 1A2 and 2C9. This results in decrease in blood levels and efficacy of some drug metabolised by CYP450 enzyme.The prescript behind the induction might be due to presence of hyperforin, which is a component of St. Johns Wort. A study by Moore et al. has shown that hyperforin activates a CYP3A4 regulator transcription. This activation thus induces CYP3A4 expression in human liver cells, thus increase the metabolic rate of drugs and subsequently decrease in therapeutic level. It can be deduced that St. Johns Wort inhibits CYP3A4 acutely and induces this enzyme upon repeated administration based on a systematic review.5An example of this herb-drug interaction is St. Johns Wort and antiretroviral drugs such as protease inhibitors (PI) and nonnucleoside reverse transcriptase inhibitors (NNRTI). St. Johns Wort has been shown to decrease plasma concentrations of the drugs by CYP3A4 induction. The effects may also be due to induction of P-glycoprotein. For instance, there was a significant reduction in concentrations of indinavir when taken concurrently with St. Johns Wort in an open-label study.5 This will lead to loss of viral control or development of virus resistance.2.2 Antidepressants medicationSt. Johns Wort also increases the neurotransmitter levels in the brain particularly serotonin through additive effect on discriminating serotonin reuptake inhibitor (SSRI) antidepressants such as fluoxetine and paroxetine. These interactions may lead to mental state changes, sweating, increased blood pressure and motor effects due to increase in serotonin level.Studies have demonstrated that St Johns Wort inhibits the synaptosomal uptake of certain neurotransmitters. It inhibits the uptake of 5-HT, noradrenaline, dopamine, glutamate and GABA. This action is not related to specific binding of the St. Johns Wort to the different transporter molecules, but associated with mechanisms related to Na+ conductive pathways.6It is found that chronic administration of St. Johns Wort downregulates 1-adrenoceptors and upregulates postsynaptic 5-HT1A receptors. Nevertheless, the study shows St. John Worts upregulates 5-HT2 receptors foreign other antidepressants.6ReferencesxxxxKupiec T, Raj V. Fatal Seizures Due to Potential Herb-Drug Interactions with Ginkgo Biloba. Journal of Analytical Toxicology 2005 Oct 29755-58Landmark CJ, Patsalos PN. Interactions between antiepileptic drugs and herbal medicines. Bol. Latinoam. Caribe Plant. Med. Aromaticas 2008 7(2)109-18Takia Y, Yokotania K, Yamadab S, Shinozukac K, Kubotad Y, Watanabed Y, Umegakia K. Ginkgo biloba extract attenuates warfarin-mediated anticoagulation through induction of hepatic cytochrome P450 enzymes by bilobalide in mice. Phytomedicine 2012 Jan 15 19(2)177-82Hammerness P, Basch E, Ulbricht C, Barr ette EP, Foppa I, Basch S, Bent S, Boon H, Ernst E. St. Johns Wort A Systematic Review of Adverse cause and Drug Interactions for the Consultation Psychiatrist. Psychosomatics 2003 July- Aug 44(4)271-82Carloa GD, Borrellia F, Izzoa AA, Ernst E. Is St Johns wort a Prozac-like herbal antidepressant? Trends in Pharmacological Sciences 2001Nov 1 22(11)559