Was wurde untersucht? Welche Unsicherheiten, Nebenwirkungen und Arzneimittelhinweise nennt die Quelle? Medizinische Studienlage und Sicherheit stehen neben der traditionellen Verwendung, mit verknüpften HealthOS-IDs.
Originalquelle und Aussage bleiben zusammen
Die englischen Originalabschnitte stammen aus NCCIH, Fachliteratur und LiverTox. Quellenprofile aus verschiedenen Publikationen sind keine zusätzlichen Pflanzenarten. Eine TCM-Kennzeichnung erscheint nur, wenn die Quelle diese Tradition ausdrücklich nennt. Traditionelle Verwendung ist kein klinischer Wirksamkeitsnachweis.
TCM-Forschung & Toxikologie
Fachquellen zu Pflanzen, Zubereitungen und Rezepturen. Publikationsdatum und Abrufdatum sind getrennt: Ein erneuter Abruf macht ältere Studien nicht zu neuer Evidenz. Tier- und Laborbefunde, Fallberichte und widersprüchliche Ergebnisse bleiben im Originalkontext.
3 passende Quellenprofile · Rezepturen, Extrakte und Pflanzen werden getrennt ausgewiesen.
3 Arzneimittelbefunde · Verknüpfte Wirkstoffe: 1 · 0 Toxizitätsbefunde · 0 Gegenanzeigen-/Vermeidungshinweise. Mehrere Befunde können dasselbe Pflanzen-Arzneimittel-Paar betreffen; auch ausbleibende und widersprüchliche Effekte bleiben enthalten.
MDPI · Zubereitung / Extrakt
Green Tea
Quelle abgerufen
Quellenbezeichnung; keine eindeutige botanische Zuordnung.
Veröffentlicht / fachlich aktualisiert: 10.10.2022 · Quelle abgerufen: 27.10.2026
Arzneimittelbeziehung · tacrolimus
3.2.2. Green Tea
Quellenbefund mit unverändertem Untersuchungskontext. Klinischer Schweregrad: nicht bewertet.
3.2.2. Green Tea
Oriental tea infusion has become popular across the globe in the recent decades. Green tea has been shown to inhibit CYPs as well as P-glycoprotein, whose role is to remove various foreign substances from cells in the body. This reducing effect, in turn, should result in an increase in plasma drug level [50,51,52]. However, the aforementioned inhibitory effect is not shared by all the components of botanical supplements and may differ between particular substances [53,54]. In one case report [18], researchers observed an increase in tacrolimus levels following green tea ingestion, and its normalization after the tea was discontinued. Further investigation showed that the patient represented a “poor metabolizer”. This case proved the importance of careful monitoring of this group of recipients, particularly considering the narrow therapeutic index of TAC. In contrast, murine models show a reduction in the Cmax and AUC of tacrolimus following the co-administration of specific catechins extracted from green tea [16]. However, polymerase chain reaction and Western blot showed a reducing effects of catechins on the expression of drug-metabolizing enzymes, drug transporters and the upregulation of nuclear receptors. This inconsistency needs to be further explored in the subsequent studies [55,56,57]. Despite the pharmacokinetic alteration following green tea intake, the protective properties of this herb constitute its main advantage. Commonly known antioxidative properties of green tea can reduce the nephrotoxic effects of tacrolimus, as well as play a role in preventing the development of cardiovascular diseases. Moreover, tea extracts prevent apoptotic cell death via modulation of mitochondrial cytochrome c release and modulation of caspase activation and also decrease ROS, NO and other detrimental substances in a dose- and time-dependent manner [58,59,60,61,62]. Theaflavins and catechins are active ingredients of the plant, and they do not demonstrate as high activity as the complete green tea extracts when tested separately [61]. All the reviews investigated only green tea, not black tea created by the fermentation of natural products; thus, the interaction with tacrolimus may be different. However, there is a need to explore various herbal–drug interactions in the future. Much of the currently available data are derived only from case reports conflicting with the established mechanisms of action, indicating other possible mechanisms. In 2011, a case of a 1.5–2-fold increase of tacrolimus concentration was observed after the ingestion of green tea [18]. Nevertheless, authors did not provide precise data concerning the type of green tea and the amount consumed.
Veröffentlicht / fachlich aktualisiert: 10.10.2022 · Quelle abgerufen: 27.10.2026
Arzneimittelbeziehung · tacrolimus
3.2.1. Panax ginseng
Quellenbefund mit unverändertem Untersuchungskontext. Klinischer Schweregrad: nicht bewertet.
3.2.1. Panax ginseng
Panax ginseng, a common component of the traditional medicine, now commonly used worldwide, presents a wide range of indications, including the enhancement of physical and cognitive functions, prevention of cancer, allergies, inflammation and cardiovascular disorders due to its antioxidative and vasorelaxant properties together with antidiabetic effects [27,28,29,30,31,32]. Ginsenosides and their glycosylated intestinal metabolites constitute the most active components in this plant extracts. Consequently, these substances were investigated with regard to the potential modulation of cytochrome P450, glucuronidation reaction and drug transporting proteins. Changes in the serum concentration of the drug depend on the particular drug involved in the drug–herb interaction. Some preclinical tests provide data about the potential inhibition of CYP2D6 and P-gp, as well as CYP3A induction, although it is vital to bear in mind that in the majority of cases these changes are not clinically significant [28,33,34]. As a herbal product, Panax ginseng comprises numerous ginsenosides, as well as other untested components, which could be inconsistent between single plants, formulations and ready products. Therefore, all of the abovementioned factors could alter the metabolism of tacrolimus. Although there are no conclusive tests excluding the impact of ginsenosides on the metabolism of tacrolimus, the risks of such an interaction are rather low; nevertheless, they should not be neglected [28,29,33,34].
Nephrotoxicity is one of the main causes of chronic allograft dysfunction and allograft failure in transplant recipients [35,36]. The main associated factor seems to be oxidative stress and the formation of reactive oxygen species (ROS) generated by calcineurin inhibitors (CNIs), including tacrolimus [36,37]. Klotho is an anti-ageing gene involved in that process, expressed mainly in the kidneys. The overexpression of that gene results in the extended lifespan in mice, and additionally, reverses the state of detrimental mutations in the nucleotide structure of Klotho, thus leading to premature ageing-like effects and decreased lifespan [38]. Lim et al. [39] investigated the potential of Panax ginseng to reduce TAC-induced oxidative stress, associated with the signalling between Klotho and the related of antioxidant pathways: phosphatidylinositol 3-kinase(PI3K)/serine-threonine kinase Akt(AKT)/forkhead box protein O3a(FoxO3a). Murine models suggest that the combination of tacrolimus with Panax ginseng promotes Klotho and its antiaging signalling, potentially via the inhibition of PI3K/AKT-induced FoxO3a phosphorylation and resulting in the enforcement binding of FoxO3a to the manganese superoxide dismutase (MnSOD) promoter region. Thereby, such a combination amplifies the production of MnSOD mRNA by enzyme expression enhancement in the mitochondria. Furthermore, an increased MnSOD concentration improves the detoxification of ROS to hydrogen peroxide and diatomic oxygen, consequently attenuating tacrolimus-induced oxidative injury in the mitochondria [39,40]. A histological examination of the renal cortex in mice treated with TAC revealed micro-injuries, atrophy and tubulointerstitial fibrosis, whereas an additional usage of Panax ginseng significantly reduced such lesions [39]. Interestingly, prolonged tacrolimus-induced oxidative stress causes adaptive changes in the cell, such as the formation of multiple autophagosome. However, the increased population of autophagosomes is not efficiently degraded due to the impaired autophagic clearance (lysosomal degradation and autophagosome fusion with lysosomes). The overflow of these structures results in the autophagic cell death. Therefore, treatment with Panax ginseng improves the autophagic clearance function by enhancing lysosomal function and autophagosome fusion with lysosomes [41,42]. Due to the excess of ROS in the entire body during tacrolimus therapy, other adverse effects are likely to occur, including direct oxidative toxic effects on the pancreatic beta cells, which may result in diabetes mellitus in the population of recipients [41,43,44]. Nevertheless, further research will elucidate whether the reduction of oxidative stress by Panax ginseng is sufficient to prevent such complex changes. Furthermore, Doh KC et al. [45] demonstrated the protective effects of Panax ginseng against the side effects of cyclosporine, where such an additional treatment was associated with a decreased blood urea nitrogen, interstitial inflammation, fibrosis and apoptosis. Another beneficial activity of Panax ginseng is the favourable modulation of immune homeostasis [34,46]. This herb is well documented to ameliorate the conditions of autoimmune patients [47,48,49]. In fact, it regulates Th17 cells population and reciprocally promotes Treg cells by inhibiting the phosphorylation of signal transducer and activator of transcription 3 phosphorylation (STAT3) pathways, thus establishing Th17/Treg balance [47]. In view of all the available data regarding Panax ginseng supplementation while receiving CNIs, its role in mitigating the chronic side effects of tacrolimus is worth emphasizing. However, the effect of Panax ginseng on CYP-mediated drug metabolism or through other pathways remains inconclusive.
Veröffentlicht / fachlich aktualisiert: 10.10.2022 · Quelle abgerufen: 27.10.2026
Arzneimittelbeziehung · tacrolimus
3.3.1. Schisandra sphenanthera
Quellenbefund mit unverändertem Untersuchungskontext. Klinischer Schweregrad: nicht bewertet.
3.3.1. Schisandra sphenanthera
A Schisandra sphenanthera ethanol extract (SchE) is a herbal medicine also referred to as a Wuzhi capsule, or a Wuhzi tablet, which has been used in the traditional Chinese medicine for thousands of years in cases of hepatitis, hepatic and renal insufficiency, menstrual dysfunction, neurosis and others [74,75,76,77]. It is often prescribed in Chinese transplant patients for tacrolimus-induced hepatitis treatment as a liver-protective agent [77,78]. Studies have shown that the co-administration of Wuhzi tablets and tacrolimus may significantly increase tacrolimus blood concentration. Schisantherin A (STA) and schisandrin A (SIA), the main active agents of SchE, inhibit CYP3A4/5 by both reversible inhibition and the permanent loss of enzyme activity through its destruction [76,79]. Other SchE components, schisandrin B and gomisin A, were found to inhibit P-glycoprotein, whereas gomisin C competitively inhibited and irreversibly deactivated CYP3A [78]. Tacrolimus is metabolized by CYP3A isoenzymes and undergoes P-glycoprotein-mediated transport; therefore, an interaction should be expected [4,76,80]. Tacrolimus blood concentrations increased 1.57–4.66-fold following SchE administration [76]. Moreover, parameters, such as the AUC, AUMC and Cmax of tacrolimus, were reported to increase significantly, although in terms of CL/F and V/F a significant decrease was observed [78,81]. The SchE effect on Cmax and AUC in rats was dose-dependent and the maximum mean plasma concentration of tacrolimus was achieved at 450 mg/kg [77]. Interestingly, a higher SchE dose did not result in an increase in tacrolimus concentration. Furthermore, a single SchE dose administration resulted in a higher mean plasma concentration and AUC compared to a multiple SchE dosing [77]. Despite the remarkable increase in the blood AUC of tacrolimus, no significant changes were found in rat tissue concentrations [82]. Moreover, studies on CYP3A5 polymorphism showed that SchE effect was more pronounced in the CYP3A5 expressers compared to the non-expressers [79,81,83]. An increase in tacrolimus concentration was lower, although still significant when combined with a long-term prednisone treatment [84]. Xin et al. reported lower mean creatinine levels and higher mean BUN levels in healthy volunteers after SchE and tacrolimus co-administration [78]. In terms of liver function, ALT and AST levels significantly decreased following 6-month SchE treatment in renal transplant patients receiving tacrolimus [85]. SchE administration in renal transplant recipients not only did not deteriorate graft function but was found to have a protective effect on its survival [81]. Side effects, such as hyperkalaemia or fever, were reported after SchE and tacrolimus co-administration and were accounted for as a result of an increased tacrolimus blood concentration [78,86]. Several population pharmacokinetic models have been developed to support the individualization of tacrolimus dosing for different groups: renal transplant recipients [81,83,85,87,88], liver transplant recipients [89,90], cardiac transplant recipients [91,92], patients with refractory nephrotic syndrome [93,94], membranous nephropathy [95,96], lupus nephritis [97,98] or myasthenia gravis [99]. SchE may significantly increase tacrolimus bioavailability and reduce its therapeutic costs by 40–60%, nevertheless, authors highly recommend blood tacrolimus concentration monitoring while co-administering with SchE [78,79,82,85].