Panax ginseng · interaction review discussion

3.2.1. Panax ginseng

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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.

Befund HOS-368840 · tacrolimus · HOS-085202 · Originalquelle ↗

Controversial Interactions of Tacrolimus with Dietary Supplements, Herbs and Food ↗

© 2022 by the authors. Miłosz Miedziaszczyk; Aleksander Bajon; Ewelina Jakielska; Marta Primke; Jędrzej Sikora; Dagmara Skowrońska; Ilona Idasiak-Piechocka. Controversial Interactions of Tacrolimus with Dietary Supplements, Herbs and Food. DOI: 10.3390/pharmaceutics14102154 · CC BY 4.0

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