The safety, immunological benefits, and efficacy of ginseng in organ transplantation

Abstract

Korean ginseng (Panax ginseng) is associated with a variety of therapeutic effects, including antioxidative, anti-inflammatory, vasorelaxative, antiallergic, antidiabetic, and anticancer effects. Accordingly, the use of ginseng has reached an all-time high among members of the general public. However, the safety and efficacy of ginseng in transplant recipients receiving immunosuppressant drugs have still not been elucidated. Transplantation is the most challenging and complex of surgical procedures and may require causation for the use of ginseng. In this regard, we have previously examined the safety, immunological benefits, and protective mechanisms of ginseng with respect to calcineurin inhibitor-based immunosuppression, which is the most widely used regimen in organ transplantation. Using an experimental model of calcineurin inhibitor-induced organ injury, we found that ginseng does not affect drug levels in the peripheral blood and tissue, favorably regulates immune response, and protects against calcineurin inhibitor-induced nephrotoxicity and pancreatic islet injury. On the basis of our experimental studies and a review of the related literature, we propose that ginseng may provide benefits in organ transplant recipients administered calcineurin inhibitors. Through the present review, we aimed to briefly discuss our current understanding of the therapeutic benefits of ginseng related to transplant patient survival.

Keywords: calcineurin inhibitor; cyclosporine A; ginseng; tacrolimus; transplantation.

Fig. 1

Conceptual summary of experimental studies using ginseng and calcineurin inhibitors. CNI, calcineurin inhibitor; Th17, T helper 17 cell; Treg, regulatory T cells.

Fig. 2

Schematic diagram summarizing the predicted mechanisms whereby ginseng influences immune regulation. Ginseng has immunological benefits via the reciprocal regulation of Th17 and Treg cells during cyclosporin A-induced immunosuppression. Th17, T helper 17 cell; Treg, regulatory T cells.

Fig. 3

Schematic diagram summarizing the predicted mechanism whereby ginseng influences autophagic clearance function. Prolonged oxidative stress induced by tacrolimus augments autophagosome formation as an adaptation to stress and lysosomal dysfunction. However, the autophagosomes are not effectively degraded due to impaired autophagic clearance (lysosomal degradation and autophagosome fusion with lysosomes). The resulting excess production of autophagosomes leads to autophagic cell death. Under these circumstances, ginseng treatment improves the autophagic clearance function by enhancing lysosomal function and autophagosome fusion with lysosomes. CNI, calcineurin inhibitor.

Fig. 4

Schematic diagram summarizing the predicted mechanism whereby ginseng influences regulation of the antiaging gene Klotho. PI3K/AKT-mediated phosphorylation of FoxO3a is induced by reduced Klotho expression in response to tacrolimus treatment. Under these conditions, FoxO3a appears to be maintained in an inactive form in the cytoplasm. However, the restoration of Klotho levels in response to ginseng treatment induces the nuclear translocation of FoxO3a via the suppression of PI3K/AKT activity and an increase in the levels of MnSOD. By maintaining Klotho expression, ginseng may prevent tacrolimus-induced oxidative damage and apoptotic cell death. These findings provide evidence for the protection mechanism of ginseng via the antiaging gene Klotho against a background of oxidative stress-associated injury. FoxO3a, forkhead box O3; P, phosphorylation; MnSOD, manganese-dependent superoxide dismutase.