Background: Chronic cyclosporine (CsA) nephropathy is associated with an accelerated ageing process. Recently, we found that ginseng treatment reduced the progression of chronic CsA nephropathy. However, it is not known that Klotho, an anti-ageing gene, is involved in the protective effect of ginseng. In this study, we evaluated the association between Klotho expression and ginseng in an experimental model of CsA-induced renal injury.

Methods: Mice were treated with CsA (30 mg/kg/day, s.c.) and Korean red ginseng extract (0.2, 0.4, 0.8 g/kg/day, P.O.) under 0.01% salt diet for 4 weeks. The effect of ginseng on CsA-induced renal injury was evaluated by assessing renal function, histopathology, oxidative stress (8-hydroxy-2'-deoxyguanosine [8-OHdG]). Klotho expression was measured using immunoblot analysis in kidney tissue. Using in vitro model, we also examined the expression Klotho during addition of ginseng extract (0.1 or 1 mg/mL) in CsA-induced injury (25 ΜM of CsA) of HK-2 cells.

Results: Four weeks of CsA treatment to mice caused renal dysfunction, typical pathologic lesions, and oxidative stress marker. Ginseng treatment reduced serum creatinine, blood urea nitrogen, 8-OHdG, and increased creatinine clearance and histopathology. Renal expression of Klotho was significantly decreased in the CsA group compared with the VH group (92 ± 3% in the CsA group vs. 100 ± 8% in the VH group, P < 0.05). However co-treatment with 0.4 or 0.8 g/kg of ginseng was restored the expression of Klotho compared with the CsA group (102 ± 2% in the CsA+ginseng0.4, 120 ± 7% in the CsA+ginseng0.8 vs. 92 ± 3% in the CsA group, P < 0.05). This Klotho expression was closely correlated with renal function and expression of oxidative stress in a ginseng-dose dependent manner during chronic CsA treatment. Consistently, additional treatment with ginseng on CsA was increased the expression of Klotho compared with CsA only group in HK-2 cells.

Conclusion: The results of our study demonstrate that ginseng-mediated upregulation of Klotho is associated with suppression of CsA-induced ageing process. Our findings provide a potential rationale for the use of ginseng as supplement in renal transplanted patient receiving CsA.

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