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Research Paper|Volume 11, Issue 15|pp 5548—5569

Ginseng increases Klotho expression by FoxO3-mediated manganese superoxide dismutase in a mouse model of tacrolimus-induced renal injury

Sun Woo Lim1,2, Yoo Jin Shin1,2, Kang Luo1,2, Yi Quan1,2, Sheng Cui1,2, Eun Jeong Ko1,2,3, Byung Ha Chung1,2,3, Chul Woo Yang1,2,3
  • 1Convergent Research Consortium for Immunologic Disease, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
  • 2Transplant Research Center, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
  • 3Division of Nephrology, Department of Internal Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
Received: May 27, 2019Accepted: July 29, 2019Published: August 10, 2019
https://doi.org/10.18632/aging.102137

Copyright © 2019 Lim et al. This is an open-access article distributed under the terms of the Creative Commons Attribution (CC BY) 3.0 License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

The antioxidant function of Klotho is well-documented as a regulatory factor implicated in countering the aging process. This study investigated whether ginseng upregulates Klotho and its antiaging signaling in a setting of calcineurin inhibitor-induced oxidative stress. Although tacrolimus treatment reduced Klotho level in the serum and kidney, ginseng treatment was found to reverse the levels. Tacrolimus-induced oxidative stress was reduced by ginseng treatment, with functional and histological improvements. Effect of ginseng on Klotho-induced manganese superoxide dismutase signaling pathway during tacrolimus treatment in mice revealed that ginseng suppressed phosphatidylinositol 3-kinase/serine-threonine kinase Akt-mediated phosphorylation of forkhead box protein O3a and promoted the binding of forkhead box protein O3a to manganese superoxide dismutase promoter. In the mitochondria, ginseng reduced mitochondrial reactive oxygen species production, mitochondrial membrane potential, and oxygen consumption rate, whereas blocking phosphatidylinositol 3-kinase activity with LY294002 enhanced them. These findings together suggested that ginseng attenuated tacrolimus-induced oxidative stress via signaling between Klotho and the phosphatidylinositol 3-kinase/serine-threonine kinase Akt/forkhead box protein O3a-related antioxidant pathway.