Protective effect of ginsenoside Rb1 against tacrolimus-induced apoptosis in renal proximal tubular LLC-PK1 cells

Dahae Lee; Dong-Soo Lee; Kiwon Jung; Gwi Seo Hwang; Hye Lim Lee; Noriko Yamabe; Hae-Jeong Lee; Dae-Woon Eom; Ki Hyun Kim; Ki Sung Kang

doi:10.1016/j.jgr.2016.12.013

Protective effect of ginsenoside Rb1 against tacrolimus-induced apoptosis in renal proximal tubular LLC-PK1 cells

J Ginseng Res. 2018 Jan;42(1):75-80. doi: 10.1016/j.jgr.2016.12.013. Epub 2017 Jan 10.

Authors

Dahae Lee¹, Dong-Soo Lee², Kiwon Jung³, Gwi Seo Hwang⁴, Hye Lim Lee⁴, Noriko Yamabe⁴, Hae-Jeong Lee⁵, Dae-Woon Eom⁶, Ki Hyun Kim¹, Ki Sung Kang⁴

Affiliations

¹ School of Pharmacy, Sungkyunkwan University, Suwon, Republic of Korea.
² Institute of Human-Environment Interface Biology, Biomedical Research Institute, Department of Dermatology, Seoul National University College of Medicine, Seoul, Republic of Korea.
³ College of Pharmacy, CHA University, Pocheon, Republic of Korea.
⁴ College of Korean Medicine, Gachon University, Seongnam, Republic of Korea.
⁵ Department of Food and Nutrition, Gachon University, Seongnam, Republic of Korea.
⁶ Department of Pathology, University of Ulsan College of Medicine, Gangneung, Republic of Korea.

Abstract

Background: The aim of the present study was to evaluate the potential protective effects of six ginsenosides (Rb1, Rb2, Rc, Rd, Rg1, and Rg3) isolated from Panax ginseng against tacrolimus (FK506)-induced apoptosis in renal proximal tubular LLC-PK1 cells.

Methods: LLC-PK1 cells were treated with FK506 and ginsenosides, and cell viability was measured. Protein expressions of mitogen-activated protein kinases, caspase-3, and kidney injury molecule-1 (KIM-1) were evaluated by Western blotting analyses. The number of apoptotic cells was measured using an image-based cytometric assay.

Results: Reduction in cell viability by 60μM FK506 was ameliorated significantly by cotreatment with ginsenosides Rg1 and Rb1. The phosphorylation of p38, extracellular signal-regulated kinases, and KIM-1, and cleavage of caspase-3, increased markedly in LLC-PK1 cells treated with FK506 and significantly decreased after cotreatment with ginsenoside Rb1. The number of apoptotic cells decreased by 6.0% after cotreatment with ginsenoside Rb1 (10μM and 50μM).

Conclusion: The antiapoptotic effects of ginsenoside Rb1 on FK506-induced apoptosis were mediated by the inhibition of mitogen-activated protein kinases and caspase activation.

Keywords: FK506-induced nephrotoxicity; KIM-1; MAPKs; caspase-3; ginsenoside Rb1.