A Hydrodistillate of <i>Gynostemma pentaphyllum</i> and Damulin B Prevent Cisplatin-Induced Nephrotoxicity In Vitro and In Vivo via Regulation of AMPKα1 Transcription
Minhyeok Song,
Minseok Kim,
Dang Hieu Hoang,
Lochana Mangesh Kovale,
Jihyun Lee,
Youngjoo Kim,
Changhyun Lee,
Jongki Hong,
Sungchul Park,
Wonchae Choe,
Insug Kang,
Sung Soo Kim,
Joohun Ha
Affiliations
Minhyeok Song
Department of Biochemistry and Molecular Biology, Graduate School, College of Medicine, Kyung Hee University, Seoul 02447, Republic of Korea
Minseok Kim
Department of Biochemistry and Molecular Biology, Graduate School, College of Medicine, Kyung Hee University, Seoul 02447, Republic of Korea
Dang Hieu Hoang
Department of Biochemistry and Molecular Biology, Graduate School, College of Medicine, Kyung Hee University, Seoul 02447, Republic of Korea
Lochana Mangesh Kovale
Department of Biochemistry and Molecular Biology, Graduate School, College of Medicine, Kyung Hee University, Seoul 02447, Republic of Korea
Jihyun Lee
Easy Hydrogen Corporation, Jeju City 63196, Republic of Korea
Youngjoo Kim
Department of Urology, College of Medicine, Jeju National University, Jeju City 63243, Republic of Korea
Changhyun Lee
Chunjieh Cooperation, Jeju City 63359, Republic of Korea
Jongki Hong
College of Pharmacy, Kyung Hee University, Seoul 02447, Republic of Korea
Sungchul Park
College of Pharmacy, Kyung Hee University, Seoul 02447, Republic of Korea
Wonchae Choe
Department of Biochemistry and Molecular Biology, Graduate School, College of Medicine, Kyung Hee University, Seoul 02447, Republic of Korea
Insug Kang
Department of Biochemistry and Molecular Biology, Graduate School, College of Medicine, Kyung Hee University, Seoul 02447, Republic of Korea
Sung Soo Kim
Department of Biochemistry and Molecular Biology, Graduate School, College of Medicine, Kyung Hee University, Seoul 02447, Republic of Korea
Joohun Ha
Department of Biochemistry and Molecular Biology, Graduate School, College of Medicine, Kyung Hee University, Seoul 02447, Republic of Korea
The clinical application of cisplatin, one of the most effective chemotherapeutic agents used to treat various cancers, has been limited by the risk of adverse effects, notably nephrotoxicity. Despite intensive research for decades, there are no effective approaches for alleviating cisplatin nephrotoxicity. This study aimed to investigate the protective effects and potential mechanisms of a Gynostemma pentaphyllum leaves hydrodistillate (GPHD) and its major component, damulin B, against cisplatin-induced nephrotoxicity in vitro and in vivo. A hydro-distillation method can extract large amounts of components within a short period of time using non-toxic, environmentally friendly solvent. We found that the levels of AMP-activated protein kinase α1 (AMPKα1), reactive oxygen species (ROS), and apoptosis were tightly associated with each other in HEK293 cells treated with cisplatin. We demonstrated that AMPKα1 acted as an anti-oxidant factor and that ROS generated by cisplatin suppressed the expression of AMPKα1 at the transcriptional level, thereby resulting in induction of apoptosis. Treatment with GPHD or damulin B effectively prevented cisplatin-induced apoptosis of HEK293 cells and cisplatin-induced acute kidney injury in mice by suppressing oxidative stress and maintaining AMPKα1 levels. Therefore, our study suggests that GPHD and damulin B may serve as prospective adjuvant agents against cisplatin-induced nephrotoxicity.