A Hydrodistillate of Gynostemma pentaphyllum and Damulin B Prevent Cisplatin-Induced Nephrotoxicity In Vitro and In Vivo via Regulation of AMPKα1 Transcription

Abstract

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.

Gynostemma pentaphyllum Hydrodistillate and Its Major Component Damulin B Promote Hair Growth-Inducing Properties In Vivo and In Vitro via the Wnt/β-Catenin Pathway in Dermal Papilla Cells

“…The hydrodistillate of G. pentaphyllum was generated by Chunjieh Cooperation (Jeju City, Korea) as previously described [34]. Around 20 kg of dried G. pentaphyllum leaves was mixed with 1.2 tons of distilled water and heated for 15 h at 109 • C under a pressure of 1.5 atmospheres.…”

“…Throughout the current experiment, we used G. Pentaphyllum hydrodistillate (GPHD), which has been reported to be safe and contains many active ingredients [34]. To examine the hair growth-inducing effects of GPHD on mice, random groups consisting of five mice in each group were administered the respective compounds.…”

“…Human dermal papilla cells (hDPCs) were treated with the indicated concentration of minoxidil (Figure 2A), GPHD (Figure 2B), and damulin B (Figure 2C,D) for 24 h. A trypan blue cell counting assay revealed the cell-proliferative effects of each reagent, while no toxicity was observed (Figure 2E). effects of damulin B, a hydroxylated dammarane-type glycoside, as the analysis of GPHD via ultra-high performance liquid chromatography-quadrupole/time-of-flight mass spectrometry (UHPLC-Q/TOF MS) had previously shown it to be a predominant component [34]. Human dermal papilla cells (hDPCs) were treated with the indicated concentration of minoxidil (Figure 2A), GPHD (Figure 2B), and damulin B (Figure 2C,D) for 24 h. A trypan blue cell counting assay revealed the cell-proliferative effects of each reagent, while no toxicity was observed (Figure 2E).…”