Protective effect of Korean Red Ginseng against FK506-induced damage in LLC-PK1 cells

Abstract

BackgroundCompound FK506 is an immunosuppressant agent that is frequently used to prevent rejection of solid organs upon transplant. However, nephrotoxicity due to apoptosis and inflammatory response mediated by FK506 limit its usefulness. In this study, the protective effect of Korean Red Ginseng (KRG) against FK506-induced damage in LLC-PK1 pig kidney epithelial cells was investigated.MethodsLLC-PK1 cells were exposed to FK506 with KRG and cell viability was measured. Western blotting and RT-PCR analyses evaluated protein expression of MAPKs, caspase-3, and KIM-1. TLR-4 gene expression was assessed. Caspase-3 activities were also determined. The number of apoptotic cells was measured using an image-based cytometric assay.ResultsThe reduction in LLC-PK1 cell viability by 60μM FK506 was recovered by KRG cotreatment in a dose-dependent manner. The phosphorylation of p38, p44/42 MAPKs (ERK), KIM-1, cleaved caspase-3, and TLR-4 mRNA expression was increased markedly in LLC-PK1 cells treated with 60μM FK506. However, with the exception of p-ERK, elevated levels of p-p38, KIM-1, cleaved caspase-3, and TLR-4 mRNA expression were significantly decreased after cotreatment with KRG. Activity level of caspase-3 was also attenuated by KRG cotreatment. Moreover, image-based cytometric assay showed that apoptotic cell death was increased by 60μM FK506 treatment, whereas it was decreased after cotreatment with KRG.ConclusionTaken together, these results suggest that the molecular mechanism of KRG in the FK506-induced nephrotoxicity may lead to the development of an adjuvant for the inhibition of adverse effect FK506 in the kidney.

Hormesis and Ginseng: Ginseng Mixtures and Individual Constituents Commonly Display Hormesis Dose Responses, Especially for Neuroprotective Effects

“…In the case of the KRG studies, hormetic dose responses were reported using five biology models (i.e., Dermal papilla cells, Park et al [95]; A549 cell-human pulmonary epithelium cells, Song et al [16,134]; HUVEC [15]; Murine osteoblastic MC3T3 cells [129,131]; LLC-PKI cells [133]) with a focus on possible clinical translation for preventing kidney toxicity during organ transplant procedures [133] and preventing osteoporosis as a result of long-term glucocorticoid treatment [131]. In the case of kidney toxicity, it is well known that the drug FK506 plays a critical role in assuring that a patient will not reject a transplanted organ.…”

“…These developments led to research showing that KRG could also be effective in preventing nephrotoxicity induced by gentamicin in rat renal tubular cells [141,142] and by chronic exposure to cyclosporine [143]. These findings led Lee et al [133] to assess whether KRG would prevent the toxicity of FK506 when both were administered at the same time. Using the LLC-PKI-pig kidney epithelial cells as their model, a toxic dose of FK506 was selected to challenge cell survival, reducing it to 60%.…”

“…From an overall perspective, the ginseng mixture studies showing hormetic dose responses used 16 different biological models (Table 1) with eight being neuronal-behavorially related models. These mixture studies also included several pre-and post-conditioning experiments [22][23][24][25][26]133]. The quantitative features of the ginseng mixture hormetic dose response studies had a median maximum stimulation of 155.5% with the stimulatory dose range being 7-fold (Table 4).…”

Neuroprotective Effects of Tetrahydrocurcumin against Glutamate-Induced Oxidative Stress in Hippocampal HT22 Cells

“…Absorbance values at 450 nm were obtained using an E-Max microplate reader (Molecular Devices, Sunnyvale, CA, USA). The viability of cells was represented by comparing the percentage of viability of the control group [30].…”

Lignan Glycosides and Flavonoid Glycosides from the Aerial Portion of Lespedeza cuneata and Their Biological Evaluations

“…As part of a continuing search for bioactive constituents from Korean medicinal plant sources [ 12 , 13 , 14 ], the methanol (MeOH) extract of the aerial portion of L. cuneata was found to exhibit cytotoxic effects on human ovarian carcinoma cells [ 15 ]. In our recent study, bioassay-guided fractionation and repeated chromatography of the MeOH extract of L. cuneata resulted in isolation of (−)-9′- O -(α- l -rhamnopyranosyl)lyoniresinol, which suppresses the proliferation of A2780 human ovarian carcinoma cells through induction of apoptosis [ 15 ].…”