Introduction As a commonly used chemotherapeutic agent, fluorouracil (5-FU) has serious dose-limiting side effects. In this study, we evaluated the synergy between red American ginseng (RAG) and 5-FU on human colorectal cancer cells, and explored the potential mechanisms. Methods Ginsenoside contents of white American ginseng (WAG) and RAG were determined by HPLC. Cell proliferation was evaluated by MTS assay. Combination Index (CI) analysis was executed using CompuSyn software. Paraptotic events were observed after crystal violet staining. Cell cycle distribution, cyclin A expression and apoptotic induction were analyzed using flow cytometry. Results We observed the heat treatment remarkably increased levels of ginsenoside Rg3, 20R-Rg3, Rk1 and Rg5. When the combinations of 5-FU and RAG were applied, cell proliferation inhibition rates were notably increased, indicating that RAG significantly enhanced 5-FU’s effect. Additionally, CI analysis suggested that there was a synergistic action of 5-FU and RAG when combined. The cell cycle data indicated 5-FU induced S phase arrest, and the combination of 5-FU and RAG increased G1 phase. Further, the RAG’s ability to enhance the anti-cancer effects of 5-FU was linked to both paraptosis and apoptosis inductions.
- MeSH
- Apoptosis drug effects MeSH
- Fluorouracil administration & dosage pharmacology MeSH
- Ginsenosides administration & dosage pharmacology MeSH
- Colorectal Neoplasms drug therapy MeSH
- Drug Therapy, Combination MeSH
- Tumor Cells, Cultured drug effects MeSH
- Drug Screening Assays, Antitumor MeSH
- Drug Synergism MeSH
- In Vitro Techniques MeSH
- Panax chemistry MeSH
- Publication type
- Research Support, Non-U.S. Gov't MeSH
Generation of reactive oxygen species significantly contributes to the pathogenesis of acute renal failure (ARF) induced by myoglobin release. Ginsenosides (GS), the principal active ingredients of ginseng, is considered as an extremely good antioxidative composition of Chinese traditional and herbal drugs. The purpose of the present study was to investigate the protective effect of ginsenoside in rats with ARF on the changes of cholinergic nervous system in the kidney as well as on the involvement of mitogen-activated protein kinases (MAPK) in the hypothalamic paraventricular nuclei (PVN). In our assay, glycerol-induced acute renal failure in rats was employed to study the protective effects of ginsenoside. Our results indicated that the treatment of ARF rats with ginsenosides for 48 h significantly reduced lipid peroxidation, restored the superoxide dismutase (SOD) level. Meanwhile, the obvious increase of choline acetyltransferase-immunoreactivity (ChAT-IR) in the proximal convoluted tubular cells (PCT) was observed by immunohistochemistry in ARF+GS group. The same effect was also observed in the changes of p-ERK1/2-IR in the hypothalamic paraventricular nuclei. Our results suggest that ginsenoside administered orally may have a strong renal protective effect against glycerol-induced ARF, reduce the renal oxidative stress, and ginsenoside can also activate the cholinergic system in PCT, simultaneously MAPK signal pathway in the PVN was also activated.
- MeSH
- Acute Kidney Injury chemically induced enzymology pathology prevention & control MeSH
- Antioxidants administration & dosage pharmacology MeSH
- Administration, Oral MeSH
- Time Factors MeSH
- Choline O-Acetyltransferase metabolism MeSH
- Cytoprotection MeSH
- Phosphorylation MeSH
- Ginsenosides administration & dosage pharmacology MeSH
- Glycerol MeSH
- Malondialdehyde metabolism MeSH
- Mitogen-Activated Protein Kinase 1 metabolism MeSH
- Mitogen-Activated Protein Kinase 3 metabolism MeSH
- Disease Models, Animal MeSH
- Paraventricular Hypothalamic Nucleus drug effects enzymology MeSH
- Oxidative Stress drug effects MeSH
- Lipid Peroxidation drug effects MeSH
- Rats, Sprague-Dawley MeSH
- Kidney Tubules, Proximal drug effects enzymology pathology MeSH
- Signal Transduction drug effects MeSH
- Superoxide Dismutase metabolism MeSH
- Up-Regulation MeSH
- Animals MeSH
- Check Tag
- Male MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
Acute renal failure (ARF) is mainly characterized by acute tubular necrosis. No significant change was found for mortality rates over the past few decades despite significant advances in supportive care. In recent years, great effort has been focused on traditional and herbal medicine, which is much less toxic than those agents conventionally used and which is nowadays considered as a novel therapeutic agent for ARF. However, the effect of ginsenosides (GS) administered orally on ARF has not been reported yet and little is known about its cellular and molecular mechanism. The purpose of the study is to investigate the protective effect of ginsenoside in rats with ARF on the changes of tyrosine hydroxylase immunoreactivity (TH-IR) as well as on the involvement of mitogen-activated protein kinases (MAPK) in the locus coeruleus. In our assay, glycerol-induced acute renal failure in rats was employed to study the protective effects of ginsenoside. Our results indicated that the treatment of ARF rats with ginsenosides for 48 h significantly reduced the serum blood urea nitrogen, creatinine level, and lipid peroxidation, restored the GSH level and the normal renal morphology. Immunohistochemistry showed that an obvious increase of TH-IR was further enhanced in ARF+GS group. The same effect was also observed in the changes of p-ERK1/2-IR in the locus coeruleus. Our results suggest that ginsenoside administered orally may have a strong renal protective effect against glycerol-induced ARF, and ginsenoside can also activate the brain catecholaminergic neurons in the locus coeruleus. Our future attention will be focused to the question whether there is a correlation between the renal protective effect of ginsenosides against acute renal failure and the activation of tyrosine hydroxylase in the locus coeruleus.
- MeSH
- Acute Kidney Injury MeSH
- Administration, Oral MeSH
- Biomarkers blood MeSH
- Time Factors MeSH
- Water Deprivation MeSH
- Blood Urea Nitrogen MeSH
- Financing, Organized MeSH
- Phosphorylation MeSH
- Ginsenosides administration & dosage pharmacology MeSH
- Glutathione metabolism MeSH
- Glycerol MeSH
- Immunohistochemistry MeSH
- Creatinine blood MeSH
- Rats MeSH
- Kidney MeSH
- Locus Coeruleus enzymology drug effects MeSH
- Malondialdehyde metabolism MeSH
- Mitogen-Activated Protein Kinase 1 metabolism MeSH
- Mitogen-Activated Protein Kinase 3 metabolism MeSH
- Disease Models, Animal MeSH
- Protective Agents administration & dosage pharmacology MeSH
- Lipid Peroxidation drug effects MeSH
- Rats, Sprague-Dawley MeSH
- Tyrosine 3-Monooxygenase metabolism MeSH
- Up-Regulation MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Male MeSH
- Animals MeSH
