ABSTRACT
Late-onset hypogonadism (LOH) is associated with advancing age and is caused by a deficiency in serum testosterone levels. The aim of this study was to examine the effect of a Dendropanax morbiferus H.Lév. leaf extract (DME) on LOH using TM3 cells and aging male rats as in vitro and in vivo models, respectively. The in vitro effects of DME on testosterone levels and 3ß-hydroxysteroid dehydrogenase (3ß-HSD) protein expression in TM3 cells were analyzed. In the in vivo experiments, DME was orally administered to rats at three doses (50, 100, and 200 mg/kg/day) for 4 weeks. DME significantly increased the testosterone levels and 3ß-HSD protein expression in TM3 cells. The DME groups showed significantly increased levels of androgenic hormones such as testosterone and dehydroepiandrosterone sulfate. The sex hormone-binding globulin production was significantly lower in the DME groups than that in the control group, while the neurohormone levels in the hypothalamic-pituitary-gonadal axis markedly increased. No significant differences were observed in the glutamic pyruvic transaminase, glutamic oxaloacetic transaminase, and prostate-specific antigen levels among the DME and control groups. The triglyceride and low-density lipoprotein cholesterol levels were significantly lower, while the high-density lipoprotein cholesterol levels were significantly higher in the DME groups than those in the control group. The latency time in the rotarod, treadmill, and swimming tests increased with the DME treatment. Furthermore, the sperm counts in the epididymis markedly increased. These results suggest that DME can be effectively used to alleviate the symptoms of LOH.
Subject(s)
Araliaceae/chemistry , Hypogonadism/drug therapy , Plant Extracts/therapeutic use , Plant Leaves/chemistry , Testosterone/metabolism , 17-Hydroxysteroid Dehydrogenases/analysis , 17-Hydroxysteroid Dehydrogenases/metabolism , Aging , Animals , Cell Line , Hypogonadism/blood , Hypogonadism/metabolism , Hypogonadism/pathology , Hypothalamo-Hypophyseal System/drug effects , Hypothalamo-Hypophyseal System/metabolism , Hypothalamo-Hypophyseal System/pathology , Leydig Cells/drug effects , Leydig Cells/metabolism , Leydig Cells/pathology , Male , Plant Extracts/chemistry , Plant Extracts/pharmacology , Rats , Rats, Sprague-Dawley , Testosterone/analysis , Testosterone/bloodABSTRACT
Dendropanax morbifera H. Lev. is well known in Korean traditional medicine for improvement of blood circulation. In this study, rutin, a bioflavonoid having anti-thrombotic and anticoagulant activities was isolated from a traditional medicinal plant, D. morbifera H. Lev. The chemical characteristics of rutin was studied to be quercetin 3-O-α-l-rhamnopyranosyl-(1-6)-ß-d-glucopyranoside using high performance liquid chromatography mass spectrometry (HPLC-MS), proton nuclear magnetic resonance ((1)H NMR) and carbon-13 nuclear magnetic resonance ((13)C NMR). Turbidity and fibrin clotting studies revealed that rutin reduces fibrin clot in concentration dependent manner. Rutin was found to prolong activated partial thromboplastin time (aPTT), prothrombin time (PT) and closure time (CT). Furthermore, it decreased the activity of pro-coagulant protein, thrombin. In vivo study showed that rutin exerted a significant protective effect against collagen and epinephrine (or thrombin) induced acute thromboembolism in mice. These results suggest that rutin has a potent to be an anti-thrombotic agent for cardiovascular diseases.
Subject(s)
Antithrombins/isolation & purification , Antithrombins/pharmacology , Araliaceae/chemistry , Plants, Medicinal/chemistry , Rutin/isolation & purification , Rutin/pharmacology , Animals , Anticoagulants/chemistry , Anticoagulants/isolation & purification , Anticoagulants/pharmacology , Antithrombins/chemistry , Blood Coagulation/drug effects , Blood Platelets/drug effects , Collagen/adverse effects , Epinephrine/adverse effects , Fibrin/metabolism , Male , Medicine, Korean Traditional , Mice , Partial Thromboplastin Time , Prothrombin Time , Rutin/chemistry , Thrombin/adverse effects , Thrombin/metabolism , Thromboembolism/chemically induced , Thromboembolism/prevention & controlABSTRACT
Dendropanax morbifera Leveille (Araliaceae) is well known in Korean traditional medicine for a variety of diseases. Rotenone is a commonly used neurotoxin to produce in vivo and in vitro Parkinson's disease models. This study was designed to elucidate the processes underlying neuroprotection of rutin, a bioflavonoid isolated from D. morbifera Leveille in cellular models of rotenone-induced toxicity. We found that rutin significantly decreased rotenone-induced generation of reactive oxygen species levels in SH-SY5Y cells. Rutin protected the increased level of intracellular Ca(2+) and depleted level of mitochondrial membrane potential (ΔΨm) induced by rotenone. Furthermore, it prevented the decreased ratio of Bax/Bcl-2 caused by rotenone treatment. Additionally, rutin protected SH-SY5Y cells from rotenone-induced caspase-9 and caspase-3 activation and apoptotic cell death. We also observed that rutin repressed rotenone-induced c-Jun N-terminal kinase and p38 mitogen-activated protein kinase phosphorylation. These results suggest that rutin may have therapeutic potential for the treatment of neurodegenerative diseases associated with oxidative stress.