Abstract. We determined the action mechanism of cordycepin, a major bioactive component of Cordyceps militaris, on responses of rat aortic smooth muscle cells (RASMCs) and on vascular disorders, especially neointimal formation. Cordycepin inhibited platelet-derived growth factor-BB (PDGF-BB)-induced RASMCs migration and proliferation in a dose-dependent manner. However, pre-treatment with N ω -nitro-L-arginine methyl ester, a nitric oxide synthase (NOS) inhibitor, and 1,3-dipropyl-8-sulphophenylxanthine (DPSPX), an A 1 / A 2 adenosinereceptor antagonist, abolished the inhibitory role of cordycepin. Cordycepin suppressed the phosphorylation of p38 mitogen-activated protein kinase (p38 MAPK) and heat shock protein 27 (Hsp27), but not that of extracellular signal-regulated kinase (ERK) 1/2 in RASMCs stimulated by PDGF-BB. The production of reactive oxygen species (ROS), O 2 − and H 2 O 2 , induced by PDGF-BB was abolished by the treatment of cordycepin. Moreover, the sprout outgrowth of aortic rings by PDGF-BB was inhibited by cordycepin. In vivo neointimal formation evoked by balloon-injury was significantly attenuated by the administration of cordycepin. These results demonstrate that cordycepin may exert inhibitory effects on PDGF-BB-induced migration and proliferation via interfering with adenosine receptor-mediated NOS pathways, thus resulting in the attenuation of neointima formation. In conclusion, cordycepin may be a potent, promising anti-atherosclerosis agent.

This study was carried out to examine the potential beneficial effect of cordycepin on the decline of testicular function induced with age. A total of 30 male Sprague-Dawley rats (twenty-four 12-month-olds and six 2-month-olds) were divided into five groups. The young control (YC) and middle-aged control (MC) groups received vehicle only. Cordycepin-treated groups were administered daily doses of oral cordycepin at 5, 10, and 20 mg/kg body weight for 4 months. As a result, the MC group exhibited epididymal weight loss, decreased sperm motility, and reduced spermatogenesis compared to the young control group. Interestingly, the epididymal weights of middle-aged rats were dose-dependently increased by treatment with cordycepin. Cordycepin also improved calcium levels and decreased urea and nitrogen, uric acid, and creatinine in the blood of middle-aged rats. In addition, cordycepin significantly increased sperm motility and the progressiveness of sperm movement. All cordycepin-treated groups showed well-arranged spermatogonia, densely packed cellular material, and increased numbers of mature spermatozoa in the seminiferous lumen compared to the middle-aged control group. These results indicate that long-term administration of cordycepin can counteract the decline of testicular function in middle-aged rats.

The present study was carried out to investigate the protective role of garlic (Allium sativum) ethanol extract (GE) in 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-induced hepatic and testicular toxicity. A total of 60 male rats (Sprague-Dawley, weighing 200 +/- 10 g) were divided into six equal groups. The normal control group (NC) received vehicle (intraperitoneally) and saline (perorally). A predetermined dosage of TCDD (40 microg/kg of body weight, i.p.) was administered to single TCDD-treated (TT) and test (GE) groups. GE was administered (perorally) at daily doses of 5 (GE5), 10 (GE10), 20 (GE 20), or 40 (GE40) mg/kg of body weight for 5 weeks, starting 1 week before the TCDD exposure. Decreases in body weight gain (P < .01) and testicular weight (P < .01) induced by TCDD were greatly attenuated by GE (P < .05-.01). TCDD-induced decreases in spermatogenesis-related panels--Johnsen's score, seminiferous tubular size, ratio of tubules with sperm, and sperm count/tubule--were greatly improved by GE treatment in a dose-dependent manner in the rats. TCDD-induced increases in serum cholesterol and triglyceride levels and glutamic oxaloacetate activity were also suppressed by GE (P < .05-.01). These results indicate that administration of garlic to TCDD-exposed rats attenuates testicular and hepatic damage, suggesting that garlic might be a useful agent that can protect human health from toxic responses induced by environmental pollutants.