Tikhonova Maria A, Yu Ching-Han, Kolosova Nataliya G, Gerlinskaya Ludmila A, Maslennikova Svetlana O, Yudina Alexandra V, Amstislavskaya Tamara G, Ho Ying-Jui
Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences, Novosibirsk, Russia; State Research Institute of Physiology and Fundamental Medicine, Siberian Branch of the Russian Academy of Medical Sciences, Novosibirsk, Russia.
School of Medicine, Chung Shan Medical University, Taiwan, ROC.
Pharmacol Biochem Behav. 2014 May;120:7-16. doi: 10.1016/j.pbb.2014.01.012. Epub 2014 Feb 1.
One of the important factors in aging is oxidative stress and aging-related disturbances are believed be ameliorated by antioxidants. Diosgenin is a bio-active ingredient of dioscorea that is widely used in Chinese medicine, shows anti-oxidant activity and improves some aging-related deficits in senescent and menopausal animals. We compared alterations in behavior, biochemical parameters (plasma levels of the uric acid, creatinine, calcium, phosphate, total cholesterol, low-density lipoprotein cholesterol and triglycerides, and the plasma activity of aminotransferases AST and ALT), and sperm motility in two models of accelerated senescence (d-galactose-induced (150 mg/kg/day, i.p., 57 days) aging in Wistar rats vs. genetically defined in OXYS rats) and examined the protective effects of diosgenin (10 or 50mg/kg/day, p.o., 57 days). Both models had augmented levels of ALT activity indicating hepatopathology. Compared to d-galactose-treated animals, OXYS rats demonstrated profound biochemical alterations (hypocalcemia, hypophosphatemia, and hypocholesterolemia) and behavioral deficits (impaired object recognition, decreased sexual motivation and locomotor activity, retarded learning) that confirmed the difference in the mechanisms of accelerated senescence in these models. We first showed diminished sperm motility in males of both models of accelerated senescence studied. Chronic diosgenin treatment failed to improve biochemical and behavioral disturbances and had some undesirable side effects on body weight and working memory in OXYS rats. However, diosgenin restored moderately decreased sperm motility in d-galactose-treated Wistar males and might be recommended for treatment of mild age-related reproductive dysfunctions.
衰老的重要因素之一是氧化应激，而抗氧化剂被认为可以改善与衰老相关的紊乱。薯蓣皂苷元是薯蓣属植物的一种生物活性成分，广泛应用于中药，具有抗氧化活性，并能改善衰老和绝经动物一些与衰老相关的缺陷。我们比较了两种加速衰老模型（Wistar大鼠腹腔注射d-半乳糖（150mg/kg/天，共57天）诱导的衰老与OXYS大鼠的基因定义衰老）中行为、生化参数（血浆尿酸、肌酐、钙、磷、总胆固醇、低密度脂蛋白胆固醇和甘油三酯水平，以及转氨酶AST和ALT的血浆活性）和精子活力的变化，并研究了薯蓣皂苷元（10或50mg/kg/天，口服，共57天）的保护作用。两种模型的ALT活性水平均升高，表明存在肝脏病变。与d-半乳糖处理的动物相比，OXYS大鼠表现出明显的生化改变（低钙血症、低磷血症和低胆固醇血症）和行为缺陷（物体识别受损、性动机和运动活动减少、学习迟缓），这证实了这些模型中加速衰老机制的差异。我们首次发现，在所研究的两种加速衰老模型的雄性动物中精子活力均降低。长期给予薯蓣皂苷元未能改善生化和行为紊乱，并且对OXYS大鼠的体重和工作记忆有一些不良副作用。然而，薯蓣皂苷元使d-半乳糖处理的Wistar雄性大鼠中度降低的精子活力得以恢复，可能推荐用于治疗轻度年龄相关的生殖功能障碍。
