Experimental and clinical evaluation of the efficacy of ecdysten in the treatment of hepatitis

The properties of ecdysten, an exdysterone-based preparation, were studied under experimental (of heliotrine induced hepatitis model in rats) and clinical (chronic viral hepatitis B) conditions. A 2-week treatment with ecdysten in a daily dose of 5 mg/kg (p.o.) significantly improved the state of rat liver, as manifested by normalization of the enzymatic activity of blood serum, stimulation of the protein and glycogen synthesis, inhibition of lipid peroxidation, and activation of all chains of microsomal oxidation of hepatocytes. The inclusion of ecdysten into a complex therapy scheme for patients with chronic viral hepatitis B (5-mg tablets twice per day over a period of 30 days) substantially improved the clinical and biochemical indices of the functional state of liver, positively influenced the humoral and cell immunity and the resistance factors, and normalized the course of autoimmune processes accompanying the liver pathology.     

Effect of ecdysterone on hyperglycemia in experimental animals

Ecdysterone, one of the insect-metamorphosing steroids isolated from plants (Amaranthaceae: Achyranthes fauriei), has been recognized to have a suppressive effect on hyperglycemia induced by several hyperglycemic agents. While the administration of ecdysterone did not alter the blood glucose level of normal animals, pretreatment with ecdysterone prior to hyperglycemic agents suppressed the hyperglycemia induced both by glucagon and by anti-insulin serum at only low levels as well. The effect of ecdysterone was also demonstrated using alloxan-diabetic animals. After the administration of ecdysterone to alloxan-diabetic mice, the blood glucose level was reduced to about one-half of the value observed before the administration of ecdysterone. The incorporation of [¹⁴C]glucose into protein of normal mouse liver and into glycogen of normal and mildly diabetic mouse liver was stimulated by treatment with ecdysterone.     

Action of phytoecdysteroids on the bile-secretory function of the normal liver and in experimental hepatitis

Phytoecdysteroids from Rhaponticum carthemoides (Willd) Iljin and Ajuga turkestanica (Rgl.) Brig in a dose of 5 mg/kg per os markedly stimulate the bile secretion in normal rats treated with single (cyasterone) and 7-day-long (ecdysterone, cyasterone) administration. The chemical composition of the bile is significantly improved because of increased levels of bile acids and bilirubin and a decreased cholesterol content. Phytoecdysteroids (ecdysterone) exert more beneficial effect on the parameters under study in rats with toxic hepatitis induced by heliotrine.     

蜕皮甾酮对HepG2细胞葡萄糖消耗的影响

目的探讨蜕皮甾酮体外降糖的作用特点或机制,即能否通过刺激胰岛素分泌而产生降糖作用。方法检测HepG2细胞24 h培养液中葡萄糖的消耗量;另外测定βTC3细胞胰岛素的释放量。结果蜕皮甾酮在1×10-6~10-4mol.L-1浓度范围内可使HepG2细胞的葡萄糖消耗量增加(44%~77%);蜕皮甾酮的降糖效能随着培养液中葡萄糖浓度的升高而降低;胰岛素对蜕皮甾酮的降糖作用没有明显的影响。蜕皮甾酮没有刺激βTC3细胞胰岛素分泌的作用。结论蜕皮甾酮可通过肝细胞发挥非胰岛素依赖的降糖作用,但不能刺激胰岛素的分泌。     

蜕皮甾酮对缺血性脑损伤的影响

研究了蜕皮甾酮对抗急性脑缺血作用及对脑缺血再灌注引起的记忆障碍的影响．结果发现：蜕皮甾酮１４４ｍｇ／ｋｇ能对抗小鼠急性脑缺血造成的损伤和由于脑缺血引起的体温下降并改善由于脑缺血再灌注引起的学习记忆障碍．蜕皮甾酮１０ｍｇ／ｋｇ还能改善大鼠脑缺血引起的脑水肿并显著降低脑缺血大鼠脑组织钙含量．表明蜕皮甾酮对缺血性脑损伤具有保护作用     

蜕皮甾酮对胰岛素抵抗细胞模型胰岛素敏感性和糖代谢的影响

目的应用高胰岛素体外诱导培养建立的胰岛素抵抗HepG2细胞模型探讨蜕皮甾酮对其胰岛素敏感性和糖代谢的影响。方法采用3H-D-葡萄糖的参入试验评价细胞的胰岛素敏感性,在诱导胰岛素抵抗HepG2细胞模型的过程中或模型建立后,培养液中加入蜕皮甾酮及吡格列酮共同孵育,观察蜕皮甾酮及吡格列酮对HepG2细胞葡萄糖参入率,同时观察蜕皮甾酮对胰岛素抵抗细胞模型葡萄糖消耗量的影响。结果含有蜕皮甾酮(浓度为1×10-6~10-4mol·L-1)的胰岛素抵抗HepG2细胞的葡萄糖参入率与葡萄糖消耗量明显高于不含蜕皮甾酮的胰岛素抵抗HepG2细胞(对照细胞,P<0·01)。蜕皮甾酮与吡格列酮对胰岛素抵抗模型细胞的葡萄糖参入率与葡萄糖消耗量差异无显著性(P>0·05)。结论蜕皮甾酮在胰岛素抵抗细胞模型中能提高胰岛素介导的葡萄糖摄取和利用能力,即增加胰岛素的敏感性;并能明显改善糖代谢。     

蜕皮甾酮对小鼠学习记忆的促进作用

采用一次性训练被动回避性条件反应方法———跳台法,观察了蜕皮甾酮（Ｅｃｄｙｓｔｅｒｏｎｅ）对小鼠学习记忆功能的影响．结果表明,蜕皮甾酮可拮抗东莨菪碱造成的记忆获得障碍,改善环己酰亚胺造成的记忆巩固不良和３０％乙醇造成的记忆再现缺失．蜕皮甾酮还具有抗急性脑缺氧作用,提示蜕皮甾酮可改善记忆障碍,具有较高的药用价值．     

蜕皮甾酮体外抑制β-淀粉样蛋白的纤维形成及神经毒性(英文)

目的　处于聚集及纤维丝状态的 β 淀粉样蛋白片段 1 - 4 2 (Aβ1 -4 2 )具有神经毒作用 ,可导致阿尔茨海默病 (AD)。本文观察蜕皮甾酮体外对Aβ1 -4 2 的聚集、纤维丝形成及其神经元毒性的影响 ,旨在为蜕皮甾酮防治AD提供依据。方法　透射电镜观察蜕皮甾酮及维生素E(VitE)对试管内Aβ1 -4 2 聚集和纤维丝形成的影响 ;MTT法及乳酸脱氢酶 (LDH)活性法检测培养的胚胎大鼠大脑皮层神经元存活率及神经元受损情况。结果　① 1 0 0 μmol·L-1 Aβ1 -4 2 分别与磷酸盐缓冲液 (PBS)、1 0 0 μmol·L-1 蜕皮甾酮和 1 0 0 μmol·L-1 VitE孵育 3d时 ,各组均无纤维丝形成 ;孵育 7d时 ,各组均见纤维丝形成 ,但蜕皮甾酮和VitE组的纤维丝形成较PBS组明显减少 ,尤以蜕皮甾酮组更明显。2 0 μmol·L-1 的蜕皮甾酮和 2 0 μmol·L-1 VitE对Aβ1 -4 2 的聚集及纤维丝形成无明显影响。② 1 0 0μmol·L-1 的Aβ1 -4 2 作用 2 4h ,神经元存活率明显下降。蜕皮甾酮或VitE 1 0～ 1 0 0 μmol·L-1 预处理 30min,再与 1 0 0 μmol·L-1 的Aβ1 -4 2 作用 2 4h ,神经元的存活率呈剂量依赖性增加 ,LDH活性呈剂量依赖性降低。结论　离体条件下 ,蜕皮甾酮可直接抑制Aβ1 -4 2 的聚集及纤维丝形成 ,减轻Aβ1 -4 2 对神经元的毒性 ,?     

Influence of mirtazapine on the sexual behavior of male rats

Rationale Impairment of sexual activity is one of the most frequent side effects of antidepressant drugs. The increase in the synaptic concentrations of serotonin seems to be mainly responsible. Mirtazapine is a novel antidepressant that increases the synaptic concentrations of both noradrenaline and serotonin; moreover, it is an antagonist at 5-HT_2C receptors, whose activation is considered to be responsible for some typical effects of serotonin on the ejaculation process (retardation of ejaculation, anorgasmia).Objectives To study the influence of mirtazapine on copulatory performance and sexual motivation in male rats, in comparison—or in combination—with fluoxetine.Methods Copulatory performance was studied either in sexually experienced or in sexually naive rats; sexual motivation was studied in sexually experienced rats. Mirtazapine (1, 5 or 10 mg/kg), fluoxetine (10 mg/kg), and the combination of mirtazapine + fluoxetine (10+10 mg/kg) were subcutaneously (s.c.) administered either acutely or daily for 13 days.Results After acute administration, mirtazapine decreased mount latency (ML) and intromission latency (IL), and increased mount frequency (MF) and ejaculation latency (EL). Fluoxetine had no significant effect on any of the sexual behavior parameters. After a 13-day treatment, mirtazapine increased ML, IL and MF; fluoxetine increased ML, IL and the intercopulatory interval (ICI); the addition of mirtazapine to fluoxetine produced a reduction of ICI and an increase of MF. Moreover, mirtazapine significantly improved the performance of rats in the sexual motivation test.Conclusions The present results show that, on the whole, the acute administration of mirtazapine improves several parameters of the copulatory performance of male rats and strongly stimulates sexual motivation, while the repeated administration produces minor, conflicting effects. This effect of mirtazapine on male rat sexual behavior is to be ascribed to the antagonism at brain ₂ adrenergic auto- and hetero-receptors, with consequent increased release of noradrenaline and serotonin, and antagonism at 5-HT_2C receptors, which are involved in the negative influence of serotonin on male sexual behavior.     

Effect of bemithyl on sexual behavior and spermatogenesis in rats

Bemithyl produced different influence on the sexual behavior (pairing motivation) and spermatogenesis in rats, depending on the dose and duration of drug administration. A three-day administration of bemithyl (20 and 200 mg/kg, p.o.) stimulated the sexual activity and spermatogenesis in male rats irrespective of the drug dose. The chronic administration of bemithyl over a period of 60 days led to a decrease in the male sexual activity and spermatogenesis index. This behavior can be related to the drug influence on the hypothalamus/pituitary structures responsible for the male rat generative function.     

Role of early GnRH administration in sexual behavior disorders of rat pups perinatally exposed to lead

The effects of maternal exposure to lead (Pb) during the perinatal (1% and 0.1% Pb) periods of sexual brain differentiation were studied in adult male offspring. Maternal Pb levels were measured after treatment. Behavioral (open field and sexual behavior), physical (sexual maturation, body and organ weights), and biochemical (testosterone levels and hypothalamic monoamine and respective metabolite levels) data were assessed in perinatally exposed offspring. The effects of gonadrotopin-releasing hormone (GnRH) administration to pups at birth on puberty and sexual behavior were also investigated in offspring postnatally exposed to the metal. Results showed that perinatal administration of the two Pb concentrations did not modify maternal weight gain; 1% Pb exposure reduced offspring body weight during the 7 days of treatment while no changes were observed after 0.1% Pb exposure; neither Pb concentration altered offspring sexual maturation; the higher Pb concentration improved sexual behavior while the 0.1% concentration reduced it; exposure to 0.1% Pb caused decrease in testis weight, an increase in seminal vesicle weight and no changes in plasma testosterone levels; hypothalamic VMA levels were increased compared to the control group; GnRH administration reversed the effects of 0.1% Pb administration on male sexual behavior. These results show that perinatal exposure to Pb had a dose-dependent effect on the sexual behavior of rats and that a decrease in GnRH source in the offspring was probably involved in the reduction of their sexual performance.     

丁螺环酮在42例抗抑郁药所致性功能障碍病人中的运用

目的 :探讨丁螺环酮在抗抑郁药所致性功能障碍中的治疗作用。方法 :对 4 2例符合抗抑郁药物所致性功能障碍的病人 ,按症状分类 ,加用丁螺环酮 2 0mg·d- 1治疗 1mo ,无效或部分有效者增加至30mg·d- 1,再持续 1mo ,测定性功能障碍在不同性别表现形式上的差异及不同类型性功能障碍的改善程度。结果 :女性多为性欲与性交疼痛的障碍 ,而男性多为性唤起与性高潮唤起上的障碍 ,丁螺环酮对性唤起及性高潮唤起的改善较性欲及性交疼痛更明显。完全改善率 71% (30 / 42 ) ,部分改善率 19%(8/ 42 ) ,未改善 10 % (4 / 42 )。对 12例无效者和部分有效者加大剂量后 ,仅 1例完全改善。结论 :丁螺环酮可以作为抗抑郁药所致性功能障碍的治疗方法之一 ,尤其是对男性病人。     

祁州漏芦中的植物甾酮类成分

自祁州漏芦 (Rhaponticumuniflorum (L .)DC .)的根中分离得到 4种植物甾酮类成分 ,根据理化常数和波谱数据鉴定为蜕皮甾酮 (ecdysterone) (1) ,筋骨草甾酮C(ajugasteroneC) (2 ) ,蜕皮甾酮 3 O β D 葡萄糖苷 (ecdysterone 3 O β D glucopyranoside) (3) ,蜕皮甾酮 2 5 O β D 葡萄糖苷(ecdysterone 2 5 O β D glucopyranoside) (4) ,其中化合物 3,4,为从本属植物中首次分离     

牛膝中脱皮甾酮的含量测定及促成骨样细胞增殖活性

牛膝为苋科牛膝属植物ＡｃｈｙｒａｎｔｈｅｓｂｉｄｅｎｔａｔａＢｌ.之干燥根 ,有散淤血、消肿痛、补肝肾、强筋骨之功效[1] ,为常用中药之一。历代文献明确为治疗“骨痹”、“骨痿”(骨质疏松症 )的方剂共 2 1个 ,涉及药物 77种 ,其中牛膝是出现频率较高的药物[2 ] 。通过研究发现牛膝的醇提物以及醇提物的乙酸乙酯萃取物对成骨样细胞ＵＭＲ10 6有显著的促进增殖作用[3] 。因此 ,我们以成骨样细胞ＵＭＲ10 6的增殖为靶向指标 ,对牛膝醇提物的乙酸乙酯萃取物再进行提取、分离、纯化 ,找出较强的促进细胞增殖的活性成分 ,并研究ＨＰＬＣ含…     

新化合物结构蜕皮甾酮衍生物TAPA降糖作用与机制的初步研究

目的:评价新化合物结构蜕皮甾酮衍生物TAPA的体内降糖作用,并对其作用机制从细胞水平上进行初步研究。方法:取大鼠随机分为正常对照组、模型组、TAPA-1(1 mg/kg)组、TAPA-5(5 mg/kg)组、TAPA-25(25 mg/kg)组和罗格列酮(2 mg/kg)组,每组10只,除正常对照组外其余各组大鼠建立2型糖尿病模型,后4组即为给药组,每日灌胃1次,连续给药28 d,给药期间每周测定大鼠摄食量、体质量、饮水量及随机血糖水平,末次给药5 h后灌胃葡萄糖测定2 h内的血糖浓度,计算血糖-时间曲线下面积(AUC)考察糖耐量。建立胰岛素抵抗肝癌细胞Hep G2,采用3H-d-葡萄糖掺入实验评价在1×10-9、1×10-7mol/L胰岛素环境下,1×10-5mol/L的TAPA和罗格列酮分别对Hep G2细胞和胰岛素抵抗Hep G2细胞的葡萄糖掺入率。取胰岛β细胞瘤细胞系3(βTC3)细胞,随机分为空白对照组、TAPA-Ⅰ(1×10-10mol/L)组、TAPA-Ⅱ(1×10-8mol/L)组、TAPA-Ⅲ(1×10-6mol/L)组和格列齐特(1×10-5mol/L)组,给药孵育24 h后测定各组细胞液中胰岛素含量。结果:与正常对照组比较,给药组大鼠的摄食量、体质量、饮水量均无明显变化;与模型组比较,给药组大鼠血糖水平在给药结束时均明显降低、糖耐量均降低(P<0.05),且降糖效果、糖耐量与TAPA剂量和给药时间均呈正相关。TAPA和罗格列酮对Hep G2细胞的葡萄糖掺入率无明显影响,能明显提高对胰岛素抵抗Hep G2细胞的葡萄糖掺入率(P<0.01)。与空白对照组比较,TAPA各剂量组βTC3细胞的胰岛素释放量无明显变化,格列齐特组βTC3细胞的胰岛素释放量明显增加(P<0.01)。结论:TAPA可降低2型糖尿病模型大鼠的血糖水平和糖耐量,体外试验认为其可增加胰岛素敏感性,但不促进胰岛素分泌。     

Effect of testosterone and dihydrotestosterone on the sexual behavior of female rats

Sexual behaviour was tested in female rats with ovariectomy treated with various sexual hormones and healthy male rats with sexual experience. There was a marked suppression of receptive behaviour in rats with ovariectomy but the proceptive one was preserved. A marked growth of lordosis, achieving the level of that in intact rats in estrus is observed after the administration of estradiol propionate (10 micrograms) and progesterone (500 micrograms). A single subcutaneous administration of testosterone dipropionate (100 micrograms) and dihydrotestosterone (DHT) with DHT-propionate (10 micrograms) to ovariectomized rats did not stimulate lordosis but preserved a high level of proceptive behaviour. Disconnections in the character of proceptive and mating behaviour show that different mechanisms are in the base of their regulation. No difference was noted in the effect of testosterone and DHT on sexual behaviour. The administration of DHT induced certain aggressiveness in the animals. No dynamics was observed in the character of the studied indicators for 3 days. The lack of differences in testosterone and DHT action on sexual behaviour of female rats shows that intracerebral aromatization is not obligatory for the manifestation of the effect.     

抗抑郁药蒲郁胶囊对雄性大鼠性功能的影响及其机制初探

目的观察蒲郁胶囊对雄性大鼠性功能与血清雄激素的影响,并与米氮平和药氟西汀进行比较,研究蒲郁胶囊的药理学特点。方法60只雄性大鼠随机分为空白、氟西汀、米氮平和蒲郁胶囊低、中、高剂量共6组。重复给药1周和2周后,通过大鼠交配行为模型和非接触行为模型观察大鼠性功能的差异;之后分别加入五羟色胺1A受体拮抗剂WAY100635和部分激动剂丁螺环酮观察交配行为和非接触性阴茎勃起行为;最后取血,分离血清,ELISA法检测各组雄性大鼠血清雄激素水平。结果氟西汀对性功能有抑制作用,而蒲郁胶囊和米氮平对大鼠性功能均无影响;3种药物对大鼠雄激素均无影响。加入WAY100635和丁螺环酮后能逆转氟西汀引起的性功能障碍,对蒲郁胶囊无影响。结论蒲郁胶囊对雄性大鼠雄激素与性功能的影响均较小,优于氟西汀等SSRIs类抗抑郁药物,其原因可能与其不影响5-HT有关。     

Cerebroprotector activity of Rhaponticum carthamoides extract in rats with brain ischemia

Electron microscopy and electrophysiological data reveal pronounced structural and functional disturbances in cerebral cortex of rats with model brain ischemia. A 5-day treatment with a dry extract from Rhaponticum carthamoides (Willd.) Iljin. in a daily dose of 150 mg/kg (p.o.) equivalent to 2.7 mg ecdysterone per kg body weight reduced manifestations of the ischemic damage, improved the structure of neurons, and restored brain activity (EEG parameters).     

国产鸸鹋蛋壳粉影响雄性小鼠性功能的初步观察

目的观察鸸鹋蛋壳粉对小鼠性功能的影响,对国产鸸鹋蛋壳的药理作用进行初步的实验研究。方法给成年雄性小鼠连续服药21d后采用小鼠交配试验测其交配的潜伏期及交配次数。给幼龄雄性小鼠连续服药30 d后检测其附性器官的脏器指数。以重复悬吊应激复制小鼠性行为障碍模型,观察雄性小鼠的交配能力。结果鸸鹋蛋壳粉能增加成年雄性小鼠的交配次数,促进未成年雄性小鼠生殖器官的生长发育,对重复悬吊应激引起的雄性小鼠性功能障碍具有一定的促进功能恢复的作用。结论国产鸸鹋蛋壳粉具有一定的增强小鼠性功能,提高小鼠性器官生长发育的作用。     

Morphine and naloxone's effects on sexual behavior of the female golden hamster

The effects of morphine and naloxone were observed after administration to female golden hamsters (Mesocricetus auratus). Large doses of morphine, 80 mg/kg, consistently produced sedation and behavioral depression of responses to nociceptive stimuli. Smaller doses of morphine (e.g., 10 mg/kg), that produced few other behavioral changes, suppressed a measure of female sexual responding. The suppressive effects on sexual behavior were reversed by 4 mg/kg of naloxone. Morphine administered intracerebroventricularly had little effect on sexual responding, even at doses which produced other side effects. Doses of 4 and 8 mg/kg of naloxone in opioid-naive subjects did not reliably alter sexual responding up to 2 hr after administration. These observations lead to the suggestion that morphine produces effects which are incompatible with full sexual functioning in female hamsters.