荜茇中胡椒碱在大鼠体内的药动学研究

目的:建立大鼠灌胃荜茇提取溶液后血浆中胡椒碱的HPLC测定方法,进行大鼠药动学研究。方法:大鼠灌胃给药(荜茇提取溶液)后,通过尾静脉取血获得血浆样品,以胡椒碱为指标,采取甲醇-水(77:23,v:v)为流动相,HypersilC18柱(250mm×4.6mm,10μm)为固定相,紫外检测波长为343nm进行测定。采用药代动力学软件DAS(ver2.0)处理,得到胡椒碱的药代动力学参数。结果:胡椒碱1.75～8.72g/ml范围内呈良好的线性关系,胡椒碱的三种浓度的平均回收率及相对标准偏差分别为88.4%(3.5%)、90.4%(2.8%)、85.9%(5.2%)。胡椒碱在大鼠体内的药代动力学过程符合一室吸收模型,主要药动学参数为tmax1/2=60min,高低剂量分别t1/2=138.78min和t1/2=125.87min,Cmax=0.46和0.27mg/L,AUC(0-t)=42.45和66.47mg/L.min,AUMC(0-t)=5355.17和7811.02。结论:荜茇在大鼠血浆中胡椒碱浓度的测定和临床前药代动力学研究。     

胡椒碱对兔实验性动脉粥样硬化的预防作用

目的 :观察蒙药荜茇的有效成分胡椒碱 (piperine)对实验性高胆固醇血症兔动脉粥样硬化形成的预防做用。方法 :新西兰兔 30只 ,根据血清总胆固醇水平分为对照组、预防组和粥样硬化组 ,每组 10只 ,实验期间 ,对照组 ,普通饲料 :预防组 ,普通饲料加胆固醇 1.2 %和 piperine0 .0 4 5 % ;粥样硬化组 ,普通饲料加胆固醇 1.2 %。 8周后处死动物 ,测定血脂水平和斑块面积。结果 :piperine降低实验性高胆固醇血症兔的血清总胆固醇 (TC)、低密度脂蛋白 -胆固醇 (L DL- C)、Apo B水平 ,对甘油三酯(TG)无明显影响。预防组和粥样硬化组动物胸主动脉斑块面积百分比分别为 0 .5 6 3± 0 .192和 0 .779± 0 .0 73内膜面积与中膜面积百分比分别为 0 .30 1± 0 .2 6 9和 0 .5 82± 0 .183,预防组斑块面积明显低于粥样硬化组 (P<0 .0 5 )。结论 :胡椒碱有效预防兔实验性粥样斑块的形成     

Antifertility effects of beta-sitosterol in male albino rats.

The effects of beta-sitosterol on fertility, epididymal sperm counts and testicular and accessory reproductive organ weights were evaluated in male albino rats. The effects were studied at two dosages (0.5 and 5 mg/kg per day rat subcutaneously) for 16, 32 and 48 days. The antifertility effect of beta-sitosterol was pronounced only at the high dose level, but there was a significant decrease in testicular weight and sperm concentrations after long-term treatment with the low dose of beta-sitosterol. The weights of all accessory sex tissues except caput epididymis increased following low dose sitosterol treatment. High dose treatment reduced the sperm concentrations as well as the weights of testis and accessory sex tissues in a time-dependent manner. Withdrawal of treatment for 30 days restored only the weights of accessory sex tissues to near normal conditions.     

Effects of Celastrus paniculatus on passive avoidance performance and biogenic amine turnover in albino rats

The effects of an indigenous drug, Celastrus oil, extracted from the seeds of Celastrus paniculatus on learning and memory in a two compartment passive avoidance task was studied in albino rats. The effects on the contents of norepinephrine (NE), dopamine (DA) and serotonin (5-HT) in the brain and on the levels of their metabolites both in the brain and urine were also assessed. Significant improvement was observed in the retention ability of the drug treated rats compared with the saline administered controls. The contents of NE, DA and 5-HT and their metabolites in the brain were significantly decreased in the drug treated group. The urinary metabolite levels were also significantly decreased except for total 3-methoxy-4-hydroxyphenyl glycol. These data indicate that Celastrus oil causes an overall decrease in the turnover of all the three central monoamines and implicate the involvement of these aminergic systems in the learning and memory process.     

胡椒碱对中枢神经系统功能的影响

 目的研究胡椒碱对动物睡眠的影响及其抗惊厥作用。方法小鼠开野实验；戊巴比妥钠诱导的小鼠睡眠实验；家兔睡眠时相分析；最大电休克发作实验；戊四唑发作阈值实验；鼠脑单胺类递质的测定。结果胡椒碱可明显减少小鼠的自主活动，并明显的延长戊巴比妥钠诱导的小鼠睡眠时间，还能显著增加家兔的深睡眠。胡椒碱有很强的抗小鼠MES和对抗戊四唑引起的小鼠阵挛性发作的作用，并可明显增加小鼠脑内单胺类神经递质5-HT的含量。结论胡椒碱延长家兔的深睡眠和抗惊厥作用可能与其增加脑内5-羟色胺含量有关。     

Some toxicological studies of Momordica charantia L. on albino rats in normal and alloxan diabetic rats

Momordica charantia L. (MC) (Cucurbitaceae) commonly known as balsam pear, bitter gourd or karela, used in several purposes in traditional medicine is an important medicinal plant. Two sets of experiments were carried out, the first experiment indicated that the LD(50) for MC juice and alcoholic extracts were 91.9 and 362.34 mg/100g b.wt., respectively, of subcutaneously "s.c." injected mice. The toxic signs were recorded within the first 24 h post-injection. The second experiment was performed to evaluate the effect of MC juice and alcoholic extracts on blood glucose and other biochemical parameters in normal and diabetic rats. Both extracts induced a significant decrease in serum glucose levels in normal and diabetic rats. The two extracts did not show any significant effect in urea, creatinine, ALT, AST and AP in normal rat, while in diabetic rats the two extracts caused a significant decrease in serum urea, creatinine, ALT, AST, AP, cholesterol and triglyceride levels. Also, these results suggested that MC extracts possesses anti-diabetic, hepato-renal protective and hypolipidemic effect in alloxan-induced diabetic rats. Thus, MC is alternative therapy that has primarily been used for lowering blood glucose levels in patients with diabetes mellitus.     

淫羊藿总黄酮对D-半乳糖致衰老大鼠睾丸病变的干预作用

目的:研究淫羊藿总黄酮(TFE)对D-半乳糖致衰老大鼠睾丸病变的影响及其可能的机制。方法:SD大鼠皮下(s.c)给予150mg/kgD-半乳糖,连续30d,造成睾丸病变。从第31天起分别给予TFE口服(P.O,50、100mg/kg)、甲基睾酮(P.O,5mg/kg)干预,连续30d。结果:TFE高剂量组相对于模型组睾丸及精囊腺脏器系数分别提高15.8%、24.8%,血清睾酮水平上升29.2%,睾丸中乳酸脱氢酶(LDH)、酸性磷酸酶(ACP)、谷氨酰转肽酶(γ-GT)活性分别提高55.0%、41.4%、33.1%,Ⅳ型胶原及羟脯氨酸含量分别下降35.3%、26.4%,基质金属蛋白酶-2(MMP-2)及基质金属蛋白酶-9(MMP-9)活性显著升高,组织损伤有明显的改善。TFE低剂量组能明显提高睾丸ACP,LDH及γ-GT的活性。结论:淫羊藿总黄酮对D-半乳糖致大鼠睾丸损伤有明显的改善作用,其机制可能与促进睾酮释放及干预MMPs有关。     

Antioxidant effect of beta-carotene on hypoxia induced oxidative stress in male albino rats.

Hypoxia is known to induce oxidative stress in organisms leading to tissue injury. In the present study beta-carotene (BC) given at 10 mg/kg body weight (BW) in reducing the oxidative stress induced by hypoxia was evaluated on male albino rats. Hypoxia exposure caused an increase in malondialdehyde (MDA) levels in plasma and tissues, a concurrent decrease in blood glutathione (GSH), glutathione peroxidase (GPx), plasma protein and plasma BC content. Hemoglobin concentration, Red blood corpuscles (RBC) and White blood corpuscles (WBC) count were also increased under hypoxia. BC supplementation reversed the trend, inducing a significant decrease (P<0.05) in MDA and subsequent increase in plasma and tissue GSH levels in animals exposed to hypoxia. Blood GPx and plasma protein also increased significantly in BC supplemented animals. BC supplementation did not alter the changes in Hb concentration, RBC and WBC count. BC has potent antioxidant activities in reducing the oxidative stress induced by hypobaric hypoxia.     

Hypolipedaemic activity of picroliv in albino rats

The hypolipidaemic action of picroliv, a standarized preparaton from Picrorhiza kurrooa, has been studied in normal as well as in triton- and cholesterol-fed rats. Serum lipids were found to be lowered by picroliv (25 mg/kg b.w.) in triton WR-1339-induced hyperlipaemia. Chronic feeding of this drug (6 mg/kg b.w.) in normal rats and in animals simultaneously treated with cholesterol (25 mg/kg b.w.) for 30 days caused lowering in the lipid and protein levels constituting β-lipoproteins followed by an increase in high density lipoprotein cholesterol in experimental animals. Picroliv alters lipolytic activities in plasma, liver, heart an adipose tissues and stimulated receptor mediated catabolism of low density lipoprotein. The lipid lowering action of the natural product is mediated through inhibition of cholesterol biosynthesis in liver, increased faecal bile acid excretion and enhanced plasma lecithin: cholesterol acyltransferase activity.     

Aspects of the male reproductive toxicity/male antifertility property of andrographolide in albino rats: effect on the testis and the cauda epididymidal spermatozoa

Previous work has shown that Andrographis paniculata leaf, when fed to male albino rats, causes the arrest of spermatogenesis. The present study was undertaken to investigate whether andrographolide, one of the major constituents of this plant, is responsible for such an effect. The compound was administered to 3-month-old male Wistar albino rats at two dose levels, for 48 days. Fertility tests, analysis of the counts, motility and abnormalities of the cauda epididymidal spermatozoa, and histopathological-evaluation of the testis were carried out. The results showed that sperm counts decreased, the spermatozoa were not motile, and several of them possessed abnormalities. The seminiferous epithelium was-thoroughly disrupted and in the seminiferous tubules, fully differentiated spermatozoa were far too limited; cells in the divisional stages were prevalent; multinucleate giant cells were abundant and Leydig cells appeared intact. It is inferred that andrographolide could affect spermatogenesis by preventing cytokinesis of the dividing spermatogenic cell lines. The multinucleate giant cells are comparable to the symplasts generated by cytochalasin-D and ursolic acid due to action at stages V-VII of the spermatogenic cycle. Sertoli cell damage and spermatotoxic effects are also apparent. Thus, the study points to a male reproductive toxic effect of this compound when used as a therapeutic; the study also confirms the possible prospective use of andrographolide in male contraception.     

Anti-ulcer activity of ethanol extract of Terminaliapallida Brandis. in Swiss albino rats

Ethanol extract of Terminalia pallida Brandis. (EETP) was evaluated for its anti-ulcer activity against various models of ulcers, such as drug-induced ulcers, histamine-induced ulcers and ethanol-induced ulcers in Swiss albino rats. The EETP at the doses of 250 and 500 mg/kg per os (p.o.) exhibited significant protection against ulcers produced by indomethacin, histamine and the effect was comparable to that of the reference drug famotidine (30 mg/kg b.w) orally. The extract also afforded significant protection against ethanol-induced gastric ulceration. Meanwhile, EETP significantly lowered the elevated lipid peroxide level (thiobarbituric acid reactive substances (TBARS)) and restored the altered glutathione level in ethanol-induced gastric ulceration. The present investigation revealed that the EETP exhibited significant anti-ulcer activity by enhancing antioxidant potential of the gastric mucosa, thereby reducing mucosal damage.     

Healing potential of Datura alba on burn wounds in albino rats

Datura alba Nees (Solanaccae) is popular all over the world for its medicinal uses in asthma, muscle spasm, whooping cough, hemorrhoids, skin ulcers, etc. In India, it is widely used traditionally for the relief of rheumatism and other painful affections. Ayurveda and Siddha practitioners use oil based preparations of this plant from ancient days to till date for all types of wounds. Hence, the present study was chosen to evaluate its scientific validity. The alcohol extract of the D. alba leaves were investigated for the evaluation of its healing efficiency on burn wound models in rats. The crude alcohol extract and one of the fractions exhibited antimicrobial effect against all the pathogens studied. A 10% (w/w) formulation of alcoholic extract was topically applied on thermal wounds. Complete wound closure was observed within 12 days in treated rats. The effect produced by the ointment, in terms of wound contracting ability, wound closure time, tissue regeneration at the wound site and histopathological characteristics were significant in treated rats. Collagen, hexosamine and gelatinase expressions were also well correlative with the healing pattern observed. The present study thus provides a scientific rationale for the traditional use of this plant in the management of wounds.     

Influence of piperine on nimesulide induced antinociception

Piperine (1-peperoyl piperidine), an alkaloid extracted from Piper nigrum Linn is an inhibitor of hepatic and other enzymes involved in the biotransformation of drugs. In the present study piperine showed a dose dependent synergistic effect on nimesulide induced antinociception, in the acetic acid induced writhing test in mice. Piperine at a dose of 10 mg/kg significantly (p < 0.001) increased the analgesic activity of nimesulide administered at a submaximal dose of 6.5 mg/kg. In the formalin test, nimesulide alone (10 mg/kg, oral) did not modify phase I or nociceptor mediated pain while a combination of nimesulide (10 mg/kg) with piperine (10 mg/kg) significantly decreased it. In phase II or inflammatory pain, duration of formalin induced behaviour was 80 ± 7 s, 61 ± 7.3 s and 5.33 ± 3.3 s in control, nimesulide treated and piperine plus nimesulide treated groups respectively, indicating a synergistic activity of piperine with nimesulide. The antinociceptive effect correlated well with increased plasma concentration of nimesulide. The plasma concentration after oral administration of nimesulide (10 mg/kg) alone was 8.03 ± 0.99 ug/mL. However, when it was administered with piperine (10 mg/kg), the plasma concentration of nimesulide increased to 11.9 ± 0.23 ug/mL. This indicates that piperine inhibits the biotransformation and metabolism of nimesulide leading to significantly (p < 0.05) higher levels of drug in the systemic circulation. The findings of the present study suggest that piperine could be used as a biological enhancer when coadministered with nimesulide. © 1998 John Wiley & Sons, Ltd.     

Antifertility efficacy of Drynaria quercifolia (L.) J. Smith on female Wister albino rats

Ethnopharmacological relevance

Plant based traditional medicines for birth control has been in practice in rural populations of North-East India, since time immemorial. Fresh rhizome of Drynaria quercifolia (L.) J. Smith is one of the plant parts used traditionally by different ethnic communities in Tripura, India for birth control. The present investigation is aimed to justify the scientific basis in traditional use of Drynaria quercifolia rhizome as anti-fertility agent.

Materials and methods

Ex-vivo uterotonic activity was done on uterine tissue. Acute toxicity test of the plant extract was carried out in rats of both sexes. The abortifacient and anti-implantation activities of the extract were investigated, in-vivo and estimated the level of different hormones release.

Results

The result revealed the effectiveness of methanol (87%) and aqueous (68%) extract of the plant on uterotonic activity. The extracts showed relatively non-toxic effect in acute toxicity study. Methanolic extract has shown higher efficacy for both abortifacient (^??p<0.01) and anti-implantation performance (^??p<0.01) and also effected hormone release level (^??p<0.01).

Conclusion

Methanolic extract of Drynaria quercifolia (L.) J. Smith rhizome has been proved to have significant anti-fertility activity.     

Hepatoprotective activity of Trianthema portulacastrum L. against paracetamol and thioacetamide intoxication in albino rats

The ethanolic extract of Trianthema portulacastrum L. (Aizoaceae) showed a significant dose dependent (100 mg, 200 mg/kg p.o. 10x) protective effect against paracetamol and thioacetamide induced hepatotoxicity in albino rats. The degree of protection was measured by using biochemical parameters like serum glutamate oxaloacetate transaminase (SGOT), serum glutamate pyruvate transaminase (SGPT), alkaline phosphatase (ALP), bilirubin (BRN), and total protein (TP). The plant extract completely prevented the toxic effects of paracetamol (acetaminophen) and thioacetamide on the above serum parameters. A significant hepatoprotective activity of the ethanolic extracts of Trianthema portulacastrum L. was reported.     

儿泻康贴膜中胡椒碱的透皮吸收研究

目的:通过研究儿泻康贴膜中的有效成分——胡椒碱的离体透皮吸收的行为及其定量分析,探讨儿泻康贴膜中的胡椒碱体外透皮的可行性,为中药内病外治提供理论依据。方法:采用Franz扩散池法,用高效液相色谱法测定胡椒碱不同时间对小鼠离体皮肤透皮吸收率。结果:胡椒碱经离体小鼠皮肤的透皮率随时间的增加而增加,52 h后胡椒碱的渗透率为78.51%,且保持基本不变。结论:胡椒碱能透皮吸收,且本方法简单,稳定易行,可控性强,重复性好,可用于儿泻康贴膜中胡椒碱的透皮吸收的测定。     

Gastroprotective activity of ginger zingiber officinale rosc., in albino rats

The cytoprotective and gastric anti-ulcer studies of ginger have been carried out in albino rats. Cytodestruction was produced by 80% ethanol, 0.6M HC1, 0.2M NaOH and 25% NaCl. Whereas gastric ulcers were produced by ulcerogenic agents including indomethacin, aspirin and reserpine, beside hypothermic restraint stress and by pylorus ligated Shay rat technique. The results of this study demonstrate that the extract in the dose of 500 mg/kg orally exert highly significant cytoprotection against 80% ethanol, 0.6M HC1, 0.2M NaOH and 25% NaCl induced gastric lesions. The extract also prevented the occurrence of gastric ulcers induced by non-steroidal anti-inflammatory drugs (NSAIDs) and hypothermic restraint stress. These observations suggest cytoprotective and anti-ulcerogenic effect of the ginger.     

Immunomodulatory and antitumor activity of Piper longum Linn. and piperine

Alcoholic extract of the fruits of the plant Piper longum and its component piperine was studied for their immunomodulatory and antitumor activity. Alcoholic extract of the fruits was 100% toxic at a concentration of 500 microg/ml to Dalton's lymphoma ascites (DLA) cells and 250 microg/ml to Ehrlich ascites carcinoma (EAC) cells. Piperine was found to be cytotoxic towards DLA and EAC cells at a concentration of 250 microg/ml. Alcoholic extract and piperine was also found to produce cytotoxicity towards L929 cells in culture at a concentration of 100 and 50 microg/ml, respectively. Administration of alcoholic extract of Piper longum (10 mg/dose/animal) as well as piperine (1.14 mg/dose/animal) could inhibit the solid tumor development in mice induced with DLA cells and increase the life span of mice bearing Ehrlich ascites carcinoma tumor to 37.3 and 58.8%, respectively. Administration of Piper longum extract and piperine increased the total WBC count to 142.8 and 138.9%, respectively, in Balb/c mice. The number of plaque forming cells also enhanced significantly by the administration of the extract (100.3%) and piperine (71.4%) on 5th day after immunization. Bone marrow cellularity and alpha-esterase positive cells were also increased by the administration of Piper longum extract and piperine.     

Sphaeranthus indicus attenuates testosterone induced prostatic hypertrophy in albino rats

The present study reports the attenuating effect of Sphaeranthus indicus extracts (SI) on prostatic hyperplasia induced by testosterone in albino rats. In vitro studies were conducted to assess the 5α‐reductase inhibitory potential of the petroleum ether, ethanolic and aqueous extracts of SI. A biochemical marker, β‐sitosterol, was isolated and extracts were characterized utilizing HPTLC. Testosterone (3 mg/kg s.c.) was administered to the rats along with the test extracts and isolated β‐sitosterol for a period of 28 days. The weight of the rats, the urine output, serum testosterone concentrations and prostate‐specific antigen (PSA) levels were recorded. The prostate/body weight ratio (P/BW) was calculated and histological studies were performed to observe the changes in the histoarchitecture of the prostate. Finasteride was used as a positive control (1 mg/kg p.o.). Sphaeranthus indicus extracts attenuated the increase in the P/BW ratio induced by testosterone in the treated groups. The petroleum ether extract exhibited the best activity, although the ethanol and aqueous extracts also exhibited significant activity. Urine output was also improved significantly, demonstrating the clinical implications of the study. Histological studies, testosterone levels which were measured weekly and PSA levels measured at the end of the study also support claims for the potential use of Sphaeranthus indicus in the treatment of prostatic hyperplasia. Copyright © 2011 John Wiley & Sons, Ltd.