Modulation of jejunal contractions by extract of Carica papaya L. seeds

Carica papaya L. (papaya) seed preparations are used in traditional medicine to expel intestinal worms in human and ruminants. In the present study, an ethanol extract of papaya seeds (EEPS; 0.1-6.4 mg/mL) caused concentration-dependent inhibition of jejunal contractions in contrast to corresponding concentrations of DMSO (solvent control). The inhibitory effect of EEPS on jejunal contractions was significantly irreversible. Previous studies have indicated that benzyl isothiocyanate (BITC) is the main bioactive compound responsible for the anthelmintic activity of papaya seeds. In the present study, standard BITC (0.01-0.64 mmol/L) also caused significant irreversible inhibition of jejunal contractions. Recovery of jejunal contractions after BITC-induced inhibition was weaker than recovery after EEPS-induced inhibition (BITC versus EEPS: 19 +/- 7% vs 38 +/- 13%). Cryosections of the jejunum showed marked morphological damage of the segments treated with BITC in contrast to DMSO-treated segments. EEPS-induced jejunal damage was, however, less marked. These results indicate that papaya seed extract and BITC, its principal bioactive constituent are capable of weakening the contractile capability of rabbit isolated jejunum. It is thus envisaged that at the toxic level that will be needed to kill and expel intestinal worms in vivo, BITC may also cause impairment of intestinal functions.     

Antioxidant potentials of Iranian Carica papaya juice in vitro and in vivo are comparable to alpha-tocopherol

Carica papaya is widely cultivated throughout the world and is used as a food and also as a traditional medicine, particularly as an antiseptic and contraceptive. The present study was designed to explore the toxicological and antioxidant potential of dried C. papaya juice in vitro and in vivo. The oral LD(50) of the juice of C. papaya was determined, and the antioxidant potentials determined by DPPH and FRAP tests. In vivo examination was performed after oral administration of dried papaya juice to rats for 2 weeks at doses of 100, 200 and 400 mg/kg. Blood TBARS and FRAP assays were used to determine the potential of the juice to act against oxidative stress. The acute toxicity test (LD(50)) demonstrated that papaya juice is not lethal up to a dose of 1500 mg/kg after oral administration and thus is considered nontoxic. In treated groups, no sign of toxicity was observed. In vitro evaluation of the antioxidant effects of papaya showed that the highest antioxidant activity (80%) was observed with a concentration of 17.6 mg/mL. Blood lipid peroxidation levels decreased significantly after administration of all doses of papaya juice (100, 200, 400 mg/kg/day) to 35.5%, 39.5% and 40.86% of the control, respectively, compared with a value of 28.8% for vitamin E. The blood total antioxidant power was increased significantly by all doses of papaya juice (100, 200, 400 mg/kg/day) to 11.11%, 23.58% and 23.14% of the control, respectively. The value for vitamin E was 18.44%. This preliminary study indicates the safety and antioxidative stress potential of the juice of C. papaya, which was found to be comparable to the standard antioxidant compound alpha-tocopherol.     

Effect of Carica papaya seed extract on female rat ovaries and uteri

The effect of an aqueous extract of Carica papaya seed for 7 and 15 days on the physiology of rat ovaries and uterus was studied. The possible reversibility of the induced effects was also investigated. The results revealed that the effects were more pronounced in the ovary than in the uterus. The changes in biochemical profile of the ovary and uterus involved alterations in the levels of ascorbic acid, ascorbigen (ASG), ascorbic acid utilization (AUU), ascorbic acid macromolecular (AA-MM) complexing, ascorbic acid free radical (AA-FR) formation, total ascorbic acid and glutathione (GSH), cholesterol, protein and glycogen. The increase in ascorbate turnover is an adaptation to overcome the harmful effect of the extract. The fertility test was 100% negative and the oestrus cycle was irregular with a predominance of dioestrus. The uterine contractility was increased. The above mentioned changes indicate that the extract manifested antifertility, antiimplantation and abortifacient effects in the treated animals. The withdrawal of treatment overcame the adverse effects of the treatment in ovary and the uterus and restored fertility.     

Opuntia ficus indica (L.) Mill. fruit juice protects liver from carbon tetrachloride-induced injury

The protective effects of the juice of Opuntia ficus indica fruit (prickly pear) against carbon tetrachloride (CCl(4))-induced hepatotoxicity were examined in rats. The animals were treated orally with the juice (3 mL/rat) 2 h after administration of the hepatotoxic agent. Preventive effects were studied by giving the juice (3 mL/rat) for 9 consecutive days. On day 9 the rats received the hepatotoxic agent. Morphological and biochemical evaluations were carried out 24, 48 and 72 h after induction of the hepatic damage. Data show that O. ficus indica fruit juice administration exerts protective and curative effects against the CCl(4)-induced degenerative process in rat liver. Histology evaluation revealed a normal hepatic parenchyma at 48 h; the injury was fully restored after 72 h. Moreover, a significant reduction in CCl(4)-induced increase of GOT and GPT plasma levels is evident; these data are in agreement with the functional improvement of hepatocytes. O. ficus indica fruit juice contains many phenol compounds, ascorbic acid, betalains, betacyanins, and a flavonoid fraction, which consists mainly of rutin and isorhamnetin derivatives. Hepatoprotection may be related to the flavonoid fraction of the juice, but other compounds, such as vitamin C and betalains could, synergistically, counteract many degenerative processes by means of their antioxidant activity.     

Contraceptive efficacy of Carica papaya seed extract in male mice (Mus musculus)

The effects of an aqueous extract of Carica papaya seeds (20 mg/kg body weight/animal/day orally and 5 mg/kg body weight/animal/day i.m. for 60 days) were investigated for contraceptive efficacy and other related side effects in male albino mice, Mus musculus. The data revealed that the extract might be causing an androgen deprived effect to target organs resulting in alterations in the internal milieu of the cauda epididymis especially. The treatment did not, however, affect the testicular sperm count suggesting that it acted at the post-testicular level which lead to a reduction of cauda epididymal sperm motility and thus the treatment brought about a significant reduction in fertility rate. The induced effects were transient and reversible upon withdrawal of the treatment, elucidating that functional sterility could be induced by the aqueous papaya seed extract in rodents.     

番木瓜中生物活性物质的提取及药理作用研究

目的建立木瓜蛋白酶的提取工艺，并对提取物进行抗炎消肿的药理作用研究。方法采用硫酸铵分级沉淀、SP-sephadex C50柱色谱、羟基磷灰石柱色谱，从番木瓜乳汁中提纯木瓜蛋白酶；利用交叉菜胶制备大鼠足趾肿胀模型研究木瓜蛋白酶的抗炎消肿活性。结果获得HPLC纯度达到99．31％的木瓜蛋白酶：腹腔注射木瓜蛋白酶对角叉菜胶引起的大鼠足趾肿胀有显著的抑制作用。结论用一种简单的方法从番木瓜中提取了高纯度的木瓜蛋白酶，并且该酶具有显著的抗炎消肿活性。     

肾性高血压大鼠模型与自发性高血压大鼠的比较

目的：探讨肾性高血压大鼠模型与自发性高血压大鼠（SHR）之间的异同,为临床治疗继发性高血压和原发性高血压提供一定实验依据。方法：采用左肾动脉结扎的方法复制肾型高血压大鼠模型,筛选造模成功的大鼠6只设为模型组,随机选取SHR大鼠6只,平衡血压2周后设为SHR组,另以6只正常sD大鼠作为空白组。采用尾动脉无创测压法检测血压,每周1次,连续4周后,心脏超声检测心脏指标,荧光实时定量PCR技术检测肝脏血管紧张素转换酶（ACE）和内皮细胞（ET）mRNA的表达水平。结果：（1）肾性高血压大鼠造模成功;（2）与空白组比较,模型组的血压显著升高（P〈0．01）;与模型组比较,SHR大鼠血压明显升高（P〈0．01）。（3）通过检测各组大鼠心脏超声发现,肾性高血压大鼠及SHR大鼠LVDd、LVDs、LVPWd、LVPWs均增大,EF显著降低（P〈0．01）。且SHR大鼠LVDd、LVDs、LVPWd、LVPWs增大较肾性高血压大鼠更为明显（P〈0．01）,EF虽无统计学意义,但仍有降低趋势。（4）通过检测肝脏ET、ACEmRNA表达量发现,与空白组比较,模型组ACE、ETmRNA的表达量均明显升高（P〈0．01）;与模型组比较,SHR组ACE、ETmRNA的表达量明显升高（P〈0．01或P〈0．05）。结论：SHR大鼠较肾性高血压大鼠模型血压高、心功能低、缩血管作用明显。     

Studies on antifertility effect of pawpaw seeds (Carica papaya) on the gonads of male albino rats

Preliminary studies on the antifertility effect of pawpaw seeds (Carica papaya) on the gonads of male albino (Wistar) rats was investigated. An oral dose of crude ripe pawpaw seeds at 100 mg/kg body weight and 50 mg/kg body weight were administered orally for 8 weeks. Histological observations at a high dose of 100 mg/kg body weight showed degeneration of the germinal epithelium and germ cells, a reduction in the number of Leydig cells and the presence of vacuoles in the tubules. At a low dose of 50 mg/kg body weight little effect was observed. However, there was disorganization in some of the seminiferous tubules while others appeared normal. Leydig cells also appeared normal compared with the controls. At a high dose the epididymis showed many empty tubules containing degenerated spermatozoa and cell debris in the lumen. The epithelium appeared normal compared with the controls. At a low dose a milder effect was observed. The epithelial tissue appeared normal. A possible mechanism of action is discusssed. Copyright © 1999 John Wiley & Sons, Ltd.     

Contraceptive evaluation and toxicological study of aqueous extract of the seeds of Carica papaya in male rabbits

The contraceptive evaluation and toxicological effects of the aqueous extract of the seeds of Carica papaya in adult male rabbits have been reported. Thirty adult male rabbits were divided into five groups of six animals each; Group I, control; Groups II-V were administered orally with aqueous extract of the seeds of C. papaya at doses of 20, 50, 75 and 100 mg/kg per day for 150 days, respectively. The body weight, reproductive organs weight, semen analysis, semen biochemistry, toxicological profiles and the fertility status have been recorded. The aqueous extract failed to exhibit contraceptive effects at any of the dose regimens tested, contrary to the observations made in the previous studies. Unaltered toxicological profiles indicated that the drug was free of side effects. The results suggest that the failure of contraceptive effects may be due to species specificity, relative resistance of the animals to the drug or lack of potency of the extract due to factors generally affect biological activity of the plant preparations.     

Mechanism of the antiasthmatic effect of total coumarins in the fruit of Cnidium monnieri (L.)Cuss

Total coumarins in the fruit of Cnidium monnieri show a marked protective effect against bronchial asthma induced by inhalation of histamine in conscious guinea pig. In vitro these total coumarins can relax the contraction of the isolated trachea in guinea pigs induced by histamine as well as increase the perfusion rate of isolated lung preparation of guinea pig. These actions, however, may be blocked by propranolol. Besides, these coumarins cannot increase the heart rate and arterial blood pressure in anesthetized rats. All this shows that the antiasthmatic effect of total coumarins in the fruit of Cnidium monnieri is mediated by beta 2-receptor.     

Effects of Carica papaya (paw paw) seeds extract on the morphology of pituitary-gonadal axis of male Wistar rats

The effects of oral administration of Carica papaya seeds extract on the morphology of pituitary, testes and sex accessory glands were studied. The C. papaya extract (50 and 200 mg/kg/day) was administered orally to sexually mature male Wistar rats for 1 and 8 weeks, respectively. The control group received corn oil (vehicle) only. The animals were killed after 1 and 8 weeks treatment for histological preparation. The microscopic examination of the sections of pituitary gonadotrophs (FSH and LH cells) treated with 200 mg/kg of C. papaya extract showed pronounced hypertrophy, while section of rats treated with 50 mg/kg showed mild hypertrophy and hyperplasia. Whereas the testes of rats treated with C. papaya extract at 50 and 200 mg/kg revealed gradual degeneration of germ cells, Sertoli cells and Leydig cells as well as germinal epithelium. However, tubules of epididymes of rats treated with extract, 200 mg/kg, appeared empty indicating the degeneration of sperm cells in the lumina. The sections of prostate glands of rats treated with 200 mg/kg extract showed coagulation of secretion in the lumina as well as empty tubules with cell debris, while the effect was reduced in rats treated with 50 mg/kg. The seminal vesicles showed progressive collapse and shrinkage of villi. These results suggest that C. papaya extract interfered with the pituitary - gonadal axis to influence male reproductive functions, which confirmed its antifertility property as reported previously.     

Evaluation of antioxidant,antiinflammatory, and gastroprotective properties of Rubus fruticosus L. fruit juice

The juice of R. fruticosus (RFJ) fruits grown in Sicily was analysed for polyphenol compounds and tested to evaluate in vitro antioxidant and in vivo antiinflammatory and gastroprotective effects. RFJ, containing mainly anthocyanins, such as cyanidin derivatives, significant amounts of phenolic acids, and smaller amounts of flavonoids, showed significant antioxidant activity in DPPH (2,2‐diphenyl‐1‐picrylhydrazyl radical) (4,147.194 ± 17.199 mg trolox equivalent [TE]/100 ml), TE antioxidant capacity (8,312.444 ± 43.055 mg TE/100 ml), ferric reducing antioxidant power (2,177.830 ± 21.015 mg TE/100 ml), oxygen radical absorbance capacity (95,377.674 ± 616.194 μmol TE/100 ml juice), and β‐carotene bleaching (72% ± 4.58) assay. In vivo studies showed that RFJ inhibit significantly the carrageenan‐induced paw oedema (63–71%) in rats and possess antiinflammatory effects particularly significant in association with phenylbutazone (94–96%). In addition, RFJ pretreatment was able to prevent the ethanol‐induced ulcerogenic effect in rats. All in vivo results were corroborated by histopathological observations and are in good agreement with antioxidant activity, confirming the relationships between biological effects observed and radical scavenging properties of RFJ.     

Characterization, anti-oxidative and anti-inflammatory effects of Costa Rican noni juice (Morinda citrifolia L.)

Aim of the study

Noni fruit (Morinda citrifolia L.) juice has been used for more than 2000 years in Polynesia as a traditional folk medicine. The aim of the present study was to finely characterize noni juice from Costa Rica and to evaluate its anti-oxidative and anti-inflammatory activities.

Materials and methods

A microfiltrated noni juice was prepared with Costarican nonis. HPLC-DAD and Electro Spray Ionization Mass Spectrometric detection (HPLC-ESI-MS) were used to identify phenolic compounds and iridoids. The anti-oxidative activity of noni juice was measured in vitro by both Oxygen Radical Absorbance Capacity (ORAC) and 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging methods. The anti-inflammatory effects of noni juice were investigated in vitro by: measuring its effect on nitric oxide and prostaglandin E2 production by activated macrophages, evaluating its inhibitory activities on cyclooxygenase (COX)-1 and -2 and in vivo on a carrageenan-induced paw oedema model in rats.

Results

Several polyphenols belonging to the coumarin, flavonoid and phenolic acid groups, and two iridoids were identified. Noni juice demonstrated a mean range free radical scavenging capacity. Furthermore, it also reduced carrageenan-induced paw oedema, directly inhibited cyclooxygenase COX-1 and COX-2 activities and inhibited the production of nitric oxide (NO) and prostaglandins E₂ (PGE₂) in activated J774 cells, in a dose dependent manner.

Conclusions

This study showed that noni's biological effects include: (1) anti-oxidant properties probably associated with phenolic compounds, iridoids and ascorbic acid and (2) anti-inflammatory action through NO and PGE₂ pathways that might also be strengthened by anti-oxidant effects.     

补肾活血方对老年高血压血压变异和抑郁指数影响

目的:探讨补肾活血方对老年原发性高血压患者血压变异和抑郁指数的影响程度。方法:随机将80例老年原发性高血压患者分为治疗组和对照组,各40例。两组均采用西药基础治疗,治疗组加服补肾活血方,观察治疗前血压变异情况;并采用老年抑郁量表评价治疗前后患者抑郁指数变化情况。结果:治疗组在降压、控制血压变异及改善老年抑郁等方面均明显优于对照组。结论:补肾活血方对老年原发性高血压患者控制血压、改善抑郁症状均有较好效果。     

Prokinetic activity of an aqueous extract from dried immature fruit of Poncirus trifoliata (L.) Raf

Aqueous extracts from dried immature fruit of Poncirus trifoliata Raf. (Rutaceae) (PF-W) are used as a traditional Korean folk medicine for the treatment of digestive dysfunction. In the present study, PF-W exhibited no significant toxicity even at a dose of 5 g/kg when orally administered to mice. The effect of PF-W on gastrointestinal (GI) motor function was investigated by examining its effect on the serum concentration of orally administered ranitidine, a putative indicator of GI motility, in human subjects. The area under the serum concentration-time curve and the peak serum concentration of ranitidine following an oral administration (300 mg/individual) were decreased by one half as the result of a predose (10 g/individual) of PF-W, except for the time to reach peak serum concentration and the serum half-life at the terminal phase of ranitidine. In rat studies, PF-W had no effect on the apparent permeability of ranitidine across the jejunum or the gastric emptying rate (GER) of phenol red. However, the transit time for charcoal in the intestine was significantly increased by the PF-W pretreatment. The above results are consistent with the hypothesis that PF-W has a unique prokinetic activity, which accelerates the transit of intestinal contents, but has no effect on the GER.     

GC-MS法测定阿育魏中脂肪酸的含量

目的：用脂肪提取器提取阿育魏种子中的脂肪酸并测定其含量。方法：以气质联用法定性和定量地分析它们的化学成分。结果：从阿育魏种子中分离出了4种脂肪酸，它们分别是亚油酸、油酸、棕榈酸、硬脂酸，其种子主要脂肪酸为亚油酸和油酸。结论：该方法操作简单、快速、准确。     

Neurophysiological effects of mistletoe (Viscum album L.) on isolated rat intestines

Mistletoe (Viscum album L.) is well known as a medicine from ancient times and the earliest notes. Today it is used as a remedy. The aim of this research was to examine the effects of mistletoe extracts and their components on some neurophysiological parameters in rat intestines. The tonus and contractile responses of isolated intestinal segments (duodenum, ileum and distal colon) were analysed. The experiment was carried out in three groups. In the first group (control group) different concentrations of acetylcholine were added into the organ bath (10-50 nmol/L). In the second group, mistletoe extracts were added into the organ bath with increasing concentrations and in the third group, atropine, a non-selective muscarinic receptor antagonist, was added into the organ bath (concentration 10(-7) mol/L) and after atropine plant extracts were administered. The results obtained suggest that extracts from different parts of mistletoe have neurophysiological effects and change intestinal contractions. The results also suggest that the effects of mistletoe extracts on intestinal contractility act via cholinergic pathways, activating muscarinic receptors in the intestines. However, in order to establish the subtype of receptors, further investigations are necessary where selective antagonists of muscarinic cholinergic receptors should be used.     

无患子皂苷对肾性高血压大鼠血压及血管活性物质的影响

目的：观察无患子皂苷对肾性高血压大鼠(renovascular hypertension rat,RHR)的降压作用及对血管紧张素Ⅱ(AngⅡ)、醛固酮(Ald)、内皮素(ET)、一氧化氮(NO)的影响。方法：采用改进的两肾一扎(2K1C)高血压大鼠模型。将大鼠均分为6组：假结扎组、模型组、卡托普利组、无患子皂苷高、中、低3个剂量组。每组10只,每天灌胃给药1次,假结扎组和模型组灌服等量蒸馏水。分别于给药后1,3,7,14,21,28,35 d测量大鼠尾动脉收缩压；取血测血中AngⅡ,Ald,ET,NO的浓度。结果：无患子皂苷给药35 d能明显降低RHR血压。RHR血浆中AngⅡ,Ald,ET含量增多,NO含量降低,无患子皂苷各剂量降低血压同时能够降低AngⅡ,Ald,ET含量,增加NO含量。结论：无患子皂苷能够降低RHR血压,并对AngⅡ,Ald,ET,NO产生一定影响,可能是其降压作用的机制之一。     

天麻钩藤饮对肾血管性高血压大鼠血压的影响

[目的]探讨天麻钩藤饮对肾血管性高血压大鼠血压的影响.[方法]48只雄性SD大鼠随机分为假手术组、模型组、卡托普利组和天麻钩藤饮组,每组12只.造模后第5周开始给药,连续治疗8周.然后观察天麻钩藤饮降压的作用.[结果]造模4周后,模型组大鼠血压明显上升(P<0.001),左肾质量(LK)和LK/RK值比假手术组明显降低(P<0.001),而右肾质量(RK)则显著增高(P<0.001),说明动物模型复制成功.8周干预治疗后,卡托普利组和天麻钩藤饮组大鼠血压均下降至达到或接近正常血压水平(P<0.01).而卡托普利的降压效果要优于天麻钩藤饮(P<0.05).[结论]天麻钩藤饮能够明显降低肾性高血压大鼠的血压水平.     

Endothelium-independent relaxation and contraction of rat aorta induced by ethyl acetate extract from leaves of Morus alba (L.)

Aim of the study

Based on screening for vasoactive traditional Chinese medicinal herbs, the present study was performed to investigate the vasoactive effects of an ethyl acetate extract from leaves of Morus alba (L.) (ELM) on rat thoracic aorta and the mechanisms underlying these effects.

Materials and methods

Isolated rat thoracic rings were mounted in an organ bath system and the effects of ELM on their responses were evaluated.

Results

ELM (0.125–32.000 g/l) induced a concentration-dependent relaxation (P < 0.01 vs. control) both in endothelium-intact and -denuded aortas precontracted by high K⁺ (6 × 10⁻² M) or 10⁻⁶ M phenylephrine (PE). In endothelium-denuded aortas, ELM at the EC₅₀ concentration reduced Ca²⁺-induced contraction (P < 0.01 vs. control) after PE or KCl had generated a stable contraction in Ca²⁺-free solution. And after incubation with verapamil, ELM induced contraction in endothelium-denuded aortas precontracted by PE (P < 0.01 vs. control); this was abolished by ruthenium red (P < 0.01 vs. ELM-treated endothelium-denuded group; P > 0.05 vs. control), but not by heparin (P > 0.01 vs. ELM-treated endothelium-denuded group; P < 0.01 vs. control).

Conclusions

The results showed that ELM had dual vasoactive effects, and the relaxation was greater than the contraction. The relaxation was mediated by inhibition of voltage- and receptor-dependent Ca²⁺ channels in vascular smooth muscle cells, while the contraction occurred via activation of ryanodine receptors in the sarcoplasmic reticulum.