Ameliorative effect of methanol extract of Rubia cordifolia in N-nitrosodiethylamine-induced hepatocellular carcinoma

Context: Rubia cordifolia Linn. (Rubiaceae) is a medicinal plant used in the ayurvedic system of medicine. It is also known as Indian Madder or Manjistha and is traditionally used as an antiinflammatory, antiseptic, and galactopurifier, but its anticancer propertis are yet not known.

Objective: The ameliorative effect of the Rubia cordifolia methanol extract on N-nitrosodiethylamine-induced experimental hepatocellular carcinogenesis in rats.

Materials and methods: Changes in liver weight, serum markers of liver damage, hydroxyl radicals, lipid peroxidation, levels of enzymic and nonenzymic antioxidants; mitochondrial and respiratory chain enzymes were also investigated using various biochemical parameters and histopathological studies. Male albino rats of Wistar strain were divided into four groups for a study period of 3 months. Animals of group I and group IV served as control and drug control, respectively. Hepatocellular carcinoma was induced in animals of groups II and III with 0.02% N-nitrosodiethylamine.

Results: Upon Rubia cordifolia methanol extract co-treatment (250, 500, and 750?mg/kg bodyweight) in group III alone levels of serum marker enzymes and antioxidants increased significantly in a dose-dependent manner. The levels of hydroxyl radicals and lipid peroxidation decreased. Mitochondrial enzymes and respiratory chain enzymes, which were decreased in N-nitrosodiethylamine-induced rats, increased significantly in RC treated rats. Further histological analysis of liver confirmed the prevention of pathological changes caused by N-nitrosodiethylamine on Rubia cordifolia supplementation.

Discussion and conclusion: These findings demonstrate that Rubia cordifolia can be a source of potent antioxidants for treatment of diseases such as cancer.     

氨丁苯酞的清除小鼠脑组织自由基及抗脂质过氧化作用

丁基苯酞 ( 3 ｎ ｂｕｔｙｐｈｔｈａｌｉｄｅ,ＮＢＰ)是我国学者从广谱抗惊药中筛选出的新型脑保护药物 ,文献报道ＮＢＰ是一个有多方面作用 ,能从多个环节阻断缺血引起的病理生理发展过程的新型抗脑缺血药物。氨丁苯酞 (ＧＺ 0 2 )是ＮＢＰ的结构衍生物 ,研究提示ＧＺ 0 2抗脑缺血损伤的作用。本文观察了ＧＺ 0 2清除自由基及抗脂质过氧化作用 ,以初步探讨其作用机制。1　材料1 1　动物　昆明种小鼠 ,由本所动物繁育中心提供。1 2　药品及试剂　氨丁苯酞 (ＧＺ 0 2 )由医科院药物研究所合成室提供 ,硫代巴比妥酸 (ＴＢＡ)为上海试剂二厂…     

海绵polymistia spongia提取物aldisin的抗脂质过氧化及清除自由基作用研究

目的研究海绵ｐｏｌｙｍｉｓｔｉａｓｐｏｎｇｉａ提取物ａｌｄｉｓｉｎ的抗脂质过氧化及清除自由基作用。方法采用ＭＤＡ－ＴＢＡ比色法测定组织匀浆中过氧化脂质（ＬＰＯ）含量；采用邻苯三酚自氧化法测定ａｌｄｉｓｉｎ对Ｏ·２自由基的清除作用；采用分光光度法测定ａｌｄｉｓｉｎ对Ｃｕ２＋－ＶｉｔＣ体系产生的·ＯＨ自由基的清除作用；采用ＥＳＲ法测定ａｌｄｉｓｉｎ对ＤＰＰＨ自由基的清除作用。结果ａｌｄｉｓｉｎ具有显著的抗脂质过氧化作用，并能有效地清除Ｏ·２、·ＯＨ和ＤＰＰＨ自由基，在０．４２６μｍｏｌ·Ｌ－１～１８．５ｍｍｏｌ·Ｌ－１浓度范围内有明显的量效关系。结论ａｌｄｉｓｉｎ是自由基清除剂。     

四氢原小檗碱同类物抑制脂质过氧化和清除羟自由基(英文)

目的:研究THPB对大鼠肝、脑脂质过氧化(LPO)和氧自由基的影响。方法:体外测定大鼠肝、脑匀浆LPO和Fe~(2 )-Vit C诱导肝、脑线粒体LPO产生的MDA,Fenton反应产生OH和邻苯三酚氧化产生O_2~-。结果:(1)THPB减少肝匀浆和线粒体MDA,其中l-THPB-18和SPD的IC_(50)为3.1和12.7μmol·L~(-1)。SPD减少脑匀浆和脑线粒体MDA,IC_(50)分别为102和35.0μmol·L~(-1)。(2)THPB能清除OH~-,其中I-THPB-18和SPD的IC_(50)为0.21和3.8μmol·L~(-1);但对O_2无抑制作用。结论:THPB能减少MDA和清除OH~-,其中THPB-18作用最强。     

Evaluation of short-term and subchronic toxicity of magnolia bark extract in rats

Magnolia bark has been traditionally used in Chinese and Japanese medicines, and its extract is a constituent of currently marketed dietary supplements and cosmetic products. The safety of magnolia bark extract (MBE) was assessed in short-term and subchronic studies. In a 21-day pilot study, rats were administered MBE at levels of 0, 60, 120, 240 or 480 mg/kg body weight (bw)/day in the diet. There were no treatment-related effects in clinical observations, macroscopic or microscopic findings, hematological, clinical chemistry, urinalysis, or organ weight measurements, and there were no deaths or significant differences in body weight and weight gain. In the 90-day study, rats were administered 0, 60, 120 or 240 mg MBE/kg bw/day in the diet. No mortality, ophthalmic abnormalities or treatment-related findings in clinical observations, hematology, coagulation or organ weight measurements were observed. There were no treatment-related macroscopic or microscopic findings. Differences between treated and control groups in body weight, weight gain, food consumption and utilization, clinical chemistry and urinalysis parameters were not considered toxicologically significant as they were not dose-related and/or because values remained within historical control ranges. These results support the safety of MBE for oral consumption.     

In vitro and in vivo antitumor activity of a methanol extract of Dregea volubilis leaves with its antioxidant effect

Context: In India, Dregea volubilis (L.f.) Benth. ex Hook.f. (Asclepediaceae), a large twining shrub with a woody vine, is used to treat tumors traditionally.

Objective: This study evaluated the in vitro and in vivo antitumor activity of the methanol extract of Dregea volubilis leaves (MEDV) and elucidated its possible mechanism of action.

Materials and methods: In vitro antitumor activity of MEDV was evaluated against Ehrlich ascites carcinoma (EAC) cell-line. In vivo antitumor and antioxidant activity of MEDV at three dose levels (50, 100, and 200?mg/kg) were determined against EAC tumor-bearing mice. After 24?h of EAC inoculation, the extract was administered for 9 consecutive days. After the administration of the last dose on the 9th day followed by 18?h fasting, mice from all groups were sacrificed to determine antitumor activity and hematological profiles along with liver related biochemical parameters like lipid peroxidation, antioxidant enzymatic activity, etc.

Results: For in vitro antitumor activity, IC₅₀ value of MEDV for EAC tumor cells was 85.51?±?4.07 µg/ml. The MEDV showed a decrease in tumor volume, packed cell volume and viable cell count and an increase in the non-viable cell count of the EAC tumor-bearing mice (p?<?0.001). Hematological profile reverted near to normal level in extract treated mice. MEDV decreased the hepatic lipid peroxidation level and enhanced superoxide dismutase and catalase level in tumor-bearing mice (p?<?0.001).

Discussion and conclusion: MEDV exhibited in vitro and in vivo antitumor activity in EAC tumor-bearing mice mediated through augmenting antioxidant defense system.     

Free Radicals and Oxygen Toxicity

Most organisms are constantly exposed to molecular oxygen, and this has become a requirement of life for many of them. Oxygen is not totally innocuous, however, and it has long been known to be toxic to many organisms, including humans. The deleterious effects of oxygen are thought to result from its metabolic reduction to highly reactive and toxic species, including superoxide anion radical and hydroxyl radical. Peroxidation of lipids is a major consequence of exposure to these species and the cell possesses various enzymes, including superoxide dismutase and catalase, as well as cellular antioxidants which are able to scavenge oxygen free radicals and repair peroxidized lipids. These aspects of oxygen toxicity are reviewed, as well as the involvement of oxygen free radicals in the toxicity of the herbicide paraquat.     

Growth inhibition and apoptosis of Ehrlich ascites carcinoma cells by the methanol extract of Eucalyptus camaldulensis

Context: Eucalyptus camaldulensis Dehnh. (Myrtaceae) is a tall evergreen tree found commonly in Bangladesh. Its use in traditional folk medicine for the treatment of various health complications are well known.

Objective: To explore the in vivo antitumor effect of Eucalyptus camaldulensis stem bark methanol extract (ME) against Ehrlich’s ascites carcinoma (EAC) in Swiss albino mice.

Materials and methods: The antitumor activity of ME was studied by determining viable tumor cell count, recording tumor weight and survival time, observing morphological changes and nuclear damage of EAC cells, and estimating hematological as well as biochemical parameters of experimental mice (25, 50 and 100?mg/kg/day for 5?d, i.p.).

Results: ME showed 96% (p?p?p?50 value (1120?mg/kg) of ME indicated its low host toxic effects. ME-treated EAC cells showed membrane blebbing, chromatin condensation, nuclear fragmentation (apoptotic features) in Hoechst 33342 staining under fluorescence microscope. The DNA profile in agarose gel (1.5%) electrophoresis also confirmed that ME caused EAC cell death by apoptosis.

Discussion and conclusion: Results showed that ME exhibits strong anticancer activity through apoptosis and stimulation of host immunity. Thus, E. camaldulensis may be considered as a promising resource in cancer chemotherapy.     

Identification,quantification of bioactive constituents,evaluation of antioxidant and in vivo acute toxicity property from the methanol extract of Vernonia cinerea leaf extract

Context: Vernonia cinerea (L.) Less [Compositae (Asteraceae)] is used traditionally for several medical purposes such as inflammation, pain, fever, and cancer.

Objectives: The present study identified the bioactive constituents in the methanol extract of Vernonia cinerea leaf and evaluated its antioxidant activity and acute toxicity.

Methods: The identification of phytochemicals was accomplished by GC-MS and the major antioxidant phenolic compounds in the extract were quantified by HPTLC analysis. To quantify the essential elements, atomic absorption spectrophotometeric analysis was carried out. Total phenol and flavonoid content was measured by Folin-Ciocalteau reagent and 2% aluminium chloride, respectively.

Results: GC-MS analysis identified the presence of 27 phytoconstituents. The predominant phenolic compound in the extract as quantified by HPTLC was gallic acid (1.92?mg/g) followed by rutin (0.705?mg/g), quercetin (0.173?mg/g), caffeic acid (0.082?mg/g) and ferulic acid (0.033?mg/g). The following elements were quantified: Fe (0.050?ppm), Mn (0.022?ppm), Co (0.0180?ppm), Pb (0.029?ppm), Hg (3.885?ppm) and Se (4.5240?ppm). The antioxidant activity of the extract increased with increasing concentration and the correlation (r²) for all in vitro assays were satisfactory.

Conclusions: V. cinerea extract has significant (p?<?0.05) antiradical activity. Hence, V. cinerea may have potential medicinal value and can be used in the formulation of pharmacological products for degenerative diseases.     

自由基与青蒿琥酯毒性机理

本文报道用电子自旋共振波谱法测定青蒿琥酯在体内、外代谢转化过程中产生的自由基;用硫代巴比妥酸法测定静脉注射该药后大白鼠的肝、肠组织内丙二醛含量的变化;及用光学和电子显微镜观察维生素E对该药所致肝肠病理变化。结果表明青蒿琥酯在体内、外代谢过程中均可产生自由基,并可引发脂质过氧化和组织损伤。使用抗氧化剂维生素E可以抑制该药自由基的产生并减轻脂质过氧化,免除组织损伤。据此认为青蒿琥酯的主要毒性作用机理之一,可能是该药在代谢过程中产生的自由基攻击不饱和脂肪酸,引发脂质过氧化,导致细胞膜结构损伤和细胞功能紊乱,从而表现出其毒性作用。     

莲心碱对氧自由基和脂质过氧化的影响

莲心碱(Liensinine,LIE)为中药莲子心中提取的一种双苄基异喹啉类生物碱,研究报道其具有降压、抗心律失常等[1]心血管活性.自由基反应在心血管损伤中起着重要作用,为了进一步了解LIE的药理作用及机制,本文报道了LIE对氧自由基和脂质过氧化(LPO)的影响.     

Hepatoprotective potential of Phyllanthus muellarianus leaf extract: studies on hepatic,oxidative stress and inflammatory biomarkers

Context: Leaves of Phyllanthus muellarianus (Kuntze) Exell. (Euphorbiacea) are widely used in the management of liver disorders in Nigeria. However, no there is no scientific validation to support this use.

Objective: Hepatoprotective effect of Phyllanthus muellarianus aqueous leaf extract was investigated in acetaminophen-induced liver injury mice.

Materials and methods: Hepatoprotective effect of Phyllanthus muellarianus aqueous leaf extract was evaluated in acetaminophen-induced hepatic damage in Swiss albino mice using biomarkers of hepatocellular indices, oxidative stress, proinflammatory factors and lipid peroxidation. Mice received distilled water, 100, 200, or 400?mg/kg b.w of Phyllanthus muellarianus aqueous leaf extract, respectively, for seven days. Treatment groups were challenged with 300?mg/kg b.w of acetaminophen on the sixth day.

Results: Oral administration of Phyllanthus muellarianus aqueous leaf extract significantly (p?Phyllanthus muellarianus aqueous leaf extract.

Conclusion: Overall, results of this study show that Phyllanthus muellarianus halted acetaminophen-mediated hepatotoxicity due to its capability to enhance antioxidant enzymes.     

Alleviation of cell damage in experimental ANP in rats by administration of chondroitin-sulfate reduces

In order to explore the effects of retrograde infusion of chondroitin-sulfate via the pancreatic duct on cytoprotection and attenuation of oxidative damage during acute necrotic pancreatitis (ANP), male Wistar rats were randomly divided into three groups: A, B (experimental groups) and C (sham operation, control group). The rats in group A was subjected to retrograde injection of 5% sodium taurocholate via the pancreatic duct, and those in group B received chondroitin-sulfate therapy after ANP induction. All rats in three groups were killed at 6 h. The levels of malondialdehyde (MAD), total superoxide dismutase (SOD), glutathione (GSH), adenosine triphosphate (ATP) and serum amylase (SAM) were measured. The morphologic changes in pancreatic tissues were observed. It was found that the level of SAM was increased in group A and group B, with corresponding pathological changes of ANP. The levels of ATP, GSH and SOD in group A were decreased markedly and MDN increased significantly as compared with those in group B (P<0.01). In group B, the histopathologic damage was attenuated to a certain extent in comparison to that in group A. It was concluded that endogenous antioxidants were significantly reduced and lipid peroxidation increased during ANP. Retrograde infusion of chondroitin-sulfate via pancreatic duct could alleviate the pancreatic cell damage as a sort of scavengers of oxygen free radicals. Translated from J Chin Med Univ, 2006, 35(3): 297–298, 301 [译自: 中国医科大学学报]     

d-儿茶素-3-O-β-D-葡萄糖苷的抗氧化作用(英文)

目的　研究粘萎陵菜含有的一种化合物 ,d 儿茶素 3 O β D 葡萄糖苷 (CGS)的保肝作用机制。方法　测定CGS在体外对NADPH 维生素C和Fe2 + 半胱氨酸系统诱发的微粒体脂质过氧化反应(丙二醛形成 )的影响 ,对黄嘌呤 黄嘌呤氧化酶系统超氧阴离子自由基产生 (还原型细胞色素C形成 )的影响 ;在体内对CCl4和乙醇诱发的小鼠肝丙二醛形成的影响。结果　体外CGS 1 0 0 μmol·L-1 能明显抑制NADPH 维生素C和Fe2 + 半胱氨酸系统诱发的大鼠脑、肝、肾微粒体丙二醛形成及黄嘌呤 黄嘌呤氧化酶系统超氧阴离子自由基的产生。在体内能抑制CCl4和乙醇诱发的小鼠肝脂质丙二醛形成。结论　CGS具有抗氧化作用     

Ameliorative and antioxidant effects of myrtle berry seed (Myrtus communis) extract during reflux-induced esophagitis in rats

Context Myrtle, Myrtus communis L. (Myrtaceae), is a medicinal plant well known for its richness in phenolic compounds and its beneficial effects for the treatment of gastrointestinal disorders.

Objective In the present work, the protective effect of the myrtle berry seed aqueous extract (MBSAE) against esophageal reflux (ER)-induced damage in esophagus mucosa as well as the mechanisms implicated was determined.

Materials and methods In this respect, adult male Wistar rats were used and divided into seven groups: Control, ER, ER?+?various doses of MBSAE, ER?+?famotidine or ER?+?gallic acid. The ER was induced and animals were per orally (p.o.) treated with MBSAE or reference molecules during 6 h. The phytochemical screening was determined using colourimetric analysis.

Results MBSAE is rich in total polyphenols and anthocyanins and exhibited an important in vitro antioxidant activity. In vivo, we firstly found that ER led to marked macroscopic and histopathological changes in esophagus. The results showed, also, that the ER was accompanied by a state of oxidative stress as assessed by an increase of lipid peroxidation, a decrease of the sulphhydryl groups and glutathione levels, as well as antioxidant enzyme activities depletion. MBSAE abrogated all morphological, histopathological and biochemical alterations. We showed also that ER increased esophageal calcium, hydrogen peroxide (H₂O₂) and free iron levels while MBSAE treatment protected against intracellular mediators deregulation.

Conclusion Our data suggest that MBSAE exerted a potential protective effect against ER-induced damage in rat esophagus, at least in part, due to its antioxidant properties.     

Mechanisms of arsenic-induced cross-tolerance to nickel cytotoxicity, genotoxicity, and apoptosis in rat liver epithelial cells.

The purpose of the present study was to investigate the mechanism of cross-tolerance to nickel in arsenic-transformed cells. Chronic arsenite-exposed (CAsE) cells (TRL 1215 cells, which had been continuously exposed to 0.5 microM arsenite for 20 or more weeks) and control TRL 1215 cells were both exposed to nickel for 24 h, and cell viability was determined by metabolic integrity. The LC(50) for nickel was 608 +/- 32 microM in CAsE cells as compared to 232 +/- 16 microM in control cells, a 2.6-fold increase. CAsE and control cells were treated with 200 microM nickel for 4 h and cellular-free radical production was measured using ESR spectrometry. Hydroxyl radical generation was decreased in CAsE cells. Thiobarbituric acid reactive substances, indicative of lipid peroxidation, and 8-oxo-2'-deoxyguanosine, indicative of oxidative DNA damage, were reduced in CAsE cells. Flow cytometric analysis using Annexin/FITC revealed that nickel-induced apoptosis was reduced in CAsE cells. CAsE cells showed generalized resistance to oxidant-induced toxicity as evidenced by a marked reduction in sensitivity to hydrogen peroxide. Interestingly, intracellular reduced glutathione (GSH) levels were significantly increased in CAsE cells, and when GSH was depleted, CAsE cells lost their nickel resistance. The mechanism of arsenic-induced cross-tolerance to cytotoxicity, genotoxicity, and apoptosis induced by nickel appears related to a generalized resistance to oxidant-induced injury, probably based, at least in part, in increased cellular GSH levels.     

实验性精索静脉曲张大鼠睾丸组织MDA、ROS和GSH-Px的改变

目的：探讨实验性精索静脉曲张大鼠睾丸组织氧化与抗氧化的改变。方法：通过手术方法建立大鼠精索静脉曲张模型。检测睾丸组织匀浆ＭＤＡ、ＲＯＳ和ＧＳＨ－Ｐｘ的含量。结果：实验组左侧睾丸组织ＭＤＡ和ＲＯＳ含量。ＧＳＨ－Ｐｘ活力均高于对照组。结论：大鼠精索静脉曲张左侧睾丸组织脂质过氧化物增多。抗氧化能力减弱。     

Analgesic and anti-inflammatory effects of the methanol stem bark extract of Prosopis africana

Prosopis africana (Guill. & Perr.) Taub. (Mimosoideae) is a shrub used for menstrual and general body pain in Nupe land in north central Nigeria. In this study, the methanol extract of the stem bark of Prosopis africana (at doses of 62.5, 125, and 250?mg/kg) was evaluated for analgesic and anti-inflammatory activities using acetic acid-induced writhing assay and carrageenan-induced inflammation in rats. The extract significantly (P <0.05) attenuated the acetic acid-induced writhing with the highest activity observed at the highest dose, 250?mg/kg (76.89%) comparable to that of piroxicam (83.16%) the standard agent used. In the carrageenan-induced inflammation assay, the extract showed significant anti-inflammatory activity (P <0.001) from the third hour. The preliminary phytochemical screening revealed the presence of flavonoids, saponins, carbohydrates, cardiac glycosides, tannins, and alkaloids. The oral median lethal dose was found to be 3807.9?mg/kg in mice and > 5000?mg/kg in rats. This study supports the folkloric claim of the use of Prosopis africana in the management of pain.     

Protective role of fucoxanthin in diethylnitrosamine-induced hepatocarcinogenesis in experimental adult rats

Hepatocellular carcinoma (HCC) accounts for majority of cancer related deaths. Two major risk factors in induction of HCC are chemical and virus, however, the possible mechanisms of their differences remain indefinable. The current study focused on protective role of Fucoxanthin (Fx) in liver affected by diethylnitrosamine (DEN)-induced HCC. In this study, levels of liver enzymes, oxidative stressors, antioxidant status, and lipoproteins were compared both in tissue and blood. Tissues were also analyzed extensively by histological studies using H and E staining and transmission electron microscopy (TEM). Rats were clustered into four groups of six experimental animals. Group I: Control rats were administered isotonic saline intraperitoneal Group II: Animals received 0.01% DEN through drinking water to induce hepatocellular carcinoma. Group III: Animals received 0.01% DEN simultaneously oral supplementation of Fx (50 mg/kg b.w). Group IV: Rats were given Fx alone (50 mg/kg b.w) orally and the treatment is for 15 weeks. Results showed the decrease in body weight, serum albumin, antioxidant enzymes, and increased all the liver enzymes, serum bilirubin, and stress markers in DEN induced rats, where as the simultaneous supplementation of Fx reverted them to normal levels. Administration of only Fx did not show any change. Therefore, Fx may serve as a chemotherapeutic agent against liver cancer.