Alkaloids from Fumaria parviflora and F. kralikii

From Fumaria parviflora Lam. were isolated the major alkaloids protopine and adlumidiceine and the minor alkaloids parfumine, fumariline, dihydrofumariline, cryptopine, (-)-stylopine, 8-oxocoptisine, sanguinarine, and oxysanguinarine. The quaternary protoberberine fraction gave coptisine. Adlumidiceine, dihydrofumariline, 8-oxocoptisine, sanguinarine, and oxysanguinarine were found in F. parviflora for the first time. F. kralikii Jordan gave, besides the major alkaloids protopine, fumarophycine, and O-methylfumarophycine, the alkaloids adlumidiceine, berberine, coptisine, cryptopine, (-)-stylopine, and (-)-canadine. Only protopine and cryptopine have been isolated from F. kralikii earlier.     

Alkaloids from Fumaria parviflora and F. kralikii*.

From FUMARIA PARVIFLORA L AM. were isolated the major alkaloids protopine and adlumidiceine and the minor alkaloids parfumine, fumariline, dihydrofumariline, cryptopine, (-)-stylopine, 8-oxocoptisine, sanguinarine, and oxysanguinarine. The quaternary protoberberine fraction gave coptisine. Adlumidiceine, dihydrofumariline, 8-oxocoptisine, sanguinarine, and oxysanguinarine were found in F. PARVIFLORA for the first time. F. KRALIKII J ORDAN gave, besides the major alkaloids protopine, fumarophycine, and O-methylfumarophycine, the alkaloids adlumidiceine, berberine, coptisine, cryptopine, (-)-stylopine, and (-)-canadine. Only protopine and cryptopine have been isolated from F. KRALIKII earlier.     

Effect of malotilate on paracetamol-induced hepatotoxicity

Malotilate (diisopropyl-1,3-dithiol-2-ylidenemalonate) prevented liver damage induced by paracetamol in male mice only when given 1 h prior to the hepatotoxic agent. Furthermore, it partially inhibited paracetamol-induced glutathione depletion in mouse liver, indicating that the antihepatotoxic activity of malotilate is related to an interaction with the bioactivation of paracetamol.     

曲尼司特对小鼠对乙酰氨基酚肝损伤的保护作用及其机理

曲尼司特对小鼠对乙酰氨基酚肝损伤的保护作用及其机理１傅阳平王键吴若（中国医学科学院，中国协和医科大学药物研究所，北京１０００５０）近来发现某些肝炎患者的肝损伤可能有过敏反应的因素参与［１］．我们观察了几种抗过敏药对不同原因引起小鼠肝损伤的作用，发现...     

Studies on protective effect of Cyperus Scariosus extract on acetaminophen and CCl4-induced hepatotoxicity

• 1.1. The hepatoprotective activity of aqueous-methanolic extract of Cyperus scariosus (Cyperaceae) was investigated against acetaminophen and CCl₄-induced hepatic damage.
• 2.2. Acetaminophen produced 100% mortality at a dose of 1 g/kg in mice while pretreatment of animals with plant extract (500 mg/kg) reduced the death rate to 30%.
• 3.3. Acetaminophen at a dose of 640 mg/kg produced liver damage in rats as manifested by the rise in serum levels of alkaline phosphatase (ALP), glutamate oxaloacetate transaminase (GOT) and glutamate pyruvate transaminase (GPT) to 430 ± 68, 867 ± 305 and 732 ± 212 IU/1 (n = 10) respectively, compared to respective control values of 202 ± 36, 59 ± 14 and 38 ± 7.
• 4.4. Pretreatment of rats with plant extract (500 mg/kg) significantly lowered (P < 0.05) the respective serum ALP, GOT and GPT levels to 192 ± 31, 63 ± 9 and 35 ± 8.
• 5.5. The hepatotoxic dose of CCl₄ (1.5ml/kg; orally) raised serum ALP, GOT and GPT levels to 328 ± 30, 493 ± 102 and 357 ± 109 IU/1 (n = 10) respectively, compared to respective control values of 177 ± 21, 106 ± 15 and 47 ± 12.
• 6.6. The same dose of plant extract (500 mg/kg) was able to significantly prevent (P < 0.05) CCl₄-induced rise in serum enzymes and the estimated values of ALP, GOT and GPT were 220 ± 30, 207 ± 95 and 75 ± 38, respectively.
• 7.7. The plant extract also prevented CCl₄-induced prolongation in pentobarbital sleeping time confirming hepatoprotectivity.
• 8.8. These results indicate that the Cyperus scariosus possesses hepatoprotective activity and thus, rationalizes the folkloric use of this plant in hepato-biliary disorders.

     

Separation and Quantification of Some Alkaloids from Fumaria parviflora by Capillary Isotachophoresis1

The isotachophoretic separation of some isoquinoline alkaloids in acid-base partially purified extracts from Bulgarian FUMARIA PARVIFLORA was studied. The electrolyte system for model mixtures of alkaloids (-)-stylopine, (-)-canadine, coptisine, berberine, protopine, cryptopine, chelidonine, bulbocapnine, papaverine, parfumine and for the plant extracts contained the leading ion K (+) (0.01 M), counter ion CH (3)COO (-), pH (L) 5.5, and the terminating ion H (+) (acetic acid 0.01 M). In the plant extracts, protopine and parfumine were quantitatively determined during F. PARVIFLORA growth and development in the term May-June 1984.     

Effect of sulphydryl drugs on paracetamol-induced hepatotoxicity in mice

It has been shown that the major in vivo biotransformation of thiol-containing drugs such as captopril (CP) and penicillamine (PA) involve mixed disulphide formation with endogenous thiols derived from cysteine. At high doses, both drugs produced a dose-dependent depletion of glutathione (GSH) and may perturb GSH and related GSH-enzymes. In this study the possible interactions of these drugs with paracetamol, which produce hepatotoxicity after GSH depletion, were investigated. Following co-administration of CP (50-250 mg/kg) or PA (43-257 mg/kg) with paracetamol (300 mg/kg), the hepatotoxic effect produced by paracetamol was diminished. The protective effect was comparable to that produced by N-acetylcysteine (500 mg/kg) and L-cysteine (500 mg/kg). However, pre-treatment with buthionine sulfoximine (BSO), a specific inhibitor of GSH synthesis, abolished the protective effects of CP, N-acetylcysteine and L-cysteine while the protective effect of PA was unaffected. This suggests that, although both CP and PA may act as alternative sulphydryl nucleophiles to GSH to prevent arylation of essential cellular macromolecules by the reactive metabolite of paracetamol, the underlying mechanisms of these drug interactions may be distinctly different.     

Effect of Teucrium stocksianum on paracetamol-induced hepatotoxicity in mice

• 1.1. Hepatoprotective activity of an ethanolic extract of Teucrium stocksianum was investigated against paracetamol-induced hepatic damage in mice.
• 2.2. Paracetamol at an oral dose of 0.6 g/kg produced about 94% mortality in mice while pretreatment with the plant extract (0.5 and 1 g/kg for 5 days) reduced the death rate to 0%.
• 3.3. Paracetamol (0.6 g/kg, orally) produced liver damage as manifested by significant rises in liver weight, plasma aspartate aminotransferase (AST) activity and bilirubin concentration, pentobarbitone-induced sleeping time, and by the significant depletion of reduced glutathione (GSH) in the liver.
• 4.4. Pretreatment of mice with T. stocksianum at the above doses significantly ameliorated all the paracetamol-induced signs of liver damage described above.
• 5.5. T. stocksianum did not produce any lethality or adverse effects in the livers of treated mice.
• 6.6. These results indicate that T. stocksianum ethanolic extract contains hepatoprotective constituents, and suggest further work on the isolation and characterization of these constituents which may potentially be used as hepatoprotective agents.

     

A comparison of the protective effects of N-acetylcysteine and S-carboxymethylcysteine against paracetamol-induced hepatotoxicity

The protective effect of the sulphur-containing amino acids N-acetylcysteine and S-carboxymethylcystein against paracetamol-induced hepatotoxicity was evaluated in the hamster by biochemical and histological methods. Of the animals receiving paracetamol alone 25% died within 24 h following administration. All surviving animals showed acute hepatocellular injury and marked loss of cytochrome P-450 and hepatic mixed-function oxidase activities. Simultaneous administration of -acetylcysteine decreased the mortality rate, partly prevented the paracetamol-induced liver damage and partly restored enzyme activities. Simultaneous administration of S-carboxymethylcysteine with paracetamol afforded no protection. Kidneys from all animals were histologically normal. Human liver microsomes and liver microsomes from 3-methylcholanthrene-pretreated hamsters metabolised paracetamol to intermediate(s) that bind covalently to microsomal proteins. The rate of covalent binding was inhibited markedly by N-acetylcycsteine and to a lesser extent by S-carboxymethylcysteine.     

Involvement of mitochondria mediated pathways in hepatoprotection conferred by Fumaria parviflora Lam. extract against nimesulide induced apoptosis in vitro

Nimesulide, a popular nonsteroidal anti-inflammatory drug, has been associated with serious hepatotoxicity. Reactive oxygen species (ROS) and mitochondrial perturbations have been implicated in drug induced hepatotoxicity, although their role in the pathway needs exploration. Study was undertaken to elucidate the effect of Fumaria parviflora Lam. (Fp) on nimesulide induced cell death in primary rat hepatocyte cultures. Fp extract treated cells showed increased viability as compared to nimesulide stressed cells as assessed by MTT assay. LDH leakage increased significantly at 500 μM nimesulide, and the data suggested that apoptosis was the predominant mechanism responsible for cell death. Nimesulide induced apoptosis was further confirmed by DNA fragmentation and chromatin condensation. Nimesulide exposure increased intracellular ROS, translocation of Bax and Bcl2 followed by mitochondrial depolarization and cytochrome c (Cyt c) release along with caspase-9/-3 activity confirming involvement of mitochondria in nimesulide induced apoptosis. Events like membrane depolarization of mitochondria, expression of Bax, Bcl2, externalization of phosphatidyl serine are substantially reversed by the pre-treatment of Fp extract. Thus, the study indicates that Fp extract modulates critical events regulating pro and anti-apoptotic proteins in mitochondria dependent apoptosis induced by nimesulide.     

Studies on the mechanism of paracetamol-induced protection against paracetamol hepatotoxicity.

In rats, 3 days treatment with paracetamol (1 oral dose of 1 g/kg daily) produced a complete protection against the hepatotoxic actions of a further dose of paracetamol as documented by determination of serum enzyme activities (glutamic-oxaloacetic transaminase, (GOT), glutamic-pyruvic transaminase (GPT), sorbitol dehydrogenase (SDH), bromsulphthalein retention and histological investigations. Subacute paracetamol treatment decreased liver glutathione levels by 46%, liver microsomal cytochrome P-450 content by 23%, hepatic hydroxylation of aniline by 29% and hepatic demethylation of aminopyrine by 46%. It afforded also some protection against the hepatotoxic actions of carbon tetrachloride, bromobenzene and thioacetamide, but did not influence the antiphlogistic activity of paracetamol (carrageenan paw edema test). Plasma and liver concentrations of free paracetamol after oral administration of 1 g/kg paracetamol were somewhat higher in the subacutely paracetamol-pretreated rats than in the non-pretreated control animals whereas no differences in the concentrations of conjugated paracetamol were found between the 2 groups. Pretreatment with paracetamol did not influence the urinary excretion of free paracetamol but caused some shift in the urinary excretion of paracetamol conjugates: pretreated rats excreted 23% less of the paracetamol glucuronide and sulfate and 33% more of the paracetamol mercapturate than the control animals. A depression of the microsomal mixed-function oxidase activity is presumed to be the main cause of the paracetamol-induced protection against paracetamol hepatotoxicity.     

Studies on the protective effect of flaxseed oil on cisplatin-induced hepatotoxicity

Cisplatin (CP) is known as one of the most potent chemotherapeutic antitumor drugs. The tissue-specific toxicity of CP in the kidneys is well documented. However, at higher doses less common toxic effects such as hepatotoxicity may arise. Since CP remains one of the most effective antineoplastic drug used in chemotherapy, strategies to protect tissues against CP toxicity are of clinical interest. Recently, ω-3 polyunsaturated fatty acids (PUFAs) from certain plants/seeds notably flaxseed have shown numerous health benefits. In view of this, the present study investigates the protective effect of flaxseed oil (FXO) on CP-induced damage in liver. Rats were pre-fed normal diet and the diet rich in FXO for 10 days and then a single dose of CP (6 mg/kg body weight) was administered intraperitoneally while still on diet. Serum/urine parameters, enzymes of carbohydrate metabolism and oxidative stress were analyzed. CP caused perturbation of the antioxidant defense as reflected by the decrease in the activities of catalase, superoxide dismutase and glutathione peroxidase. Further the activities of various enzymes involved in glycolysis, tricarboxylic acid cycle, gluconeogenesis and hexose monophosphate shunt pathways were determined and were found to be differentially altered by CP treatment. However, these alterations were ameliorated in CP-treated rats fed on FXO. Present results show that dietary supplementation of FXO in CP-treated rats ameliorated CP-induced hepatotoxic and other deleterious effects due to its intrinsic biochemical/antioxidant properties.     

The protective effect of tinoridine against carbon tetrachloride hepatotoxicity

The effect of tinoridine, an anti-inflammatory drug with a potent anti-peroxidative ability, on CCl₄ hepatotoxicity was investigated in rats. CCl₄ administration to rats produced not only marked increases in serum glutamic-oxaloacetic transaminase and glutamic-pyruvic transaminase but also decreases in liver microsomal cytochrome P-450 and glucose-6-phosphatase. These CCl₄-induced alterations in the enzyme activities were markedly decreased by pretreatment with tinoridine. The protective effect of tinoridine was also ascertained by histologic evaluation. α-Tocopherol also showed a similar protection, but anti-inflammatory drugs such as phenylbutazone, indomethacin, ibuprofen, and prednisolone failed to protect against the CCl₄-induced hepatotoxicity. These findings suggest that the anti-peroxidative action of tinoridine contributes to the protective effect against CCl₄ hepatotoxicity.     

GC-MS analysis and hepatoprotective activity of the n-hexane extract of Acrocarpus fraxinifolius leaves against paracetamol-induced hepatotoxicity in male albino rats

Context: In Egypt, the burden of liver diseases is exceptionally high.

Objective: To investigate the components of the n-hexane extract of Acrocarpus fraxinifolius Arn. (Leguminosae) and its hepatoprotective activity against paracetamol (APAP)-induced hepatotoxicity in rats.

Material and methods: TRACE GC ultra gas chromatogaphic spectrometry was used for extract analysis. Thirty albino rats were divided into six groups (five rats in each). Group 1 was the healthy control; Groups 2 and 3 were healthy treated groups (250 and 500?mg/kg b.w. of the extract, respectively) for seven days. Group 4 was hepatotoxicity control (APAP intoxicated group). Groups 5 and 6 received APAP?+?extract 250 and APAP?+?extract 500, respectively.

Results: Chromatographic analysis revealed the presence of 36 components. Major compounds were α-tocopherol (18.23%), labda-8 (20)-13-dien-15-oic acid (13.15%), lupeol (11.93%), phytol (10.95%) and squalene (7.19%). In the acute oral toxicity study, the mortality rates and behavioural signs of toxicity were zero in all groups (doses from 0 to 5?g/kg b.w. of A. fraxinifolius). LD₅₀ was found to be greater than 5?g/kg of the extract. Only the high dose (500?mg/kg b.w.) of extract significantly alleviated the liver relative weight (4.01?±?0.06) and biomarkers, as serum aspartate aminotransferase (62.87?±?1.41), alanine aminotransferase (46.74?±?1.45), alkaline phosphatase (65.96?±?0.74), lipid profiles (180.39?±?3.51), bilirubin profiles (2.30?±?0.06) and hepatic lipid peroxidation (114.20?±?2.06), and increased body weight (11.58?±?0.20), serum protein profile (11.09?±?0.46) and hepatic total antioxidant capacity (23.78?±?0.66) in APAP-induced hepatotoxicity in rats.

Conclusion: Our study proves the antihepatotoxic/antioxidant efficacies of A. fraxinifolius hexane extract.     

蚯蚓提取物对微循环障碍形成的保护作用

目的研究蚯蚓提取物对金黄地鼠血液微循环障碍形成的保护作用及其机理。方法以高分子右旋糖酐所致血液微循环障碍模型为基础 ,采用直观图像图示法和体外红细胞聚集试验 ,研究蚯蚓提取物对金黄地鼠颊囊血液微循环障碍的改善及体外红细胞聚集情况。结果以 2 0、1 0 0、2 0 0mg kg剂量经口给予蚯蚓提取物 3d ,可明显减少体内微血管中血细胞聚集团块和加快微血流速度 (P <0 .0 1 ) ,各观察时间点的红细胞聚集均显著低于阴性对照组 (P <0 .0 1 ) ;体外试验表明 ,在中、低切变率时 ,体外红细胞聚集状态得到明显改善 ,红细胞主要呈串珠及缗钱状 ,与阴性对照组相比有显著性统计学差异 (P <0 .0 5 )。结论蚯蚓提取物对微循环障碍形成具有一定的保护作用 ,是一种微血流改善剂     

The protective effect of taurine against thioacetamide hepatotoxicity of rats

Thioacetamide (TAA) administration (three consecutive intraperitoneal injections of 400 mg/kg at 24-h interval) to rats resulted in hepatic injury as assessed by the measurement of serum transaminase activities and histopathological findings. This treatment caused an increase in the levels of malondialdehyde (MDA), diene conjugates (DCs) and glutathione (GSH) and the activity of superoxide dismutase SOD ), and a decrease in the levels of vitamins E and C and the activity of glutathione peroxidase (GSH-Px) in the liver of rats. Taurine administration (400 mg/kg, i.p., every 12 h and started 24 h prior to the first TAA injection) was found to decrease serum transaminase activities and hepatic lipid peroxidation without any significant change in hepatic antioxidant system. Histopathological findings also suggested that taurine has ameliorated effect on TAA-induced hepatic necrosis. These results indicate that taurine treatment, together with TAA administration, diminished the severity of the liver injury by decreasing oxidative stress due to its possible scavenger effect.     

五味子与黄芪多糖协同保护对乙酰氨基酚致小鼠急性肝损伤

目的：研究五味子提取物和黄芪多糖配伍后对对乙酰氨基酚引起小鼠急性肝损伤的协同保护作用及其机制。方法：以对乙酰氨基酚500mg／kg腹腔注射给药造成小鼠急性肝损伤模型,通过测定小鼠血清丙氨酸氨基转移酶（ALT）、门冬氨酸氨基转移酶（AST）的活性、肝组织还原性谷胱甘肽（GSH）和丙二醛（MDA）含量及观察肝组织病理学改变,以评价五味子提取物、黄芪多糖及其组合物对小鼠肝损伤的保护作用。结果：五味子提取物（270mg／kg）和黄芪多糖（900mg／kg）单独给药对对乙酰氨基酚肝损伤小鼠的血清ALT、AST和肝组织GSH和MDA没有显著性影响。30、90和270mg／kg五味子提取物分别与100、300和900mg／kg黄芪多糖配伍,可使对乙酰氨基酚肝损伤小鼠血清ALT、AST活性及肝组织MDA含量显著降低（P〈0．05或P〈0．01）,肝组织GSH含量显著提高（P〈0．05或P〈0．01）,肝组织细胞的病变程度得到明显改善。在高剂量配伍下,各指标的五味子提取物和黄芪多糖间相互作用指数CDI均小于0．7。结论：五味子提取物和黄芪多糖通过协同提高对乙酰氨基酚致肝损伤小鼠肝脏的还原性谷胱甘肽和抗氧化水平,降低血清ALT和AST水平,减轻肝组织细胞的损伤。