Stabilization of lysosomal membrane and cell membrane glycoprotein profile by Semecarpus anacardium linn. nut milk extract in experimental hepatocellular carcinoma

Semecarpus anacardium Linn. nut milk extract administered orally at a dose of 200 mg/kg/day for 14 days exerted an in vivo stabilizing effect on lysosomal membrane and glycoprotein content in rat hepatocellular carcinoma. This was demonstrated in normal rats and in animals whose biomembranes were rendered fragile by induction of hepatocellular carcinoma with aflatoxin B(1) and subsequent treatment with Semecarpus anacardium nut extract. In this condition, the discharge of lysosomal enzymes increased significantly with a subsequent increase in glycoprotein components. The nut extract administration reversed these adverse changes to near normal in treated animals. The possible reason for this reversal is discussed. Such stabilization of biomembranes by Semecarpus anacardium nut extract may have a beneficial effect in the treatment of hepatocellular carcinoma and other cancers involving abnormal fragility of lysosomes and glycoprotein content providing the extract demonstrates safety in a full toxicity study.     

Recuperative effect of Semecarpus anacardium linn. nut milk extract on carbohydrate metabolizing enzymes in experimental mammary carcinoma-bearing rats

Semecarpus anacardium Linn. of the family Anacardiaceae has many applications in the Ayurvedic and Siddha systems of medicine. We have tested the antitumour activity of Semecarpus anacardium nut extract against experimental mammary carcinoma in animals. As there is a direct relationship between the proliferation of tumour cells and the activities of the glycolytic and gluconeogenic enzymes, we studied changes in the activities of enzymes involved in this metabolic pathway in the liver and kidney. The enzymes investigated were glycolytic enzymes, namely hexokinase, phosphoglucoisomerase, aldolase and the gluconeogenic enzymes, namely glucose-6-phosphatase and fructose-1,6-biphosphatase in experimental rats. A significant rise in glycolytic enzyme activities and a simultaneous fall in gluconeogenic enzyme activities were found in mammary carcinoma bearing rats. Drug administration returned these enzyme activities to their respective control activities.     

Studies on the mechanism of action of Semecarpus anacardium in rheumatoid arthritis

Semecarpus anacardium nuts are used for variety of disorders in Ayurveda. A chloroform extract of the nut significantly reduced acute carrageenan-induced paw oedema in rats and was active against the secondary lesions of adjuvant-induced arthritis. Delayed hypersensitivity induced in mice by sheep red blood cells as an antigen was potentiated by the extract.     

Analgesic, antipyretic and Ulcerogenic properties of an indigenous formulation--Kalpaamruthaa

A modified indigenous Siddha formulation Kalpaamruthaa (KA), containing Semecarpus anacardium nut milk extract (SA), dried powder of Emblica officinalis (EO) fruit and honey was evaluated for its analgesic, antipyretic and Ulcerogenic properties. Both SA and KA, at a dose of 150 mg/kg b. wt were compared with the standard drug diclofenac sodium. KA exhibited an enhanced effect on all properties compared with that found with sole SA treatment, and is likely to be due to synergistic and additive interactions within the complex mixture of phytochemicals present in KA.     

Anticancer potency of the milk extract of Semecarpus anacardium Linn. nuts against aflatoxin B1 mediated hepatocellular carcinoma bearing wistar rats with reference to tumour marker enzymes

Aflatoxin B₁ is an important consideration in the aetiology of human and animal hepatocellular carcinoma. The influence of the drug, Semecarpus anacardium Linn. nut extract, on hepatocarcinogenicity of aflatoxin B₁ was evaluated in adult albino male Wistar rats. Aflatoxin B₁ was administered intraperitoneally to induce hepatocellular carcinoma. These cancer bearing animals were treated with Semecarpus anacardium Linn. nut extract (200 mg/kg body weight/day) in sunflower oil orally for 14 days. The plasma and the liver tumour tissue were investigated biochemically for lactate dehydrogenase, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase and γ‐glutamyl transpeptidase. The elevation of plasma concentration of these enzymes were indicative of the persistent deteriorating effect of aflatoxin B₁ in cancer bearing animals. Lactate dehydrogenase and aminotransferases levels were decreased in liver, whereas alkaline phosphatase and γ‐glutamyl transpeptidase were increased in cancer conditions. These enzyme levels were reversed to near normal control values in drug treated animals. The analysis of marker enzyme activities clearly indicates the antitumour efficacy of Semecarpus anacardium Linn. nut extract on aflatoxin B₁ induced hepatocellular carcinoma. Copyright © 1999 John Wiley & Sons, Ltd.     

Cytotoxic effect of root extract of Tiliacora racemosa and oil of Semecarpus anacardium nut in human tumour cells

Tiliacora racemosa and Semecarpus anacardium, the two plants frequently used in Ayurvedic medicine for the treatment of cancerous diseases, have been selected to examine their action in four human tumour cell lines: acute myeloblastic leukaemia (HL-60), chronic myelogenic leukaemia (K-562), breast adenocarcinoma (MCF-7) and cervical epithelial carcinoma (HeLa). In cells grown in appropriate media the ethanol extract of T. racemosa root, the total alkaloids isolated from this organ and S. anacardium nut oil prepared according to the Ayurvedic principle were found to have cytotoxic activity. The alkaloid fraction from T. racemosa had maximum cytotoxicity and was effective against all four cell lines. S. anacardium oil was cytotoxic only in leukaemic cells. These herbal preparations were not cytotoxic towards normal human lymphocytes, suggesting their action is specific for tumour cells. On microscopic examination the cells treated with these agents exhibited characteristic morphological features of apoptosis, such as cell shrinkage, and the formation of apoptotic bodies. Fluorescent staining with propidium iodide revealed distinct chromatin condensation and nuclear fragmentation. The apoptotic index paralleled the cytotoxic parameters, and fragmented DNA extracted free of genomic DNA from treated cells displayed a typical ladder pattern on gel electrophoresis. Apoptosis induced by alkaloids and phenolics, the active principles present in T. racemosa and S. anacardium, respectively, was found to be mediated by the activation of caspases.     

决明子水提液对大鼠肝脏CYP450酶的影响

该文研究决明子水提液对大鼠肝脏CYP450酶酶活性、mRNA及蛋白表达水平的影响。取SD大鼠,口服灌胃受试药物后,处死,用冰冷生理盐水灌流肝脏,提取大鼠肝脏微粒体、肝脏总RNA和总蛋白,采用Cocktail体外孵育法结合液质联用(LCMS)技术对大鼠肝脏中CYP1A2,2B1,2C11,2D2,2E1,3A1各亚酶的酶活性进行测定,并应用荧光定量PCR技术和Western blot对上述亚型的mRNA和蛋白表达水平进行检测。结果表明,酶活性方面,决明子水提液组与空白组比较可明显诱导CYP1A2,2B1,2C11,2D2,2E1,3A1的酶活性,其中决明子低剂量组对CYP2D2有明显的抑制作用,中、高剂量组对CYP2D2有明显的诱导作用,且都呈剂量依赖性增加,但对CYP3A1的诱导不呈剂量依赖性;mRNA表达方面,决明子水提液对CYP1A2,2C11,2D2,2E1mRNA的表达具有显著诱导作用,其中对CYP1A2,2D2,2E1诱导作用呈剂量依赖性,与酶活性水平具有一致性,对CYP2B1,3A1没有明显作用;蛋白表达方面,决明子水提液对CYP2C11,2E1的表达也具有诱导作用,但没有统计学差异。决明子水提液对CYP450同工酶不同程度诱导或抑制作用,特别是对于CYP2C11,2E1亚型酶,酶活性与mRNA,蛋白表达水平具有一致性,提示当与这些酶底物合并用药时,尤其是与CYP2C11,2E1代谢有关的药物合用时,应充分考虑到潜在的有益和不利的药物相互作用。     

Cyclooxygenase inhibitory flavonoids from the stem bark of Semecarpus anacardium Linn

The ethyl acetate extract of stem bark of Semecarpus anacardium showing in vivo anti-in fl ammatory activity in carrageenan induced rat paw edema assay was investigated in order to identify its active compounds. Chemical investigation of the ethyl acetate extract of S.anacardium afforded 3,4,2',4'-tetrahydroxychalcone (butein) and 7,3',4'-trihydroxy fl avone. Evaluation of COX-1 inhibitory activity of 3,4,2',4'-tetrahydroxychalcone and 7,3',4'-trihydroxy fl avone provided the IC(50) values of 28.4 and 36.7 micro M respectively. Further investigation of these compounds for COX-2 inhibitory activity revealed moderate potency towards this enzyme.     

Protective effect of Hemidesmus indicus L. R. Br. against bromobenzene-induced mitochondrial dysfunction in rat kidney

Hemidesmus indicus (HI) is used in ancient Indian traditional herbal medicine to treat hepatic and renal disorders. The present study was designed to investigate the protective effect of HI aqueous extract against bromobenzene induced mitochondrial dysfunction in rat kidneys. Rats were administered bromobenzene with or without prior administration of HI or vitamin E. At the end of the experiment animals were sacrificed and kidneys were obtained to study mitochondrial function, oxidative stress parameters and histopathology. Administration of bromobenzene caused significant changes like: decrease in the mitochondrial respiration and P/O ratios, increase in lipid peroxidation and protein oxidation, and decrease in the activities of antioxidant enzymes (catalase, glutathione reductase, glutathione peroxidase and superoxide dismutase) in mitochondria with significant histopathological changes in the kidney. Prior administration of HI extract showed a significant protection against bromobenzene induced changes in the kidney and this effect is attributed to the antioxidant and free radical scavenging potential of the HI. The protection was much better with HI compared to vitamin E.     

枳椇子醋酸乙酯提取物对大鼠肝P450同工酶的影响

目的：观察枳椇子醋酸乙酯提取物对大鼠肝P450同工酶的影响。方法：大鼠分别灌胃给予枳椇子醋酸乙酯提取物相当于生药量0.14,0.17,0.2 g·kg^-1,连续10 d,采用紫外分光光度法测定细胞色素P450与NADPH-细胞色素C(P-450)还原酶含量及苯胺羟化酶(ANH)、氨基比林N-脱甲基酶(ADM)、红霉素N-脱甲基酶(ERD)的活性。采用RT-PCR技术检测大鼠肝脏CYP1A1,CYP2C11,CYP2E1,CYP3A1基因的水平。结果：枳椇子醋酸乙酯提取物对细胞色素P450及NADPH-细胞色素C(P-450)还原酶含量无显著影响；可抑制苯胺羟化酶(ANH)活性,抑制率可达31.5%；可增加氨基比林N-脱甲基酶(ADM)活性,可达42.4%；而对红霉素N-脱甲基酶(ERD)的活性没有明显变化。在mRNA水平上,CYP2E1基因的表达水平没有变化；CYP1A1,CYP2C11和CYP3A1基因表达水平则明显增加。结论：枳椇子醋酸乙酯提取物对大鼠肝P450同工酶的影响表现出特异性,对不同的P450同工酶作用不同。     

Antioxidant properties of Asparagus racemosus against damage induced by gamma-radiation in rat liver mitochondria

The possible antioxidant effects of crude extract and a purified aqueous fraction of Asparagus racemosus against membrane damage induced by the free radicals generated during gamma-radiation were examined in rat liver mitochondria. gamma-Radiation, in the dose range of 75-900 Gy, induced lipid peroxidation as assessed by the formation of thiobarbituric acid reactive substances (TBARS) and lipid hydroperoxides (LOOH). Using an effective dose of 450 Gy, antioxidant effects of A. racemosus extract were studied against oxidative damage in terms of protection against lipid peroxidation, protein oxidation, depletion of protein thiols and the levels of the antioxidant enzyme, superoxide dismutase. An active fraction consisting of polysaccharides (termed as P3) was effective even at a low concentration of 10 microg/ml. Both the crude extract as well as the P3 fraction significantly inhibited lipid peroxidation and protein oxidation. The antioxidant effect of P3 fraction was more pronounced against lipid peroxidation, as assessed by TBARS formation, while that of the crude extract was more effective in inhibiting protein oxidation. Both the crude extract and P3 fraction also partly protects against radiation-induced loss of protein thiols and inactivation of superoxide dismutase. The inhibitory effects of these active principles, at the concentration of 10 microg/ml, are comparable to that of the established antioxidants glutathione and ascorbic acid. Hence our results indicate that extracts from A. racemosus have potent antioxidant properties in vitro in mitochondrial membranes of rat liver.     

Effect of Coccinia indica leaf extract on plasma antioxidants in streptozotocin- induced experimental diabetes in rats

The present study was carried out to investigate the antioxidant effect of an ethanolic extract of Coccinia indica leaves, an indigenous plant used in Ayurvedic Medicine in India, in Streptozotocin-diabetic rats. Oral administration of Coccinia indica leaf extract (CLEt) (200 mg/kg body weight) for 45 days resulted in a significant reduction in plasma thiobarbituric acid reactive substances, hydroperoxides, vitamin E and ceruloplasmin. The extract also caused a significant increase in plasma vitamin C and reduced glutathione, which clearly shows the antioxidant property of CLEt. The effect of CLEt at 200 mg/kg body weight was more effective than glibenclamide.     

Modulatory influence of Andrographis paniculata on mouse hepatic and extrahepatic carcinogen metabolizing enzymes and antioxidant status

The effects of two doses (50 and 100 mg/kg body wt/day for 14 days) of an 80% hydroalcohol extract of Andrographis paniculata and butylated hydroxyanisole (BHA) were examined on drug metabolizing enzymes, antioxidant enzymes, glutathione content, lactate dehydrogenase (LDH) and lipid peroxidation in the liver of Swiss albino mice (6-8 weeks old). The effect of the extract and BHA were also examined on lung, kidney and forestomach for the activities of glutathione S-transferase (GST), DT-diaphorase (DTD), superoxide dismutase (SOD) and catalase. A significant increase in the levels of acid soluble sulphydryl (-SH) content, cytochrome P450, cytochrome P450 reductase, cytochrome b5 reductase, GST, DTD and SOD were observed at both dose levels of extract treatment while catalase, glutathione peroxidase and glutathione reductase (GR) showed significant increases only at the higher dose in the liver. Both Andrographis treated groups showed a significant decrease in activity of LDH and malondialdehyde (MDA) formation. BHA treated mice showed a significant increase in the levels of cytochrome b(5), GST, DTD, -SH content, GR and catalase in liver; while LDH and MDA levels were reduced significantly compared with their control values. In the lung, SOD, catalase and DTD, in the kidney catalase, DTD and GST, and in the forestomach SOD and DTD showed a significant increase at both dose levels of treatment. In BHA treated mice GST, DTD and catalase were significantly induced in the lung and along with these enzymes SOD was also induced in the kidney. In the case of the forestomach of BHA treated mice GST, DTD and SOD were enhanced significantly. These findings indicate the chemopreventive potential of Andrographis paniculata against chemotoxicity including carcinogenicity.     

复方中药抑制非酒精性脂肪肝细胞色素P450ⅡE1表达的实 …

目的：研究复方中药对非酒精性脂肪肝细胞色素Ｐ４５０Ⅱ Ｅ１（ＣＹＰⅡＥ１）表达的影响。方法：用高脂饲料诱导大鼠脂肪肝模型,同时给予复方中药干预,观察肝组织病理形态的变化和肝细胞色素Ｐ４５０ⅡＥ１的表达,测定肝丙二醛（ＭＤＡ）和超氧化坡化酶（ＳＯＤ）、谷胱甘肽（ＧＳＨ）、维生素Ｅ以及甘油三酯（ＴＧ）含量的变化。并与对照组比较。结果：中药组的肝组织脂肪变性基本恢复正常,免疫组化证明复方中药能显著抑制脂     

Antioxidant activity of Tinospora cordifolia roots in experimental diabetes.

We made an attempt to study the antioxidant properties of Tinospora cordifolia roots, an indigenous plant used in Ayurvedic medicine in India in alloxan diabetic rats. Oral administration of an aqueous T. cordifolia root extract (TCREt) (2.5 and 5.0 g/kg) for 6 weeks resulted in a decrease in the levels of plasma thiobarbituric acid reactive substances, ceruloplasmin and alpha-tocopherol in alloxan diabetic rats. The root extract also causes an increase in the levels of glutathione and vitamin C in alloxan diabetes. The root extract at a dose of 5.0 g/kg showed the highest effect. The effect of TCREt was more effective than glibenclamide. Insulin restored all the parameters to near normal levels.     

Impact of Andrographis paniculata crude extract on mouse hepatic cytochrome P450 enzymes

Modulatory influence of Andrographis paniculata crude extract on cytochrome P450 (CYP) enzymes was performed by administration of the crude extract of Andrographis paniculata to ICR male mice. Total hepatic P450 content was not significantly modified by either the aqueous or the alcoholic extracts of Andrographis paniculata. Assessment of hepatic microsomal P450 activities by alkoxyresorufin O-dealkylations noted that both the aqueous and alcoholic extracts of Andrographis paniculata significantly increased ethoxyresorufin O-dealkylase and pentoxyresorufin O-dealkylase activities, while those of methoxyresorufin O-dealkylase activities were not elevated. These results suggested that Andrographis paniculata might effectuate hepatic cytochrome P450 enzymes of which CYP1A1 and CYP2B are the responsive P450 isoforms.     

Mangifera indica L. Extract and Mangiferin Modulate Cytochrome P450 and UDP‐Glucuronosyltransferase Enzymes in Primary Cultures of Human Hepatocytes

The aqueous stem bark extract of Mangifera indica L. (MSBE) has been reported to have antioxidant, anti‐inflammatory and analgesic properties. In previous studies, we showed that MSBE and mangiferin, its main component, lower the activity of some cytochrome P‐450 (P450) enzymes in rat hepatocytes and human liver microsomes. In the present study, the effects of MSBE and mangiferin on several P450 enzymes and UDP‐glucuronosyltransferases (UGTs) in human‐cultured hepatocytes have been examined. After hepatocytes underwent a 48‐h treatment with sub‐cytotoxic concentrations of the products (50–250 µg/mL), a concentration‐dependent decrease of the activity of the five P450 enzymes measured (CYP1A2, 2A6, 2C9, 2D6 and 3A4) was observed. For all the activities, a reduction of at least 50% at the highest concentration (250 µg/mL) was observed. In addition, UGT activities diminished. MSBE considerably reduced UGT1A9 activity (about 60% at 250 µg/mL) and lesser effects on the other UGTs. In contrast, 250 µg/mL mangiferin had greater effects on UGT1A1 and 2B7 than on UGT1A9 (about 55% vs. 35% reduction, respectively). Quantification of specific mRNAs revealed reduced CYP3A4 and 3A5 mRNAs content, and an increase in CYP1A1, CYP1A2, UGT1A1 and UGT1A9 mRNAs. No remarkable effects on the CYP2A6, 2B6, 2C9, 2C19, 2D6 and 2E1 levels were observed. Our results suggest that the activity and/or expression of major P450 and UGT enzymes is modulated by MSBE and that potential herb–drugs interactions could arise after a combined intake of this extract with conventional medicines. Therefore, the potential safety risks of this natural product derived by altering the ADMET properties of co‐administered drugs should be examined. Copyright © 2012 John Wiley & Sons, Ltd.     

Antioxidant effect of EGb 761 on hydrogen peroxide-induced lipoperoxidation of G-6-PD deficient erythrocytes

In order to reduce the haemolytic susceptibility of glucose-6-phosphate dehydrogenase (G-6-PD) deficient erythrocytes, Ginkgo biloba extract (EGb 761) and vitamin E (vit E) were used as antioxidant agents and their effects compared. The erythrocyte suspensions from control and G-6-PD deficient patients were subjected to hydrogen peroxide (H2O2) incubation for 1 h. The produced thiobarbituric acid reactive substance (TBARS) levels measured as nmol/g Hb were compared with those of the erythrocytes administered 250 microg/mL EGb 761 or vit E previously or concomitantly with H2O2. Preincubation with EGb 761 reduced the TBARS levels from 317.14 +/- 25.27 to 160.09 +/- 21.97 nmol/g Hb in controls and from 348.24 +/- 7.79 to 205.60 +/- 14.22 nmol/g Hb in deficient erythrocytes. Concomitant application of EGb 761 with H2O2 resulted in similar but less reduction. The antioxidative effects of vitamin E were comparable to those of EGb 761. Contrary to the results obtained from oxidant conditions, the antioxidant characteristics of EGb 761 and vitamin E were not observed when they were applied directly to the erythrocytes without oxidative stress. The findings demonstrate that irrespective of administration time, EGb 761 significantly reduced TBARS levels in the erythrocytes of control and G-6-PD deficient patients subjected to oxidative stress.     

Protective effect of Phyllanthus fraternus against bromobenzene-induced mitochondrial dysfunction in rat kidney

Phyllanthus fraternus (PF) (Euphorbiaceae) is used in ancient Indian traditional phytomedicine to treat various human diseases including hepatic and renal disorders. The present study was designed to investigate the protective effect of PF aqueous extract against bromobenzene-induced mitochondrial dysfunction in rat kidney, compared with vitamin E used as positive control. Male Wistar rats divided into six (A-F) groups and the experimental animals were administered bromobenzene with or without prior administration of PF extract or vitamin E. Animals were sacrificed and the kidneys obtained for studying mitochondrial function and histopathology. Administration of bromobenzene caused significant changes, including decrease in the mitochondrial respiration and P/O ratios, an increase in lipid peroxidation and protein oxidation, and a decrease in the activities of antioxidant enzymes (catalase, superoxide dismutase, glutathione reductase, and glutathione peroxidase) in mitochondria with significant histopathological changes in the kidney. However, prior administration of the PF extract showed significant protection against bromobenzene induced renal damage by reversing all above parameters. Mitochondrial dysfunction induced by bromobenzene was protected much better with the PF extract than with vitamin E. These results suggested that the Phyllanthus fraternus extract is an efficient armament against nephrotoxicity induced by bromobenzene.