In vitro antioxidant,antidiabetic and antilipidemic activities of Symplocos cochinchinensis (Lour.) S. Moore bark

Symplocos cochinchinesis is used in Indian system of traditional medicine to treat diabetes mellitus. The present study investigates the in vitro antioxidant, antidiabetic and antilipidemic activities of S. cochinchinensis bark methanolic extract (SCBe) in streptozotocin (STZ) induced diabetic rats. In in vitro studies SCBe showed very good scavenging activity on 2,2-diphenyl-picrylhydrazyl (DPPH) (IC₅₀ 820.34 ± 1.74 μg/ml), hydroxyl (IC₅₀ 884.19 ± 0.45 μg/ml) and nitric oxide (IC₅₀ 860.21 ± 1.18 μg/ml) radicals, as well as high reducing power. SCBe (250 and 500 mg/kg) was administered to STZ (40 mg/kg) induced diabetic rats for 28 days. SCBe showed a significant decrease in blood glucose and significant increase in plasma insulin and liver glycogen levels in treated diabetic rats. Further, SCBe showed antilipidemic activity as evidenced by significant decrease in serum TC, TG, LDL-C levels and significant increase in HDL-C level in treated diabetic rats. SCBe also restored the altered plasma enzymes (SGOT, SGPT and ALP), total protein, urea and creatinine levels to near normal. The action of SCBe was comparable to the antidiabetic drug glibenclamide. Results of this experimental study indicated that SCBe possessed antioxidant, antidiabetic and antilipidemic activities.     

Protective effects of Coriandrum sativum extracts on carbon tetrachloride-induced hepatotoxicity in rats

Oxidative damage is implicated in the pathogenesis of various liver injuries. The study was aimed to investigate the antioxidant activity of Coriandrum sativum on CCl₄ treated oxidative stress in Wistar albino rats. CCl₄ injection induced oxidative stress by a significant rise in serum marker enzymes and thiobarbituric acid reactive substances (TBARS) along with the reduction of antioxidant enzymes. In serum, the activities of enzymes like ALP, ACP and protein and bilirubin were evaluated. Pretreatment of rats with different doses of plant extract (100 and 200 mg/kg) significantly lowered SGOT, SGPT and TBARS levels against CCl₄ treated rats. Hepatic enzymes like SOD, CAT, GPx were significantly increased by treatment with plant extract, against CCl₄ treated rats. Histopathological examinations showed extensive liver injuries, characterized by extensive hepatocellular degeneration/necrosis, inflammatory cell infiltration, congestion, and sinusoidal dilatation. Oral administration of the leaf extract at a dose of 200 mg/kg body weight significantly reduced the toxic effects of CCl₄. The activity of leaf extract at the dose of 200 mg/kg was comparable to the standard drug, silymarin. Based on these results, it was observed that C. sativum extract protects liver from oxidative stress induced by CCl₄ and thus helps in evaluation of traditional claim on this plant.     

Phenolic composition and biological activities of Juniperus drupacea Labill. berries from Turkey

The present study was designed to define the phenolic profile and the biological potential of berries methanol extract of Juniperus drupacea Labill. from Turkey.The total phenolic content (Folin-Ciocalteau assay) was 48.06 ± 0.99 mg GAE/g extract. The HPLC-DAD-ESI-MS analysis allowed the determination of the complete phenolic profile of J. drupacea berries. Phenolic acids represented more than 60% of the total phenolics, and tyrosol was the major one (1324 ± 0.64 μg/g extract); within the flavonoids amentoflavone was detected as the main constituent (927 ± 0.35 μg/g extract).The extract exhibited good antioxidant properties, as determined by different in vitro models: DPPH test (IC₅₀ 0.38 ± 0.02 mg/mL), reducing power (12.63 ± 0.14 ASE/mL), Fe²⁺ chelating ability (IC₅₀ 2.26 ± 0.06 mg/mL), and TBA test (IC₅₀ 2.47 ± 1.13 μg/mL).Cytotoxicity against Artemia salina was highlighted (LC₅₀ 489.47 ± 27.8 μg/mL), and a significant decrease (p ? 0.05; p ? 0.01) in HepG2 cells viability was observed at the higher concentrations (5-10 μg/mL).The extract displayed good antibacterial activity towards Gram-positive bacteria and in particular Staphylococcus aureus was the most susceptible strain (MIC 78.12 μg/mL).     

Essential oil composition and antioxidant activities of Curcuma aromatica Salisb.

The chemical composition of the hydro-distilled essential oil from leaves of Curcuma aromatica Salisb. was analysed by GC–MS. Twenty-three compounds representing 94.29% of the total oil were identified. The antioxidant activities of the oil and various extracts of C. aromatica were evaluated by using 2,2-diphenyl-1-picrylhydrazyl (DPPH) and superoxide radical-scavenging assays. The oil and methanol extract showed potent DPPH radical-scavenging activities (IC₅₀ = 14.45 and 16.58 μg/ml, respectively), which were higher than butylated hydroxyanisole (IC₅₀ = 18.27 μg/ml). The extracts also exhibited remarkable superoxide radical-scavenging activities (IC₅₀ = 22.6–45.27 μg/ml) and the activity in the methanol extract was superior to all other extracts (IC₅₀ = 22.6 μg/ml). Furthermore, the amount of total phenolic compounds was determined and its content in ethyl acetate extract was the highest as compared to other extracts. The results indicate that the oil and extracts of C. aromatica could serve as an important bio-resource of antioxidants for using in the food industries.     

Antioxidant activity and total phenolic content of ethanolic extract of Caesalpinia bonducella seeds

The aim of this study was to assess the in vitro potential of ethanolic extract of Caesalpinia bonducella seeds as a natural antioxidant. The DPPH activity of the extract (20, 40, 50, 100 and 200 μg/ml) was increased in a dose dependent manner, which was found in the range of 38.93–74.77% as compared to ascorbic acid (64.26–82.58%). The IC₅₀ values of ethanolic extract and ascorbic acid in DPPH radical scavenging assay were obtained to be 74.73 and 26.68 μg/ml, respectively. The ethanolic extract was also found to scavenge the superoxide generated by EDTA/NBT system. Measurement of total phenolic content of the ethanolic extract of C. bonducella was achieved using Folin–Ciocalteau reagent containing 62.50 mg/g of phenolic content, which was found significantly higher when compared to reference standard gallic acid. The ethanolic extract also inhibited the hydroxyl radical, nitric oxide, superoxide anions with IC₅₀ values of 109.85, 102.65 and 89.84 μg/ml, respectively. However, the IC₅₀ values for the standard ascorbic acid were noted to be 70.79, 65.98 and 36.68 μg/ml respectively. The results obtained in this study clearly indicate that C. bonducella has a significant potential to use as a natural antioxidant agent.     

Antioxidant and antidermatophytic activities of essential oil and extracts of Metasequoia glyptostroboides Miki ex Hu

This study was undertaken to assess the antioxidant and antidermatophytic potential of the essential oil and extracts (hexane, chloroform, ethyl acetate and methanol) of Metasequoia glyptostroboides Miki ex Hu. Antioxidant activity was evaluated by using 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay. The free radical scavenging activities of the oil and ethyl acetate extract were found to be superior (IC₅₀ = 9.1 and 14.24 μg/ml, respectively) as compared to butylatedhydroxyanisole (BHA), (IC₅₀ = 18.27 μg/ml). Also the ethyl acetate extract revealed the highest phenolic contents (93.26 mg/g of dry wt) as compared to the other extracts. Further, oil (1250 μg/disc) and extracts (1750 μg/disc) revealed 35.33–67.66 and 18.0–53.3% antidermatophytic effect, respectively, along with their respective MIC values (62.5–500 and 250–4000 μg/ml) against Trichophyton rubrum KCTC 6345, T. rubrum KCTC 6375, T. rubrum KCTC 6352, T. mentagrophytes KCTC 6085, T. mentagrophytes KCTC 6077, T. mentagrophytes KCTC 6316, Microsporum canis KCTC 6591, M. canis KCTC 6348 and M. canis KCTC 6349. The oil also had a strong detrimental effect on spore germination as well as concentration and time-dependent kinetic inhibition of M. canis KCTC 6591.     

Chemical compositions,antifungal and antioxidant activities of essential oil and various extracts of Melodorum fruticosum L. flowers

This research presents the chemical composition antifungal and antioxidant activities of essential oils and various extracts from Melodorum fruticosum flowers. The essential oil composition of M. fruticosum flowers were investigated by GC–MS with 88 identified volatile constituents. Phenyl butanone, linalool, benzyl alcohol, α-cadinol, globulol and viridiflorol were found to be the major components, respectively. The dichloromethane extract played a major role as a remarkable fungicide according to their inhibition action against all tested pathogens followed by hexane extract, essential oil and methanol extract, respectively, along with their respective MIC values ranging from 125 to 1000 μg/ml. The dichloromethane extracts were also evaluated to be superior to all extracts tested with an IC₅₀ value of 87.6 μg/ml whereas other extracts showed their IC₅₀ values ranging from 100.13 to 194.50 μg/ml.     

Protective effects of Salvia plebeia compound homoplantaginin on hepatocyte injury

Salvia plebeia R. Br is a traditional Chinese herb which has been considered as an inflammatory mediator used for treatment of many infectious diseases including hepatitis. Previously, the compound homoplantaginin was isolated in our group. Hence, we evaluated the protective effects of homoplantaginin on hepatocyte injury. Homoplantaginin displayed an antioxidant property in a cell-free system and showed IC₅₀ of reduction level of DPPH radical at 0.35 μg/ml. In human hepatocyte HL-7702 cells exposed to H₂O₂, the addition of 0.1–100 μg/ml of homoplantaginin, which did not have a toxic effect on cell viability, significantly reduced lactate dehydrogenase (LDH) leakage, and increased glutathione (GSH), glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) in supernatant. In vivo assay, we employed the model of Bacillus Calmette–Guérin (BCG)/lipopolysaccharide (LPS)-induced hepatic injury mice to evaluate efficacy of homoplantaginin. Homoplantaginin (25–100 mg/kg) significantly reduced the increase in serum alanine aminotranseferase (ALT) and aspartate aminotransferase (AST), decreased the levels of tumor necrosis factor-α (TNF-α) and interleukin-1 (IL-1). The same treatment also reduced the content of thiobarbituric acid-reactive substances (TBARS), elevated the levels of GSH, GSH-Px and SOD in hepatic homogenate. The histopathological analysis showed that the grade of liver injury was ameliorated with reduction of inflammatory cells and necrosis of liver cells in homoplantaginin treatment mice. These results suggest that homoplantaginin has a protective and therapeutic effect on hepatocyte injury, which might be associated with its antioxidant properties.     

In vitro inhibitory effects of asiaticoside and madecassoside on human cytochrome P450

The inhibitory effects and types of inhibition of asiaticoside and madecassoside on human CYPs were studied in vitro using recombinant human CYPs. The median inhibitory concentrations (IC₅₀) of asiaticoside and madecassoside were determined for CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP2E1 and CYP3A4. Asiaticoside inhibited CYP2C19 (IC₅₀ = 412.68 ± 15.44 μM) and CYP3A4 (IC₅₀ = 343.35 ± 29.35 μM). Madecassoside also inhibited CYP2C19 (IC₅₀ = 539.04 ± 14.18 μM) and CYP3A4 (IC₅₀ = 453.32 ± 39.33 μM). Asiaticoside and madecassoside had no effect on the activities of CYP1A2, CYP2C9 and CYP2D6 and CYP2E1. Assessment of mechanism-based inhibition and the type of inhibition were performed for asiaticoside and madecassoside with CYP2C19 and CYP3A4. These results suggested that madecassoside is a mechanism-based inhibitor of CYP2C19 and CYP3A4. Assessment of mechanism-based inhibition by asiaticoside was limited by its low solubility. Asiaticoside exhibited non-competitive inhibition of CYP2C19 (K_i = 385.24 ± 8.75 μM) and CYP3A4 (K_i = 535.93 ± 18.99 μM). Madecassoside also showed non-competitive inhibition of CYP2C19 (K_i = 109.62 ± 6.14 μM) and CYP3A4 (K_i = 456.84 ± 16.43 μM). These results suggest that asiaticoside and madecassoside could cause drug-drug interactions via inhibition of CYP2C19 and CYP3A4. An in vivo study is needed to examine this further.     

Modulation of human neutrophil oxidative metabolism and degranulation by extract of Tamarindus indica L. fruit pulp

The tamarind (Tamarindus indica L.) is indigenous to Asian countries and widely cultivated in the American continents. The tamarind fruit pulp extract (ExT), traditionally used in spices, food components and juices, is rich in polyphenols that have demonstrated anti-atherosclerotic, antioxidant and immunomodulatory activities. This study evaluated the modulator effect of a crude hydroalcoholic ExT on some peripheral human neutrophil functions. The neutrophil reactive oxygen species generation, triggered by opsonized zymosan (OZ), n-formyl-methionyl-leucyl-phenylalanine (fMLP) or phorbol myristate acetate (PMA), and assessed by luminol- and lucigenin-enhanced chemiluminescence (LumCL and LucCL, respectively), was inhibited by ExT in a concentration-dependent manner. ExT was a more effective inhibitor of the PMA-stimulated neutrophil function [IC₅₀ (in μg/10⁶cells) = 115.7 ± 9.7 (LumCL) and 174.5 ± 25.9 (LucCL)], than the OZ- [IC₅₀ = 248.5 ± 23.1 (LumCL) and 324.1 ± 34.6 (LucCL)] or fMLP-stimulated cells [IC₅₀ = 178.5 ± 12.2 (LumCL)]. The ExT also inhibited neutrophil NADPH oxidase activity (evaluated by O₂ consumption), degranulation and elastase activity (evaluated by spectrophotometric methods) at concentrations higher than 200 μg/10⁶ cells, without being toxic to the cells, under the conditions assessed. Together, these results indicate the potential of ExT as a source of compounds that can modulate the neutrophil-mediated inflammatory diseases.     

Potential analgesic,anti-inflammatory and antioxidant activities of hydroalcoholic extract of Areca catechu L. nut

The hydroalcoholic extract of Areca catechu L. (ANE) nut was screened for its analgesic, anti-inflammatory and in vitro antioxidant potential. Three doses of ANE (250, 500 and 1000 mg/kg orally) were tested for analgesic and anti-inflammatory activities. Evaluation of analgesic activity of ANE was performed using hot plate and formalin test in mice. ANE showed maximum increase in hot plate reaction time (56.27%, p < 0.01), while reduced the duration of licking/biting behaviors in first (39.45%, p < 0.05) and second (92.71%, p < 0.01) phases of the formalin test indicating significant analgesic activity. ANE reduced the paw edema considerably (86.79% inhibition after 24 h, p < 0.01) in dose-dependent manner compared to carrageenan-induced rat. In addition, in vitro antioxidant activity of ANE was investigated by total phenolic content (TPC) and hydrogen peroxide assay. The IC₅₀ observed in hydrogen peroxide assay was 83.14 μg/ml and TPC 120.56 ± 21.09 mg QE/g. Altogether, these results suggest that the hydroalcoholic extract of Areca catechu could be considered as a potential analgesic, anti-inflammatory and antioxidant agent.     

Zizyphusspina-christi protects against carbon tetrachloride-induced liver fibrosis in rats

The study of chronic hepatic fibrosis has been receiving an escalating attention in the past two decades. The aim of the study was to examine the effects of the water extract of Zizyphus spina-christi (L.) (ZSC) on carbon tetrachloride (CCl₄)-induced hepatic fibrosis. ZSC extract was daily administered [alone (ZSC-control group) or along with CCl₄ (protected groups)] at 0.125 (low dose), 0.250 (medium dose) and 0.350 (high dose) g/kg b.wt. for 8 weeks. Histo-pathological, biochemical and histology texture analyses revealed that ZSC significantly impede the progression of hepatic fibrosis. ZSC resulted in a significant amelioration of liver injury judged by the reduced activities of serum ALT and AST. Oral administration of ZSC has also restored normal levels of malondialdehyde and retained control activities of endogenous antioxidants such as SOD, CAT and GSH. Furthermore, ZSC reduced the expression of α-smooth muscle actin, the deposition of types I and III collagen in CCl₄-injured rats. Texture analysis of microscopic images along with fibrosis index calculation showed improvement in the quality of type I collagen distribution and its quantity after administration of ZSC extract. These results demonstrate that administration of ZSC may be useful in the treatment and prevention of hepatic fibrosis.     

Chemical composition of essential oils in Zataria multiflora Boiss. from different parts of Iran and their radical scavenging and antimicrobial activity

The objective of the study was to characterize the chemical constituents, antioxidant and antibacterial properties of five ecotypes of Zataria multiflora Boiss. essential oil with respect to main phytogeographic grown towns in Iran. Our investigation showed that the plants had essential oil yield ranging from 1.59 ± 0.86% to 0.99 ± 0.29% v/w. There were qualitative similarities among the oils from different origins, whereas the amounts of some components were varied. From different samples, 34, 34, 32, 29 and 53 various compounds were identified, representing 98.32%, 97.77%, 99.5%, 98.38% and 96.54% of total oils, respectively. The highest oxygenated monoterpens value in this study stood at 72.99%. Moreover, thymol, a phenolic compound of oxygenated monoterpens, was the most abundant component in GC/MS ranging from 27.05% to 64.87%. In the DPPH antioxidant assay, all samples exhibited a remarkable activity with a higher degree of IC₅₀ = 19.7 ± 0.7 μg/ml almost similar to BHT (18.1 ± 0.4 μg/ml). Escherichia coli O157:H7 was the most resistant and Candida tropicalis was the most vulnerable organisms with MICs of 16 and 0.062 mg/ml, respectively. In conclusion, it seemed that geographical variation might have influenced the oil compounds either quantitatively or qualitatively.     

Assessment of a dry extract from milk thistle (Silybum marianum) for interference with human liver cytochrome-P450 activities

The effect of a standardised dry extract from Silybum marianum (HEPAR-PASC®) on the enzyme kinetics of cytochrome-P450 isoenzymes (CYP) was investigated with primary human hepatocytes and human liver microsomes in order to assess the potential for drug-drug interactions. A cytotoxic effect on hepatocytes was observed at concentrations at and above 50 μg/ml. The EC₅₀ value was calculated to be 72.0 μg/ml. Therefore, the chosen test concentrations for CYP induction on human hepatocytes were 50, 10, and 1.5 μg/ml, which allowed for interpretation of the clinical significance of the data with a range of 50-1-fold c_max at maximal recommended doses. No induction was observed at the lowest concentration of 1.5 μg/ml, which is close to c_max. The extract did not induce CYP 3A4 at any of the tested concentrations. A low or marginal induction of 1A2, 2B6, and 2E1 at the maximum concentration of 50 μg/ml was observed. CYP inhibition on human microsomes was tested at concentrations of 150, 15, and 1.5 μg/ml. No or minor CYP inhibition was observed for all CYPs tested at the lowest concentration of 1.5 μg/ml, i.e. CYPs 1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1, and 3A4. At concentrations of 15 and 150 μg/ml the extract significantly inhibited CYP 2B6, 2C8, 2C9, 2C19, 2E1, and 3A4. In these cases, K_i values were determined. All K_i values exceeded c_max by at least a factor of 10-fold. According to FDA regulations 1 > c_max/K_i > 0.1 indicates, that drug-drug interactions are possible for CYPs 2C8, and 2C9, but not likely, and are remote for CYPs 2C19, 2D6, and 3A4.     

Wild mushrooms Clitocybe alexandri and Lepista inversa: In vitro antioxidant activity and growth inhibition of human tumour cell lines

The in vitro antioxidant and growth inhibitory activity of extracts obtained from two Portuguese wild mushrooms (Clitocybe alexandri and Lepista inversa) was studied in human tumour cell lines. The extracts were phenolic (methanolic and ethanolic) and polysaccharidic (boiling water). The antioxidant activity assays included evaluation of radical-scavenging capacity, reducing power and inhibition of lipid peroxidation measured in liposome solutions. Extract-induced cell growth inhibition was measured in four different tumour cell lines (lung, breast, colon and gastric cancer) using the SRB assay. The polysaccharidic extract of L. inversa was the most potent as antioxidant (EC₅₀ < 1.8 ± 0.1 mg/ml), while the phenolic ethanolic extract of C. alexandri was the most potent as inhibitor of growth of the studied cancer cell lines (GI₅₀ < 26.0 ± 1.3 μg/ml). Together, these activities indicate that these mushrooms are promising sources of bioactive compounds.     

Amelioration effects against N-nitrosodiethylamine and CCl(4)-induced hepatocarcinogenesis in Swiss albino rats by whole plant extract of Achyranthes aspera

Objective:

The prevalence of oxidative stress may be implicated in the etiology of many pathological conditions. Protective antioxidant action imparted by many plant extracts and plant products make them a promising therapeutic drug for free-radical-induced pathologies. In this study, we assessed the antioxidant potential and suppressive effects of Achyranthes aspera by evaluating the hepatic diagnostic markers on chemical-induced hepatocarcinogenesis.

Materials and Methods:

The in vivo model of hepatocarcinogenesis was studied in Swiss albino rats. Experimental rats were divided into five groups: control, positive control (NDEA and CCl₄), A. aspera treated (100, 200, and 400 mg/kg b.w.). At 20 weeks after the administration of NDEA and CCl₄, treated rats received A. aspera extract (AAE) at a dose of 100, 200, and 400 mg/kg once daily route. At the end of 24 weeks, the liver and relative liver weight and body weight were estimated. Lipid peroxidation (LPO), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione-S-transferase (GST), and reduced glutathione (GSH) were assayed. The hepatic diagnostic markers namely serum glutamic oxaloacetic transminase (AST), serum glutamic pyruvate transminase (ALT), serum alkaline phosphatase (ALP), gamma glutamyl transpeptidase (GGT), and bilirubin (BL) were also assayed, and the histopathological studies were investigated in control, positive control, and experimental groups.

Results:

The extract did not show acute toxicity and the per se effect of the extract showed decrease in LPO, demonstrating antioxidant potential and furthermore no change in the hepatic diagnosis markers was observed. Administration of AAE suppressed hepatic diagnostic and oxidative stress markers as revealed by decrease in NDEA and CCl₄ -induced elevated levels of SGPT, SGOT, SALP, GGT, bilirubin, and LPO. There was also a significant elevation in the levels of SOD, CAT, GPx, GST, and GSH as observed after AAE treatment. The liver and relative liver weight were decreased after treatment with AAE in comparison to positive control group. The architecture of hepatic tissue was normalized upon treatment with extract at different dose graded at 100, 200, and 400 mg/kg. b.w. in comparison to positive control group.

Conclusion:

These results suggest that A. aspera significantly alleviate hepatic diagnostic and oxidative stress markers which signify its protective effect against NDEA and CCl⁴-induced two-stage hepatocarcinogenesis.     

Biological activities of Portuguese propolis: Protection against free radical-induced erythrocyte damage and inhibition of human renal cancer cell growth in vitro

This study reports for the first time the biological properties of Portuguese propolis. The antioxidant potential of propolis samples from Bornes (Northeast) and Fundão (Centre) regions of Portugal was evaluated by their ability to inhibit the 2,2′-azobis(2-amidinopropane) dihydrochloride (AAPH)-induced oxidative hemolysis and lipid peroxidation in human erythrocytes. Bornes and Fundão propolis strongly protected the erythrocyte membrane from hemolysis (IC₅₀ of 6.3 ± 0.7 and 10.4 ± 2.7 μg/ml, respectively), in a time- and concentration-dependent manner. This effect was found to be significantly higher than that presented by ascorbic acid (IC₅₀ of 31.0 ± 5.6 μg/ml). In addition, human erythrocytes treated with propolis extracts showed concentration-dependent decrease in levels of malondialdehyde, a breakdown product of lipid peroxidation. Propolis extracts were also assayed for their anticancer properties on human renal cell carcinoma (RCC). Primary cultures of normal and cancerous renal cells derived from RCC patients, in addition to A-498 cell line, were treated with propolis extracts (0-100 μg/ml). Cytotoxic and antiproliferative effects were determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Propolis extracts exhibited selective toxicity against malignant cells compared to normal cells. In vitro RCC growth was strongly inhibited by Bornes and Fundão propolis in a concentration-dependent manner. Our results indicate that Portuguese propolis constitutes an excellent source of effective natural antioxidant and chemopreventive agents.     

A search for hepatoprotective activity of aqueous extract of Rhus coriaria L. against oxidative stress cytotoxicity

The protective effects of different concentrations of aqueous extract of Rhus coriaria L. fruit (75 and 100 μg/ml) and also gallic acid (100 μM) as one of its main components were examined against oxidative stress toxicity induced by cumene hydroperoxide (CHP) in isolated rat hepatocytes. Both extract concentrations and gallic acid (100 μM) significantly (P < 0.05) protected the hepatocyte against all oxidative stress markers including cell lysis, ROS generation, lipid peroxidation, glutathione depletion, mitochondrial membrane potential decrease, lysosomal membrane oxidative damage and cellular proteolysis. Aqueous extracts of Rhus coriaria L. (75 and 100 μg/ml) were more effective than gallic acid (100 μM) in protecting hepatocytes against CHP induced lipid peroxidation (P < 0.05). On the other hand gallic acid (100 μM) acted more effective than aqueous extracts of Rhus coriaria L. (75 and 100 μg/ml) at preventing hepatocyte membrane lysis (P < 0.05). In addition H₂O₂ scavenging effect of both extract concentrations (75 and 100 μg/ml) were determined in hepatocytes and compared with gallic acid (100 μM). Gallic acid (100 μM) was more effective than aqueous extracts of Rhus coriaria L. (75 and 100 μg/ml) at H₂O₂ scavenging activity (P < 0.05).     

Evaluation of in vitro cytotoxicity of 6-benzylaminopurine carboplatin derivatives against human cancer cell lines and primary human hepatocytes

A series of seven platinum(II) cyclobutane-1,1-dicarboxylato (cbdc) complexes {[Pt(cbdc)(L_n)₂], 1-7}, derived from carboplatin by a substitution of two NH₃ molecules for two 2,6,9-trisubstituted 6-benzylaminopurine-based N-donor ligands (L_n), was studied by the MTT assay for their in vitro cytotoxic activity against seven human cancer cell lines, i.e. lung carcinoma (A549), cervix epithelioid carcinoma (HeLa), osteosarcoma (HOS), malignant melanoma (G361), breast adenocarcinoma (MCF7), ovarian carcinoma (A2780) and its cisplatin-resistant analogue (A2780cis), and against two primary cultures of human hepatocytes (LH31 and LH32). The prepared complexes were cytotoxic against several cancer cells, in some cases even more than cisplatin. The best results were achieved for complexes 1 (IC₅₀ = 17.4 ± 2.0 μM) and 2 (IC₅₀ = 14.8 ± 2.1 μΜ) against HOS cells, 1 (IC₅₀ = 15.1 ± 6.8 μM), 2 (IC₅₀ = 13.6 ± 5.2 μM) and 6 (IC₅₀ = 19.0 ± 6.6 μM) against MCF7, 6 (IC₅₀ = 6.4 ± 0.1 μM) against A2780, and 1-6 (IC₅₀ = 15.6 ± 4.0, 12.9 ± 3.7, 15.8 ± 3.8, 16.6 ± 5.5, 22.1 ± 2.5, and 5.6 ± 1.7 μM, respectively) against A2780cis. Viability of human hepatocytes was not declined by the tested complexes up to the concentration of 50 μM (for 1, 3-7) and 20 μM (for 2; caused by lower solubility of this complex).