Protective effect of chicory and/or artichoke leaves extracts on carbon tetrachloride and gamma-irradiation-induced chronic nephrotoxicity in rats.

The prevalence of chronic kidney disease (CKD) is in progress that causes kidney failure, leading to global problems. This manuscript investigated the nephroprotective effects of chicory (CLE) and/or artichoke (ALE) leaves extracts on carbon tetrachloride (CCl4 ) and gamma-irradiation (Rad)-induced chronic nephrotoxicity in rats. Rats were divided into 10 groups (10 animals/group): group 1: control, groups 2-7 rats were treated with CLE, ALE, CLE/ALE, CCl4 , Rad, and CCl4 /Rad, respectively. Groups 8 to 10, rats were intoxicated with CCl4 /Rad, and treated with CLE, ALE, and CLE/ALE extracts, respectively, for 4 weeks. The data demonstrated that CCl4 administration or Rad exposure induced high levels of urea and creatinine, with low levels of total protein and albumin in the serum. However, high levels of malondialdehyde (MDA), nitric oxide (NO), hydrogen peroxide (H2 O2 ), some pro-inflammatory markers such as interleukins (IL-1ß, IL-2, IL-6), TNF-α, NF-κB, the fibrotic marker; TGF-ß1, calcium, and copper, low contents of reduced glutathione (GSH), iron, and zinc, and suppression of the antioxidant enzymes' activity, superoxide dismutase (SOD), and catalase (CAT) were observed. In addition, the Wnt and ß-catenin protein expression ratios were up-regulated in the kidney tissues of the CCl4 , and Rad intoxicated animals. However, the combined treatment CCl4 /Rad augmented these measurements. On the other hand, CLE, ALE, and CLE/ALE treatments demonstrated nephroprotection in the kidney tissues of CCl4 /Rad intoxicated animals, in the order of CLE/ALE>ALE>CLE by ameliorating the investigated parameters. Kidney tissues' histopathological examinations confirmed these results. In conclusion, CLE and/or ALE demonstrated nephroprotection against CCl4 /Rad co-toxicity mediated by down-regulation of renal Wnt/ß-catenin protein expressions.

Artichoke for biochemistry, histology, and gene expression in obstructive jaundice.

OBJECTIVE: This study aimed to evaluate the hepatoprotective effect of artichoke leaf extract (Cynara scolymus) in experimental obstructive jaundice. METHODS: Rats were separated into three groups, namely, sham, control, and artichoke leaf extract. Ischemia was created for 60 min, and then liver tissue and blood samples were taken at the 90th minute of reperfusion. Artichoke leaf extract was given at a 300 mg/kg dose 2 h before the operation. Antioxidant enzyme activities and biochemical parameters were examined from the tissue and serum. Histopathological findings of the liver were scored semiquantitatively. RESULTS: Antioxidant enzyme activities in the artichoke leaf extract group were statistically significantly higher than that in the other two groups. Biochemical parameters, which show hepatocellular damage, were found to be similar in both sham and artichoke leaf extract groups. Although the values in the sham group were higher than the artichoke group in terms of protein and gene expressions, no statistically significant difference was found between these two groups. Regarding the hepatocellular effects of obstructive jaundice, the artichoke leaf extract group showed lower scores than the control group in all histopathological scores. CONCLUSION: The results of this study showed that artichoke leaf extract had a hepatoprotective effect that was associated with the antioxidant and anti-inflammatory effects of artichoke leaf extract.

Effect of Artichoke (cynara scolymus) on cardiac markers, lipid profile and antioxidants levels in tissue of HFD-induced obesity.

Obesity plays a pivotal role in the insulin resistance disease, which is related to hypertension, hyperlipidemia, type 2 diabetes mellitus, and an increased risk of cardiovascular disease. The purpose of the present study was done to evaluate the effect of artichoke leaves extract (ALE) in the high-fat diet (HFD)-induced cellular obesity and cardiac damage in Wistar rats. Body and organ weights, serum lipid profile, cardiac markers, and antioxidants enzymes were measured. Oral administration of ALE at two doses 200 and 400 mg/kg for a period of 60 days showed a significant decrease in body and organ weights, serum total cholesterol, triglycerides, LDH, ALT accompanied by decreasing in oxidative stress biomarker (MDA, and AOPP) and increasing antioxidant enzymes (SOD, CAT, and GPx) levels as compared to HFD groups. The histological findings showed a cardioprotective effect of ALE. These findings suggest that ALE exert anti-oxidant cardiac effects in HFD- induced obese rats.

Preventive effect of Artichoke (Cynara scolymus L.) in kidney dysfunction against high fat-diet induced obesity in rats.

A high-fat diet (HFD) promotes oxidative stress, which contributes to the development of kidney dysfunction. We examined the protective effects of an ethanol extract of artichoke leaves (EEA) compared to Atorvastatin (ATOR) in the kidney of Wistar rats fed a high-fat diet. The experimental animals were divided into five groups: control (Cont), HFD, HFD treated with EEA (200 mg/kg), HFD treated with EEA (400 mg/kg), and HFD treated with ATOR. Organ weights, lipid profile, renal markers, and antioxidants enzymes were measured. Oral administration of EEA (200 and 400 mg/kg) for 60 days showed a significant decrease in organ weights and kidney markers levels accompanied by decreasing in oxidative stress biomarkers as compared to HFD groups. The histological findings showed a renoprotective effect of artichoke extract. These findings suggest that EEA exerts anti-oxidant kidney effects in HFD- induced obese rats.

Artichoke extracts with potential application in chemoprevention and inflammatory processes

Abstract The aim of this work is to study three cultivars of artichoke (Cynara cardunculus var. scolymus): Gauchito, Guri and Oro Verde in terms of their in vitro chemoprevention and anti-inflammatory properties. These cultivars show good productive performance. The phenolic composition of their fresh leaves and edible bracts was analyzed by high performance liquid chromatography and high resolution mass spectrometry (HPLC-HRMS), showing mainly caffeoylquinic acids and flavonoids. Caffeoylquinic acids were quantified and the highest content was found in Gauchito cultivar. In this cultivar, the content of dicaffeoylquinic acids in fresh bracts was six times higher than that in fresh leaves (10064.5 ± 378.3 mg/kg versus 1451.0 ± 209.3 mg/kg respectively). Luteolin flavonoids were detected in leaves. The extracts from fresh bracts and leaves were assessed in their in vitro bioactivity against human neuroblastoma cells (SH-SY5Y). Inhibition of SH-SY5Y cells proliferation by Gauchito and Guri leaf extracts (8 µg/mL) was higher than 50 %. The leaf extracts of the same cultivars showed an inhibitory effect on human interferon IFN-I, decreasing its activity 50% at 40 µg/mL. Interestingly, the bract extracts did not show in vitro bioactivity at these concentrations, nor did the pure compounds chlorogenic acid, cynarin, apigenin and luteolin (at 2 µg/mL). These results suggest that Gauchito and Guri leaf extracts have potential for human neuroblastoma chemoprevention and treatment of inflammatory processes.

Efficacy of an herbal compound in decreasing steatosis and transaminase activities in non-alcoholic fatty liver disease: A randomized clinical trial

Abstract Hepatoprotective effects of many herbal agents have been reported in animal studies and clinical trials. In this study, five hepatoprotective plants with potent antioxidant, anti-inflammatory, and hypolipidemic effects were chosen to prepare a polyherbal compound for managing NAFLD. Sixty patients with NAFLD were randomly divided into treatment and control groups (2:1 ratio). Both group were advised to take healthy diet and exercise. The treatment group also received herbal capsules containing 400 mg of the mixture of Anethum graveolens, Citrus aurantium, Cynara scolymus, Portulaca oleracea, and Silybum marianum (2 capsules, thrice daily, for two months). The liver ultrasound and biochemical markers including the serum lipids, liver enzymes, and glucose were evaluated before starting the study and at the end of the treatment. Thirty patients in the treatment group and sixteen patients in the control group completed the study. The herbal compound significantly decreased the serum level of alanine transaminase (ALT), aspartate transaminase (AST), and total cholesterol. Treatment with the herbal compound significantly improved the grade of the fatty liver, but no significant change was found in the control group. In conclusion, the formulated herbal compound appeared to be effective in biochemical improvement and decreasing the grade of the fatty liver in the patients with NAFLD.

Characterization Of Secondary Metabolites From The Rhizome Of Cynara Scolymus And Their Antioxidant Properties.

The aerial portions of Cynara scolymus commonly have been eaten as vegetables or functional foods by the people lived in Mediterranean region. In preliminary antioxidant screening, the rhizome portions (CSR) of this species showed better potential than leaves ones. However, neither phytochemical nor pharmacology studies of CSR have been reported to date. The purpose of this research was to identify the active components from CSR through bioassay-guided fractionation. The antioxidant properties of secondary metabolites 1-9 were evaluated in this investigation. Compounds 4-6, 8, and 9 showed antioxidant activities based on DPPH free radical scavenging activity with IC50 values of 22.91-147.21 µM. Besides, compound 8 significantly and dose-dependently reduced H2O2-induced ROS levels in keratinocyte HaCaT cells without cytotoxicity toward HaCaT. Overall, our studies demonstrated the rhizome of C. scolymus could be used as a new natural antioxidant like the edible aerial portions and phenolic compounds are the active components.

Phytochemical analysis and in vitro and in vivo evaluation of biological activities of artichoke (Cynara scolymus L.) floral stems: Towards the valorization of food by-products.

Artichoke floral stems (AFS) food waste by-products were examined for their phytochemical constituents and their in vitro and in vivo biological activities. Although that the highest total phenol content and total flavonoid content were found in ethyl acetate extract, methanol extract possessed the strongest DPPH and ABTS radical scavenging activity, and showed the highest reducing ferric antioxidant power (FRAP). The anti-acetylcholinesterase activity was higher in butanol extract, whereas the ethyl acetate extract had the highest inhibitory effect on heat-induced protein denaturation. In alloxan-induced diabetic mice, the AFS methanol extract (AFSE) rich in caffeoylquinic acids and flavones reduced blood glucose, alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase, creatinine, and improved liver, and renal antioxidative status. Administration of AFSE to diabetic mice reduced total cholesterol, triglycerides, LDL-cholesterol, and the atherogenic index of plasma (AIP) suggesting its hypolipidemic action. Overall, AFS could be considered as attractive source of health-promoting ingredients.

Physiochemical, kinetic and thermodynamic studies on Aspergillus wewitschiae MN056175 inulinase with extraction of prebiotic and antioxidant Cynara scolymus leaves fructo-oligosaccharides.

Utilization of agricultural wastes as cheap natural resources for production of bioactive products is currently attracting global attention. For this purpose, this study focused on isolation of Aspergillus wewitschiae MN056175 as promising producer of inulinase, then investigating physiochemical, kinetics and thermodynamics of the obtained inulinase, and its ability to extract bioactive fructo-oligosaccharides (FOS) from Cynara scolymus leaves (artichoke leaves, AL). A. wewitschiae MN056175 inulinase gave the maximum activity at temperature 60 °C and inulin concentration 1%. The kinetics including Km and Vmax were determined to be 105.26 mg·ml-1 and 83.33 µmol·ml-1·min-1, respectively. The thermodynamics including, Ea (activation energy) and Ed (activation energy for denaturation) were determined to be 21.82 and 73.21 kJ·mol-1, Kd, T1/2, D-value, ΔH°, ΔG° and ΔS° at 40, 50 and 60 °C which indicated the stability of A. wewitschiae MN056175 inulinase. Moreover, this inulinase was capable of hydrolyzing Cynara scolymus leaves into reducing sugar and 15 FOS with different DP, total carbohydrate, and protein content under different conditions designed by central composite design (CCD). The 15 AL FOS showed different high antioxidant and prebiotic activities. Central FOS with probiotic bacteria exhibited significant antimicrobial activity against tested gram positive bacteria in a way higher than those recorded against gram negative bacteria.

Assessment of cytotoxicity and immune compatibility of phytochemicals-mediated biosynthesised silver nanoparticles using Cynara scolymus.

The study was focused on the phytochemicals-mediated biosynthesis of silver nanoparticles using leaf extracts and infusions from Cynara scolymus. To identify the antioxidant activity and total phenolic content, the 1,1-diphenyl-1-picrylhydrazyl and Folin-Ciocalteau methods were applied, respectively. The formation and stability of the reduced silver ions were monitored by UV-vis spectrophotometer. The particle sizes of the silver nanoparticles were characterised using the dynamic light scattering technique and scanning electron microscope. The phase composition of the obtained silver nanoparticles was characterised by X-ray diffraction. The silver nanoparticles suspension, artichoke infusion, and silver ions were separately tested towards potential cytotoxicity and pro-inflammatory effect using mouse fibroblasts and human monocytes cell line, respectively. The total phenolic content and antioxidant activity of ethanol extract and infusion were found significantly higher as compared to aqueous extract and infusion. The UV-visible spectrophotometric analysis revealed the presence of the characteristic absorption band of the Ag nanoparticles. Moreover, it was found that with the increasing volume of plant extract, the average size of particles was increased. Biocompatibility results evidently showed that silver nanoparticles do not induce monocyte activation, however in order to avoid their cytotoxicity suspension at a concentration <2 ppm should be applied.

Metabolome based classification of artichoke leaf: A prospect for phyto-equivalency of its different leaf origins and commercial preparations.

The growing interest in assuring phytomedicines efficacy and moreover the increase in requirements for its safety drive the development of analytical methods for its quality control assurance. Herein, we present a nuclear magnetic resonance (NMR) fingerprinting approach of artichoke leaf material from different origins and in its commercial preparations. Under optimized conditions, we were able to simultaneously identify 23 metabolites including sugars, amino and organic acids, sesquiterpene lactones, flavones, cinnamates, inulin, fatty acids and nitrogenous bases. Principal component analysis (PCA) was used to reveal for differences among artichoke specimens. PCA score plot derived from the aromatic region (5-10 ppm) provided better classification model than that of full scan (0-10 ppm), and revealing for enrichment of wild Egyptian and Tanzanian artichoke in sesquiterpene viz. aguerin B versus O-caffeoylquinic acid and luteolin abundance in cultivated leaf. PCA analysis of 3 commercial artichoke preparations showed discrimination of a silymarin-containing capsule suggesting that NMR can distinguish liver-aid herbal preparations based on its different chemical composition. Quantitative 1H NMR (qHNMR) was further employed to assess major metabolites levels and revealing for the enrichment of cultivated plants in cinnamates viz. (E)-cinnamaldehyde (1.1 mg/g) and O-caffeoyl quinic acid (15.09 mg/g,). To the best of our knowledge, this study provides the first approach utilizing NMR fingerprinting to assess for phytoequivalency among artichoke leaf and in its preparations.

Synergistic Hepatoprotective and Antioxidant Effect of Artichoke, Fig, Blackberry Herbal Mixture on HepG2 Cells and Their Metabolic Profiling Using NMR Coupled with Chemometrics.

The edible plants have long been reported to possess a lot of biological activities. Herein, the hepatoprotective and the antioxidant activities of the aqueous infusion of the edible parts of Cynara cardunculus, Ficus carica, and Morus nigra and their herbal mixture (CFM) was investigated in vitro using CCl4 induced damage in HepG2 cells. The highest amelioration was observed via the consumption of CFM at 1 mg/ml showing 47.00% and 37.09% decline in aspartate transaminase and alanine transaminase and 77.32% and 101.02% increase in reduced glutathione and superoxide dismutase comparable to CCl4 treated cells. Metabolic profiling of their aqueous infusions was done using nuclear magnetic resonance spectroscopic experiments coupled with chemometrics particularly hierarchical cluster analysis (HCA) and principal component analysis (PCA). The structural closeness of the various metabolites existing in black berry and the mixture as reflected in the PCA score plot and HCA processed from the 1 H-NMR spectral data could eventually explained the close values in their biological behavior. For fig and artichoke, the existence of different phenolic metabolites that act synergistically could greatly interpret their potent biological behavior. Thus, it can be concluded that a herbal mixture composed of black berry, artichoke, and fig could afford an excellent natural candidate to combat oxidative stress and counteract hepatic toxins owing to its phenolic compounds.

Long Term Exposure to Polyphenols of Artichoke (Cynara scolymus L.) Exerts Induction of Senescence Driven Growth Arrest in the MDA-MB231 Human Breast Cancer Cell Line.

Polyphenolic extracts from the edible part of artichoke (Cynara scolymus L.) have been shown to be potential chemopreventive and anticancer dietary compounds. High doses of polyphenolic extracts (AEs) induce apoptosis and decrease the invasive potential of the human breast cancer cell line, MDA-MB231. However, the molecular mechanism underlying AEs antiproliferative effects is not completely understood. We demonstrate that chronic and low doses of AEs treatment at sublethal concentrations suppress human breast cancer cell growth via a caspases-independent mechanism. Furthermore, AEs exposure induces a significant increase of senescence-associated ß-galactosidase (SA-ß-gal) staining and upregulation of tumour suppressor genes, p16(INK4a) and p21(Cip1/Waf1) in MDA-MB231 cells. AEs treatment leads to epigenetic alterations in cancer cells, modulating DNA hypomethylation and lysine acetylation levels in total proteins. Cell growth arrest correlates with increased reactive oxygen species (ROS) production in AEs treated breast cancer cells. Inhibition of ROS generation by N-acetylcysteine (NAC) attenuates the antiproliferative effect. These findings demonstrate that chronic AEs treatment inhibits breast cancer cell growth via the induction of premature senescence through epigenetic and ROS-mediated mechanisms. Our results suggest that artichoke polyphenols could be a promising dietary tool either in cancer chemoprevention or/and in cancer treatment as a nonconventional, adjuvant therapy.

An integrated approach to the evaluation of a metabolomic fingerprint for a phytocomplex. Focus on artichoke [Cynara cardunculus subsp. scolymus] leaf.

The availability of reliable herbal formulations is essential in order to assure the maximal activity and to limit unwanted side-effects. The correct concentration of declared components of herbal products is a matter of health legislation and regulation, but is still a topic under debate in the field of quality control assessment. In the present work specific constituents of artichoke leaf extracts, considered as a test herbal product, were measured by standard spectrophotometric and HPLC methods (for quantitative determination of some components only), and results were correlated with the ESI-MS (showing the full metabolomic fingerprint). Phytocomplex stability over time was also investigated in batches submitted to different storage conditions. The results indicated excellent agreement between the two approaches in the measurement of total caffeoylquinic acids and chlorogenic acid contents, but the metabolomic ESI-MS method approach provides a more complete evaluation and monitoring of the composition of a herbal product, without focusing only on a single/few compound measurements. Therefore, the ESI-MS method can be proposed for the evaluation of the quality of complex matrices, such as those in a phytocomplex. Another aspect lies in the possibility to obtain a broad-spectrum stability control of herbal formulations, requiring minimal sample pre-processing procedures.

Salinity source-induced changes in yield, mineral composition, phenolic acids and flavonoids in leaves of artichoke and cardoon grown in floating system.

BACKGROUND: Leaves of artichoke (Cynara cardunculus L. subsp. scolymus (L.) Hegi) and cardoon (Cynara cardunculus L. var. altilis DC) are traditionally used as herbal medicine. Moderate salt stress could enhance antioxidant activity and phytochemicals in leaves. The aim of this study was to evaluate the effect of chloride salts (NaCl, KCl and CaCl2) on biomass production, mineral composition, phenolic and flavonoid contents and antioxidant activity in leaves of artichoke and cardoon grown in a floating system. RESULTS: In both crops, NaCl and KCl treatments reduced biomass production, while similar values were recorded in CaCl2 and control treatments. In both crops, KCl treatment enhanced total phenolic and flavonoid contents, antioxidant activity and target polyphenols in leaves harvested at 48, 82 and 105 days after sowing (DAS), while leaf quality was improved by NaCl and CaCl2 treatments only at 82 and 105 DAS. Irrespective of salinity, leaves of cardoon had higher total phenolic and flavonoid contents, antioxidant activity and target polyphenols than those of artichoke. CONCLUSION: The results showed that application of KCl can be considered an effective way to produce high-quality leaves of artichoke and cardoon during the whole cropping cycle, although resulting in a 30% reduction in plant biomass.

Production of novel antioxidative phenolic amides through heterologous expression of the plant's chlorogenic acid biosynthesis genes in yeast.

Phenolic esters like chlorogenic acid play an important role in therapeutic properties of many plant extracts. We aimed to produce phenolic esters in baker's yeast, by expressing tobacco 4CL and globe artichoke HCT. Indeed yeast produced phenolic esters. However, the primary product was identified as N-(E)-p-coumaroyl-3-hydroxyanthranilic acid by NMR. This compound is an amide condensation product of p-coumaric acid, which was supplied to the yeast, with 3-hydroxyanthranilic acid, which was unexpectedly recruited from the yeast metabolism by the HCT enzyme. N-(E)-p-coumaroyl-3-hydroxyanthranilic acid has not been described before, and it shows structural similarity to avenanthramides, a group of inflammation-inhibiting compounds present in oat. When applied to mouse fibroblasts, N-(E)-p-coumaroyl-3-hydroxyanthranilic acid induced a reduction of intracellular reactive oxygen species, indicating a potential therapeutic value for this novel compound.

Heavy metal contents in horticultural crops of a representative area of the European Mediterranean region.

Heavy metal content (Cd, Co, Cr, Cu, Fe, Mn, Ni, Pb and Zn) was analysed in the edible parts of two types of horticultural crops (leaf and inflorescence crops) from 30 agricultural fields in Castellón (Spain), a representative area of the European Mediterranean region. Selected soil properties relevant to control the mobility and bioavaibility of heavy metals were analysed for the general characterisation of these agricultural soils. The levels of clay, high percentages of organic matter and the presence of carbonate seem to suggest an important retention of heavy metals by these components in most of these soils. However, the high salinity in some fields (>4 dS/m) seems to facilitate the mobility of some heavy metals (e.g. Cu). The mean values of total contents of heavy metals in soils were similar to values obtained in other works on Spanish agricultural soils. However, there were some fields with a metal content (particularly Cu, Pb or Zn) higher than these works, reflecting an important anthropogenic source. In seven fields, the crop contents of Cd and/or Pb were higher than the maximum levels established by the Commission Regulation no. 466/2001 for horticultural crops. Heavy metal contents in leaf crops were higher than in inflorescence crops, except for Zn. The differences for Cd, Cr, Cu, Fe and Mn contents between these two types of crops were statistically significant. The analysis of crop heavy metal contents showed a higher absorption and/or accumulation of heavy metals in leaf crops than in inflorescence crops. Differences in crop characteristics seem to be responsible for the differential accumulation of heavy metals. Furthermore, agronomic practices and other sources of heavy metals (e.g. atmospheric deposition for Cd and Pb) may also have some influence on crop accumulation. Given the relevance of horticultural crops in the Mediterranean diet, it is highly necessary to extend the experience of this work to other areas of the European Mediterranean region.

Characterization and quantification of anthocyanins in selected artichoke (Cynara scolymus L.) cultivars by HPLC-DAD-ESI-MSn.

The anthocyanin pattern of artichoke heads (Cynara scolymus L.) has been investigated by high-performance liquid chromatography-electrospray ionization mass spectrometry. For this purpose a suitable extraction and liquid chromatographic method was developed. Besides the main anthocyanins-cyanidin 3,5-diglucoside, cyanidin 3-glucoside, cyanidin 3,5-malonyldiglucoside, cyanidin 3-(3''-malonyl)glucoside, and cyanidin 3-(6''-malonyl)glucoside-several minor compounds were identified. Among these, two peonidin derivatives and one delphinidin derivative were characterized on the basis of their fragmentation patterns. To the best of our knowledge this is the first report on anthocyanins in artichoke heads consisting of aglycones other than those of cyanidin. Quantification of individual compounds was performed by external calibration. Cyanidin 3-(6''-malonyl)glucoside was found to be the major anthocyanin in all the samples analyzed. Total anthocyanin content ranged from 8.4 to 1,705.4 mg kg(-1) dry mass.