Reducción de las enfermedades cardiovasculares e hipercolesterolemia por mezclas de extractos de plantas comestibles: un estudio del perfil lipídico, estrés oxidativo y testosterona en ratas

The present study was postulated to prepare and evaluate the influence of two plant food extract mixtures on plasma lipid profile, oxidative stress and testosterone levels in rats fed a hypercholesterolemic diet. The safety of the studied extract mixtures was evaluated through the determination of liver and kidney functions. The total phenolic contents, tocopherols, fatty acids and unsaponifiable matter (UNSAP) in the extract mixtures were determined. Rats fed a hypercholesterolemic diet were given a daily oral dose (300 mg/kg rat body weight) of either mixture I or II for a month and compared with a control hypercholesterolemic group and a normal control group. Results showed that α-tocopherol was 0.750 and 4.017 mg, γ-tocopherol was 0.564 mg and 0 and δ-tocopherol was 15.23mg and 0.634mg/100g for mixtures I and II, respectively. The phenolic contents in mixtures I and II were 36.74 and 23.72 g gallic acid equivalent/100g mixture, respectively. The GLC investigation of UNSAP revealed that stigmasterol and b-sitosterol were the major phytosterols in mixtures I and II, respectively followed by campesterol in both. The GLC analysis of the fatty acids showed that oleic acid was the major fatty acid in both extract mixtures. Results from the animal experiment showed that feeding a hypercholesterolemic diet produced a significant increase in total lipids, total cholesterol (T-Ch), triglycerides (TGs), low density lipoprotein cholesterol (LDLCh), T-Ch/HDL-Ch, TGs/HDL-Ch and malondialdehyde (MDA) and a significant reduction in high density lipoprotein cholesterol (HDL-Ch), vitamin E, b-carotene and testosterone. Rats fed a hypercholesterolemic diet and given mixture I or II showed significant improvements in plasma lipid profile compared to the hypercholesterolemic control group. This improvement was associated with a significant reduction in oxidative stress reflected by an elevation in plasma levels of antioxidants (vitamin E and b-carotene) and a reduction in plasma MDA levels. The plasma level of testosterone increased significantly in the rats fed the hypercholesterolemic diet and given mixture I or II compared to the hypercholesterolemic control. Plasma testosterone showed a significant negative correlation with plasma TGs and TGs/HDL-Ch in the hypercholesterolemic control rats. The studied extract mixtures showed complete safety towards liver and kidney functions. In conclusion the tested extract mixtures showed an improvement in the plasma lipid profile, a significant increase in testosterone and a decrease in oxidative stress with promising prevention of atherosclerosis and cardiovascular diseases. The antiatherogenic effect of the extract mixtures may be due to the presence of phenolic compounds, phytosterols, tocopherols and unsaturated fatty acids.El presente estudio fue dirigido a preparar y evaluar la influencia de dos mezclas de extractos de plantas comestibles sobre el perfil lipídico del plasma, estrés oxidativo y nivel de testosterona en ratas alimentadas con una dieta hipercolesterolemica. La salubridad de las mezclas de extractos estudiadas fue evaluada mediante la determinación de las funciones del hígado y del riñón. El contenido total de fenoles, tocoferoles, ácidos grasos, y materia insaponificable (UNSAP) fueron determinado en la mezclas de extractos. Las ratas fueron alimentadas con dietas hipercolesterolémica junto con una dosis oral diaria de (300 mg/kg de peso) cada mezcla I y II durante un mes y comparada con un control hipercolesterolémico y un control normal. Los resultados muestran que el contenido de α-tocopherol fue 0.750 y 4.017 mg, γ-tocopherol fue 0.564 mg y 0 y δ-tocopherol fue 15.23mg y 0.634mg/100g de mezcla I y II, respectivamente. El contenido de fenoles en las mezcla I and II fue 36.74 y 23.72 g equivalentes de ácido gálico/100g de mezcla, respectivamente. La investigación por GLC de UNSAP reveló que el estigmasterol y el b-sitosterol fueron los principales fitoesteroles de las mezclas I y II, respectivamente seguido por el campesterol en ambos casos. El análisis por GLC de los ácidos grasos mostró que el ácido oleico fue el ácido graso mayoritario en ambas mezclas de extractos. Los resultados con animales de experimentación mostraron que la alimentación con dietas hipercolesterolémicas produce un incremento significativo en los lípidos totales, colesterol total (T-Ch), triglicéridos (TGs), colesterol en lipoproteínas de baja densidad (LDL-Ch), en las relaciones T-Ch/ HDL-Ch y TGs/HDL-Ch y malondialdehido (MDA) y una significativa reducción en el colesterol de las lipoproteínas de alta densidad (HDL-Ch), vitamina E, b-caroteno and testosterona. Las ratas alimentadas con dietas hipercolesterolémicas junto con mezclas I y II mostraron una mejora significativa del perfil lipídico del plasma comparado con el grupo control hypercholesterolémico. Esta mejora estuvo asociada con una significativa reducción del estrés oxidativo reflejado por la elevación de los niveles de antioxidantes en el plasma (vitamin E y bcarotene) y reducción de los niveles de MDA en plasma. Los niveles de testosterona en plasma aumentaron significativamente en ratas alimentadas con dietas hipercolesterolémicas junto con mezclas I y II en comparación con el control hipercolesterolémico. La testosterona del plasma mostró una correlación negativa significativa con los TGs y TGs/HDL-Ch en ratas control hipercolesterolémicas. Las mezclas de los extractos estudiados mostraron una completa salubridad hacia las funciones del hígado y el riñón. En conclusión las mezclas mostraron una mejora del perfil lipídico del plasma, un significativo incremento en la testosterona, y un descenso del estrés oxidativo con una prometedora prevención de las enfermedades cardiovasculares y ateroesclerosis. El efecto anti-aterogénico de las mezclas de los extractos puede ser debida a la presencia de compuestos fenólicos, fitoesteroles, tocoferoles y ácidos grasos insaturados

Immunohistochemical analysis of tumor-infiltrating lymphocytes in breast carcinoma: Relation to prognostic variables

Background: The role of the tumor-infiltrating lymphocytes in invasive breast cancer and its correlation with different prognostic variables were always a matter of controversy in the literature. Aim: To determine the relative density of T lymphocytes, CD4+ cells, CD8+ cells, and B lymphocytes in breast cancer and assess their relationships with clinicopathologic parameters. Materials and Methods: Paraffin-embedded tissue sections from 48 invasive ductal carcinomas and 30 benign breast lesions were examined by means of immunohistochemistry to demonstrate CD3+, CD4+, CD8+, and CD20+. The immunophenotyped cells were semi-quantitatively graded into: Absent, intermediate, and extensive. Results: All lymphocyte populations were significantly more expressed in breast carcinomas than in benign lesions (P = 0.0001 for CD3+ and CD4+, P = 0.001 for CD8+, and P = 0.002 for CD20+ cells). In breast carcinoma, B and T cells were co-expressed in 33 of 48 tumors (68.8%). However, T cells were the predominant immunophenotype being noted in 81% of tumors, compared to B cells which were expressed in 50% of tumors. T cells, CD4+ and CD8+ cells were directly associated with patient′s age (P = 0.004, P = 0.001, and P = 0.01, respectively). Clinical stages III and IV showed a significantly higher density of T and CD4+ lymphocytes than stage II (P = 0.004 and P = 0.009, respectively). Also, T and CD4+ cells were directly related to the histologic grade (P = 0.004 and P = 0.001, respectively). On the contrary, B lymphocytes were not related to any of the above-mentioned parameters. Conclusion: Although B and T lymphocytes were co-expressed in breast cancer, T lymphocytes and their subpopulations seem to have the upper hand in predicting the biological behavior. They probably promote neoplastic progression rather than acting as an antitumor immune response

Rice bran as source of nutraceuticals for management of cardiovascular diseases, cardio-renal syndrome and hepatic cancer

Introduction: The interrelation between cardiovascular diseases (CVDs) and renal dysfunction and the beneficial role of nutraceuticals are worthy to be studied. Nutraceuticals with anticancer effects are gaining great importance. The aim of this research was studying the anti-cancer, CVDs prevention and renal dysfunction properties of γ-oryzanol (γ-O) and rice bran oil/γ-O mixture (RBO/γ-O) as nutraceuticals. Methods: Rats were divided into 7 groups. Group 1 was fed on balanced diet and served as normal control (NC). Group 2 consumed high-fat-sucrose diet (HFSD) as CVD control. Groups 3 and 4 were fed on HFSD and treated by γ-O and RBO/γ-O, respectively. Group 5 was maintained on HFSD with cisplatin injection (cardiorenal syndrome control) (CRSC). Groups 6 and 7 were treated like group 5 and given either γ-O or RBO/γ-O. Plasma lipid profile, malondialdehyde (MDA), tumor necrosis factor-α (TNF-α), catalase activity, creatinine and urea were determined besides urinary creatinine clearance. Nutraceuticals’ anticancer effect was assessed in hepatocellular carcinoma cell (HepG2) line. Results: Significant increases (P < 0.05) in lipid parameters with reduction of high-density lipoprotein cholesterol (HDL-C) were noticed in CVD control compared to NC group; the same changes were demonstrated in CRSC with lesser extent. In CVD control and CRSC groups; a significant increase (P < 0.05) in MDA and TNF-α with a reduction in catalase were noticed. Kidney dysfunction was demonstrated in the CRSC group. Administration of both RBO/γ-O and γ-O produced variable improvements in all parameters in both models and had anticancer effects. Conclusion: RBO/ γ-O and γ-O had protective effects on CVDs and cardiorenal syndrome as well as anti-hepatocellular carcinoma activities with superiority of RBO/γ-O

Prevention of renal dysfunction by nutraceuticals prepared from oil rich plant foods

Objective: To investigate the protective effect of extracts prepared from avocado, walnut, flaxseed and Eruca sativa seeds in a rat model of kidney dysfunction induced by intraperitoneal cisplatin. Methods: Ethanol and petroleum ether extracts mixture was prepared from each plant. Six groups of rats were conducted; control healthy, cisplatin group and four test groups where rats were given daily oral dose of each extract mixture before cisplatin injection. Different biochemical and cytogenetic parameters and kidney histopathology were determined. Acute toxicity was tested for the nutraceuticals. Total phenolic contents, fatty acids (FA) and unsaponifiable matter were assessed in the extracts. Results: Walnut ethanol extract showed the highest content of total phenolic. FA analysis revealed that all the studied plants were rich in unsaturated FA. Gas-liquid chromatographic investigation of the unsaponifiable matter showed the presence of campesterol, stigmasterol and β-sitosterol in all the studied plants. Cisplatin treatment induced significant increase in plasma urea, creatinine and malondialdehyde along with significant reduction of plasma albumin, total protein, catalase and total antioxidant as well as reduction in creatinine clearance. Histopathological examination proved the induction of kidney dysfunction. Some sorts of chromosomal aberration and sperm-shape abnormalities were noticed after cisplatin treatment. Administration of extracts mixtures produced improvements in biochemical, histopathological and cytogenetic parameters. Conclusions: Administration of the studied nutraceuticals proved to possess protective role against cisplatin-induced nephrotoxicity, chromosomal aberration and abnormal sperms. All studied nutraceuticals showed complete safety

Protective Role of Nigella sativa Seed Meal and Its Alcohol Extract in Hepatorenal Syndrome Model in Rats

ABSTRACT Hepatorenal syndrome (HRS) is a major health problem where the functions of both liver and kidney are affected. The aim of the present research was to evaluate the protective effect of Nigella sativa meal and its ethanol extract in hepatorenal syndrome model in rats. Proximate composition and amino acid contents of Nigella sativa meal were analyzed. Total phenolic contents and phenolic compounds were determined in the ethanol extract. HRS was induced in rats via intraperitoneal injection of galactosamine. Three weeks prior to HRS induction, one group of rats was given daily oral dose of Nigella sativa meal alcohol extract, another group was fed on diet containing Nigella sativa meal, the third group served as control with HRS. A control normal group was run without any treatments. Different biochemical and nutritional parameters were followed. Gene expression of Interlukin 6 (IL-6) in both liver and kidney was determined. Safety of ethanol extract was assessed through acute toxicity test. Results showed that Nigella sativa meal contain 27.1% protein and a Fischer ratio of 3.303. Total phenolic content was 42.64 ± 0.929 mg gallic acid equivalent/g dry ethanol extract, identified phenolic compounds were protochatechuic, chlorogenic, vanillic, sinapic, coumaric and cinnamic acid and chrysin. HRS control group showed liver and kidney dysfunction reflected in the elevated plasma creatinine, urea, transaminases activity, total and direct bilirubin and endothelin 1 and urinary N-acetyl-β-DGlucosaminidase together with reduction in plasma albumin and creatinine clearance. Treatment with either forms of Nigella sativa significantly improved all determined parameters except for creatinine and creatinine clearance. Reduction in hemoglobin, plasma total antioxidant capacity and calcium along with elevation of plasma malondialdehyde and tumor necrosis factor-α were noticed in HRS control. All these parameters were significantly improved on treatment with Nigella sativa meals and extract except for calcium in case of the extract. Total cholesterol and high density lipoprotein cholesterol showed dyslipidemia in HRS control which were significantly ameliorated on consumption of Nigella sativa meals and extract. Liver and kidney Interlukin 6 gene expression was significantly enhanced in HRS control and significantly down regulated on treatment with Nigella sativa meals and extract. Ethanol extract showed complete safety on the highest tested dose

Photo-transfer of tl grade natural calcium fluoride by induced ultra- violet irradiation 46

ABSTRACT Natural CaF2 shows four main glow peaks. The third one (P3) at 453K is considered as the dosimetry peak. By deconvolution (CGCD) technique this peak could be analysed into 3 simple overlapping peaks at 440, 455 and 482K. The kinetic parameters of these peaks have been calculated, like its activation energy (E), frequency factor (s), mean life time (τ) and the resonance escape probability (P). The chemical composition of CaF2 has been analysed specially the major elements as well as the trace elements. The photo-transfer phenomenon has been studied in some details. This transfer due to P3 with UV exposure increase with increasing time till 120 seconds then shows saturation. The rate of photo-transfer is increased by increasing the pre-gamma exposure. From the experimental results and theoretical calculations, it could be evaluated that the first part of P3 will be decayed after 5.05 years while the last part of the same peak could be disappear after 88.73 years when the irradiated TL material is stored at 25 o C

New insights into the anticancer effects of Polycladia crinita aqueous extract and its selenium nanoformulation against the solid Ehrlich carcinoma model in mice via VEGF, notch 1, NF-кB, cyclin D1, and caspase 3 signaling pathway

Background: Phaeophyceae species are enticing interest among researchers working in the nanotechnology discipline, because of their diverse biological activities such as anti-inflammatory, antioxidant, anti-microbial, and anti-tumor. In the present study, the anti-cancer properties of Polycladia crinita extract and green synthesized Polycladia crinita selenium nanoparticles (PCSeNPs) against breast cancer cell line (MDA-MB-231) and solid Ehrlich carcinoma (SEC) were investigated.Methods: Gas chromatography–mass spectroscopy examinations of Polycladia crinita were determined and various analytical procedures, such as SEM, TEM, EDX, and XRD, were employed to characterize the biosynthesized PCSeNPs. In vitro, the anticancer activity of free Polycladia crinita and PCSeNPs was evaluated using the viability assay against MDA-MB-231, and also cell cycle analysis by flow cytometry was determined. Furthermore, to study the possible mechanisms behind the in vivo anti-tumor action, mice bearing SEC were randomly allocated into six equal groups (n = 6). Group 1: Tumor control group, group 2: free SeNPs, group 3: 25 mg/kg Polycladia crinita, group 4: 50 mg/kg Polycladia crinita, group 5: 25 mg/kg PCSeNPs, group 6: 50 mg/kg PCSeNPs.Results: Gas chromatography–mass spectroscopy examinations of Polycladia crinita extract exposed the presence of many bioactive compounds, such as 4-Octadecenoic acid-methyl ester, Tetradecanoic acid, and n-Hexadecenoic acid. These compounds together with other compounds found, might work in concert to encourage the development of anti-tumor activities. Polycladia crinita extract and PCSeNPs were shown to inhibit cancer cell viability and early cell cycle arrest. Concentrations of 50 mg/kg of PCSeNPs showed suppression of COX-2, NF-кB, VEGF, ki-67, Notch 1, and Bcl-2 protein levels. Otherwise, showed amplification of the caspase 3, BAX, and P53 protein levels. Moreover, gene expression of caspase 3, caspase 9, Notch 1, cyclin D1, NF-кB, IL-6, and VEGF was significantly more effective with PCSeNPs than similar doses of free extract.Conclusion: The PCSeNPs mediated their promising anti-cancerous action by enhancing apoptosis and mitigating inflammation, which manifested in promoting the total survival rate and the tumor volume decrease

Anti-inflammatory potential of Penicillium brefeldianum endophytic fungus supported with phytochemical profiling

Abstract Various factors contribute to the development of the acute inflammation process, like the pro-inflammatory cytokines, certain enzymes as well as oxidative stress mediators. The anti-inflammatory potential of the endophytic fungus Penicillium brefeldianum was explored in carrageenan-induced inflammation in rats. After isolation of the fungus from Acalypha hispida leaves, it was identified by 18S rRNA gene sequencing. Then, its phytochemical profile was elucidated using LC–ESI–MS/MS technique. There was a remarkable decrease in the edema weight in the endophytic fungi-treated group (200 mg/kg). Also, this group had few inflammatory cells and thickened epidermis with underlying moderate collagenosis when stained with haematoxylin and eosin. Besides, immunostaining with monoclonal antibodies of cyclooxygenase-2 and tumor necrosis factor alpha showed a decrease in the positive immune cells in the endophytic fungi treated group (200 mg/kg) in relation to the positive control. Interestingly, the levels of the inflammatory as well as oxidative stress markers, including prostaglandin E2, nitric oxide, and malondialdehyde, which are hallmarks of the inflammatory process, considerably diminished (p < 0.05) in this group. qRT-PCR was utilised to elucidate the impact of the endophytic fungi treatment on the expression of interleukins (IL-1β and IL-6) genes, which decreased in comparison with the positive control group. Consequently, we can deduce that P. brefeldianum endophytic fungus has a promising anti-inflammatory potential and should be extensively studied on a broader range in the near future. Graphical Abstrac

Promising Antiviral Activity of Agrimonia pilosa Phytochemicals against Severe Acute Respiratory Syndrome Coronavirus 2 Supported with In Vivo Mice Study

The global emergence of the COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has focused the entire world&rsquo;s attention toward searching for a potential remedy for this disease. Thus, we investigated the antiviral activity of Agrimonia pilosa ethanol extract (APEE) against SARS-CoV-2 and it exhibited a potent antiviral activity with IC50 of 1.1 &plusmn; 0.03 &micro;g/mL. Its mechanism of action was elucidated, and it exhibited a virucidal activity and an inhibition of viral adsorption. Moreover, it presented an immunomodulatory activity as it decreased the upregulation of gene expression of COX-2, iNOS, IL-6, TNF-&alpha;, and NF-&kappa;B in lipopolysaccharide (LPS)-induced peripheral blood mononuclear cells. A comprehensive analysis of the phytochemical fingerprint of APEE was conducted using LC-ESI-MS/MS technique for the first time. We detected 81 compounds and most of them belong to the flavonoid and coumarin classes. Interestingly, isoflavonoids, procyanidins, and anthocyanins were detected for the first time in A. pilosa. Moreover, the antioxidant activity was evidenced in DPPH (IC50 62.80 &micro;g/mL) and ABTS (201.49 mg Trolox equivalents (TE)/mg) radical scavenging, FRAP (60.84 mg TE/mg), and ORAC (306.54 mg TE/g) assays. Furthermore, the protective effect of APEE was investigated in Lipopolysaccharides (LPS)-induced acute lung injury (ALI) in mice. Lung W/D ratio, serum IL-6, IL-18, IL-1&beta;, HO-1, Caspase-1, caspase-3, TLR-4 expression, TAC, NO, MPO activity, and histopathological examination of lung tissues were assessed. APEE induced a marked downregulation in all inflammation, oxidative stress, apoptosis markers, and TLR-4 expression. In addition, it alleviated all histopathological abnormalities confirming the beneficial effects of APEE in ALI. Therefore, APEE could be a potential source for therapeutic compounds that could be investigated, in future preclinical and clinical trials, in the treatment of patients with COVID-19