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1.
Acta cir. bras ; 37(2): e370204, 2022. graf
Article En | LILACS, VETINDEX | ID: biblio-1374066

Purpose: To evaluate the protective effect of Cuscuta chinensis Lam. polysaccharides (PCCL) on 5-fluorouracil-(5-FU)-induced intestinal mucositis (IM) in mice. Methods: PCCL was orally administered at a dose of 20 mg·kg­1 for 7 days and its protective effect on 5-FU-induced IM (5-FU, 50 mg·kg­1 for 5 days) was evaluated by monitoring changes in body weight, degree of diarrhea, levels of tissue inflammatory factors (tumor necrosis factor α, interleukin 6, and interleukin 1ß levels), apoptosis rates, and the expression levels of caspase-3, Bax and Bcl-2. Results: The severity of mucosal injury (as reflected by body weight changes, degree of diarrhea, height of villi, and damage to crypts) was significantly attenuated by PCCL administration. PCCL also reduced the levels of tissue inflammatory factors, the apoptosis rate, and the expression of caspase-3 and Bax, and increased Bcl-2 expression. Conclusions: PCCL administration may be significantly protective against 5-FU-induced IM by inhibiting apoptosis and regulating the abnormal inflammation associated with it.


Animals , Mice , Polysaccharides/therapeutic use , Cuscuta/chemistry , Mucositis/drug therapy , Fluorouracil/adverse effects , Protective Agents/analysis
2.
Toxins (Basel) ; 13(12)2021 12 11.
Article En | MEDLINE | ID: mdl-34941724

We are studying the structures of bacterial toxins that form ion channels and enable macromolecule transport across membranes. For example, the crystal structure of the Staphylococcus aureus α-hemolysin (α-HL) channel in its functional state was confirmed using neutron reflectometry (NR) with the protein reconstituted in membranes tethered to a solid support. This method, which provides sub-nanometer structural information, could also test putative structures of the Bacillus anthracis protective antigen 63 (PA63) channel, locate where B. anthracis lethal factor and edema factor toxins (LF and EF, respectively) bind to it, and determine how certain small molecules can inhibit the interaction of LF and EF with the channel. We report here the solution structures of channel-forming PA63 and its precursor PA83 (which does not form channels) obtained with small angle neutron scattering. At near neutral pH, PA83 is a monomer and PA63 a heptamer. The latter is compared to two cryo-electron microscopy structures. We also show that although the α-HL and PA63 channels have similar structural features, unlike α-HL, PA63 channel formation in lipid bilayer membranes ceases within minutes of protein addition, which currently precludes the use of NR for elucidating the interactions between PA63, LF, EF, and potential therapeutic agents.


Antigens, Bacterial/analysis , Antigens, Bacterial/chemistry , Bacillus anthracis/chemistry , Bacterial Toxins/analysis , Bacterial Toxins/chemistry , Protective Agents/analysis , Protective Agents/chemistry , Kinetics , Molecular Structure , Scattering, Small Angle
3.
J Sep Sci ; 44(17): 3305-3318, 2021 Sep.
Article En | MEDLINE | ID: mdl-34185383

Hyperlipidemia is recognized as one of the most important risk factors for morbidity and mortality due to cardiovascular diseases. Daming capsule, a Chinese patent medicine, has shown definitive efficacy in patients with hyperlipidemia. In this study, serum biochemistry and histopathology assessment were used to investigate the lipid-lowering effect of Daming capsule. Furthermore, urinary metabolomics based on ultra high performance liquid chromatography with quadrupole time-of-flight mass spectrometry was conducted to identify the urinary biomarkers associated with hyperlipidemia and discover the underlying mechanisms of the antihyperlipidemic action of Daming capsule. After 10 weeks of treatment, Daming capsule significantly lowered serum lipid levels and ameliorated hepatic steatosis induced by a high-fat diet. A total of 33 potential biomarkers associated with hyperlipidemia were identified, among which 26 were robustly restored to normal levels after administration of Daming capsule. Pathway analysis revealed that the lipid-lowering effect of Daming capsule is related to the regulation of multiple metabolic pathways including vitamin B and amino acid metabolism, tricarboxylic acid cycle, and pentose phosphate pathway. Notably, the study demonstrates that metabolomics is a powerful tool to elucidate the multitarget mechanism of traditional Chinese medicines, thereby promoting their research and development.


Drugs, Chinese Herbal/analysis , Hyperlipidemias/urine , Hypolipidemic Agents/analysis , Metabolomics , Protective Agents/analysis , Protective Agents/therapeutic use , Administration, Oral , Animals , Capsules/analysis , Capsules/metabolism , Capsules/therapeutic use , Chromatography, High Pressure Liquid , Diet, High-Fat/adverse effects , Drugs, Chinese Herbal/metabolism , Drugs, Chinese Herbal/therapeutic use , Hyperlipidemias/drug therapy , Hyperlipidemias/metabolism , Hypolipidemic Agents/metabolism , Hypolipidemic Agents/therapeutic use , Male , Mass Spectrometry , Protective Agents/metabolism , Rats , Rats, Wistar , Software , Time Factors
4.
Article En | MEDLINE | ID: mdl-34052752

Detailed metabolic profiling of needles of five Pinus species was investigated using complementary HPLC-MS/MS techniques together with supervised and unsupervised chemometric tools. This resulted in putative identification of 44 compounds belonging to flavonoids, phenolics, lignans, diterpenes and fatty acids. Unsupervised principal component analysis showed that differences were maintained across the metabolites characteristic of each Pinus species, are mainly related to di-O-p-coumaroyltrifolin, p-coumaroyl quinic acid derivative, arachidonic acid, hydroxypalmitic acid, isopimaric acid and its derivative. A supervised Partial Least Squares regression analysis was performed to correlate HPLC-MS/MS profiles with the variation observed in the in vitro anticholinesterase, antiaging and anti-diabetic potential. All investigated Pinus extracts exerted their antiaging activity via increasing telomerase and TERT levels in normal human melanocytes cells compared to the control (untreated cells). Profound inhibition activities of acetylcholinesterase and dipeptidyl peptidase-4 were also observed with P. pinea and P. canariensis extracts having comparable antidiabetic activities to sitagliptin as a standard antidiabetic drug. Our findings suggested that pine needles are a good source of phenolics and diterpenoids that have possible health promoting activities in management and alleviation of diabetic conditions and Alzheimer disease.


Chromatography, High Pressure Liquid/methods , Metabolome/physiology , Pinus , Tandem Mass Spectrometry/methods , Cholinesterase Inhibitors/analysis , Cholinesterase Inhibitors/chemistry , Cholinesterase Inhibitors/metabolism , Diterpenes/analysis , Diterpenes/chemistry , Diterpenes/metabolism , Flavonoids/analysis , Flavonoids/chemistry , Flavonoids/metabolism , Hypoglycemic Agents/analysis , Hypoglycemic Agents/chemistry , Hypoglycemic Agents/metabolism , Metabolomics , Pinus/chemistry , Pinus/metabolism , Plant Extracts/chemistry , Protective Agents/analysis , Protective Agents/chemistry , Protective Agents/metabolism , Solid Phase Extraction/methods
5.
J Sci Food Agric ; 101(13): 5314-5324, 2021 Oct.
Article En | MEDLINE | ID: mdl-34032287

Soy contains many bioactive phytochemicals, such as isoflavones, which have the effect of preventing many cancers. Some studies have shown the beneficial effect of soy-based food and isoflavone intake on gastric cancer (GC), while others claimed no effect. Therefore, whether the beneficial effect of soy-based food is related to its fermentation or whether its protective effect comes from isoflavones still remains inconclusive. Our aim was to investigate the relationship between total soybean, fermented soybean, non-fermented soybean and isoflavone intake, and the risk of GC. Ten cohort studies and 21 case-control studies involving 916 354 participants were included. The association between soy-based food and isoflavone intake and the risk of GC was calculated with the pooled relative risks (RRs) for the highest versus lowest intake categories. The results showed that isoflavone intake might be a protective factor to GC, but the result was not statistically significant (RR = 0.92; 95% CI: 0.79-1.07). However, total soybean intake could significantly decrease the risk of GC by 36% (RR = 0.64; 95% CI: 0.51-0.80), which might be credited to non-fermented soybean products (RR = 0.79; 95% CI: 0.71-0.87). In contrast, high intake of fermented soybean products could increase the risk of GC (RR = 1.19; 95% CI: 1.02-1.38). High intake of total soybean and non-fermented soybean products could reduce the risk of GC, and high intake of fermented soybean products could increase the risk, which indicated that the beneficial effect of soy-based food might be related to its non-fermentation. However, high intake of isoflavones may not be associated with the incidence of GC. © 2021 Society of Chemical Industry.


Glycine max/metabolism , Isoflavones/metabolism , Protective Agents/metabolism , Stomach Neoplasms/metabolism , Adult , Aged , Aged, 80 and over , Cohort Studies , Female , Humans , Isoflavones/analysis , Male , Middle Aged , Protective Agents/analysis , Risk Factors , Seeds/chemistry , Seeds/metabolism , Soy Foods/analysis , Glycine max/chemistry , Stomach Neoplasms/epidemiology , Stomach Neoplasms/prevention & control , Young Adult
6.
Int J Mol Sci ; 22(4)2021 Feb 08.
Article En | MEDLINE | ID: mdl-33567754

The placental barrier can protect the fetus from contact with harmful substances. The potent neurotoxin methylmercury (MeHg), however, is very efficiently transported across the placenta. Our previous data suggested that L-type amino acid transporter (LAT)1 is involved in placental MeHg uptake, accepting MeHg-L-cysteine conjugates as substrate due to structural similarity to methionine. The aim of the present study was to investigate the antioxidant defense of placental cells to MeHg exposure and the role of LAT1 in this response. When trophoblast-derived HTR-8/SVneo cells were LAT1 depleted by siRNA-mediated knockdown, they accumulated less MeHg. However, they were more susceptible to MeHg-induced toxicity. This was evidenced in decreased cell viability at a usually noncytotoxic concentration of 0.03 µM MeHg (~6 µg/L). Treatment with ≥0.3 µM MeHg increased cytotoxicity, apoptosis rate, and oxidative stress of HTR-8/SVneo cells. These effects were enhanced under LAT1 knockdown. Reduced cell number was seen when MeHg-exposed cells were cultured in medium low in cysteine, a constituent of the tripeptide glutathione (GSH). Because LAT1-deficient HTR-8/SVneo cells have lower GSH levels than control cells (independent of MeHg treatment), we conclude that LAT1 is essential for de novo synthesis of GSH, required to counteract oxidative stress. Genetic predisposition to decreased LAT1 function combined with MeHg exposure could increase the risk of placental damage.


Large Neutral Amino Acid-Transporter 1/metabolism , Methylmercury Compounds/analysis , Methylmercury Compounds/pharmacology , Oxidative Stress/drug effects , Placenta/drug effects , Protective Agents/pharmacology , Apoptosis , Cell Survival , Cells, Cultured , Female , Glutathione/metabolism , Humans , Placenta/metabolism , Placenta/pathology , Pregnancy , Protective Agents/analysis
7.
Molecules ; 25(24)2020 Dec 10.
Article En | MEDLINE | ID: mdl-33321994

Lycii Fructus is a traditional medicine used to prevent liver and kidney diseases, which commonly derives from Lycium chinense and Lycium barbarum. Here, the extracts and ethyl acetate-soluble fractions of L. chinense fruits exhibited better hepatoprotective effects than those of L. barbarum, which was likely due to differences in their composition. Therefore, GC-MS and HPLC analyses were conducted to characterize the metabolite differences between L. chinense and L. barbarum. Based on amino acid (AA) and phenolic acid (PA) profiling, 24 AAs and 9 PAs were identified in the two species. Moreover, each species exhibited unique and readily distinguishable AA and PA star graphic patterns. HPLC analysis elucidated composition differences between the ethyl acetate-soluble layers of the two compounds. Further, NMR analysis identified their chemical structures as 4-(2-formyl-5-(hydroxymethyl)-1H-pyrrol-1-yl)butanoic acid and p-coumaric acid. The higher content of 4-(2-formyl-5-(hydroxymethyl)-1H-pyrrol-1-yl)butanoic acid was detected in L. chinense, whereas the content of p-coumaric acid was higher in L. barbarum. Therefore, the differences in the relative contents of these two secondary metabolites in the ethyl acetate-soluble layer of Lycii Fructus could be a good marker to discriminate between L. chinense and L. barbarum.


Hepatocytes/drug effects , Lycium/chemistry , Lycium/classification , Plant Extracts/chemistry , Plant Extracts/pharmacology , Protective Agents/chemistry , Protective Agents/pharmacology , Amino Acids , Cell Survival/drug effects , Chemical Fractionation , Dose-Response Relationship, Drug , Gas Chromatography-Mass Spectrometry , Hep G2 Cells , Humans , Hydroxybenzoates , Molecular Structure , Phytochemicals/chemistry , Phytochemicals/isolation & purification , Phytochemicals/pharmacology , Plant Extracts/analysis , Plant Extracts/isolation & purification , Protective Agents/analysis , Protective Agents/isolation & purification
8.
Food Chem Toxicol ; 139: 111248, 2020 May.
Article En | MEDLINE | ID: mdl-32156568

Polyphenols are secondary metabolites widely distributed in many plant foods, such a tea, coffee, chocolate and fruits. The consumption of these compounds is related to the improvement or amelioration of many diseases, including diabetes. Nevertheless, the great barrier to the therapeutic use of polyphenols is the low bioavailability of these compounds once ingested. For that reason, the encapsulation of polyphenols in different matrices may protect them from digestion and improve their release and subsequent absorption to obtain target-specific health effects. Some studies have reported the beneficial effect of encapsulation to increase both bioavailability and bioaccessibility. However, these works have mostly been carried out in vitro and few studies are specifically addressed at improving diabetes. In the current work, an overview of the knowledge related to nanoparticles and their use in the diabetic condition has been reviewed.


Diabetes Mellitus/therapy , Polyphenols/pharmacokinetics , Animals , Antioxidants/analysis , Antioxidants/pharmacokinetics , Biological Availability , Cacao/chemistry , Coffee/chemistry , Disease Management , Disease Models, Animal , Evidence-Based Medicine , Fruit/chemistry , Humans , Hypoglycemic Agents/analysis , Hypoglycemic Agents/pharmacokinetics , Nanoparticles/chemistry , Polymers/chemistry , Polyphenols/analysis , Protective Agents/analysis , Protective Agents/pharmacokinetics , Tea/chemistry
9.
Food Funct ; 11(4): 3134-3143, 2020 Apr 01.
Article En | MEDLINE | ID: mdl-32207479

Hawthorn including many plants from the genus Crataegus (C.) is used for traditional medicines, herbal drugs, and dietary supplements all over the world. In China, C. pinnatifida Bge. var. major N, E. Br, and C. pinnatifida Bge. are two major species that are used as hawthorn. The purpose of this study is to assay the myocardial protection of hawthorn fruit processed with honey (MSZ) and screen the chemical basis of MSZ on this effect. Firstly, ultra-performance liquid chromatography-quadrupole time of flight-mass spectrometry (UPLC/Q-TOF-MS) was used to analyze the chemical constituents of the sliced dry fruit of hawthorn (SZ) and MSZ. Principal component analysis (PCA) was used to differentiate them. Orthogonal partial least squares-discriminate analysis (OPLS-DA) was applied to screen different compounds between SZ and MSZ, and 32 different compounds were selected. Then a pharmacodynamic test to investigate their protective effect against myocardial ischaemia was carried out. The results demonstrated that the protective effect of MSZ was better than that of SZ on the same dose. Finally, the chemical basis for the protective effect provided by MSZ against myocardial ischaemia was speculated based on correlation analysis. Taken together, all these results suggest that phenylpropanoids, organic acids, tannins, and flavonoids might be the chemical basis of MSZ protecting against myocardial ischaemia.


Crataegus/chemistry , Honey/analysis , Myocardial Ischemia/drug therapy , Protective Agents/analysis , Protective Agents/pharmacology , Animals , Chromatography, Liquid , Crataegus/classification , Fruit/chemistry , Male , Mass Spectrometry , Plant Extracts/analysis , Plant Extracts/pharmacology , Principal Component Analysis , Rats , Rats, Sprague-Dawley
10.
Biomed Chromatogr ; 34(6): e4817, 2020 Jun.
Article En | MEDLINE | ID: mdl-32112425

Folium Camelliae Nitidissimae (jinhuacha in Chinese, JHC) is a kind of caffeine-less tea with antioxidant, antitumor and antibacterial effects. Studies on the chemical profiles and hepatoprotective effects of JHC extracts have not been systematically conducted so far. This study comprehensively investigated the compound profiles of JHC extract by ultrafast liquid chromatography with quadrupole time-of-flight tandem mass spectrometry. We also determined JHC's hepatoprotective effects against CCl4 -induced liver injury in mice. A JHC extract was administered orally to mice at 1.95 and 7.80 g/kg body weight once daily for 14 consecutive days prior to CCl4 treatment. Eighty-four compounds including flavonoids, organic acids, catechins, coumarins, phenylpropanol, amino acids, anthraquinones, saponins and nucleosides in JHC extract were authentically identified or tentatively identified by comparing MS information and retention times with those of authentic standards or available references. JHC administration significantly decreased elevated levels of aspartate aminotransferase and alanine aminotransferase in mouse serum, inhibited hepatic malondialdehyde formation and enhanced glutathione and superoxide dismutase activities in the liver of CCl4 -treated mice. The histological observations also further supported the results. These results demonstrate that JHC contains various chemical compounds and its hepatoprotective effects against CCl4 -induced liver injury correlated with decreasing lipid oxidation are significant.


Camellia , Chemical and Drug Induced Liver Injury/metabolism , Drugs, Chinese Herbal , Protective Agents , Animals , Carbon Tetrachloride/adverse effects , Chromatography, High Pressure Liquid , Drugs, Chinese Herbal/analysis , Drugs, Chinese Herbal/chemistry , Drugs, Chinese Herbal/pharmacology , Flavonoids/analysis , Flavonoids/chemistry , Flavonoids/pharmacology , Liver/drug effects , Mice , Protective Agents/analysis , Protective Agents/chemistry , Protective Agents/pharmacology , Tandem Mass Spectrometry
11.
J Chromatogr Sci ; 58(5): 411-417, 2020 Apr 25.
Article En | MEDLINE | ID: mdl-32086519

A binary mixture of Silymarin (SR) and Vitamin E (VE) acetate, of an antioxidant and a hepatoprotective effect, has been analyzed using a sensitive, selective and economic high performance thin layer chromatographic (HPTLC) method in their pure forms, pharmaceutical formulation and spiked human plasma. SR and VE were separated on 60F254 silica gel plates using hexane:acetone:formic acid (7:3:0.15, v/v/v) as a developing system with UV detection at 215 nm. The method was evaluated for linearity, accuracy, precision, selectivity, limit of detection (LOD) and limit of quantification (LOQ). SR and VE were detected in the linear range of 0.2-2.5 and 0.2-4.5 µg/band, respectively. Method validation was done as per ICH guidelines and acceptable results of accuracy of 99.86 ± 1.190 and 100.22 ± 1.609 for SR and VE, respectively were obtained. The method has been successfully applied for determination of the studied drugs in their pharmaceutical formulation without any interference from excipients, and in spiked plasma samples. Results obtained by the developed HPTLC-densitometric method were statistically compared to those obtained by the reported HPLC methods and no significant difference was found between them.


Chromatography, Thin Layer/methods , Silymarin/analysis , Vitamin E/analysis , Capsules/analysis , Chromatography, High Pressure Liquid , Densitometry , Excipients , Humans , Limit of Detection , Protective Agents/analysis , Reproducibility of Results , Silymarin/blood , Solvents/chemistry , Ultraviolet Rays , Vitamin E/blood
12.
Int J Environ Health Res ; 30(6): 630-642, 2020 Dec.
Article En | MEDLINE | ID: mdl-31081360

This study aimed to investigate the effect of red orange juice supplementation (ROJS) on performance, cardiovascular parameters, muscle damage and oxidative stress markers of athletes following exercise under polluted air. Eleven soccer players performed a Yo-Yo Intermittent Recovery Test Level-1 in polluted area (PA) and non-polluted area (NPA). Participants are invited to drink 500 ml of red orange or placebo (PLA) juice 2.5 h before the test. Blood samples were collected at rest and 3 min after each session to assess creatine kinase (CK), lactate dehydrogenase, malondialdehyde (MDA) and total antioxidant status. Our results showed that, VO2max, heart rate and systolic blood pressure post-exercise were significantly altered by pollution with both supplements, but the damage was lowered more with ROJS than PLA. Concerning muscle damage and oxidative stress markers, orange juice supplementation blunted the effect of pollution on CK levels post-exercise (p > 0.05) and decreases significantly (p < 0.05) the MDA levels post-exercise in PA and NPA compared to PLA supplementation. In conclusion, ROJS seemed to be an appropriate strategy to reduce the risk of exposure to pollution especially on muscle damage and oxidative stress markers.


Air Pollution/adverse effects , Athletic Performance , Cardiovascular Physiological Phenomena , Citrus sinensis , Dietary Supplements/analysis , Fruit and Vegetable Juices/analysis , Protective Agents/pharmacology , Athletes/statistics & numerical data , Biomarkers/metabolism , Cardiovascular Physiological Phenomena/drug effects , Diet , Humans , Male , Muscles/drug effects , Muscles/physiology , Oxidative Stress , Protective Agents/analysis , Soccer , Tunisia
13.
J Agric Food Chem ; 68(7): 1862-1870, 2020 Feb 19.
Article En | MEDLINE | ID: mdl-31290324

Plant sterol (PS) (1 g/100 mL) enriched milk-based fruit beverages with or without galactooligosaccharides (GOS) (1.8 g/100 mL) were used in differentiated Caco-2 cells. Their potential cytopreventive effect against oxidative stress induced by cholesterol oxidation products (COPs) and their anti-inflammatory properties were evaluated. Preincubation (24 h) with bioaccessible fractions from beverages without and with GOS (MfB and MfB-G) completely prevented the COPs (60 µM/4 h) induced oxidative stress independent to GOS presence with exception to calcium influx and GSH content, where a partial protective effect was observed. Besides, MfB produced a significant (p < 0.05) reduction of IL-8 (40%) and IL-6 (50%) after IL-1ß-induction (1 ng/mL/24 h) through the inhibition of NF-κB p65 translocation into the nucleus (16%) compared to control cells, while GOS presence compromised their anti-inflammatory effect. Therefore, PS-enriched milk-based fruit beverage could be an interesting strategy to prevent intestinal injury produced by COPs and to attenuate the pro-inflammatory process in intestinal human diseases. GOS addition had no extra beneficial antioxidant effect and even reduced their anti-inflammatory properties.


Anti-Inflammatory Agents/metabolism , Beverages/analysis , Oligosaccharides/analysis , Phytosterols/metabolism , Protective Agents/metabolism , Anti-Inflammatory Agents/analysis , Caco-2 Cells , Cytoprotection , Humans , Interleukin-1beta/genetics , Interleukin-1beta/metabolism , Oligosaccharides/metabolism , Oxidative Stress , Phytosterols/analysis , Protective Agents/analysis , Transcription Factor RelA/genetics , Transcription Factor RelA/metabolism
14.
Comput Biol Chem ; 84: 107196, 2020 Feb.
Article En | MEDLINE | ID: mdl-31881525

'Bottom-up', i.e., molecule to medicine strategy for the discovery of new drugs takes enormous time and cost. In most of the cases, inherent toxicity and undesired side effects of the developed drug hinder its way beyond the early stages of development. In this regard, the systems pharmacology can play an excellent role by reducing the cost and time of drug development through rationalization and/or repurposing of traditional drugs with known side effects. In the present study, our aim was to develop an integrated systems biology method for the prediction of active ingredients of a traditional medicine and their potential targets inside the body. Further, we evaluated the predictive capacity of the developed method in a preclinical animal model. Here, we have prepared a formulation (SKP17LIV01) from an extract of eight medicinal plants traditionally used as liver medicine and identified the constituents using UHPLC-MS technique. Using systems biology approach, we have rationalized the components of the formulation for potential use in the treatment of heavy metal-induced hepatotoxicity. The active ingredients and potential therapeutic targets were also predicted. A detailed biochemical, histopathological and molecular study on the mice model of lead toxicity confirms the efficacy of the formulation as per prediction by the systems pharmacology approach. The study may open a new frontier for re-discovery of drugs that are already used in traditional medicine.


Chemical and Drug Induced Liver Injury/drug therapy , Plant Extracts/analysis , Plant Extracts/therapeutic use , Protective Agents/analysis , Protective Agents/therapeutic use , Animals , Chromatography, High Pressure Liquid , Female , Lead/toxicity , Liver/drug effects , Liver/pathology , Magnoliopsida/chemistry , Mass Spectrometry , Medicine, Traditional , Mice , Plants, Medicinal/chemistry , Systems Biology/methods
15.
Chem Res Toxicol ; 32(12): 2411-2421, 2019 12 16.
Article En | MEDLINE | ID: mdl-31682104

Renal injury is the main adverse reaction of cisplatin, and many traditional Chinese medicines (TCMs) were proven active against renal toxicity. Here, an integrated metabolomics and network pharmacology strategy was proposed to discover active TCM ingredients for the alleviation of cisplatin nephrotoxicity. First, by interrogating the Human Metabolome Database (HMDB) we collected targets connected to 149 cisplatin nephrotoxicity-related metabolites. Second, targets of kidney damage were obtained from the Therapeutic Target Database (TTD), PharmGKB, Online Mendelian Inheritance in Man (OMIM), and Genetic Association Database (GAD). Common targets of both dysregulated metabolites and kidney damage were then used for TCM active ingredient screening by applying the network pharmacology approach. Eventually, 22 ingredients passed screening criteria, and their antinephrotoxicity activity was assessed in human kidney tubular epithelial (HK2) cells. As a result, 14 ingredients were found to be effective, in which kaempferol showed relatively better activity. Further metabolomics analysis revealed that kaempferol exerted an antinephrotoxicity effect in rats by regulating amino acid, pyrimidine, and purine metabolism as well as lipid metabolism. Collectively, this proposed integrated strategy would promote the transformation of metabolomics research in the field of drug pair discovery for the purpose of reduced toxicity and increased efficiency.


Cisplatin/toxicity , Drugs, Chinese Herbal/pharmacology , Kidney Diseases/prevention & control , Kidney/drug effects , Protective Agents/pharmacology , Animals , Apoptosis/drug effects , Cell Line, Transformed , Drugs, Chinese Herbal/analysis , Humans , Kaempferols/analysis , Kaempferols/pharmacology , Kidney/pathology , Metabolomics/methods , Pharmacology/methods , Protective Agents/analysis , Rats
16.
Sci Total Environ ; 694: 133716, 2019 Dec 01.
Article En | MEDLINE | ID: mdl-31756789

This study aims to quantify the selenium contribution from tuna to the Spanish diet and evidence the Se protective role against mercury and inorganic arsenic toxicity. Selenium concentrations in tuna were determined by ICP-MS spectrometry (expressed as mg kg-1), and the risk assessment was evaluated joined to Hg and iAs contrasting criteria of regulatory agencies with those that consider the Se protective role. Differences between Se average concentrations in fresh (1.24) and preserved (1.17) tuna were not statistically significant. In canned tuna species, Se presented higher mean levels in Thunnus albacares (1.28) than Thunnus alalunga (1.01) with statistically significant differences (p = 0.002), and among canned preparations a decreasing sequence was observed in different preparation-packaging media: oil (1.42) > natural (1.01) > pickled (0.92). Statistical study showed Hg-iAs as the only pair significantly correlated in all samples. The HI (sum of individual target hazard quotients -THQs-) on the consumption of tuna in Spain, due to exposure to Se, Hg and iAs, revealed the possibility of risk of adverse chronic effects in the six-year-old children group (1.09). According to the maximum allowable tuna consumption rate in meals/week (CRmw) and the THQs obtained, tuna intake, especially in children, should be moderated. The health benefit values (HBVSe) were positive in all samples, 14.53 and 15.65 in fresh and preserved tuna, respectively, which allows tuna to be considered safe. The benefit-risk value (BRV) evidenced the Se molar excess with respect to Hg that reached a surplus of 14.32% on Se AI in adults. Since iAs reduces the Se bioavailability, applying a new BRV criterion, the aforementioned percentage decreased to 13.49% of Se AI. In conclusion, tuna offers high levels of selenium to counteract adverse effects by the presence of Hg and iAs, and to provide consumers an important source of this essential element safely.


Arsenic/analysis , Dietary Exposure/statistics & numerical data , Mercury/analysis , Protective Agents/analysis , Selenium/analysis , Tuna , Adult , Animals , Child , Food Contamination , Humans , Risk Assessment
17.
Rev. esp. enferm. dig ; 111(11): 823-827, nov. 2019. ilus, tab, graf
Article En | IBECS | ID: ibc-190504

Background and aims: to investigate the potential effect and mechanism of Salvia miltiorrhiza in Gynura segetum-induced hepatic sinusoidal obstruction syndrome (HSOS). Methods: the mice were gavaged with PBS, Gynura segetum or Gynura segetum, along with 100 or 200 mg/kg Salvia miltiorrhiza. Histological scoring and liver function were performed. The expression of tumor necrosis factor-alpha (TNF-alfa), vascular cellular adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1) and nuclear transcription factor P65 (NF-κBp65) were determined by reverse transcriptase polymerase chain reaction (RT-PCR) and western blot. Results: liver function were effectively improved in the Salvia miltiorrhiza groups. The levels of TNF-alfa, VCAM-1, ICAM-1 and NF-κBp65 were significantly lower in the Salvia miltiorrhiza groups than in the Gynura segetum group. Conclusions: Salvia miltiorrhiza has a therapeutic effect on Gynura segetum-induced HSOS


No disponible


Animals , Rats , Salvia miltiorrhiza , Plant Extracts/pharmacokinetics , Hepatic Veno-Occlusive Disease/drug therapy , Cell Adhesion Molecules/drug effects , Tumor Necrosis Factor-alpha/drug effects , Vascular Cell Adhesion Molecule-1/drug effects , Transcription Factor RelA/drug effects , Disease Models, Animal , Hepatic Veno-Occlusive Disease/chemically induced , Liver Function Tests/methods , Protective Agents/analysis
18.
Exp Appl Acarol ; 79(2): 187-194, 2019 Oct.
Article En | MEDLINE | ID: mdl-31598890

A choice test bioassay was devised to screen compounds as potential semiochemicals (e.g., kairomones or allomones that mediate aggregation, attraction or repellence) for the obligate parasitic mite, Psoroptes ovis. The choice test used filter paper discs in a 1:4 test:control ratio and was found to be a reliable, effective and efficient method. Four mammalian lipid components were assessed as potential attractants-linoleic acid, arachidonic acid, methyl myristate and squalene-, and the insect/tick repellent DEET for potential repellence. Linoleic acid was significantly attractive to P. ovis adult females and has the potential to act as an attractant. Identification of P. ovis semiochemicals, especially attractants, would be beneficial in the development of novel control methods and tools for this species. This is essential considering the increase in resistance to the limited prophylactic chemical treatments in the UK, and the high prevalence of scab infections.


Chemotaxis , Lipids/analysis , Mite Infestations/veterinary , Protective Agents/analysis , Psoroptidae/physiology , Sheep Diseases/prevention & control , Tick Control/methods , Animals , Female , Mite Infestations/prevention & control , Sheep
19.
Chem Biodivers ; 16(12): e1900428, 2019 Dec.
Article En | MEDLINE | ID: mdl-31637808

The present study was performed to assess the HPLC-DAD analysis as well as antioxidant and protective effects of Tunisian Rhanterium suaveolens (Rs) against acetamiprid (ACT) induced oxidative stress on mice erythrocytes. The in vitro assays showed that the methanolic extract of Rs has an impressive antioxidant effect proved by testing the total antioxidant and scavenging activities using BCB, DPPH and ABTS assays, respectively. Moreover, qualitative and quantitative analysis using HPLC-DAD revealed the richness of Rs in polyphenols where p-Coumaric, Apigenin-7-glucoside and Ferulic acid were detected as the most abundant polyphenols. In the in vivo experiment, ACT, used as a toxicity model, was given to mice at a dose of 20 mg/kg. The latter was the origin of hemolytic anemia characterized by a significant decrease in red blood cells, hemoglobin and hematocrit levels and an increase in bilirubin, LDH, osmotic fragility, reticulocytes and white blood cells number. Characteristic erythrocyte morphological alterations were also determined as spherocytosis, schistocytosis and dacryocystitis. The oxidative status of ACT-treated mice was also altered manifested by a significant increase in MDA and GSH levels and a decrease in SOD, CAT and GPx activities. When receiving the Rs methanolic extract at a dose of 300 mg/kg, all the parameters cited above were restored in mice. These remarkable corrections could only confirm the important antioxidant effect and the noticeable protective properties that possess Rs owing to its broad range of secondary bioactive metabolites.


Antioxidants/analysis , Asteraceae/chemistry , Chromatography, High Pressure Liquid/methods , Neonicotinoids/pharmacology , Oxidative Stress/drug effects , Protective Agents/analysis , Animals , Antioxidants/chemistry , Antioxidants/pharmacology , Asteraceae/metabolism , Erythrocytes/cytology , Erythrocytes/drug effects , Erythrocytes/metabolism , Flavonoids/chemistry , Flavonoids/pharmacology , Mice , Plant Extracts/chemistry , Polyphenols/chemistry , Polyphenols/pharmacology , Protective Agents/chemistry , Protective Agents/pharmacology , Superoxide Dismutase/metabolism , Tunisia
20.
J Food Sci ; 84(10): 3027-3036, 2019 Oct.
Article En | MEDLINE | ID: mdl-31529805

This study aimed to investigate the effect of Se (Selenium) treatment on nutritional quality in radish sprouts. The results showed that 15 µM sodium selenite significantly increased phenolics compounds, flavonoids compounds, anthocyanins, and some essential amino acid content, while improving the total antioxidant capacity of radish sprouts. Besides, the Se-enriched radish sprouts significantly alleviated the liver damage caused by carbon tetrachloride (CCl4 ) in mice and improved the antioxidant capacity of the liver in mice, whereas the Se-enriched radish sprouts alleviated the inflammatory reaction and apoptosis caused by CCl4 . These results imply that Se-enriched radish sprouts have a positive impact on mice with CCl4 -induced liver injury, and that in future Se-enriched radish sprouts could be developed into an effective food and health care product for the liver injury prevention. PRACTICAL APPLICATION: Because selenium is an essential trace element in the human body, selenium-enriched sprouts can help eliminate free radicals in the body, relieve aging, and selenium-deficient diseases. They are easy to grow and have low costs. Hence, selenium-enriched sprouts have a great potential of being widely consumed.


Carbon Tetrachloride/adverse effects , Chemical and Drug Induced Liver Injury, Chronic/diet therapy , Protective Agents/metabolism , Raphanus/metabolism , Selenium/metabolism , Animals , Anthocyanins/analysis , Anthocyanins/metabolism , Antioxidants/analysis , Antioxidants/metabolism , Chemical and Drug Induced Liver Injury, Chronic/etiology , Chemical and Drug Induced Liver Injury, Chronic/metabolism , Chemical and Drug Induced Liver Injury, Chronic/prevention & control , Flavonoids/analysis , Flavonoids/metabolism , Humans , Liver/metabolism , Male , Phenols/analysis , Phenols/metabolism , Protective Agents/analysis , Raphanus/chemistry , Raphanus/growth & development , Rats , Rats, Wistar , Seedlings/chemistry , Seedlings/growth & development , Seedlings/metabolism , Seeds/chemistry , Seeds/growth & development , Seeds/metabolism , Selenium/analysis
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