Methodology to detect oxidised phospholipids and their relevance in disease

Author(s):  
Ahilanandan Dushianthan ◽  
Anthony Postle

Unsaturated membrane phospholipids are susceptible to oxidation, either by reactive oxygen species or enzymatically, to generate a complex mixture of peroxy and hydroxyl species. They can then spontaneously decompose to truncated oxidised phospholipids composed of aldehyde, carboxyl and hydroxyl species of five to nine carbon atoms chain length, many of which exhibit potent biological activities. In addition, aldehydes can form Schiff's base reactions with protein lysines to form oxidised lipid:protein adducts. While a selection of oxidised phospholipids have been characterised in detail by a range of mass spectrometry techniques, including direct infusion and liquid chromatography mass spectrometry, there are relatively few reports of comprehensive analyses of oxidised phospholipids in disease states. Oxidised phospholipid species are widely thought to be central to the pathology of many diseases, but there is relatively little direct evidence to confirm this in vivo. This review provides an overview of the various analytical methodologies and then summarises their application to examples of chronic and acute disease, cardiovascular disease and acute respiratory distress syndrome, respectively. It highlights the gaps in information and indicates directions for future research.

2021 ◽  
Vol 42 ◽  
pp. e67649
Author(s):  
Marta Sánchez ◽  
Elena González-Burgos ◽  
Irene Iglesias ◽  
M. Pilar Gómez-Serranillos Cuadrado

Valeriana officinalis L. (Caprifoliaceae family) has been traditionally used to treat mild nervous tension and sleep problems. The basis of these activities are mainly attributed to valerenic acid through the modulation of the GABA receptor. Moreover, V. officinalis is claimed to have other biological activities such as cardiovascular benefits, anticancer, antimicrobial and spasmolytic.  The current review aims to update the biological and pharmacological studies (in vitro, in vivo and clinical trials) of V. officinalis and its major secondary metabolites in order to guide future research. Databases PubMed, Science Direct and Scopus were used for literature search including original papers written in English and published between 2014 and 2020. There have been identified 33 articles which met inclusion criteria. Most of these works were performed with V. officinalis extracts and only a few papers (in vitro and in vivo studies) evaluated the activity of isolated compounds (valerenic acid and volvalerenal acid K). In vitro studies focused on studying antioxidant and neuroprotective activity. In vivo studies and clinical trials mainly investigated activities on the nervous system (anticonvulsant activity, antidepressant, cognitive problems, anxiety and sleep disorders). Just few studies were focused on other different activities, highlight effects on symptoms of premenstrual and postmenopausal syndromes. Valeriana officinalis continues to be one of the medicinal plants most used by today's society for its therapeutic properties and whose biological and pharmacological activities continue to arouse great scientific interest as evidenced in recent publications. This review shows scientific evidence on traditional uses of V. officinalis on nervous system.


Author(s):  
V P Butler ◽  
D Tse-Eng ◽  
H L Nossel

Fibrin II formation may be essential in thrombosis. Measurement of free FPB is the only direct index of fibrin II formation but is complicated by the fact that carboxypeptidase B rapidly cleaves the COOH-terminal arginine from FPB in human plasma. To facilitate the assay of Desarg-FPB as an index of in vivo FPB release, the immuno-chemical reactivity of Desarg-FPB with anti-FPB sera has been studied. As previously reported, Desarg-FPB was considerably less effective (0.7-17%) than FPB in inhibiting the binding of an 125I-FPB analog by five of six rabbit antisera studied in detail. Surprisingly, Desarg-FPB was 4 to 27 times.more effective than FPB in inhibiting the binding of an 125I-Desarg-FPB analog by the six anti-FPB sera. For example, in the case of antiserum R-28, FPB was 145 times more effective than Desarg-FPB in inhibiting the binding of the 125I-FPB analog but Desarg-FPB was 27 times more effective than FPB in inhibiting the binding of the 125I-Desarg-FPB analog. These findings indicate that the FPB and Desarg-FPB analogs are bound by different antibody populations. We suggest that carboxypeptidase B converts some molecules of FPB-protein conjugates to Desarg-FPB derivatives during the immunization of rabbits. From a practical point of view, the difference in reactivity of the different antisera has enabled the rational selection of anti-FPB sera for use in the assay of Desarg-FPB and its distinction from FPB. With the use of an appropriate antiserum, Desarg-FPB levels have been measured in clinical blood samples and the sensitivity is such that distinction can be made between levels in normal individuals and in disease states.


2010 ◽  
Vol 299 (2) ◽  
pp. H347-H355 ◽  
Author(s):  
Ji-Yoon Noh ◽  
Kyung-Min Lim ◽  
Ok-Nam Bae ◽  
Seung-Min Chung ◽  
Sang-Wook Lee ◽  
...  

Increased phosphatidic acid (PA) and phospholipase D (PLD) activity are frequently observed in various disease states including cancers, diabetes, sepsis, and thrombosis. Previously, PA has been regarded as just a precursor for lysophosphatidic acid (LPA) and diacylglycerol (DAG). However, increasing evidence has suggested independent biological activities of PA itself. In the present study, we demonstrated that PA can enhance thrombogenic activities in human erythrocytes through phosphatidylserine (PS) exposure in a Ca2+-dependent manner. In freshly isolated human erythrocytes, treatment of PA or PLD induced PS exposure. PA-induced PS exposure was not attenuated by inhibitors of phospholipase A2or phosphatidate phosphatase, which converts PA to LPA or DAG. An intracellular Ca2+increase and the resultant activation of Ca2+-dependent PKC-α appeared to underlie the PA-induced PS exposure through the activation of scramblase. A marginal decrease in flippase activity was also noted, contributing further to the maintenance of exposed PS on the outer membrane. PA-treated erythrocytes showed strong thrombogenic activities, as demonstrated by increased thrombin generation, endothelial cell adhesion, and erythrocyte aggregation. Importantly, these procoagulant activations by PA were confirmed in a rat in vivo venous thrombosis model, where PA significantly enhanced thrombus formation. In conclusion, these results suggest that PA can induce thrombogenic activities in erythrocytes through PS exposure, which can increase thrombus formation and ultimately contribute to the development of cardiovascular diseases.


2020 ◽  
Vol 11 (4) ◽  
pp. 5876-5885
Author(s):  
Alfred Maroyi

Gardenia ternifolia Schum. & Thonn. is a shrub or small tree widely used as a traditional medicine throughout its distributional range in tropical Africa. Gardenia ternifolia is widespread in tropical Africa, extending from Senegal eastwards to Ethiopia and Kenya, through the Democratic Republic of Congo (DRC) southwards to Namibia, South Africa and Mozambique. This study was aimed at providing a critical review of the medicinal uses, phytochemistry and biological activities of G. ternifolia. Documented information on the medicinal uses, phytochemistry and biological activities of G. ternifolia was collected from several online sources which included Scopus, Google Scholar, PubMed and Science Direct. Additional information was gathered from pre-electronic sources such as book chapters, books, journal articles and scientific publications obtained from the university library. This study showed that the species is widely used as an aphrodisiac and protective charm, and traditional medicine for headache, migraine, respiratory infections, sore eyes, hypertension, diabetes, gastro-intestinal problems, erectile dysfunction, malaria, convulsions and epilepsy. Phytochemical compounds identified from the species include alkaloids, anthocyanins, coumarins, flavonoids, phenols, quinones, saponins, steroids, stereoisomeric neolignans, tannins and terpenoids. Pharmacological research revealed that G. ternifolia extracts and compounds isolated from the species have antibacterial, antiviral, anti-inflammatory, antileishmanial, antioxidant, antiplasmodial, antisickling, antitheilerial, hepatotoxicity, larvicidal and cytotoxicity activities. Future research on G. ternifolia should focus on detailed phytochemical evaluations, including toxicological, in vivo and clinical studies to corroborate the traditional medical applications of the species.


2020 ◽  
Author(s):  
Alexander R. Loftis ◽  
Genwei Zhang ◽  
Coralie Backlund ◽  
Anthony J. Quartararo ◽  
Novalia Pishesha ◽  
...  

AbstractTargeting of antigens to erythrocytes can be used to selectively mitigate their immunogenicity, but the methods to equip a variety of cargoes with erythrocyte-targeting properties are limited. Here we identified a D-peptide that targets murine erythrocytes and decreases anti-drug antibody responses when conjugated to the protective antigen from Bacillus anthracis, a protein of therapeutic interest. The D-peptide likewise decreases inflammatory anti-ovalbumin (OVA) CD8+ T cell responses when attached to a peptide antigen derived from OVA. To discover this targeting ligand, we leveraged mass spectrometry to decode a randomized D-peptide library selected in mice, extending the application of synthetic libraries to in vivo affinity selections.


2022 ◽  
Vol 20 (2) ◽  
pp. 389-401
Author(s):  
Jiaqi Yuan ◽  
Yunting Wang ◽  
Shengquan Mi ◽  
Jiayu Zhang ◽  
Yaxuan Sun

Purpose: To determine the metabolism of caffeic acid in rats. Methods: Sprague-Dawley rats were intragastrically administered caffeic acid in saline suspension, and biological samples collected. After sample pretreatment by solid phase extraction, ultra-high performance liquid chromatography combined with quadrupole-time of flight mass spectrometry system (UHPLC-Q-TOF-MS/MS) was established to rapidly screen and characterize caffeic acid metabolites in rats. Waters HSS T3 UPLC chromatographic column (2.1 mm × 100 mm, 1.7 μm) was applied for the gradient elution with aqueous solution of formic acid (A)-acetonitrile (B). Mass spectral data for the biological samples in electrospray positive and negative ion modes were collected and analyzed by SCIEX OS 1.3 workstation. Results: Based on their precise molecular weights and multistage mass spectrometry cleavage information, caffeic acid and 21 metabolites in vivo were identified. The results demonstrate that the biotransformation of caffeic acid in vivo was mainly achieved via hydrogenation, hydroxylation, methylation, sulfonation, glucuronidation, acetylation, and composite reactions. Conclusion: The metabolites and metabolic pathways of caffeic acid in rats have been rapidly elucidated, and its potential pharmacodynamics forms have been clarified. This provides a valuable and meaningful reference for the study of caffeic acid metabolites, biological activities, and its medicinal material basis in vivo.


2021 ◽  
Vol 9 ◽  
Author(s):  
Yinzhi Lang ◽  
Yongzhen Zhang ◽  
Chen Wang ◽  
Limei Huang ◽  
Xiaoxiao Liu ◽  
...  

Human milk oligosaccharides (HMOs) exhibit various biological activities for infants, such as serving as prebiotics, blocking pathogens, and aiding in brain development. HMOs are a complex mixture of hetero-oligosaccharides that are generally highly branched, containing multiple structural isomers and no intrinsic chromophores, presenting a challenge to both their resolution and quantitative detection. While liquid chromatography-mass spectrometry (LC-MS) has become the primary strategy for analysis of various compounds, the very polar and chromophore-free properties of native glycans hinder their separation in LC and ionization in MS. Various labeling approaches have been developed to achieve separation of glycans with higher resolution and greater sensitivity of detection. Here, we compared five commonly used labeling techniques [by 2-aminobenzamide, 2-aminopyridine, 2-aminobenzoic acid (2-AA), 2,6-diaminopyridine, and 1-phenyl-3-methyl-5-pyrazolone] for analyzing HMOs specifically under hydrophilic-interaction chromatography-mass spectrometry (HILIC-MS) conditions. The 2-AA labeling showed the most consistent deprotonated molecular ions, the enhanced sensitivity with the least structural selectivity, and the sequencing-informative tandem MS fragmentation spectra for the widest range of HMOs; therefore, this labeling technique was selected for further optimization under the porous graphitized carbon chromatography-mass spectrometry (PGC-MS) conditions. The combination strategy of 2-AA labeling and PGC-MS techniques provided online decontamination (removal of excess 2-AA, salts, and lactose) and resolute detection of many HMOs, enabling us to characterize the profiles of complicated HMO mixtures comprehensively in a simple protocol.


Author(s):  
JAYKUMAR MANE ◽  
DHEERAJ NAGORE ◽  
SOHAN CHITLANGE

The aim of this systematic review is to provide an in-depth study of ethnological uses, phyto-chemistry, pharmacological activities, and toxicological research in Uraria picta (Jacq.), to identify remaining gaps, and to provide a basis for future research. By searching for the words “U. picta” and “Prishnaparni” in electronic databases such as SciFinder, Web of Science, PubMed, and Google Scholar, information on common uses, phytochemistry, and pharmacological activities was systematically collected. Phytochemical analysis of U. picta shows various components such as alkaloids, flavonoids, steroids, terpenoids, phenols, and saponins. The extracts and their isolated components showed numerous in vitro and in vivo pharmacological effects, including urinary tract diseases, tumors, edema, smoking, and dyspnea. On the other hand, searches of patent databases found almost seven applications, highlighting the differences between a large number of published scientific articles and non-existent patent applications. This event demonstrates the technological potential of undiscovered species. Ethnographic research shows that U. picta, an important Asian medicinal plant, is used to treat many diseases. In this review, the ethnobotanical, phytochemical, pharmacological, and ethnological properties of various morphological parts of the U. picta plant are highlighted. Future research has provided information for commercial research and has shown that this herb has tremendous potential for pharmaceutical and nutritional applications.


2020 ◽  
Vol 10 (5) ◽  
pp. 280-286
Author(s):  
Alfred Maroyi

Adenia gummifera (Harv.) Harms is a climber or liane widely used as traditional medicine throughout its distributional range in tropical Africa. Adenia gummifera occurs naturally in the Democratic Republic of Congo (DRC), Eswatini, Ethiopia, Kenya, Malawi, Mozambique, Seychelles, Somalia, South Africa, Tanzania, Uganda, Zambia and Zimbabwe. This study is aimed at providing a critical review of the medicinal uses, phytochemistry and biological activities of A. gummifera. Documented information on the medicinal uses, phytochemistry and biological activities of A. gummifera was collected from several online sources, which included Scopus, Google Scholar, PubMed and Science Direct. Additional information was gathered from pre-electronic sources such as book chapters, books, journal articles and scientific publications sourced from the university library. This study showed that the species is widely used as an emetic and a protective charm, and, as traditional medicine for infertility, sexually transmitted infections, gastro-intestinal infections, leprosy, respiratory infections, malaria and menstrual problems. Phytochemical compounds identified from the species include polyacetylenic diepoxide, alkaloids, flavonoids, flavonol, modeccin, proanthocyanidins, tetraphyllin, phenolics, polyphenol and tannins. Pharmacological research revealed that A. gummifera extracts and compounds isolated from the species have antibacterial, antifungal, acetylcholinesterase inhibitory (AChEI), anaesthetic, antioxidant, antiplasmodial and cytotoxicity activities. Future research on A. gummifera should focus on detailed phytochemical evaluations including toxicological, in vivo and clinical studies to corroborate the traditional medical applications of the species.


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