Oxidized Phospholipids in Healthy and Diseased Lung Endothelium

Circulating and cell membrane phospholipids undergo oxidation caused by enzymatic and non-enzymatic mechanisms. As a result, a diverse group of bioactive oxidized phospholipids generated in these conditions have both beneficial and harmful effects on the human body. Increased production of oxidized phospholipid products with deleterious effects is linked to the pathogenesis of various cardiopulmonary disorders such as atherosclerosis, thrombosis, acute lung injury (ALI), and inflammation. It has been determined that the contrasting biological effects of lipid oxidation products are governed by their structural variations. For example, full-length products of 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine oxidation (OxPAPC) have prominent endothelial barrier protective and anti-inflammatory activities while most of the truncated oxidized phospholipids induce vascular leak and exacerbate inflammation. The extensive studies from our group and other groups have demonstrated a strong potential of OxPAPC in mitigating a wide range of agonist-induced lung injuries and inflammation in pulmonary endothelial cell culture and rodent models of ALI. Concurrently, elevated levels of truncated oxidized phospholipids are present in aged mice lungs that potentiate the inflammatory agents-induced lung injury. On the other hand, increased levels of full length OxPAPC products accelerate ALI recovery by facilitating production of anti-inflammatory lipid mediator, lipoxin A4, and other molecules with anti-inflammatory properties. These findings suggest that OxPAPC-assisted lipid program switch may be a promising therapeutic strategy for treatment of acute inflammatory syndromes. In this review, we will summarize the vascular-protective and deleterious aspects of oxidized phospholipids and discuss their therapeutic potential including engineering of stable analogs of oxidized phospholipids with improved anti-inflammatory and barrier-protective properties.

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Oxidized Phospholipids in Control of Endothelial Barrier Function: Mechanisms and Implication in Lung Injury

Frontiers in Endocrinology ◽

10.3389/fendo.2021.794437 ◽

2021 ◽

Vol 12 ◽

Author(s):

Pratap Karki ◽

Konstantin G. Birukov

Keyword(s):

Lung Injury ◽

Vascular Inflammation ◽

Barrier Properties ◽

Vascular Lesion ◽

Oxidation Products ◽

Endothelial Barrier ◽

Oxidized Phospholipids ◽

Barrier Dysfunction ◽

Lipid Oxidation Products ◽

Anti Inflammatory

Earlier studies investigating the pathogenesis of chronic vascular inflammation associated with atherosclerosis described pro-inflammatory and vascular barrier disruptive effects of lipid oxidation products accumulated in the sites of vascular lesion and atherosclerotic plaque. However, accumulating evidence including studies from our group suggests potent barrier protective and anti-inflammatory properties of certain oxidized phospholipids (OxPLs) in the lung vascular endothelium. Among these OxPLs, oxidized 1-palmitoyl-2-arachdonyl-sn-glycero-3-phosphocholine (OxPAPC) causes sustained enhancement of lung endothelial cell (EC) basal barrier properties and protects against vascular permeability induced by a wide variety of agonists ranging from bacterial pathogens and their cell wall components, endotoxins, thrombin, mechanical insults, and inflammatory cytokines. On the other hand, truncated OxPLs cause acute endothelial barrier disruption and potentiate inflammation. It appears that multiple signaling mechanisms triggering cytoskeletal remodeling are involved in OxPLs-mediated regulation of EC barrier. The promising vascular barrier protective and anti-inflammatory properties exhibited by OxPAPC and its particular components that have been established in the cellular and animal models of sepsis and acute lung injury has prompted consideration of OxPAPC as a prototype therapeutic molecule. In this review, we will summarize signaling and cytoskeletal mechanisms involved in OxPLs-mediated damage, rescue, and restoration of endothelial barrier in various pathophysiological settings and discuss a future potential of OxPAPC in treating lung disorders associated with endothelial barrier dysfunction.

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Therapeutic Potential of Iridoid Derivatives: Patent Review

Inventions ◽

10.3390/inventions4020029 ◽

2019 ◽

Vol 4 (2) ◽

pp. 29 ◽

Cited By ~ 2

Author(s):

Hidayat Hussain ◽

Ivan R. Green ◽

Muhammad Saleem ◽

Muhammad Liaquat Raza ◽

Mamona Nazir

Keyword(s):

Therapeutic Potential ◽

Biological Effects ◽

Antimalarial Drugs ◽

Biologically Active ◽

Future Research ◽

Patent Review ◽

Wide Range ◽

Anti Inflammatory ◽

Plant Families

Iridoids belong to a family of monoterpenoids comprising the cyclopentan[c]-pyran system; this class of compounds offers a wide range of biological effects, namely antileishmanial, anticancer, antiplasmodial, and anti-inflammatory potency. To date, a large number of biologically active iridoid derivatives have been reported from various plant families, including Rubiaceae, Plantaginaceae, Scrophulariaceae, and Verbenaceae. Furthermore, iridoids have the potential to form conjugates with other anticancer, antidiabetic, antileishmanial, and antimalarial drugs which synergistically have the potential to increase their effects. Additionally, future research should focus on the synthesis of halo analogs as well as preparing homo dimers or heterodimers of iridoids, since these might quite conceivably possess an increased bioactivity.

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Lipid Oxidation Products in the Pathogenesis of Inflammation-related Gut Diseases

Current Medicinal Chemistry ◽

10.2174/0929867324666170619104105 ◽

2018 ◽

Vol 25 (11) ◽

pp. 1311-1326 ◽

Cited By ~ 26

Author(s):

Barbara Sottero ◽

Daniela Rossin ◽

Giuseppe Poli ◽

Fiorella Biasi

Keyword(s):

Lipid Oxidation ◽

Intestinal Inflammation ◽

Biological Effects ◽

Oxidation Products ◽

Cholesterol Oxidation ◽

Intestinal Damage ◽

Therapeutic Benefits ◽

Lipid Oxidation Products ◽

Wide Range ◽

Mucosal Barrier Function

Background: A defective mucosal barrier function is the principal cause of the uncontrolled onset and progression of a number of human inflammatory gut diseases, most of which are characterized by chronic intermittent immune and inflammatory responses leading to structural intestinal damage, which can represent a potential risk for colorectal cancer development. During the active disease phase the production of pro-inflammatory cytokines and chemokines, and the induction of oxidative reactions by activated leukocytes and epithelial cells represent the main event in the intestinal inflammation. Objective: Oxidative stress plays a key role in the development of intestinal damage. Indeed reactive oxygen species and their oxidized by-products regulate redox-sensitive signaling pathways and transcription factors, which sustain inflammation within the intestinal layer. Methods: Polyunsaturated fatty acids and cholesterol are the principal targets of oxidative modifications. These lipids, which are cell membrane constituents or are present in food, readily undergo non-enzymatic oxidation to form chemically-reactive species that can induce a wide range of biological effects including inflammation, programmed cell death, and proliferation. Results and Conclusions: In this review we summarize the current knowledge on the role of lipid oxidation products in regulating redox pathways involved in the pathogenesis of inflammation- related gut diseases. In particular, lipid peroxidation end products, such as isoprostanes and aldehydes, and cholesterol oxidation-derived oxysterols are taken into consideration. Results and Conclusions: The control of oxidative damage and consequently tissue local over-production of lipid oxidation products by using specific antioxidant and anti-inflammatory molecules in the diet may have clinical and therapeutic benefits.

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Enhanced Bilosomal Properties Resulted in Optimum Pharmacological Effects by Increased Acidification Pathways

Pharmaceutics ◽

10.3390/pharmaceutics13081184 ◽

2021 ◽

Vol 13 (8) ◽

pp. 1184

Author(s):

Armin Mooranian ◽

Thomas Foster ◽

Corina M Ionescu ◽

Daniel Walker ◽

Melissa Jones ◽

...

Keyword(s):

Bile Acids ◽

Biological Effects ◽

Cellular Respiration ◽

Full Potential ◽

Protective Effects ◽

Pharmacological Effects ◽

Β Cells ◽

Positive Effects ◽

Wide Range ◽

Anti Inflammatory

Introduction: Recent studies in our laboratory have shown that some bile acids, such as chenodeoxycholic acid (CDCA), can exert cellular protective effects when encapsulated with viable β-cells via anti-inflammatory and anti-oxidative stress mechanisms. However, to explore their full potential, formulating such bile acids (that are intrinsically lipophilic) can be challenging, particularly if larger doses are required for optimal pharmacological effects. One promising approach is the development of nano gels. Accordingly, this study aimed to examine biological effects of various concentrations of CDCA using various solubilising nano gel systems on encapsulated β-cells. Methods: Using our established cellular encapsulation system, the Ionic Gelation Vibrational Jet Flow technology, a wide range of CDCA β-cell capsules were produced and examined for morphological, biological, and inflammatory profiles. Results and Conclusion: Capsules’ morphology and topographic characteristics remained similar, regardless of CDCA or nano gel concentrations. The best pharmacological, anti-inflammatory, and cellular respiration, metabolism, and energy production effects were observed at high CDCA and nano gel concentrations, suggesting dose-dependent cellular protective and positive effects of CDCA when incorporated with high loading nano gel.

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Zanjabeel (Zingiber officinale Roscoe.): An Evidence-Based Review of Anti-nociceptive, Anti-inflammatory, Antioxidant, and Antimicrobial Properties

Journal of Complementary and Alternative Medical Research ◽

10.9734/jocamr/2021/v15i330269 ◽

2021 ◽

pp. 26-35

Author(s):

Fatima Khan ◽

Mohd Nayab ◽

Abdul Nasir Ansari

Keyword(s):

Therapeutic Potential ◽

Antioxidant Properties ◽

Plant Secondary Metabolites ◽

Zingiber Officinale ◽

Extensive Study ◽

The Body ◽

Wide Range ◽

Zingiber Officinale Roscoe ◽

Medicinal Properties ◽

Anti Inflammatory

Ginger has been appreciated for over 2500-3000 years in many parts of the world due to its numerous scientific properties. The ginger plant (Zingiber officinale Roscoe) belongs to the Zingiberaceae family. It is a known food and flavoring ingredient reputed for its wide range of medicinal properties that have been widely used in Chinese, Ayurvedic, and Unāni Tibb worldwide, since antiquity. Ginger has long been used to cure a variety of ailments, including diarrhea, stomach discomfort, indigestion, and nausea. It is a versatile herb with phenomenal phytotherapeutic and medicinal properties. Active ingredients available in ginger such as 6-gingerol, 6-shogaol, 6-paradol, and zingerone are responsible for upgrading enzyme actions and balancing circulation through rejuvenating the body with physical re-strengthening. Gingerols, the key phenolic plant secondary metabolites responsible for its distinct flavor and health benefits, are found in the rhizome of ginger Extensive study has been undertaken over the last two decades to uncover bioactive ingredients and the therapeutic potential of ginger. This review considers ginger's chemical composition and the most recent study findings on its possible health advantages, such as analgesic, anti-inflammatory, antibacterial, and antioxidant properties due to its phytochemistry. Overall, clinical trials are needed to confirm these prospective various health advantages of ginger in human subjects and the most efficacious dosage, based on the current body of scientific literature.

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Inflammatory profile of oxidized phospholipids

Thrombosis and Haemostasis ◽

10.1160/th06-08-0474 ◽

2007 ◽

Vol 97 (03) ◽

pp. 348-354 ◽

Cited By ~ 56

Author(s):

Valery Bochkov

Keyword(s):

Endothelial Cells ◽

Lipid Oxidation ◽

Chronic Inflammation ◽

Oxidation Products ◽

Oxidized Phospholipids ◽

Protective Mechanisms ◽

Receptor Signalling ◽

Lipid Oxidation Products ◽

Inflammatory Profile ◽

Biological Situation

SummaryLipid oxidation products and in particular oxidized phospholipids (OxPL) are increasingly recognized as inducers of chronic inflammation characteristic of atherosclerosis. OxPL stimulate production of chemokines and adhesion of monocytes to endothelial cells. However, accumulating data suggest that, in addition to the proatherogenic and proinflammatory effects, OxPL can stimulate antiinflammatory and tissue-protective mechanisms. Thus, depending on the biological situation, OxPL can either stimulate or inhibit inflammation. In this review, the inflammatory properties of OxPL are discussed together with the underlying receptor, signalling and transcriptional mechanisms.

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The Clinical and Biological Effects of Homeopathically Prepared Signaling Molecules: A Scoping Review

Homeopathy ◽

10.1055/s-0041-1732305 ◽

2021 ◽

Author(s):

Raj Kumar Manchanda ◽

Meeta Gupta ◽

Ankit Gupta ◽

Robbert van Haselen

Keyword(s):

Scoping Review ◽

Clinical Studies ◽

English Language ◽

Therapeutic Potential ◽

Polycystic Ovary ◽

Biological Effects ◽

Signaling Molecules ◽

Respiratory Allergies ◽

Wide Range ◽

External Stimuli

Abstract Background Signaling molecules such as cytokines and interleukins are key mediators for the immune response in responding to internal or external stimuli. Homeopathically prepared signaling molecules have been used therapeutically for about five decades. However, these types of products are not available in many countries and their usage by homoeopaths is also infrequent. The aim of this scoping review is to map the available pre-clinical and clinical data related to the therapeutic use of homeopathically prepared signaling molecules. Methods We conducted a scoping review of clinical and pre-clinical studies of therapeutically used signaling molecules that have been prepared in accordance with an officially recognized homeopathic pharmacopoeia. Articles in peer-reviewed journals reporting original clinical or pre-clinical research of homeopathically prepared signaling molecules such as interleukins, cytokines, antibodies, growth factors, neuropeptides and hormones, were eligible. Non-English language papers were excluded, unless we were able to obtain an English translation. An appraisal of eligible studies took place by rating the direction of the outcomes on a five-point scale. The quality of the papers was not systematically assessed. Results Twenty-eight eligible papers, reporting findings for four different manufacturers' products, were identified and reviewed. Seventeen papers reported pre-clinical studies, and 11 reported clinical studies (six experimental, five observational). A wide range of signaling molecules, as well as normal T-cell expressed specific nucleic acids, were used. A majority of the products (21 of 28) contained two or more signaling molecules. The most common clinical indications were psoriasis, vitiligo, rheumatoid arthritis, respiratory allergies, polycystic ovary syndrome, and herpes. The direction of the outcomes was positive in 26 papers and unclear in two papers. Conclusion This scoping review found that there is a body of evidence on the use of homeopathically prepared signaling molecules. From a homeopathy perspective, these substances appear to have therapeutic potential. Further steps to explore this potential are warranted.

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Biocompatible N-acetyl-nanoconstruct alleviates lipopolysaccharide-induced acute lung injury in vivo

Scientific Reports ◽

10.1038/s41598-021-01624-5 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Seongchan Kim ◽

Shin Young Kim ◽

Seung Joon Rho ◽

Seung Hoon Kim ◽

So Hyang Song ◽

...

Keyword(s):

Acute Lung Injury ◽

Lung Injury ◽

Inflammatory Responses ◽

Therapeutic Potential ◽

Intratracheal Instillation ◽

Sprague Dawley ◽

In Vivo Experiments ◽

Anti Inflammatory

AbstractOxidative stress plays important roles in inflammatory responses during acute lung injury (ALI). Recently, nanoconstruct (Nano)-based drug-delivery systems have shown promise in many models of inflammation. In this study, we evaluated the anti-inflammatory effects of N-acetylcysteine (NAC) loaded in a biocompatible Nano using a rat model of ALI. We synthesized a Nano with a good NAC-releasing capacity using porous silica Nano, which was used to produce Nano/NAC complexes. For in vivo experiments, Sprague–Dawley rats were intraperitoneally administered NAC or Nano/NAC 30 min after intratracheal instillation of lipopolysaccharide. After 6 h, bronchoalveolar lavage fluids and lung tissues were collected. The anti-oxidative effect of the Nano/NAC complex was confirmed by demonstrating reduced levels of reactive oxygen species after treatment with the Nano/NAC in vitro. In vivo experiments also showed that the Nano/NAC treatment may protect against LPS‐induced ALI thorough anti‐oxidative and anti‐inflammatory effects, which may be attributed to the inactivation of the NF‐κB and MAPK pathways. In addition, the effects of Nano/NAC treatment were shown to be superior to those of NAC alone. We suggest the therapeutic potential of Nano/NAC treatment as an anti‐inflammatory agent against ALI. Furthermore, our study can provide basic data for developing nanotechnology-based pharmacotherapeutics for ALI.

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Dimethyl Fumarate Ameliorates Lipopolysaccharide-induced Acute Lung Injury by Inhibiting NLRP3 Inflammasome-mediated Pyroptosis

10.21203/rs.3.rs-626638/v1 ◽

2021 ◽

Author(s):

Huayu Li ◽

Mengyan Li ◽

Chao Dong ◽

Bing Liu

Keyword(s):

Acute Lung Injury ◽

Lung Injury ◽

Nlrp3 Inflammasome ◽

Therapeutic Potential ◽

Critical Role ◽

Specific Effect ◽

Dimethyl Fumarate ◽

Related Factor ◽

Pyrin Domain ◽

Anti Inflammatory

Abstract Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are clinically severe respiratory disorders, and there are currently no Food and Drug Administration-approved drug therapies. It is established that Dimethyl fumarate (DMF) exhibits anti inflammatory effects, however, the specific effect of DMF on ALI remains largely unknown. The aim of the present study was to investigate whether, and by which mechanism, DMF alleviated lipopolysaccharide (LPS)-induced ALI. We found that intraperitoneal injection of DMF markedly reduced the pulmonary injury, decreased pulmonary edema and pulmonary permeability. Emerging studies suggested that the NOD-like receptor pyrin domain containing 3 (NLRP3) inflammasome-mediated pyroptosis played a critical role during ALI. NLRP3 inflammasome-mediated pyroptosis is significantly activated with the cleavage of caspase-1 and GSDMD occurring in the lung of LPS-induced ALI. DMF inhibited the activation of the NLRP3 inflammasome and pyroptosis in both lung of ALI mice and LPS-induced BEAS-2B cells. Mechanistically, DMF enhanced expressions of Nuclear factor erythroid-2-related factor 2 (Nrf2), leading to inactivation of NLRP3 inflammasome and reduction of pyroptosis in both ALI mice and LPS-induced BEAS-2B cells. Conversely, Nrf2 inhibitor reduced the inhibitory effects of DMF on NLRP3 inflammasome and pyroptosis, and consequently blocked the improvement roles of DMF on ALI in mice. This study for the first time demonstrated that DMF could improve LPS-induced ALI via inhibiting NLRP3 inflammasome and pyroptosis, and that these effects were mediated by triggering Nrf2 expression, suggesting a therapeutic potential of DMF as an anti-inflammatory agent for ALI/ARDS treatment.

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The capability of minor quaternary benzophenanthridine alkaloids to inhibit TNF-α secretion and cyclooxygenase activity

Acta Veterinaria Brno ◽

10.2754/avb201786030223 ◽

2017 ◽

Vol 86 (3) ◽

pp. 223-230 ◽

Cited By ~ 1

Author(s):

Jan Hošek ◽

Kristýna Šebrlová ◽

Petra Kaucká ◽

Ondřej Peš ◽

Eva Táborská

Keyword(s):

Biological Effects ◽

Benzophenanthridine Alkaloids ◽

Additional Information ◽

Tnf Α ◽

Wide Range ◽

Anti Inflammatory ◽

Factor Α ◽

Relationship Of ◽

Sanguinarine And Chelerythrine

Quaternary benzophenanthridine alkaloids are known to have a wide range of biological effects, including antimicrobial, antifungal, anti-inflammatory, and antitumour activities. However, only sanguinarine and chelerythrine have been studied intensively. The aim of this study was to evaluate the anti-inflammatory potential of the five minor quaternary benzophenanthridine alkaloids sanguilutine, sanguirubine, chelirubine, chelilutine, and macarpine in vitro and to compare them with more thoroughly studied sanguinarine and chelerythrine. Before making cell-based assays, the cytotoxicity of the alkaloids was evaluated. The anti-inflammatory potential of the chosen alkaloids was evaluated as for their ability to modulate the lipopolysaccharide-induced secretion of tumour necrosis factor α (TNF-α) in the macrophage-like cell line THP-1. The cyclooxygenase (COX)-1 and COX-2 inhibitory activities were also measured. The results indicate that the presence of a methylenedioxy ring attached at carbon (C)7-C8 is important for reducing the secretion of TNF-α. Interestingly, this effect did not show a simple dependence on concentration. The selected alkaloids showed little or no anti-COX activity. The results obtained from the present experiments may provide additional information useful in understanding the structure-to-activity relationship of the quaternary benzophenanthridine alkaloids. The anti-inflammatory potential and the cytotoxic effect are driven by the presence of a methylenedioxy ring attached at C7-C8 and C2-C3, respectively.

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