Food Hazards and Quality Control in Table Olive Processing with a Special Reference to Functional Compounds

Louden³

2021

In Vivo

Background/Aim: Alterations of plasma membrane fluidity are characteristic of many diseases but the intentional modulation of membrane fluidity with drugs has been less studied. We examined the therapeutic potential of the membrane fluidizer diethyl azelate (DEA) and related azelates. Materials and Methods: The effects of azelates on plasma membrane fluidity and cell signaling were examined in primary human and murine cells and in vivo. Endpoints were queried using single target and multiplexed immunoassays. Results: Unique membrane-fluidizing properties and biomarker signatures suggest that azelates are not prodrugs. DEA decreased cytokine signaling from pattern recognition receptors in human dendritic cells, disabled membrane attack of cholera toxin in vitro, and prevented immunosuppression by anthrax lethal toxin in vitro and in vivo. In the murine sepsis model, DEA increased survival and reduced organ damage. Conclusion: Azelates represent a new class of drugs, membrane active immunomodulators, which target an innate homeostatic mechanism, adaptive membrane fluidity modulation.

mentioning

confidence: 99%

Adaptive Membrane Fluidity Modulation: A Feedback Regulated Homeostatic System and Target for Pharmacological Intervention

Louden³

2021

In Vivo

“…For example, the fatty acid azelaic acid has been used in the treatment of dermatological diseases for decades (25,26). Diethyl azelate, a natural product made by plants and animals and unwittingly used by humanity over many millennia (27)(28)(29)(30)(31)(32)(33)(34), is also a promising drug candidate (21).…”

Section: Maims Hiding In Plain Sightmentioning

confidence: 99%

Adaptive Membrane Fluidity Modulation: A Feedback Regulated Homeostatic System Hiding in Plain Sight

2021

In Vivo

The structure of the plasma membrane affects its function. Changes in membrane fluidity with concomitant effects on membrane protein activities and cellular communication often accompany the transition from a healthy to a diseased state. Although deliberate modulation of membrane fluidity with drugs has not been exploited to date, the latest data suggest the "druggability" of the membrane. Azelaic acid esters (azelates) modulate plasma membrane fluidity and exhibit a broad range of immunomodulatory effects in vitro and in vivo. Azelates represent a new class of drugs, membrane active immunomodulators (MAIMs), which use the entire plasma membrane as the target, altering the dynamics of an innate feedback regulated homeostatic system, adaptive membrane fluidity modulation (AMFM). A review of the literature data spanning >200 years supports the notion that molecules in the MAIMs category including known drugs do exert immunomodulatory effects that have been either neglected or dismissed as off-target effects.A literature search was conducted using PUBMED, MEDLINE, and Library of Congress databases to capture peer-reviewed research articles (including reviews and metaanalyses), published through August 27, 2021, with the earliest record dating from 1801. The search terms included "plasma membrane" AND "fluidity" OR "plasticity" OR "rigidity". Secondary searches combined keywords consisting of individual chemical entities listed in this manuscript (for example, cholesterol, ethanol, turpentine) and physiological conditions (for example pain, fever, disease). The collected abstracts and/or full papers were surveyed by both authors in order to confirm article relevancy to the topic.

“…Azelate content in foods is increased by fermentation due to bacterial metabolism of acyl glycerol fatty acids and esterification of the resulting medium chain fatty acids [8]. Fermentation of olives by Lactobacilli to render them edible [9] converts some of the oleic acid into AZA and azelates [10]. Fermentation of rice also results in the formation of fatty acid ethyl esters [11].…”

Section: Introductionmentioning

confidence: 99%

Azelaic Acid Esters as Pluripotent Immunomodulatory Molecules: Nutritional Supplements or Drugs

2021

Nutraceuticals

Azelaic acid and its esters, the azelates, occur naturally in organisms ranging from plants to humans. We have shown that diethyl azelate (DEA) exhibits a broad range of immunomodulatory activities in vitro and in vivo, and mitigates insulin resistance. To further investigate the therapeutic utility of DEA, we evaluated its mutagenicity in Salmonella typhimurium strains, examined metabolism of DEA in rat, dog, monkey and human primary hepatocytes and in human saliva, determined pharmacokinetics of DEA after an oral dose in rats, and queried its physicochemical properties for drug-like characteristics. DEA was not mutagenic in bacterial strains ± rat liver metabolic activation system S-9. It was chemically unstable in hepatocyte culture medium with a half-life of <1 h and was depleted by the hepatocytes in <5 min, suggesting rapid hepatic metabolism. DEA was also quickly degraded by human saliva in vitro. After an oral administration of DEA to rats, the di- and monoester were undetectable in plasma while the levels of azelaic acid increased over time, reached maximum at <2 h, and declined rapidly thereafter. The observed pharmacological properties of DEA suggest that it has value both as a drug or a nutritional supplement.