1-O-alkyl-glycerols from Squid Berryteuthis magister Reduce Inflammation and Modify Fatty Acid and Plasmalogen Metabolism in Asthma Associated with Obesity.

Asthma associated with obesity is considered the most severe phenotype and can be challenging to manage with standard medications. Marine-derived 1-O-alkyl-glycerols (AGs), as precursors for plasmalogen synthesis, have high biological activity, making them a promising substance for pharmacology. This study aimed to investigate the effect of AGs from squid Berryteuthis magister on lung function, fatty acid and plasmalogen levels, and cytokine and adipokine production in obese patients with asthma. The investigational trial included 19 patients with mild asthma associated with obesity who received 0.4 g of AGs daily for three months in addition to their standard treatment. The effects of AGs were evaluated at one and three months of treatment. The results of the study demonstrated that intake of AGs increased the FEV1 and FEV1/VC ratios, and significantly decreased the ACQ score in 17 of the 19 patients after three months of treatment. The intake of AGs increased concentration of plasmalogen and n-3 PUFA in plasma, and modified leptin/adiponectin production by adipose tissue. The supplementation of AGs decreased the plasma levels of inflammatory cytokines (TNF-α, IL-4, and IL-17a), and oxylipins (TXB2 and LTB4), suggesting an anti-inflammatory property of AGs. In conclusion, 1-O-alkyl-glycerols could be a promising dietary supplement for improving pulmonary function and reducing inflammation in obese asthma patients, and a natural source for plasmalogen synthesis. The study highlighted that the beneficial effects of AG consumption can be observed after one month of treatment, with gradual improvement after three months of supplementation.

Protective Properties of Marine Alkyl Glycerol Ethers in Chronic Stress.

In this paper we discuss the effect of alkyl glycerol ethers (AGs) from the squid Berryteuthis magister on a chronic stress model in rats. The study was performed on 32 male Wistar rats. Animals received AGs at a dose of 200 mg/kg through a gavage for six weeks (1.5 months), and were divided into four groups: group 1 (control), group 2 (animals received AGs), group 3 (stress control), group 4 (animals received AGs and were subjected to stress). Chronic immobilization stress was induced by placing each rat into an individual plexiglass cages for 2 h daily for 15 days. The serum lipid spectrum was evaluated by the content of total cholesterol, triglycerides, high-density lipoprotein cholesterol, low lipoprotein cholesterol and very low-density lipoprotein cholesterol. The atherogenic coefficient was calculated. The hematological parameters of peripheral blood were evaluated. The neutrophil-lymphocyte ratio was counted. The levels of cortisol and testosterone in blood plasma were determined. AGs at the selected dose did not have a significant effect on the body weight of rats in the preliminary period of the experiment. Under stress, the body weight gain, the concentrations of very low-density lipoprotein cholesterol and blood triglycerides decreased significantly. The neutrophil-lymphocyte ratio in animals treated with AGs shifted towards lymphocytes. A favorable increase in the percentage of lymphocytes was found in the stressed group of animals treated with AGs. So, for the first time, it was found that AGs prevent stress-induced suppression of the immune system. This confirms the benefit of AGs for the immune system under chronic stress. Our results prove the efficiency of the use of AGs for treating chronic stress, a serious social problem in modern society.

Staphylococcus aureus is able to generate resistance to novel lipoglycopeptide antibiotic gausemycin A.

Gausemycin A is the first member of the novel lipoglycopeptides family produced by Streptomyces roseoflavus INA-Ac-5812. Gausemycin A has a pronounced bactericidal activity against methicillin-resistant Staphylococcus aureus. However, the ability of S. aureus to be resistant to gausemycin A has not been investigated yet. Using serial passaging, we have obtained the resistant variant S. aureus 5812R, which is 80 times more resistant compared to the parent strain. Susceptibility testing of S. aureus 5812R revealed the acquisition of cross-resistance to daptomycin, cefazolin, tetracycline, and gentamicin, while the resistance to vancomycin, nisin, and ramoplanin was absent. Whole genome sequencing revealed single nucleotide polymorphism (SNP) and deletions in S. aureus 5812R, among which are genes encoding efflux pump (sepA), the two-component Kdp system (kdpE), and the component of isoprenoid biosynthesis pathway (hepT). Phenotypically, S. aureus 5812R resembles a small-colony variant, as it is slow-growing, forms small colonies, and is deficient in pigments. Profiling of fatty acids (FA) composition constituting the cytoplasmic membrane of S. aureus 5812R revealed the prevalence of anteiso-branched FA, while straight FA was slightly less present. The evidence also showed that the gausemycin A-resistant strain has increased expression of the cls2 gene of the cardiolipin synthase. The performed checkerboard assay pointed out that the combination of gausemycin A and ciprofloxacin showed a synergistic effect against S. aureus 5812R.

Chimyl Alcohol Exhibits Proinflammatory Activity in vivo and in vitro.

Marine organisms are among the prominent and abundant sources of 1-O-alkyl-sn-glycerols, including chimyl alcohol (CA), batyl alcohol and selachyl alcohol. These biologically active compounds are precursors in plasmalogen and phospholipid biosynthesis, which are the main irreplaceable components of cell membranes. The results of this study demonstrate that CA promotes the activation of immune processes in the mouse spleen and in the mouse macrophage cell culture RAW 264.7. We studied the effect of CA on the spleen weight, as well as on the proliferation process and expression of interleukin-1ß (IL-1ß) and CD86 - a marker of the proinflammatory M1-type macrophage cell surface in experimental animals. We used the RAW 264.7 macrophage cell culture to assess the CA cytotoxicity, its effect on reactive oxygen species (ROS), nitric oxide (NO) production and lysosomal activity, as well as IL-1ß and CD86 expression in vitro. In vivoand in vitro experiments have shown that CA: (1) enhances cell proliferation without changing the spleen's weight, (2) increases the activity of the proinflammatory marker CD86, (3) increases the level of ROS/NO/lysosome activity, and (4) does not affect the level of IL-1ß. Our study reveals that CA has a complex immunostimulation effect in vitro and in vivo, which opens up prospects for further study of its biological activity.

Alkyl Glycerol Ethers as Adaptogens.

Τhis mini-review summarizes the hematopoietic and immunostimulating properties of alkyl glycerol ethers (AGs) reported earlier in the literature available to us. The role of AGs in the nervous system and aging of the body are also briefly described. We made an attempt to consider the data in terms of adaptation. The hematopoietic, immunostimulating and antioxidant properties of AGs in a variety of experimental situations, including stress, as well as the protective action of AGs against some adaptation diseases, allow us to consider them as substances that prevent some negative effects of stress and promote adaptation. The new approach to AGs as adaptogens seems promising and opens good opportunities for their new application.

Action of alkyl glycerol ethers and n-3 polyunsaturated fatty acids diet on hematological parameters of blood and liver plasmalogen level in aged rats.

One of the ways to reduce age-related changes can be a diet correction by adding biologically active substances. We studied the effect of a diet including alkyl glycerol ethers (AGs) and n-3 polyunsaturated fatty acid (PUFA) concentrate isolated from the hepatopancreas of Berrytheuthis magister squid on hematological parameters and plasmalogens level in the liver of elderly rats. The senile animals showed decrease in hemoglobin, a three-fold decrease in leukocytes, a three-fold increase in platelet count, and a double decrease of blood coagulation time in the peripheral blood. Age-related changes in rats were characterized by the development of anemia, hypercoagulation, and a decrease in the number of immunocompetent cells. AGs, both separately and in combination with n-3 PUFAs, induced an increase in the number of red blood cells and hemoglobin, a decrease in the number of platelets, and an immunostimulating activity. Under the action of AGs and n-3 PUFAs, the concentration of plasmalogens and docosahexaenoic acid in the rat liver increased 2- and 1.5 folds, respectively. PRACTICAL APPLICATION: This study showed that the combined use of AGs and n-3 PUFAs improves the rheological properties of the blood and the state of the immune system during aging. The enrichment of diet with dietary supplements, whose structure contains AGs and n-3 PUFAs can increase the content of plasmalogens in the body.

Protective action of alkylglycerols under stress.

The adaptogenic properties of alkylglycerols (AGs) after 1 month's treatment were investigated in a rat model of acute immobilization stress (AIS). The animals receiving AGs 157 mg/kg showed a body weight (BW) decrease in addition to a more pronounced increase in the adrenal glands index under stress conditions. Also, AGs at this dose prevented AIS-induced catalase inhibition. In addition, antiulcerative AG effects were already detected at a dose of 15 mg/kg. The data indicate that AGs promote adrenal gland activation in AIS. At the same time, AGs neutralize some of negative effects of stressful conditions, which include restoration of the oxidation-reduction balance, reduction of gastric mucosal stress lesion formation.LAY SUMMARYThe effect of alkylglycerols, ether lipids from marine organisms, was studied in stressed animals. AGs have antioxidant activity and can be useful in the complex therapy of stomach lesions.

1-O-alkylglycerols from the hepatopancreas of the crab Paralithodes camtschaticus, liver of the squid Berryteuthis magister, and liver of the skate Bathyraja parmifera, and their anticancer activity on human melanoma cells.

1-O-alkylglycerols (AKG) are a class of natural ether lipids derived from 1-O-alkyl-2,3-diacyl-sn-glycerols by deacylation. In this study, 1-O-alkylglycerol (AKG) composition was investigated in the hepatopancreas lipids of the crab Paralithodes camtschaticus and the liver lipids of the squid Berryteuthis magister and the skate  Bathyraja parmifera. One of the principal AKG in marine organisms was 1-O-hexadecyl-sn-glycerol (AKG 16:0). To assess AKG influence on melanoma, we evaluated the cytotoxicity and antiproliferative actions of natural AKG 16:0 and synthetic 1-O-octyl-sn-glycerol (AKG 8:0) on three human melanoma cell lines SK-Mel-5, SK-Mel-28, and RPMI-7951. Natural AKG 16:0 in concentration up to 20 µM was not toxic to all cell lines. AKG 8:0 showed no toxicity to cells SK-Mel-5 and SK-Mel-28 in concentrations up to 20 µM but had moderate cytotoxicity to RPMI-7951 cells with an IC50 of 13 µM. Both investigated substances inhibited the proliferation, formation, and growth of cell colonies of RPMI-7951. PRACTICAL APPLICATIONS: AKG exhibit a variety of biological activities, including anticancer effects. In this study, the liver lipids of the skate B. parmifera and the hepatopancreas lipids of crab P. camtschaticus were shown to be sources of AKG. Our data showed that AKG can be used to prevent the formation of new colonies of malignant cells in combination therapy against melanoma. The results will be useful for future studies involving marine ether lipids and the examination of their anticancer properties against malignant cells.

Neuron-astrocyte interactions in spinal cord dorsal horn in neuropathic pain development and docosahexaenoic acid therapy.

The analgesic activity of docosahexaenoic acid (DHA, 22:6 n-3) was studied using a chronic constriction injury (CCI) rat model. Animals were subcutaneously injected with DHA emulsion at a dose of 4.5mg/kg (125mМ/kg) daily during 2weeks after surgery. We characterized the dynamics of GFAP-positive astrocyte, substance P (SP) and nNOS-positive neurons activity in the spinal cord dorsal horn (SCDH) superficial lamina. We found that DHA treatment decrease the intensity and duration of neurogenic pain syndrome, results in earlier stabilization of weight distribution, prevents the cold allodynia and dystrophic changings in denervated limb tissue. DHA treatment reduced the reactive astrocyte number, decrease SP-immunopositive fibers and nNOS-positive neurons number in the SCDH in neuropathic pain.

Technological approach of 1-O-alkyl-sn-glycerols separation from Berryteuthis magister squid liver oil.

Biological active compounds, 1-O-alkyl-sn-glycerols (AG), were isolated from liver oil of the squid Berryteuthis magister. The main components of the initial lipids were 1-O-alkyl-2,3-diacyl-sn-glycerols (38.50 %) and triacylglycerols (24.26 %). The first step of separation was the alkaline hydrolysis of oil to form a lipid mixture consisting of AG, free fatty acids and cholesterol. AG were separated by double recrystallization from acetone at -20 °C and 1 °C. A simple procedure is proposed for obtaining AG with a purity of 99.22 %, the main component of which is chimyl alcohol (94.39 %). Purity and structure of the obtained products were confirmed by GC and GC-MS technique. Isolated AG may be used in nutrition and cosmetics.

Analgetic effect of docosahexaenoic acid is mediated by modulating the microglia activity in the dorsal root ganglia in a rat model of neuropathic pain.

The analgetic activity of docosahexaenoic acid (DHA, 22:6 n-3) was studied using a chronic constriction injury (CCI) model in rats, and the dynamics of iba-1 (+) microglia/macrophages in the dorsal root ganglia (DRG) were characterized. DHA reduced the intensity and duration of neurogenic pain. The application of DHA led to an earlier stabilization of weight bearing in the incapacitance test and prevented the development of cold allodynia and degenerative changes in tissues of the denervated limb. DHA treatment significantly reduced satellite glia reaction and expression of the pro-apoptotic p53 protein in the DRG. Thus, DHA's anti-pain effect may be a result of the modulation of microglia/macrophages activity and the development of neuroprotective effects at the level of the dorsal root ganglia.