The inhibitory effect of Cannabis Sativa L. and Morus nigra L. against lipid peroxidation in goat liver and brain homogenates

The present study was aimed to evaluate the antioxidant potential and inhibitory effect ofCannabis sativa and Morus nigra against lipid peroxidation in goat brain and liver homogenates. The formation of free radicals, highly reactive oxygen species (ROS) and reactive nitrogen species (RNS) is a normal metabolic process for cellular signaling and countering the antigens. However, they may cause serious damage if they produced at amplified tolls. In addition, metabolic disorders also serve as sources of these reactive species. Although the issue can be addressed through supplements and other phytochemicals. In this study, two plant species were evaluated for their biological potential by employing a spectrum of antioxidant assays. The antioxidant activity was performed by lipid peroxidation assay. The water extract prepared from leaves of Cannabis sativa and Morus nigra showed significant (P<0.05) inhibition as compared to control i.e., 522.6±0.06 and 659.97±0.03 µg/mL against iron-induced lipid peroxidation in goat brain homogenate while the inhibitions were 273.54±0.04 and 309.18±0.05 µg/mL against nitroprusside induced lipid peroxidation of the brain. The iron and nitroprusside induced lipid peroxidation was also significantly inhibited by leaf extracts of Cannabis sativa and Morus nigra in liver homogenates such as 230.63±0.52 and 326.91±0.01 µg/mL (iron-induced) while 300.47±0.07 and 300.47±0.07 µg/mL (nitroprusside induced), respectively. The extracts of Cannabis sativa extract showed promising activity (96.04±0.060%) against DPPH radicals while Morus nigra showed a moderate activity (34.11±0.120%). The results suggest that different accessions ofCannabis sativa and Morus nigra are a potential source of antioxidants and have a therapeutic effect against disease induced by oxidative stress and hence can be used for novel drug discovery and development.

Antioxidant Effect via Bioconversion of Isoflavonoid in Astragalus membranaceus Fermented by Lactiplantibacillus plantarum MG5276 In Vitro and In Vivo

In this study, the antioxidant mechanism of Astragalus membranaceus fermented by Lactiplantibacillusplantarum MG5276 (MG5276F-AM) was evaluated in HepG2 cells and in an animal model. HPLC analysis was performed to confirm the bioconversion of the bioactive compounds in A. membranaceus by fermentation. Calycosin and formononetin, which were not detected before fermentation (NF-AM), were detected after fermentation (MG5276F-AM), and its glycoside was not observed in MG5276F-AM. In HepG2 cells, MG5276F-AM alleviated H2O2-induced oxidative stress by mediating lipid peroxidation and glutathione levels, and upregulated antioxidant enzymes including catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx). In the tBHP-injected mouse model, administration of MG5276F-AM reduced hepatic aspartate transaminase, alanine transaminase, and lipid peroxidation. MG5276F-AM also modulated antioxidant enzymes as well as HepG2 cells. Thus, fermentation of A. membranaceus with L. plantarum MG5276 elevated the isoflavonoid aglycone by hydrolysis of its glycosides, and this bioconversion enhanced antioxidant activity both in vitro and in vivo.

Chemistry and Biochemistry Aspects of the 4-Hydroxy-2,3-trans-nonenal

4-hydroxy-2,3-trans-nonenal (C9H16O2), also known as 4-hydroxy-2E-nonenal (C9H16O2; HNE) is an α,β-unsaturated hydroxyalkenal. HNE is a major aldehyde, formed in the peroxidation process of ω-6 polyunsaturated fatty acids (ω-6 PUFAs), such as linoleic and arachidonic acid. HNE is not only harmful but also beneficial. In the 1980s, the HNE was regarded as a “toxic product of lipid peroxidation” and the “second toxic messenger of free radicals”. However, already at the beginning of the 21st century, HNE was perceived as a reliable marker of oxidative stress, growth modulating factor and signaling molecule. Many literature data also indicate that an elevated level of HNE in blood plasma and cells of the animal and human body is observed in the course of many diseases, including cancer. On the other hand, it is currently proven that cancer cells divert to apoptosis if they are exposed to supraphysiological levels of HNE in the cancer microenvironment. In this review, we briefly summarize the current knowledge about the biological properties of HNE.

Olfactory receptor 2 in vascular macrophages drives atherosclerosis by NLRP3-dependent IL-1 production

Sniffing out atherosclerosis Olfactory receptors are best known for their presence in the nose and their role in detecting smells, but they are also present in other tissues and perform additional biological functions. For example, vascular macrophages involved in the pathogenesis of atherosclerosis express multiple subtypes of olfactory receptors. Orecchioni et al . focused on olfactory receptor 2, a receptor for the compound octanal, and identified its contribution to atherosclerosis pathogenesis and the formation of atherosclerotic plaques (see the Perspective by Rayner and Rasheed). The authors show that most of the octanal was not directly derived from the diet, but rather was generated as a by-product of lipid peroxidation, suggesting a potential pathway for intervention. —YN

Persistent Oxidative Stress and Inflammasome Activation in CD14highCD16− Monocytes From COVID-19 Patients

The poor outcome of the coronavirus disease-2019 (COVID-19), caused by SARS-CoV-2, is associated with systemic hyperinflammatory response and immunopathology. Although inflammasome and oxidative stress have independently been implicated in COVID-19, it is poorly understood whether these two pathways cooperatively contribute to disease severity. Herein, we found an enrichment of CD14highCD16− monocytes displaying inflammasome activation evidenced by caspase-1/ASC-speck formation in severe COVID-19 patients when compared to mild ones and healthy controls, respectively. Those cells also showed aberrant levels of mitochondrial superoxide and lipid peroxidation, both hallmarks of the oxidative stress response, which strongly correlated with caspase-1 activity. In addition, we found that NLRP3 inflammasome-derived IL-1β secretion by SARS-CoV-2-exposed monocytes in vitro was partially dependent on lipid peroxidation. Importantly, altered inflammasome and stress responses persisted after short-term patient recovery. Collectively, our findings suggest oxidative stress/NLRP3 signaling pathway as a potential target for host-directed therapy to mitigate early COVID-19 hyperinflammation and also its long-term outcomes.

Fatty Acid Changes in Nearshore Phytoplankton under Anthropogenic Impact as a Biodiversity Risk Factor for the World’s Deepest Lake Baikal

In this study, we present results on fatty acid analysis of phytoplankton of Lake Baikal, the world’s deepest lake, which differs from other lakes by its oceanic features. Since we used a large-mesh net, the net sample phytoplankton were primarily represented by the large elongated diatom Synedra acus. subsp. radians (Kützing) Skabichevskij. The similar algae composition of net samples of spring season phytoplankton collected at different sites of the lake allows us to compare results of the fatty acid analysis of these samples. The phytoplankton diversity of the sedimentation samples was contrary represented by 32 algae species. There are clear changes in the fatty acid composition of net phytoplankton exposed to anthropogenic impacts of varying intensity. The content of polyunsaturated fatty acids in phytoplankton collected from central stations (pelagic stations at a distance of ~10–30 km from the shoreline) without anthropogenic impact was higher by up to 15% than phytoplankton collected from nearshore stations (littoral stations at a distance of ~0.01–0.05 km from the shoreline) and offshore stations (pelagic stations at a distance of ~3 km from the shoreline). The interlaboratory precision of fatty acid determination of phytoplankton is estimated as ≤10%. We found high content of the lipid peroxidation marker (80–340 μg g−1 of dry weight) in phytoplankton from nearshore and offshore stations with intensive anthropogenic impact. In phytoplankton from central stations, we did not find any lipid peroxidation. Determination of unsaturated fatty acids, coupled with analysis of fatty acid peroxidation products, can be used to evaluate the level of anthropogenic impact in terms of ecological health and biodiversity conservation.

Hsp90 Induces Acsl4-dependent Glioma Ferroptosis via Dephosphorylate Ser637 at Drp1

Background: Ferroptosis is a newly identified form of regulated cell death (RCD) characterized by the iron-dependent lipid reactive oxygen species (ROS) accumulation, but its exact mechanism in gliomas remains elusive. Acyl–coenzyme A (CoA) synthetase long-chain family member 4 (Acsl4), a pivotal enzyme in the regulation of lipid biosynthesis, has been found to benefit the initiation of ferroptosis, but its role in gliomas likewise needs clarification. Erastin, widely investigated as an inducer of ferroptosis, was recently found to regulate lipid peroxidation by regulating Acsl4 other than glutathione peroxidase 4 (GPX4) in ferroptosis. Methods: Relationship between Hsp90, Drp1 and Acsl4 was determined by Co-immunoprecipitation/ Mass spectrometry and western blot assay. The impact of Hsp90 and Drp1 on Acsl4-dependent ferroptosis was examined by lipid peroxidation indicators in patient-derived PL1 and PG7 cells. The morphological changes of mitochondria are observed by confocal-fluorescence microscopy and transmission electron microscope. Therapeutic efficacy of Erastin-induced ferroptosis in vivo was examined in xenograft mouse models.Results: In this study, we demonstrated that heat shock protein 90 (Hsp90) and dynamin-related protein 1 (Drp1) actively regulated Acsl4 expression in erastin-induced ferroptosis in gliomas. Hsp90 overexpression and calcineurin (CN)–mediated Drp1 dephosphorylation at serine 637 (Ser637) promoted ferroptosis by altering mitochondrial morphology and increasing Acsl4-mediated lipid peroxidation. Importantly, the Hsp90–Acsl4 pathway mediated Acsl4-dependent ferroptosis, amplifying the anticancer activity of erastin in vitro and in vivo. Conclusions: Our study not only uncovered an important role of Hsp90–Drp1–Acsl4 pathway in erastin-induced ferroptosis but also reveals an efficient mechanism of Acsl4 as a potential therapeutic target to ferroptosis-mediated glioma therapy.