Oxidatively Active Plant Phenolics Detected by UHPLC-DAD-MS after Enzymatic and Alkaline Oxidation

We developed a combination of methods to estimate the alkaline oxidative conditions of the midgut of insect larvae and to reveal the alkaline and enzymatic oxidative activities for individual phenolic compounds present in the larval host plants. First, we monitored the in vitro isomerization of 5-O-caffeoylquinic acid (5-CQA) into 3-CQA, 4-CQA and 5-CQA at pH 9.0–11.0. Then we calculated the isomer ratios of 3-CQA, 4-CQA and 5-CQA from the frass of eight species of insect herbivores fed on foliage containing 5-CQA. The isomer ratios suggested that the midgut pH of these larvae ranged from 9.4 to around 10.1. Second, we developed an in situ enzymatic oxidation method that enabled oxidation of phenolics in a frozen plant sample at 30 °C by species- and tissue-specific enzymes. Then we measured the alkaline and enzymatic oxidative activities of the individual phenolics in 20 plant species by quantifying the proportion of the compound concentration lost due to the auto-oxidation of a plant extract at pH 10 and due to the enzymatic oxidation of the frozen plant sample at 30 °C. Our results showed that both of the oxidative activity types depended primarily on the type of phenolic compound, but the enzymatic oxidative activity depended also on the plant species and tissue type. This combination of methods offers an approach to characterize a wide array of phenolics that are susceptible to oxidation by the plant enzymes and/or by the alkaline conditions estimated to prevail in the insect midgut. We propose that these kinds of compound-specific results could guide future studies on specific plant-herbivore interactions to focus on the phenolics that are likely to be active rather than inactive plant phenolics.     

Virtual Screening of Small Drug‐Like Compounds Stimulating the Enzymatic Activity of Kallikrein‐Related Peptidase 3 (KLK3)

Kallikrein‐related peptidase 3 (KLK3) is a prostatic serine protease shown to possess antiangiogenic properties which are exerted via its proteolytic activity. The antiangiogenic effect indicates that KLK3 may slow down the growth of prostate cancer; this makes it an interesting target for new therapies for prostate cancer. In this work, new drug‐like compounds were discovered that stimulate the proteolytic activity of KLK3. The compounds were identified using 2D similarity search and 3D pharmacophore‐based virtual screening, and their ability to stimulate KLK3 was verified by enzymatic activity assays. The effect of the molecules alone was modest, but in synergy with a cyclic peptide the most potent molecule was found to stimulate KLK3 activity significantly: up to 351 % of the activity of KLK3. This demonstrates that small drug‐like compounds can be beneficial tools in studying the antiangiogenic properties of KLK3.     

α‐, γ‐ and δ‐ Tocopherols as inhibitors of isomerization and decomposition of cis,trans methyl linoleate hydroperoxides

The effects of α‐, γ‐ and δ‐tocopherols on the stability and decomposition reactions of lipid hydroperoxides were studied. Isomerization and decomposition of cis,trans methyl linoleate hydroperoxides (cis,trans ML‐OOH) in hexadecane at 40 °C were followed by high‐performance liquid chromatography. Due to its higher hydrogen donating ability, α‐tocopherol was more efficient than γ‐ and δ‐tocopherols in inhibiting the isomerization of cis,trans ML‐OOH to trans,trans ML‐OOH. α‐Tocopherol stabilized hydroperoxides into the cis,trans configuration, whereas γ‐ and δ‐tocopherols allowed hydroperoxides to convert into trans,trans isomers. Thus, the biological importance of α‐tocopherol as compared to other tocopherols may be partly due to its better efficacy in protecting the cis,trans configuration of hydroperoxides formed, for example, in the enzymatic oxidation of polyunsaturated fatty acids. The isomeric configuration of hydroperoxides has an impact on biological activities of further oxidation products of polyunsaturated fatty acids. Paradoxically, the order of activity of tocopherols with regard to hydroperoxide decomposition was different from that obtained for hydroperoxide isomerization. γ‐ and δ‐tocopherols were more efficient inhibitors of ML‐OOH decomposition when compared to α‐tocopherol. A loss of antioxidant efficiency, observed as the tocopherol concentration increased from 2 to 20 mM, was highest for α‐tocopherol but was also evident for γ‐ and δ‐tocopherols. Thus, the differences in the relative effects of tocopherols at differing concentrations seem to result from a compromise between their radical scavenging efficiency and participation in side reactions of peroxidizing nature.     

A study on the influence of fucosterol on thermal polymerisation of purified high oleic sunflower triacylglycerols

Δ⁵‐Avenasterol, an ethylidene side‐chain phytosterol, was described as an antipolymerisation agent for thermooxidised oils. This paper investigates the potential of its commercially available geometrical isomer, fucosterol, as an antipolymerisation agent for high oleic sunflower oil (HOSO). Purified triacylglycerols were prepared from HOSO and incubated in an oven, at 180°C, with or without fucosterol, sitosterol and stigmasterol. Analysis of polymers and dimers (by high‐performance size exclusion chromatography) showed that fucosterol did not affect the rate of polymerisation of purified HOSO triacylglycerols in our model. Comparison with α‐tocopherol, showed that this tocol inhibited the polymerisation of the oil while fucosterol did not. © 1999 Society of Chemical Industry     

Protective Effects of Meldonium in Experimental Models of Cardiovascular Complications with a Potential Application in COVID-19

Right ventricular (RV) and left ventricular (LV) dysfunction is common in a significant number of hospitalized coronavirus disease 2019 (COVID-19) patients. This study was conducted to assess whether the improved mitochondrial bioenergetics by cardiometabolic drug meldonium can attenuate the development of ventricular dysfunction in experimental RV and LV dysfunction models, which resemble ventricular dysfunction in COVID-19 patients. Effects of meldonium were assessed in rats with pulmonary hypertension-induced RV failure and in mice with inflammation-induced LV dysfunction. Rats with RV failure showed decreased RV fractional area change (RVFAC) and hypertrophy. Treatment with meldonium attenuated the development of RV hypertrophy and increased RVFAC by 50%. Mice with inflammation-induced LV dysfunction had decreased LV ejection fraction (LVEF) by 30%. Treatment with meldonium prevented the decrease in LVEF. A decrease in the mitochondrial fatty acid oxidation with a concomitant increase in pyruvate metabolism was noted in the cardiac fibers of the rats and mice with RV and LV failure, respectively. Meldonium treatment in both models restored mitochondrial bioenergetics. The results show that meldonium treatment prevents the development of RV and LV systolic dysfunction by enhancing mitochondrial function in experimental models of ventricular dysfunction that resembles cardiovascular complications in COVID-19 patients.     

Effect of silane treatment parameters on the silane layer formation and bonding to thermoplastic urethane

Enhancing adhesion is of primary importance in preparation of insert injection molded plastic–metal hybrids. Here, the combination of coupling agent application parameters and steel oxide microstructure effects on the adhesion in thermoplastic urethane–stainless steel hybrids was studied. The stainless steel oxide structure was first modified by electrolytical polishing and subsequent oxidation treatment, then the steel was coated with N-(β-aminoethyl)-γ-aminopropyltrimethoxysilane (γ-AEAPS) prior to overmolding with thermoplastic urethane. The properties of formed silane coatings and ultimately the thermoplastic urethane–stainless steel hybrids were determined by several microscopical methods, infrared spectroscopy and mechanical testing. The bond strength of hybrids depended on the silane layer thickness. Also the stainless steel surface oxide structure had a remarkable influence on the coating formation and the resulting hybrid bond strength.     

Phytosterol content in seven oat cultivars grown at three locations in Sweden

The total and individual sterol content in 21 oat samples (seven cultivars grown at three different locations in Sweden) were analysed by gas chromatography after acid hydrolysis. The total sterol content in these oat cultivars varied between 350–491 µg g⁻¹ of dry weight of kernel. The most abundant phytosterol was β‐sitosterol (237–321 µg g⁻¹) followed by campesterol (32–46 µg g⁻¹), Δ⁵‐avenasterol (15–47 µg g⁻¹) and stigmasterol (11–21 µg g⁻¹). There was a statistically significant difference in total sterol content between cultivars (p < 0.05) but no effect was found for cultivation location. Furthermore when contents of Δ⁵‐avenasterol in hexane‐extracted oat oil and acid‐hydrolysed oat samples were compared, it was noticed that the content of Δ⁵‐avenasterol was lowered due to acid hydrolysis. © 1999 Society of Chemical Industry     

Toxicological effects of dehydroabietic acid (DHAA) on the trout, Salmo gairdneri Richardson, in fresh water

Toxicological and physiological effects of dehydroabietic acid (DHAA), a major poison to fishes in pulp and paper mill effluents, were studied by two experiments with rainbow trout, Salmo gairdneri Richardson: in the first, fish were acutely exposed for 4 days to an average DHAA concentration of 1.2 mg l⁻¹ (Exp. I) and in the second for 30 days to an average of 20 μg DHAA l⁻¹ (Exp. II).Compared to the controls, fish of Exp. I displayed a decreased relative weight of liver, an increased blood haematocrit, and increased haemoglobin as well as plasma protein concentrations. The aspartate aminotransferase activity of heart muscle was significantly elevated, as was also the lactate dehydrogenase (LDH) of white muscle tissue. In the blood plasma, the proportion of muscle type LDH activity was simultaneously increased. UDP-glucuronyl-transferase activities of liver and kidney were strongly decreased. Results suggest an increased and altered use of body energy reserves, decreased plasma volume and impaired liver function.Fish of Exp. II showed an increased relative weight of spleen. In addition, liver and gill LDH shifted towards heart-type. We conclude that 20 μg l⁻¹ is close to the “minimum effective concentration” of DHAA to rainbow trout.     

One-pot synthesis and characterization of subnanometre-size benzotriazolate protected copper clusters

A simple one-pot method for the preparation of subnanometre-size benzotriazolate (BTA) protected copper clusters, Cu(n)BTA(m), is reported. The clusters were analyzed by optical and infrared spectroscopy, mass spectrometry and transmission electron microscopy together with computational methods. We suggest a structural motif where the copper core of the Cu(n)BTA(m) clusters is protected by BTA-Cu(i)-BTA units.