HBK-14 and HBK-15 do not influence blood pressure, lipid profile, glucose level, or liver enzymes activity after chronic treatment in rats

Older and even new antidepressants cause adverse effects, such as orthostatic hypotension, hyper- or hypoglycemia, liver injury or lipid disorders. In our previous experiments we showed significant antidepressant- and anxiolytic-like activities of dual 5-HT1A and 5-HT7 antagonists with α1-adrenolitic properties i.e. 1-[(2,6-dimethylphenoxy)ethoxyethyl]-4-(2-methoxyphenyl)piperazine hydrochloride (HBK-14) and 1-[(2-chloro-6-methylphenoxy)ethoxyethyl]-4-(2-methoxyphenyl)piperazine hydrochloride (HBK-15). Here, we evaluated the influence of chronic administration of HBK-14 and HBK-15 on blood pressure (non-invasive blood pressure measurement system for rodents), lipid profile (total cholesterol, low density lipoproteins-LDL, high density lipoproteins-HDL, triglycerides), glucose level, and liver enzymes activity (aspartate aminotransferase, alanine aminotransferase, γ-glutamyl transferase). We determined potential antihistaminic (isolated guinea pig ileum) and antioxidant properties (ferric reducing ability of plasma-FRAP, non-protein thiols-NPSH, stable free radical diphenylpicrylhydrazyl-DPPH) cytotoxicity. Our experiments revealed that HBK-14 and HBK-15 did not influence blood pressure, lipid profile, glucose level or liver enzymes activity in rats after 2-week treatment. We also showed that none of the compounds possessed antioxidant or cytotoxic properties at antidepressant- and anxiolytic-like doses. HBK-14 and HBK-15 very weakly blocked H1 receptors in guinea pig ileum. Positive results of our preliminary experiments on the safety of HBK-14 and HBK-15 encourage further studies concerning their effectiveness in the treatment of depression and/or anxiety disorders

Voltammetric Determination of Isopropylmethylphenols in Herbal Spices

Thymol and carvacrol—the components of herbal spices—are known for their broad biological activity as antimicrobials and antioxidants. For this reason, it is important to develop new methods for their determination in plant material. A simple, rapid, and sensitive method for determination of total content of these analytes in herbal spices using differential pulse voltammetry (DPV) has been developed. The basis of the research is the oxidation process of isopropylmethylphenols on a platinum microelectrode in glacial acetic acid containing acetonitrile (20%, v/v) and 0.1 mol L−1 sodium perchlorate as the supporting electrolyte. Linear voltammetric responses for thymol and carvacrol were obtained in a wide concentration range from 0.39–1105 and 0.47–640 µg mL−1, with a low detection limit of 0.04 and 0.05 µg mL−1, respectively. The analysis was performed using the multiple standard addition method. The results of the voltammetric determination are in good agreement with the data of the standard chromatographic method. To the best of our knowledge, this is the first presentation of an electrochemical procedure to determine these compounds in these environmental and electrode materials

Hypotensive activity of HBK-14 after chronic treatment

Tło: Zaburzenia depresyjne są coraz bardziej rozpowszechnione. Wiele obecnie stosowanych leków nie jest wystarczająco skuteczna lub powoduje liczne działania niepożądane, dlatego ważne jest poszukiwanie nowych substancji aktywnych. Wcześniejsze badania wykazały, że związek HBK-14 - antagonista receptorów 5-HT1A i 5-HT7 o potwierdzonym potencjalnym działaniu antydepresyjnym i przeciwlękowym -posiada również właściwości α1-adrenolityczne, co może być przyczyną efektów niepożądanych, w szczególności obniżania ciśnienia krwi.Cel: Oznaczenie wpływu związku HBK-14 na ciśnienie tętnicze krwi u szczura po podaniu przewlekłym. Określenie wpływu związku HBK-14 na profil lipidowy i węglowodanowy, aktywność enzymów wątrobowych w osoczu krwi szczura oraz aktywność antyoksydacyjną po podaniu przewlekłym.Materiały i Metodyka: Pomiaru ciśnienia na tętnicy ogonowej szczura dokonywano 3 razy w tygodniu przez 14 dni po 7 dniach aklimatyzacji szczurów. Badany związek podawano dootrzewnowo w dawkach działających ośrodkowo codziennie o tej samej porze. Poza tym po zakończeniu eksperymentu i odstawieniu paszy na 24 godziny przy pomocy gotowych, komercyjnych testów przeprowadzono oznaczenia biochemiczne poziomu cholesterolu całkowitego, LDL, HDL, triglicerydów, glukozy, aktywności enzymów wątrobowych oraz aktywności antyoksydacyjnej.Wyniki: Związek HBK-14 nie wpływał na ciśnienie tętnicze krwi u szczurów po podaniu przewlekłym. Nie wpływał istotnie na profil lipidowy i węglowodanowy. Nie spowodował wzrostu aktywności enzymów wątrobowych. W przeprowadzonych badaniach nie wykazał aktywności antyoksydacyjnej.Wnioski: HBK-14 nie wykazał niekorzystnego wpływu na ciśnienie tętnicze, profil lipidowy i węglowodanowy oraz działania uszkadzającego wątrobę po podaniu przewlekłym, co niewątpliwie zachęca do dalszych badań nad tym związkiem.Introduction: Depressive disorders are more and more prevalent. Many currently used drugs are not sufficiently effective and couse numerous adverse effects, therefore it is important to search for new active substances. Previous studies showed that HBK-14 - 5-HT1A and 5-HT7 receptors antagonist, with antidepressant- and anxiolytic-like properties possess α1-adrenolytic properties which can cause undesirable effects like the reduction of blood pressure.Aim: The aim of this study was to evaluate the influence of HBK-14 on rat blood pressure after chronic treatment. Determination of the effect of HBK-14 on lipid and carbohydrate profile, liver enzymes activity in rat plasma as well as antioxidant activity after chronic treatment.Materials and Methods: Blood pressure was measured on the rat caudal artery, 3 times a week for 14 days, after 7 days of habituation period. The tested compound at active antidepressant- and anxiolytic-like doses was administered intraperitoneally, daily at the same time. In addition, after the end of the experiment and the withdrawal of feed for 24 hours, the biochemical parameters like total cholesterol, LDL, HDL, glucose level, liver enzymes activity and antioxidant activity were performed using standard spectrometric assay kits.Results: Compound HBK-14 did not influence blood pressure as well as lipid profile and glucose level after chronic administration. It did not cause an increase of activity of liver enzymes. The tested substance did not demonstrate antioxidant activity.Conclusions: HBK-14 showed no effect on blood pressure, lipid and carbohydrate profile as well as damaging effects on liver after chronic administration, which encourages further research on this compound

Application of a Carbon Fiber Microelectrode as a Sensor for Apocynin Electroanalysis

In this study, a carbon fiber microelectrode (CF) was applied for the investigation of the electrochemical behavior of the natural antioxidant, apocynin (APO). Given the limited solubility of APO in water, a mixture of anhydrous acetic acid (AcH) with 20%, v/v acetonitrile (AN) and 0.1 mol L−1 sodium acetate (AcNa) was used. The electrochemical properties of APO were examined through linear sweep voltammetry (LSV), differential pulse voltammetry (DPV), and cyclic voltammetry (CV). The anodic oxidation of APO, which is the basis of the method used, proved to be diffusion-controlled and proceeded with a two-electron and one proton exchange. Both radicals and radical cations, arising from the first and second step of electrode reactions, respectively, underwent subsequent chemical transformations to yield more stable final products (EqCiEiCi mechanism). Using optimized DPV conditions, the anodic peak current of APO at a potential of 0.925 V vs. Ag/AgCl showed a good linear response within the concentration range of 2.7 × 10−6–2.6 × 10−4 mol L−1. The detection and quantification limits were determined as 8.9 × 10−7 and 2.7 × 10−6 mol L−1, respectively. The developed DPV method enabled the successful determination of APO in herbal extracts and in dietary supplements. It should be noted that this is the first method to be used for voltammetric determination of APO

Effect of Iota-Carrageenan and Its Hydrolysates on the Stability of Milk Ice Cream Mixes

The objective of this research was to determine the influence of iota-carrageenan and its acid and enzymatic hydrolysates on the physical properties of milk ice cream mixes. The main factors considered were the Turbiscan stability index, backscattering profile, particle size distribution and median diameter (D50), the consistency index and the flow behavior index of ice cream mix before and after 24 h of maturation at 4°C. The microstructure of emulsion was also analysed based on confocal laser scanning microscopy (CLSM). The addition of iota-carrageenan resulted in lower stability of emulsion compared to emulsions with its acid and enzymatic hydrolysates. The sedimentation, coalescence and flocculation were observed based on the backscattering profile and CLSM images. The addition of stabilisers contributed to an increase in D50 of ice cream mix from 17.56 to 37.05–45.50 µm before maturation and from 34.73 to 46.73 µm after maturation. The iota-carrageenan after commercial lactase treatment improved the stability of milk ice cream mixes by increasing the consistency index to 0.104 and a flow behaviour index to 0.702. Finally, it may be concluded that the stabilisers used – iota-carrageenan and its hydrolysates – significantly influenced the physical properties of milk ice cream mixes and, hence, can be used as beneficial ingredients in the recipe of milk ice cream mixes

Antioxidant Properties of Wafers with Added Pumpkin Seed Flour Subjected to In Vitro Digestion

In this study, our research aim was to assess the influence of pumpkin seed flour addition on the antioxidant properties, consumer acceptability, functional properties, and texture of wafers. The in vitro gastrointestinal digestion process was used to assess the effectiveness of fortification in terms of the potential bioavailability of phenolic compounds and peptides. The antioxidant activity of the obtained hydrolysates and potentially bioavailable fractions (≤3.5 kDa) was tested. The highest antiradical activity and Fe2+ chelation ability (IC50) were noted for the fraction obtained from wafers with the greatest addition of pumpkin seed flour—Pf4 (0.49 mg/mL for ABTS+*, 3.84 mg/mL for DPPH*, and 2.04 mg/mL for Fe2+ chelation). The addition of pumpkin seed flour caused the color of the wafers to change to a darker one (24.46% differences in L* between C and P4), which influenced consumer ratings. This study shows that adding pumpkin seed flour increases the peptide and phenolic contents of wafers (1.13 mg/mL and 1.01 mg/mL of peptides and 0.429 mg/mL and 0.351 mg/mL of phenolics for P4 and C hydrolysates, respectively) and enhances their antioxidant activity, with only minimal effects on taste, aroma, crispness, water and fat adsorption capacity, and foaming ability. Fractions ≤ 3.5 kDa showed greater antioxidative activity than hydrolysates, and the addition of pumpkin seed flour improved these properties. To sum up, pumpkin seeds are a valuable source of antioxidant compounds (phenolic compounds and peptides) and can be used to enrich various products

HBK-15, a Multimodal Compound, Showed an Anxiolytic-Like Effect in Rats

Anxiety is a common mental disorder, and its prevalence has lately increased because of the COVID-19 pandemic. Unfortunately, the available anxiolytics are often ineffective, and most possess addictive potential. Thus, searching for novel compounds is essential. In our previous studies, we selected a multimodal compound, HBK-15, which showed a fast antidepressant-like effect in animal models of depression. HBK-15 demonstrated a high affinity for serotonin 5-HT(1A) receptors and moderate for 5-HT(7), dopamine D(2), and α(1)-adrenoceptors. Based on the receptor profile and preliminary studies, we aimed to investigate the anxiolytic potential of HBK-15 using the conditioned-response rat model of anxiety, i.e., the Vogel drinking test. We performed hot plate and free-drinking tests to exclude false positive results in the Vogel test. Using radioligand binding studies, we also investigated the affinity of the compound for the selected biological targets, which play a role in anxiety. Our experiments revealed that HBK-15 showed an anxiolytic-like effect in rats (5 mg/kg) without influencing the pain threshold or the amount of water consumed in the free-drinking test. Furthermore, the tested compound did not show a significant affinity for the selected biological targets, which suggests that its anxiolytic-like mechanism of action could be connected with the interaction with other receptors. This study indicates that multimodal compounds with a receptor profile similar to HBK-15 could be an attractive therapeutic option for patients with a generalized anxiety disorder. However, more studies are required to determine the exact mechanism of action of HBK-15 and its safety profile

Influence of UV nail lamps radiation on human keratinocytes viability

Abstract Ultraviolet nail lamps are becoming increasingly popular, however, the safety of their use remains controversial. The following article directly responds to recently published literature data and aims to determine the viability of human keratinocytes irradiated by a UV nail-drying machine. Cells were exposed to 365–405 nm wavelength UV light emitted by a nail drying machine in two time variants: 4 and 20 min, with and without sunscreen cream SPF50 protection, and compared to the untreated control. Compared to the control, cell viability after irradiation for 4 min decreased insignificantly (p < 0.1), however for 20 min decreased by 35% (p < 0.0001). Furthermore, cells with sunscreen protection compared to those without showed significantly increased viability, regardless of time-variant (p < 0.0001). The study shows that 4-min irradiation does not significantly reduce the viability of human keratinocytes and the time of 20 min significantly alters the research results compared to 4 min, which corresponds to real conditions. The results suggest that typical manicure exposure time does not significantly affect keratinocyte viability, which could increase the risk of developing skin cancers. Despite the above results, it is recommended to use sunscreen protection on your hands during the procedure, which significantly increases the viability of keratinocytes during ultraviolet nail lamp radiation