Pharmacological Substances Research Articles

N-Acetylcysteine and Hydrogen Sulfide in Coronavirus Disease 2019.

Significance: Hydrogen sulfide (H2S) is one of the three main gasotransmitters that are endogenously produced in humans and are protective against oxidative stress. Recent findings from studies focusing on coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), shifted our attention to a potentially modulatory role of H2S in this viral respiratory disease. Recent Advances: H2S levels at hospital admission may be of importance since this gasotransmitter has been shown to be protective against lung damage through its antiviral, antioxidant, and anti-inflammatory actions. Furthermore, many COVID-19 cases have been described demonstrating remarkable clinical improvement upon administration of high doses of N-acetylcysteine (NAC). NAC is a renowned pharmacological antioxidant substance acting as a source of cysteine, thereby promoting endogenous glutathione (GSH) biosynthesis as well as generation of sulfane sulfur species when desulfurated to H2S. Critical Issues: Combining H2S physiology and currently available knowledge of COVID-19, H2S is hypothesized to target three main vulnerabilities of SARS-CoV-2: (i) cell entry through interfering with functional host receptors, (ii) viral replication through acting on RNA-dependent RNA polymerase (RdRp), and (iii) the escalation of inflammation to a potentially lethal hyperinflammatory cytokine storm (toll-like receptor 4 [TLR4] pathway and NLR family pyrin domain containing 3 [NLRP3] inflammasome). Future Directions: Dissecting the breakdown of NAC reveals the possibility of increasing endogenous H2S levels, which may provide a convenient rationale for the application of H2S-targeted therapeutics. Further randomized-controlled trials are warranted to investigate its definitive role.

Study on the Spectrum-Effect Relationship of the Traditional Effect of Saponins in Glycyrrhiza uralensis Fisch.

Licorice is a traditional Chinese medicine that has been used for a long time in China and still in great use today. The effect of licorice on tonifying spleen and invigorating qi has been proved for thousands of years, but the material basis of its effect is not clear. In this paper, we established the fingerprints of 21 batches of licorice collected from different origins in China with High-Performance Liquid Chromatography (HPLC) to identify the common peaks. Its effect of tonifying spleen and invigorating qi was confirmed through a series of praxiology experiments. The spectrum-effect relationship between HPLC fingerprints and its effect of tonifying spleen and invigorating qi of licorice was examined by gray relational analysis and partial least squares regression analysis. Results showed that the effect of licorice on tonifying spleen and invigorating qi resulted from various compounds and peaks. X2–X6 is presumed to be the main pharmacological substance base. This research successfully identified the spectrum-effect relationship between HPLC fingerprints and the effect of licorice on tonifying spleen and invigorating qi. The research method based on the spectrum-effect relationship helps provide new research ideas and strategies for the study of the basis of the medicinal materials and quality control of traditional Chinese medicine.

Sub-acute injection toxicity of Florfenicol VS 30

This study is aimed at identifying organs and/or target organs systems that are most sensitive to the toxic effect of the drug under study, as well as determining the level of cumulation and reversibility of pathological changes in the animal body influenced by the pharmacological substance. During a 14-day sub-acute (intramuscular injection) experiment on outbred rats, it has been found that doses of 2.260 mg/kg (1/5 of LD50=1.1300 mg/kg) and 1130 mg/kg (1/10 of LD50=1.1300 mg/kg) were toxic and the dose of 565 mg/ kg was threshold (1/20 of LD50=1.1300 mg/kg). The investigated product Florfenicol VS 30 (developed by VETSFERA, Russia) in the tested doses caused a significant decrease in the body weight and significant changes in hematological and biochemical blood parameters. Integral indices in test groups were characterized by severe depression, decreased food activity, weakened skeletal muscle tone, and poor skin turgor. Gastrointestinal disorders were observed during all weight recording periods, while animals were injected with toxic doses. By day 14 of the experiment, the drug at a dose of 565 mg/kg (tolerable level) caused no changes in the behavior of experimental rats or their functional states. The disturbed hemopoiesis and significant hypoproteinemia revealed were reversible.

Chemical analysis and bioactivity evaluation of the stem of Rheum tanguticum

Rhubarb (Dahuang in Chinese), belongs to the family Polygonaceae, genus Rheum, has been employed as a traditional Chinese medicinal material for a long time. Rheum officinale, R. palmatum, R. tanguticum, R. rhaponticum, R. ribes, R. franzenbachii, and R. rhabarbarum have been reported to possess many pharmacological active substances that are used to treat diseases. The petioles of R. rhabarbarum, R. ribes, R. rhaponticum are well-known vegetables in some regions of the world. Based on this folk application and active ingredients that may be present in stems, the present study was conducted to analyze the content of nutritional components and active secondary metabolism components, and evaluate the antimicrobial activity and antioxidant activity with prepared solvent extracts. Methods published by the Association of Official Analytical Chemistry (AOAC) was used to determine the total protein, crude fat, crude fiber, vitamin C, ash, and moisture contents. The results showed that the inflorescence stem of R. tanguticum contained a higher content of crude fiber (89.14%) and vitamin C (16.96%). The content of total protein and crude fat was 8.49% and 1.34% respectively. The results showed that the DPPH Radical Scavenging Activity of the extract had a concentration-dependent effect. The highest activity (83.4%) of the methanol extract sample was recorded at 1.0 mg/mL and the lowest activity, 15.56%, was recorded at 0.2 mg/mL. 0.485 mg/mL was needed to achieve a 50% toxicity. The flavonoid and total phenolic contents of the inflorescence stem of R. tanguticum were found to be 0.022 mg/g and 4.138 mg/g respectively. A concentration of 10 mg/mL successfully inhibited the growth of the pathogenic microorganisms, Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus and Bacillus subtilis using the paper disc diffusion method. In summary, the results of this study confirm that the inflorescence stem of R. tanguticum contains some rich nutritional components and bioactive secondary metabolism components that are beneficial for human health as edible parts or processed products. The results of bioactivity evaluation in this study also showed that the inflorescence stem of R. tanguticum could be developed natural antioxidant and antibacterial agent as a potential resource. This may possibly provide a feasible solution for non-medicinal parts utilization.

Super-Treg: Toward a New Era of Adoptive Treg Therapy Enabled by Genetic Modifications.

Regulatory Tcells (Treg) are essential components of peripheral immune homeostasis. Adoptive Treg cell therapy has shown efficacy in a variety of immune-mediated diseases in preclinical studies and is now moving from phase I/IIa to larger phase II studies aiming to demonstrate efficacy. However, hurdles such as in vivo stability and efficacy remain to be addressed. Nevertheless, preclinical models have shown that Treg function and specificity can be increased by pharmacological substances or gene modifications, and even that conventional T cells can be converted to Treg potentially providing new sources of Treg and facilitating Treg cell therapy. The exponential growth in genetic engineering techniques and their application to T cells coupled to a large body of knowledge on Treg open numerous opportunities to generate Treg with “superpowers”. This review summarizes the genetic engineering techniques available and their applications for the next-generation of Super-Treg with increased function, stability, redirected specificity and survival.

A clinical trials corpus annotated with UMLS entities to enhance the access to evidence-based medicine

BackgroundThe large volume of medical literature makes it difficult for healthcare professionals to keep abreast of the latest studies that support Evidence-Based Medicine. Natural language processing enhances the access to relevant information, and gold standard corpora are required to improve systems. To contribute with a new dataset for this domain, we collected the Clinical Trials for Evidence-Based Medicine in Spanish (CT-EBM-SP) corpus.MethodsWe annotated 1200 texts about clinical trials with entities from the Unified Medical Language System semantic groups: anatomy (ANAT), pharmacological and chemical substances (CHEM), pathologies (DISO), and lab tests, diagnostic or therapeutic procedures (PROC). We doubly annotated 10% of the corpus and measured inter-annotator agreement (IAA) using F-measure. As use case, we run medical entity recognition experiments with neural network models.ResultsThis resource contains 500 abstracts of journal articles about clinical trials and 700 announcements of trial protocols (292 173 tokens). We annotated 46 699 entities (13.98% are nested entities). Regarding IAA agreement, we obtained an average F-measure of 85.65% (±4.79, strict match) and 93.94% (±3.31, relaxed match). In the use case experiments, we achieved recognition results ranging from 80.28% (±00.99) to 86.74% (±00.19) of average F-measure.ConclusionsOur results show that this resource is adequate for experiments with state-of-the-art approaches to biomedical named entity recognition. It is freely distributed at: http://www.lllf.uam.es/ESP/nlpmedterm_en.html. The methods are generalizable to other languages with similar available sources.

ОБЗОР СОВРЕМЕННЫХ МЕТОДОВ ПРОИЗВОДСТВА ИМПРЕГНИРОВАННЫХ ШОВНЫХ МАТЕРИАЛОВ

The modern medical process poses new challenges, classical suture materials have ceased to satisfy surgeons with both their sanogenetic properties and physical properties. These properties are capable of giving threads the production methods described in the article. Among these methods, there are two fundamental differences: an active pharmacological substance is applied in the process of creating a thread, and a substance is applied to an already finished thread, which fundamentally affects the physical and biological parameters.

BCG, muramylpeptides, trained immunity (part II): a low molecular weight alternative to multicomponent bacterial immunostimulants for prevention of respiratory infections during a pandemic

During a pandemic, nonspecific immunoprophylaxis of SARS-CoV-2 infection and other acute respiratory infections (ARI), which can worsen the course of COVID-19, is increasingly in demand in addition to specific immunization. BCG vaccine appears to be one of the candidate immunostimulants in this regard. At the same time, other microbe-derived preparations capable of inducing a state of trained immunity deserve attention. BCG and other bacterial immunostimulatory agents containing a large number of biologically active subunits have long been considered as objects of search for promising pharmacological substances. The review analyzes the linkages between BCG, mycobacterial adjuvants, bacterial lysates, trained immunity, muramylpeptides (MPs) and NOD2 receptors in light of the choice of a low molecular weight alternative to multicomponent bacterial immunostimulants for ARI prevention during the COVID-19 pandemic. The search for key molecules by which bacteria stimulate innate and adaptive immune responses proceeds in a spiral. On different loops of this spiral, MPs have repeatedly reproduced the nonspecific effects of multicomponent bacterial adjuvants, vaccines and immunostimulants. MPs and peptidoglycans containing MPs determine the adjuvant properties of the cell walls of mycobacteria and their peptide-glycolipid fraction (wax D). MPs were able to replace Mycobacterium tuberculosis in complete Freunds adjuvant. MPs determine the NOD2-dependent ability of BCG to induce trained immunity. Probably, MPs provide NOD2-mediated long-term prophylactic action of bacterial lysates. All of the above has prompted revisiting the previously obtained evidence of the efficacy of glucosaminylmuramyl dipeptide (GMDP) as a NOD2 agonist in treatment/prevention of respiratory infections. We speculate here that MPs, in particular GMDP, at rational dosing regimens will be able to reproduce many aspects of the nonspecific effects of BCG and multicomponent bacterial immunostimulants in preventing ARI during the COVID-19 pandemic and in the post-pandemic period.

Prevalence of use of permitted pharmacological substances for recovery among athletes

Objectives: Food supplements and medicines which are not on the list of prohibited substances of the World Anti-Doping Agency are included in the group of permitted pharmacological agents for athlete’s recovery. The aim of this study was to describe qualitatively and quantitatively food supplements (FS) and over-the-counter drugs use among athletes in the last six month. Methods: This was a cross sectional study. Data on food supplements and the over-the-counter drugs, usage were collected during 2018 by self-administered, anonymous questionnaire. Results: A total of 112 athletes completed the survey. A total of 51.8% (n = 58) athletes reported the use of food supplements. The use of medical supplements was reported by 50.0% (n = 56) of athletes, 26.8% (n = 30) reported using ergogenic supplements, 1.8% (n = 2) using of sports food and 4.5% (n = 5) using other supplements. The use of over-the-counter drugs was reported by 35.7% (n = 40) of athletes. The over-the-counter analgesic drugs were used by 95% (n = 38) of over-the-counter drug users. Concomitant administration two or more over-the-counter drugs was reported by 40% (n = 16) athletes. Doctors and coaches had no advisory role in the use of food supplements or over-the-counter drugs.

Pharmacological and recreational substance abuse – An emerging risk to cardiovascular health among the younger population

Pharmacological and recreational substance abuse – An emerging risk to cardiovascular health among the younger population

Оценка кумулятивных свойств препарата Дельцид 7,5®

Cumulative properties (accumulation of a substance or its effect upon repeated administration in equal doses) is determined on the basis of a quantitative indicator – the cumulation coefficient. Before carrying out chronic toxicological experiments, it is necessary to determine the cumulation index of the pharmacological substance – the ratio of LD50 with a single administration to LD50 with multiple administration. According to the Lim method, the cumulative properties of the drug Delcid 7,5® were studied, the cumulation coefficient of the drug was Kkum = 1,09. In accordance with the classification of chemicals, including pesticides by L.I. For a bear, the drug belongs to a group of substances with pronounced cumulation.

COVID-19: Analysis of Drug Repositioning Practice.

An outbreak of a new coronavirus disease (COVID-19) in China in December 2019 became the epicenter for the spread of a global pandemic. The SARS-CoV-2 coronavirus causes a cascade of respiratory diseases similar to severe acute respiratory syndrome (SARS). Currently, there is no effective, specific, and safe treatment for COVID-19 to suppress the virus in the human body. The present study searched for pharmacological substances with antiviral activity for possible drug repositioning based on experimental and theoretical information in a series of publications on in vitro assays of agents against SARS-CoV-2. An analysis identified 46 well-known pharmaceutical substances that could be used for drug repositioning to create a therapy for COVID-19.

Benzodiazepine tranquilizers abolish the stress-induced increase of the brain ghrelin level in DANIO RERIO

Danio reriohas firmly established itself as a successful model for research in many areas of biology and medicine, first of all for developing new medicines.
 The aimof our study was to evaluate ghrelin level in zebrafish brain after stress and after phenazepam usage on stressed fish.
 Methods.In our study 96Danio rerio, predatorCichlasoma nicaraguensishave been used. The fish have been kept at anormal room temperature (2223C) with standard feeding time (twice per day). The level of neuropeptides has been tested by ELISA test. During experiment a fish has been firstly placed in a beaker with a dissolved pharmacological substance, then has been transferred into a tank with predator. In the end of experiment, it has been put into a novel tank for 6 min. The decapitation has been made. Thebrain has been divided into three anatomical parts:telencephalonjust behind the olfactory bulb, the middle partcorpora bigemiaandcerebellum, which is situated behind thecorpora bigemia. After that the material for ELISA test was made using GhrelinFISH, MyBioSource ELISA kit.
 Results.In the control group ghrelin has been determined only in thecerebellumin 57.14% of all fish. In the experiment with predator ghrelin has been found in all tested brain parts of fish, but in thetelencephalonthere was the highest level. Inthe experiment with phenazepam usage only and phenazepam administration after predator stress, the ghrelin value has not been determined atall.
 Conclusion.Thus we have found out that the ghrelin value increases after predator stress and the drug phenazepam eliminated it completely after its administration. We may suppose that the administration of anxiolytics such as phenazepam can reduce the anxiety inDanio rerio.

Benzodiazepine tranquilizers abolish the stress-induced increase of the brain ghrelin level in DANIO RERIO

Danio reriohas firmly established itself as a successful model for research in many areas of biology and medicine, first of all for developing new medicines.
 The aimof our study was to evaluate ghrelin level in zebrafish brain after stress and after phenazepam usage on stressed fish.
 Methods.In our study 96Danio rerio, predatorCichlasoma nicaraguensishave been used. The fish have been kept at anormal room temperature (2223C) with standard feeding time (twice per day). The level of neuropeptides has been tested by ELISA test. During experiment a fish has been firstly placed in a beaker with a dissolved pharmacological substance, then has been transferred into a tank with predator. In the end of experiment, it has been put into a novel tank for 6 min. The decapitation has been made. Thebrain has been divided into three anatomical parts:telencephalonjust behind the olfactory bulb, the middle partcorpora bigemiaandcerebellum, which is situated behind thecorpora bigemia. After that the material for ELISA test was made using GhrelinFISH, MyBioSource ELISA kit.
 Results.In the control group ghrelin has been determined only in thecerebellumin 57.14% of all fish. In the experiment with predator ghrelin has been found in all tested brain parts of fish, but in thetelencephalonthere was the highest level. Inthe experiment with phenazepam usage only and phenazepam administration after predator stress, the ghrelin value has not been determined atall.
 Conclusion.Thus we have found out that the ghrelin value increases after predator stress and the drug phenazepam eliminated it completely after its administration. We may suppose that the administration of anxiolytics such as phenazepam can reduce the anxiety inDanio rerio.

Importance of dermocosmetics in the management of acne

Acne is the major dermatological disease as per the number of patients affected. Adolescents are suffering acne, but also more and more post-adolescent women. Acne is a multifactorial disease involving four main pathogenic pathways: increased and altered sebum production; inflammation; changes in the keratinization process resulting in abnormal keratinization; and follicular colonization by C. acnes. Until now, the treatment is mostly based on pharmacological substances, which often present side effects and for this reason offer bad compliance from the patients. Nevertheless, a number of dermocosmetics contain active ingredients, most of them vegetal, capable of focusing all four pathogenic pathways and obtaining satisfactory results. The most relevant seboregulator substances are butyl avocadate, but also epigallocatechin-3-gallate. In the category of antimicrobial agents, the most commonly used are tea tree oil, decanediol and Quassia amara extract. Among anti-inflammatory substances, we can mention Salix alba and Gingko biloba extracts, but also zinc, panthenol and superoxide dismutase. As per anti-keratolytic agents, alpha-hydroxy acids are commonly used, as well as salicylic acid, a beta-hydroxy acid. Nicotinamide is an ingredient of choice due to its multiple positive effects on the pathogenesis of acne. Early management of acne is crucial, in order to limit its symptoms and severity, but also avoid sequelae as serious as prolonged erythema or acne scars. This early management must be based on a holistic approach of acne, not necessarily including pharmacological treatment, but dermocosmetics, in particular in case of mild acne or as maintenance treatment. In this holistic approach, emphasis must be given on cleansing and moisturizing of the skin, and sun protection.

The study of neuroprotective effects and underlying mechanism of Naoshuantong capsule on ischemia stroke mice

BackgroundNaoshuantong capsule (NSTC) is an oral Chinese medicine formula composed of Typhae Pollen, Radix Paeoniae Rubra, Curcumae Radix, Gastrodiae Rhizoma and Radix Rhapontici. It has been widely used at the acute and recovery stage of ischemic stroke since 2001. Comparing with its wide clinical application, there are only few studies emphasize on investigating its pharmacological effects.MethodsTo more generally elucidate the underlying mechanisms in this study, we identified active ingredients in NSTC by a network pharmacology approach based on transcriptomics analysis and pharmacological experiments. Modified neurological severity scores and morphometric analysis using Nissl staining were employed to evaluate the neuroprotective effects of NSTC on ischemia stroke in mice.ResultsThe results showed that NSTC had preventive and protective effects on ischemia stroke, featuring repair of brain tissue during the sub-acute stage of stroke. This may attribute to the underlying mechanisms including anti-inflammatory, antioxidant, and anti-apoptotic activities, as well as an attenuation of excitatory amino acids (EAAs) toxicity of the active ingredients, especially the most active apigenin, from NSTC. Specifically, naringenin, calycosin, gastrodin, caffeic acid, paeoniflorin, and β-elemene seem to be also pharmacological active substances responsible for the anti-inflammatory effects. Meanwhile, 13-hydroxygemone, gastrodin, and p-hydroxybenzyl alcohol contributed to the attenuation of EAAs toxicity Furthermore, apigenin, naringenin, calycosin, gastrodin, and β-elemene accelerated the repair of brain ischemic tissue by up-regulating the expression of TGF-β1 levels.ConclusionsThe present study identifies the active ingredients of NSTC and illustrates the underlying mechanism using a combination of network pharmacology, transcriptomics analysis, and pharmacological experiments.

Advances in pharmacotherapy of cataracts

Cataracts, the leading cause of vision impairment worldwide, arise from abnormal aggregation of lens proteins. According to the World Health Organization, cataracts cause more than 40% of blindness cases. As the population ages, the prevalence of cataracts will increase rapidly. Although cataract surgery is regarded as effective, it still suffers from complications and high cost, and could not meet the increasingly surgery demand. Therefore, pharmacological treatment for cataracts is a cheaper and more readily available option for patients, which is also a hot topic for years. Anti-cataract drug screening was previously mainly based on the specific pathogenic factors: oxidative stress, excess of quinoid substances, and aldose reductase (AR) activation. And several anti-cataract drugs have been applied in the clinic, while the effect is still unsatisfied. Makley and Zhao recently identified two kinds of novel pharmacological substances (25-hydroxycholesterol, lanosterol) that can reverse lens opacity by dissolving the aggregation of crystallin proteins, indicating that protein aggregation is not an endpoint and could be reversed with specific small-molecule drugs, significantly boosting the development of the cataract pharmacopeia and being regarded as a new dawn for cataract treatment. Our team built a novel optimized platform and had screened several potential therapeutic agents from a collection of lanosterol derivatives. In this review, we would mainly focus on the advancement of cataract pharmacotherapy based on the targets for anti-cataract drugs.

COVID-19: анализ практики репозиционирования лекарственных препаратов

В декабре 2019 г. вспышка новой коронавирусной болезни (COVID-19) в Китае стала отправной точкой развития общемировой пандемии. Вирус SARS-CoV-2 вызывает каскад респираторных заболеваний, сходных с тяжелым острым респираторным синдромом. В настоящий момент не существует эффективной, специфической и безопасной терапии для подавления взаимодействия этого вируса с организмом человека. При поиске фармакологических субстанций с противовирусной активностью ведутся исследования в области репозиционирования лекарственных средств на основе экспериментальной и теоретической информации, представленной в ряде публикаций, посвященных тестированию in vitro средств в отношении SARS-CoV-2. Анализ научных публикаций позволил идентифицировать 46 фармацевтических субстанций, которые могут быть использованы для репозиционирования лекарств при создании терапии против COVID-19.

Chemopreventive Potential of Caryophyllane Sesquiterpenes: An Overview of Preliminary Evidence.

Simple SummaryCaryophyllane sesquiterpenes are unique natural compounds widely occurring in nature, especially in plant essential oils, that are characterized by multiple properties of pharmacological interest. Although β-caryophyllene is the most investigated compound, its metabolite β-caryophyllene oxide and the analogues α-humulene and isocaryophyllene have been evaluated, too. Previous studies showed a polypharmacological profile of these compounds and a possible interest in cancer research; however, emerging evidence have highlighted a complex pool of healing properties, including a block of carcinogen-mediated DNA damage and cytoprotection against anticancer drug toxicity in noncancerous cells, along with antiproliferative and chemosensitizing activitives in cancer cells, thus suggesting their promising role as chemopreventive agents. In line with this evidence, the present review provides the pharmacological basis to support a further therapeutic interest for caryophyllane sesquiterpenes as chemopreventive agents. Moreover, possible structure–activity relationships and future research directions have been highlighted.Chemoprevention is referred to as a strategy to inhibit, suppress, or reverse tumor development and progression in healthy people along with high-risk subjects and oncologic patients through using pharmacological or natural substances. Numerous phytochemicals have been widely described in the literature to possess chemopreventive properties, although their clinical usefulness remains to be defined. Among them, caryophyllane sesquiterpenes are natural compounds widely occurring in nature kingdoms, especially in plants, fungi, and marine environments. Several structures, characterized by a common caryophyllane skeleton with further rearrangements, have been identified, but those isolated from plant essential oils, including β-caryophyllene, β-caryophyllene oxide, α-humulene, and isocaryophyllene, have attracted the greatest pharmacological attention. Emerging evidence has outlined a complex polypharmacological profile of caryophyllane sesquiterpenes characterized by blocking, suppressing, chemosensitizing, and cytoprotective properties, which suggests a possible usefulness of these natural substances in cancer chemoprevention for both preventive and adjuvant purposes. In the present review, the scientific knowledge about the chemopreventive properties of caryophyllane sesquiterpenes and the mechanisms involved have been collected and discussed; moreover, possible structure–activity relationships have been highlighted. Although further high-quality studies are required, the promising preclinical findings and the safe pharmacological profile encourage further studies to define a clinical usefulness of caryophyllane sesquiterpenes in primary, secondary, or tertiary chemoprevention.

The Level of Reactive Carbonyl Derivatives of Proteins, Malondialdehyde, and Catalase Activity in the Brain of Rats after Therapy Following Chronic Unpredictable Moderate Stress

BACKGROUND: Understanding the mechanisms of the behavioral disorders’ emergence under the influence of chronic stress is the most important aspect of the subsequent development of a strategy for its therapy and prevention. Changes in the oxidative metabolism processes can be decisive in the development of the pathogenetic cascade in the brain. Information about these processes can be obtained by studying protein carbonylation, lipid peroxidation, and catalase activity (CA). The complexity of the therapeutic impact in various behavioral disorders implies the search for new pharmacological substances and the study of the previously known drugs’ effects based on the available scientific data.
 AIM: The aim of the study was to study the reactive carbonyl derivatives of proteins (RCDP), malondialdehyde (MDA), and CA in the brain of rats after therapy following chronic unpredictable moderate stress (CUMS).
 METHODS: Forty male outbred rats weighing 450–500 g were used in this study. For 21 days, all animals were exposed to the diverse stress factors for developing the CUMS. The animals were divided into four groups of 10 rats, each using randomized selection. The rats of one group were euthanized by decapitation with subsequent brain harvesting (Group 4). Remaining three groups of rats were treated with placebo (Group 1), harmine hydrochloride (Group 2), and amitriptyline (Group 3) for 21 days. Upon completion of therapy, all rats were also euthanized by decapitation with subsequent brain harvesting. The levels of RCDP, MDA, and CA were studied in their brain, and after that, we compared the multiple studied indicators in four groups.
 RESULTS: The results of the rat brain examinations in four groups showed that RCDP level in Group 2 was significantly lower than in Group 4 (p = 0.000). Similarly, in Group 1, it was lower than in Group 4 (p = 0.021), plus, it did not differ statistically from the harmine hydrochloride group (p = 1,000). Indicators of Groups 3 and 4 did not have any significant differences in RCDP level, too, (p = 0.799); however, the RCDP level in Group 2 was significantly lower than in Group 3 (p = 0.040). MDA indicators did not show significant differences; however, a tendency for lower values was revealed in Group 1 (p = 0.233) and Group 2 (p = 0.151). CA in Group 4 was lower than that in Group 1 (p = 0.000), Group 2 (p = 0.001), and Group 3 (p = 0.003) contemporaneously, while all treatment groups were comparable (p = 1.000).
 CONCLUSION: The result of exposure to chronic stress can be reproduced with the best quality in the CUMS model. The neurobiological foundations of the model make it possible to assess biochemical markers of oxidative metabolism and evaluate the possibilities of pharmacological correction of stress-induced behavioral disorders. To assess the mechanisms of autoregulation of oxidative metabolism, this study included a placebo group (Group 1), the level of RCDP in which was significantly higher in comparison with Group 3 and Group 4 and slightly lower than in Group 2. In this study, harmine hydrochloride demonstrated activity exceeding amitriptyline, particularly limiting the process of protein carbonylation, not noted for amitriptyline. According to the results of the RCDP assessment in the CUMS model, the process of protein carbonylation can be considered to be one of the significant factors in the deactivation of neurotransmitters. The CA levels determined in all groups allowed us to consider this marker as the most sensitive to the effects of stress, which possibly has an inhibitory effect on catalase, as its activity in all groups after therapy was more than two-fold higher than in animals right after CUMS. We can assume that CA plays an important role in starting the processes of autoregulation of oxidative metabolism. The study was carried out as a part of the implementation of the scientific and technical program No. BR05236584 “Development of new herbal preparations and their pharmacological and clinical studies” (O.0820). (2018–2020) in the priority area, “Life and Health Sciences.”