Nikolay Innokentievich Suslov

Introduction: Extracts of the Aconite genus are used for medicinal purposes in China, Korea, Japan, and India. Extracts of the Aconite genus contain the highly toxic alkaloid aconitine and a number of low-toxicity alkaloids with medicinal properties. One of these alkaloids is songorine. The objective of the review is an analysis of data on the anxiolytic, antinociceptive, antiinflammatory, anticancer, cardioprotective, and proliferative effects of songorine. Methods: The information was retrieved from PubMed between from 1835 and 2026. Results: It was demonstrated that songorine has anxiolytic, antinociceptive, anti-inflammatory, anticancer, cardioprotective, and proliferative properties. The anti-inflammatory effect of songorine is accompanied by a decrease in pro-inflammatory cytokine production and a reduction of neutrophil invasion in injured tissue. The role of the GABAA, dopamine D2, peripheral κ-opioid, cannabinoid CB1, and other receptors in the effects of songorine is discussed. The involvement of protein kinases in the proliferative effect of songorine is demonstrated. The role of transcription factors NF-κB, Nrf2, STAT3, and protein synthesis in the effects of songorine is discussed. Discussion: Despite accumulated experimental data demonstrating a broad spectrum of pharmacological effects of songorine, including anxiolytic, analgesic, anti-inflammatory, and cardioprotective effects, a number of unresolved questions remain related to an incomplete understanding of the molecular targets and signaling pathways. Furthermore, most results were obtained in preclinical models, limiting their direct extrapolation to clinical practice. Conclusion: Songorine is discussed for use in the treatment of depression, chronic pain, chronic inflammation, and cancer. It can be used to accelerate wound healing, in the treatment of sepsis, doxorubicin-induced cardiomyopathy, and stress-induced cardiac injury.

Introduction: Impairment of the erectile component of the copulatory cycle represents a significant clinical and social problem, substantially reducing the quality of life in men. The highest incidence of this pathology is observed in male patients over 50 years of age, which is associated with an age-related decrease in gonadal hormonal function. In the present paper, the results of experimental studies evaluating the efficacy of co-administration of Siberian fir polyprenols and Panax ginseng in a model of copulatory function impairment caused by androgen deficiency are demonstrated. Materials and Methods: The focus of the study was a herbal preparation being a pharmaceutical composition of Siberian fir polyprenols and Panax ginseng. The experiment was conducted in 26 sexually mature category-I male SD rats (Sprague Dawley with body weight of 250-300 g and aged 12 weeks). Siberian fir polyprenols were administered at a dose of 23 mg/kg combined with Panax ginseng at a dose of 1.5 ml/kg. The treatment course duration was 7 days. Tribestan (Sofarma, Bulgaria) at a dose of 70 mg/kg was used as a reference drug. Reduction in copulatory activity caused by androgen deficiency was modeled by administering synestrol to male rats. The level of copulatory activity was assessed by the paired sexual behavior test. Results and Discussion: The results of experimental studies showed that the administration of synestrol to male rats led to the suppression of their copulatory activity. The groups of animals receiving Siberian fir polyprenols and Panax ginseng against the background of synestrol administration exhibited a statistically significant increase in the number of animals with rising copulatory activity (the number of mating attempts increased, and cases of ejaculation were reported). The pharmacological activity of the reference drug Tribestan was manifested at the level of tendencies. Conclusion: The present paper demonstrates that Siberian fir polyprenols (dosed at 23 mg/kg) in combination with Panax ginseng tincture (dosed at 1.5 ml/kg) prove effective in stimulating the copulatory activity of male rats under conditions of androgen deficiency.

Разработка новых анксиолитических препаратов имеет важное значение, поскольку в настоящее время в развитых странах растет число заболеваний, связанных с тревожными расстройствами, а препараты для лечения таких заболеваний вызывают огромное число побочных эффектов, особенно при систематическом употреблении, что привлекает большое внимание к их безопасности. 4,10-Диморфолинацетил-2,6,8,12-тетраацетил-2,4,6,8,10,12-гексаазаизовюрцитан перспективен в качестве анксиолитического средства с низкой токсичностью. Высокая вероятность проявления 4,10-диморфолинацетил-2,6,8,12-тетраацетил-2,4,6,8,10,12-гексаазаизовюрцитаном анксиолитической активности была рассчитана с помощью интернет-платформы Pass-online. В данной статье рассматривается его способ получения с выходом 83 % и чистотой 99,6 %, а также биологические исследования in vivo, которые подтверждают точность прогноза in silico.

Introduction . Opioid and cannabinoid receptors are involved in the antinociceptive effects of songorine, a diterpene alkaloid isolated from the above-ground parts of Aconitum barbatum, as demonstrated in various models of chemical and thermal pain. The involvement of opioid receptors in songorine is antinociceptive mechanism necessitates studying its potential side effects, characteristic of narcotic analgesics. TRPA1 receptor involvement in songorine is analgesic mechanism is possible, requiring further investigation in models of mechanical hyperalgesia with formalin. Aim: To study the antinociceptive activity of the diterpenoid alkaloid songorine at a dose of 25 μg/kg in the Randall-Selitto test against formalin-induced hyperalgesia and its potential opioid-like side effects. Material and Methods . The study was performed on outbred male CDI and mice male CBA mice obtained from the Department of Experimental Biological Models at the E.D. Goldberg Research Institute of Pharmacology and Regenerative Medicine Tomsk NRMC. Songorine, a diterpene alkaloid of the atizine series, was administered orally to the animals at a previously established effective dose of 25 μg/kg. Tramadol (KRKA) at a dose of 20 mg/kg and ketorolac (Dr. Reddy´s Laboratories Ltd.) at a dose of 6 mg/kg were used as reference drugs. Antinociceptive activity was studied using the Randall-Selitto test with a Ugo Basile (Italy) analgesy-meter on a mechanical pain model, with and without formalin-induced hyperalgesia. To study the effect of songorine on the frequency of breathing in non-narcotized mice, the number of respiratory movements per minute was recorded after 5-fold administration of the alkaloid and the reference drug tramadol. The withdrawal syndrome was assessed using the non-selective opioid receptor antagonist naloxone (Sigma). The effect of the alkaloid on gastrointestinal smooth muscle was studied in the “charcoal meal” test. Results. Songorine is antinociceptive effect in the Randall-Selitto test upon single administration is comparable to ketorolac and tramadol, but less prolonged than the latter. Songorine is pronounced analgesic activity in formalin-induced hyperalgesia suggests the possible involvement of TRPA1 receptors in its mechanism of action. The study of possible undesirable effects of the course per os administration of the diterpene alkaloid songorine at a dose of 25 μg/kg showed that it does not cause the development of respiratory depression, withdrawal syndrome and drug-induced obstipation. Conclusion. In the Randall-Selitto test, TRPA1 receptor involvement in the antinociceptive activity of songorine was established against a background of formalin hyperalgesia. The diterpene alkaloid songorine at subchronic administration at a dose of 25 μg/kg does not show the side effects characteristic of morphine-like drugs.

Introduction: The study was aimed at a comparative analysis of the anti-inflammatory and analgesic activities of diterpene alkaloid songorine obtained from Aconitum barbatum and its cell culture. Materials and Methods: Experiments were performed on 60 male mice of the CBA line. The object of the study was the diterpene alkaloid of songorine (25 µg/kg) isolated from Aconitum barbatum, as well as obtained from the callus culture of cells. Comparative study of analgesic and anti-inflammatory activities of the alkaloid obtained from different sources was carried out under conditions of the formalin test and abdominal constriction test. Diclofenac sodium (10 mg/kg) and paracetamol (85 mg/kg) were used as comparison drugs. Control animals received distilled water. All substances were administered to mice per os for 5 days, the last time – 1 hour before the onset of the damaging effect. Results and Discussion: Under the formalin test conditions, the analgesic activity of songorine from both sources was manifested in the second phase of pain response. The anti-inflammatory activity in this model of both “standard” and ”culture” songorine was comparable to that of diclofenac sodium. Probably, pharmacological activity of alkaloid in the formalin test is provided by suppression of proinflammatory mediators and TRPA1-receptors. In the abdominal constriction test, all investigated substances showed a pronounced analgesic effect maximum under the action of songorine in vitro. In addition, songorine from both sources, in contrast to the reference drug, provided a reliable phlogolytic effect. Probably, the pharmacological activity of songorine in this model is provided by its suppressive action against endogenous mediators of pain and inflammation and of TRPV1-receptors. Conclusion: Comparative analysis of the analgesic and anti-inflammatory effects of songorine (25 µg/kg) from Aconitum barbatum after a 5-dose regimen demonstrated comparability with “culture” songorine (25 µg/kg).

The aim of this study was a qualitative and quantitative analysis of macro- and (ultra)trace elements, the main groups of biologically active substances (BAS) of organic nature in the shoots of bilberry (Vaccinium myrtillus L., family Ericaceae), collected after fruit harvesting in the Tomsk region (Tomsk and Zyryansky districts). The study of the elemental composition was carried out after ashing using the methods of emission spectral and instrumental neutron activation analysis with irradiation with thermal neutrons. Determination of classes of BAS of organic nature and their representatives was carried out using chemical reactions, chromatography (sorbents: silica gel, cellulose) using reliable samples, spectroscopy in the UV, visible and IR rangles of the spectrum. As a result of applying the method of emission spectrometry, 45 elements were determined, among which 18 are (conditionally) essential. The macroelements K, Ca, P, Na, Si, Mg and the trace element Mn dominate in the composition of the ash of bilberry shoots after harvesting the fruits. Using the method of neutron activation analysis, the presence of 27 elements was established, nine of which are classified as (conditionally) essential. The data indicate the predominance of Ca, Fe, Na, as well as Ba, Rb, Sr in the ashes of the shoots of the plant after harvesting the fruits. The results of the study show that the Tomsk and Zyryansk districts of the region belong to the background territories. The specificity of bilberry shoots after harvesting the fruits of the Tomsk region is reflected in the highest concentration of the characteristic group of elements (Ba, Sr, Sb, Hf, Fe, Rb), which follows from the formation of chelate complexes and strong organometallic compounds. In the composition of bilberry shoots after harvesting the fruits, the main groups of BAS of a phenolic nature are: simple phenols, flavonoids, phenolcarboxylic acids, coumarins and tannins; triterpene compounds, sterols, water-soluble polysaccharides, carotenoids, amino acids are also present. The research results show the possibility of using plant shoots after harvesting fruits as pharmaceutical raw materials for the development of medicines based on them, including for correcting disorders of higher integrative functions of the brain.

Введение. Болезнь Альцгеймера все чаще становится причиной ранней инвалидизацией и смерти. Попытки создания фармакотерапевтического средства, дающего эффективный результат в лечении этой патологии, до сегодняшнего дня не увенчались успехом. В данной статье приведены результаты экспериментальных исследований, ставящие целью создание более эффективного средства лечения данного заболевания. Материалы и методы. Объектом исследования явились полипренолы, выделенные из пихты сибирской (Abiessibirica Ledeb.). Эксперименты выполнены на 108 аутбредных половозрелых мышах-самцах стока СDI массой тела 28 – 30г (в возрасте 5 недель). Эффект суммы полипренолов на обучаемость и память исследовался в интервале доз – 5, 20, 50, 100, 200 и 500 мг/кг массы тела мыши. В качестве препарата сравнения использовали глиатилин в дозе 90 мг/кг. Экспериментальная модель нарушения когнитивных функций создавалась хроническим (в течение 20 дней) внутрибрюшинным введением скополамина в дозе 2 мг/кг. Нарушение когнитивных функций оценивались по изменениям показателей выработки и воспроизведения условного рефлекса пассивного избегания (УРПИ). Результаты и их обсуждение. Результаты проведенных экспериментов показали, что хроническое введение скополамина вызвало выраженное снижение воспроизводимости УРПИ. Одновременно с этим изучаемая субстанция в дозах 20 и 50 мг/кг. Глиатилин оказывал близкое по характеру действие. Авторы полагают что в развитии антиамнестического эффекта участвуют холинергические рецепторы. Заключение. Приведенное доклиническое исследование показывает, что найдено новое средство с антиамнестическим действием на основе суммы полипренолов Пихты сибирской (Abies sibirica Ledeb.), семейство Сосновые (fam. Pinaceae). Данное средство может быть использовано для лечения заболеваний нейродегенеративных патологических процессов, в частности болезни Альцгеймера.

Biologically active compounds of natural or synthetic origin have a complex structure and generally contain various structural groups among which polycyclic cage amines are found. Hexaazaisowurtzitanes are representatives of these amines and studies on their biological activity began less than two decades ago, starting with research on the environmental impact of CL-20. This research helped to evaluate the risks of potential pollution in the habitat environments of living organisms and determine whether the chemical compounds in question could be utilized in pesticides, herbicides, fungicides, or medicinal drugs. The nomenclature of hexaazaisowurtzitane compounds has recently been expanded significantly, and some of them have demonstrated promise in the design of medicinal drugs. This paper review studies the pharmacological activity of the acyl derivatives of hexaazaisowurtzitane. Most of the compounds have been found to possess a high analgesic activity, providing a solution to the pressing issue of pain management in current pharmacology. Analgesic drugs currently used in the clinical practice do not meet all of the efficacy and safety requirements (gastro-, nephro-, hepato-, haematotoxicity, etc.). The material presented in the seven sections of this paper highlights information about hexaazaisowurtzitane derivatives. Furthermore, they have been observed to exhibit anti-inflammatory, anticonvulsant, antihypoxic, and antimetastatic activities, which render them highly promising for evaluation in various fields of medicinal practice.

Описан способ получения перспективного ненаркотического анальгетического средства вещества с выраженной противовоспалительной активностью из класса гексаазаизовюрцитанов. Рассмотрены способы снижения стоимости получения целевого вещества и приведены его полные физико-химические характеристики. Эффективность и безопасность полученного средства показана на нескольких животных моделях.

Introduction: This article studies the wound healing activity of the flavonoid schaftoside – apigenin -6-C-β-D glucopyranosyl 8-C-α-L arabinopyranoside (C26H28O14) isolated from the above-ground part of Lyсhnis chalcedonica L. Materials and Methods: The experiments were carried out on sexually mature mongrel male CD-1 mice. The wound healing effect of schaftoside was studied on a model of a plane skin wound. Schaftoside was applied externally (topically) in the form of an aqueous solution using a pipette of 100 mcl per wound at concentrations of 0.1 uG/mL, 1.5 uG/mL, 3.0 uG/mL, one time per day during the entire period of wound healing from the first day after the wound had been induced until its complete epithelialization. Aloe juice (100 mcL per wound) was used as a positive control. A solvent (water) – 100 mcL per wound – was applied to control animals. Results and Discussion: The results of our study on the model of a plane skin wound showed that the compound schaftoside isolated from Lyсhnis chalcedonica, when applied externally (topically) at concentrations of 0.1 uG/mL, 1.5 uG/mL, 3.0 uG/mL, contributes to a significant reduction in the size of plane skin wounds, comparable to the action of aloe juice (the comparison drug). The wound healing effect is more pronounced at the first, second, and third weeks of the healing process, i.e. at the stage of inflammation, proliferation, and activation of the repair process. Under the influence of schaftoside at a concentration of 3.0 uG/mL, a more complete epithelialization was recorded than in the group where the comparison drug (aloe juice) was applied. Conclusion: Our study for the first time shows a pronounced wound healing effect from aqueous solution of the flavonoid schaftoside from Lyсhnis chalcedonica on the model of a plane skin wound in mice. Graphical Abstract