Abstract—The review presents information from the literature and our own data on some pharmacological properties of Sorbus aucuparia L. Particular attention is paid to the research in experimental oncology.

We studied the effect of an anthocyanin-containing complex from the fruits of S. aucuparia L. on doxorubicin-induced genotoxicity in bone marrow cells of C57BL/6 mice. The complex reduced the genotoxic effect doxorubicin in metaphase plates of bone marrow cells in 24, 48 h, and 10 days after the administration of the cytostatic. The mean number of single fragments and the fraction of cells with gaps and aberrant metaphases also decreased.

Anthocyanins are flavonoid compounds belonging to the group of polyphenols. A. melanocarpa ( Michx. ) Elliott chokeberry is known to be rich in these bioactive substances. The previously conducted chemical analysis showed that an anthocyanin-containing complex obtained from A. melanocarpa fruits comprise anthocyanins, flavonoids, phenolic acids, and catechins, with anthocyanins being the dominant components. A large amount of data indicates that Aronia fruits exhibit a wide spectrum of pharmacological activity. In this work, we assess the safety of an anthocyanin-containing complex obtained from A. melanocarpa fruits by its genotoxic study followed by an analysis of its effect on mutagenesis. To this end, a model of doxorubicin-induced genotoxicity in bone marrow cells of C57Bl/6 mice was used. The plant complex under study at a dose of 225 mg/kg had no effect the cytogenetic parameters of animal bone marrow cells after a single or double administration. The use of the anthocyanin-containing complex led to a decrease in DNA damage caused by the administration of doxorubicin, 24 and 48 hours after the introduction of a cytostatic agent. Hence, the data obtained can serve as the basis for the creation of a drug corrector for cycplasms.

A method for production of a promising non-narcotic analgesic of the hexaazaisowurtzitane class is developed. Data on the physicochemical characteristics and conditions for obtaining the target substance are presented. The effectiveness of the resulting agent is shown in several animal models. A pronounced analgesic effect of the newly synthesized compound 4-(3,4-dibromothiophenecarbonyl)-2,6,8,10,12-pentaacetyl-2,4,6,8,10,12-hexaazaisowurtzitane comparable or even superior to that of tramadol was revealed.

The results of studying the effect of the anthocyanin-containing complex from Sorbus aucuparia L. on the main indicators of erythropoiesis in the blood and bone marrow of mice with Lewis lung carcinoma against the background of doxorubicin administration were presented. It was shown that administration of the anthocyanin-containing complex from S. aucuparia L. to animals with the tumor prevented the development of anemic syndrome by promoting regeneration of the erythropoiesis after its depletion caused by single administration of a cytostatic agent.

Mountain ash (Sorbus aucuparia L.) is a prominent representative of phenolic medicinal plants. A widespread and cultivated plant, it has a sufficient raw material base not only of fruits, but also of other parts of the plant (leaves, flowers); it is a promising source of biologically active complexes for the development of new medical drugs. In the work, the content of the main groups of phenolic compounds in plant extracts from fruits, leaves and flowers of S. aucuparia L. was determined. Extracts were obtained using the original technology with acidified 95% ethanol. The content of the sum of phenolic compounds was determined, as well as the content of anthocyanins, flavonoids, phenolic acids, tannins. The effect of these phenol-containing complexes on the development of transplanted tumors (Lewis lung carcinoma, lung cancer-67) and the effectiveness of cyclophosphane treatment were studied. It was revealed that the use of plant complexes leads to a significant inhibition of the development of metastases in the lungs, as well as an increase in the antitumor and anti-metastatic activity of cyclophosphane in combined treatment. The new data obtained are of interest for further study of these phenol-containing complexes in order to create drugs based on them to increase the effectiveness of chemotherapy for malignant neoplasms.

A method of preparing the potential analgesic substance 4,10-bis((±)-5-benzoyl-2,3-dihydro-1H-pyrrolo-[1,2-a]pyrrole-1-carbonyl)-2,6,8,12-tetraacetyl-2,4,6,8,10,12-hexaazatetracyclo[5,5,03,11,05,9]dodecane is described in detail. Different conditions for preparing the target substance are considered and its full physicochemical properties are presented. Marked analgesic activity of this innovatory compound was found in conditions of thermal nociception in the hotplate test and acute visceral and somatic deep pain in the acetic writhings test.

We studied the effect of an anthocyanin-containing complex from Sorbus aucuparia L. on the main indicators of erythropoiesis in the blood and bone marrow of mice against the background of doxorubicin treatment. It was shown that administration of an anthocyanincontaining complex from S. aucuparia L. prevented the development of anemic syndrome by stimulating regeneration of the erythroid lineage of hematopoiesis after its devastation by single administration of the cytostatic.

Black chokeberry is an official drug raw material and is used as a multivitamin drug. Black chokeberry guarantees the supply of raw materials as it grows all over the Russian Federation end is a promising sourse of phenolic compounds for new drugs. Objective: to develop the most favorable conditions for extraction of bioactive compounds from black chokeberry and to assess its anti-metastatic activity. To extract bioactive compounds from black chokeberry the method of multistep repercolation with completed cycle was used. To assess the factors controlling the raw material extraction the technique of mathematic simulation for latin square. The technique of liquid anthocyanins and catechins rich black chokeberry extraction was given with the following parameters: extragent – 95% acidified alcohol, phase relation – 1 : 5, number of percolators – 5. The content of biologically active substances in the extract obtained with 95% acidified ethyl alcohol was determined by conventional methods. In the composition of the extract, the content of anthocyanins (5.83±0.25%), catechins (0.22±0.02%), tannins (4.65±0.30%), phenolic acids (0.27±0.01%) and other biologically active substances was determined. To assess the antitumor properties of the chokeberry fruit extract, the Lewis lung carcinoma model was used. It was found that the proposed extract reliably inhibits the development of metastases and increases the antimetastatic activity of cyclophosphamide in combined treatment, is of interest as a means for increasing the effectiveness of tumor chemotherapy.

The authors have used the model of indomethacine‑induced injuries of rat’s stomach to assess gastroprotective action of calcium alginate, and revealed that preliminary intragastric introduction of calcium alginate hampers the formation of destructive injuries of mucous coat of stomach. The authors believe their findings allow to consider calcium alginate as drug intended to prevent ulcer‑related injury caused by nonsteroidal antiinflammatory drugs.

One of prospective methods for immunotherapy of tumors is modulation via immunological checkpoints, specifically, via the PD-1(CD279)/PD-L1(CD274) system. Interactions between tumor cell receptor (CD279) and the ligand on lymphocytes (CD274) leads to lymphocyte inactivation, which allows tumor escape from the immune control. Experiments on C57BL/6 mice with Lewis lung carcinoma demonstrate the possibility of reducing the expression of CD279 and CD274 on the peripheral blood and tumor tissue lymphocytes under the effects of Tussilago farfara L. polysaccharides. This phenomenon can underlie the antitumor and antimetastatic effects of these substances.

Myelotoxicity is a serious side effect of anticancer drugs. The search for drugs that can reduce the hematological complications of chemotherapy through modulation of hematopoietic stem cells is an urgent task of oncopharmacology. In the present study we showed that administration of Tussilago farfara L. polysaccharides to C57BL/6 mice treated with cyclophosphamide can increase the number of hematopoietic stem cells (CD117 + 34 + ) in the bone marrow.

A complex of biologically active compounds was isolated from Lychnis chalcedonica L. cultivated at the Siberian Botanical Garden at Tomsk State University. HPLC analysis found that the isolated compounds were flavonoids with retention times 10.40, 12.45, 13.29, and 15.47 min. The major flavonoid constituent was vicenin with tr = 13.29 min and a peak area of 87.4%. The flavonoid complex of L. chalcedonica was studied using three transplanted tumor models, i.e., Lewis lung carcinoma (LLC), melanoma B-16 (B-16), and lung cancer RL-67 (RL-67). Tests on C57BL/6 mice showed that the L. chalcedonica flavonoid complex inhibited development of melanoma B-16. Co-administration of L. chalcedonica flavonoids and cyclophosphamide enhanced the antitumor effect of the cytostatic in animals with B-16, RL-67, and LLC.

A possibility for correction of damaging effects of polychemotherapy on the intestinal epithelium with Tussilago farfara L. polysaccharides was studied on C57Bl/6 mice with Lewis lung carcinoma. The polysaccharides had protective and/or stimulating effects on the intestinal epithelium during polychemotherapy and promoted reparative regeneration in the intestine.

Pronounced analgesic activity of the innovative compound 4-(3,4-dibromthiophencarbonyl)-2,6,8,12-tetraacethyl-2,4,6,8,10,12hexaazatetracyclo[5,5,0,03, 11,05, 9] dodecane (thiowurtzine) was observed in the thermal nociceptive hot plate test and in the acute visceral and somatic deep pain model (acetic acid writhing test). In these experimental models, naloxone-sensitive thiowurtzine-induced analgesia was revealed. The absence of tropism to peripheral opioid receptors in the acetic acid writhing test was demonstrated using naloxone methiodide. Course administration of low-toxic thiowurtzine in effective doses was not associated with ulcerogenic damage to the gastric mucosa in experimental animals.

Интерферон-гамма (ИФН) играет важную роль в иммунных механизмах сдерживания опухолевого процесса, однако в определенных условиях может оказывать проопухолевое действие. Релиз-активные антитела (РА АТ) к ИФН изменяют конформацию молекулы этого цитокина, облегчают его связывание с рецептором и усиливают продукцию эндогенного ИФН. Цель настоящего исследования состояла в изучении влияния РА АТ к ИФН на имеющийся опухолевый процесс на моделях меланомы и карциносаркомы. Методика. Было изучено влияние препарата на течение опухолевого процесса в моделях меланомы В-16 у мышей и карциносаркомы Уокера 256 у крыс. Результаты. У мышей с меланомой В-16, чувствительной к ИФН, тестируемый препарат не стимулировал рост и метастазирование опухоли. В модели карциносаркомы Уокера 256 у крыс РА АТ к ИФН также не влияли на размер опухоли, однако значительно ингибировали гематогенное метастазирование. Заключение. В настоящем исследовании не было выявлено стимулирования опухолевого процесса и метастазирования препаратом РА АТ к ИФН. Interferon-gamma (IFN) plays an important role in antitumor immunity; however, in some circumstances, it may also favor tumor immune evasion. Released-active (RA) anti-IFN antibodies (Abs) are able to induce conformational changes in the IFN molecule and to facilitate its receptor binding, which results in enhanced production of this cytokine. The aim of the present study was to evaluate the effect of RA anti-IFN Abs on the tumor growth in models of melanoma and carcinosarcoma. Methods. The ability of anti-IFN RA Abs to influence the tumor growth was evaluated in the models of melanoma B16 in mice and Walker 256 carcinosarcoma in rats. Results. The exposure of mice with IFN-sensitive melanoma B16 to the tested drug did not result in stimulation of tumor growth and metastasis. RA anti-IFN Abs also did not affect the tumor size in the rat model of Walker 256 carcinosarcoma but significantly inhibited the hematogenous metastasis. Conclusion. In the present study, no stimulation of the tumor process and metastasis by RA anti-IFN Abs were found.

The composition of phenolic compounds of rowanberry (Sorbus aucuparia L.) fruit extracts prepared with 40% ethanol and 95% acidified ethanol was studied. The differences in the content of flavonoids, including anthocyanins, and phenolic acids were shown. It was found that the antimetastatic activity of cyclophosphamide was most efficiently increased by the rowanberry fruit extract in 95% acidified ethanol enriched in anthocyanins. The aim of the present research was to investigate the effect of hydroalcoholic extracts of rowanberry fruit on the development of Lewis lung carcinoma and the antitumor activity of cyclophosphamide and to reveal the most effective extract containing a phenolic complex for its further study as a promising drug.

The experiments on C57Bl/6 mice with Lewis lung carcinoma showed that addition of Tussilago farfara L. polysaccharides to conventional cisplatin/paclitaxel polychemotherapy moderated neutropenia caused by antitumor therapy and increased its efficiency. The stimulating effect of polysaccharides on the granulopoietic lineage cells is comparable with that of recombinant CSF Neupogen.