RESUMO
Many human diseases including cancer, degenerative and autoimmune disorders, diabetes and others are multifactorial. Pharmaceutical agents acting on a single target do not provide their efficient curation. Multitargeted drugs exhibiting pleiotropic pharmacological effects have certain advantages due to the normalization of the complex pathological processes of different etiology. Extracts of medicinal plants (EMP) containing multiple phytocomponents are widely used in traditional medicines for multifactorial disorders' treatment. Experimental studies of pharmacological potential for multicomponent compositions are quite expensive and time-consuming. In silico evaluation of EMP the pharmacological potential may provide the basis for selecting the most promising directions of testing and for identifying potential additive/synergistic effects. Multiphytoadaptogen (MPhA) containing 70 major phytocomponents of different chemical classes from 40 medicinal plant extracts has been studied inâ vitro, inâ vivo and in clinical researches. Antiproliferative and anti-tumor activities have been shown against some tumors as well as evidence-based therapeutic effects against age-related pathologies. In addition, the neuroprotective, antioxidant, antimutagenic, radioprotective, and immunomodulatory effects of MPhA were confirmed. Analysis of the PASS profiles of the biological activity of MPhA phytocomponents showed that most of the predicted anti-tumor and anti-metastatic effects were consistent with the results of laboratory and clinical studies. Antimutagenic, immunomodulatory, radioprotective, neuroprotective and anti-Parkinsonian effects were also predicted for most of the phytocomponents. Effects associated with positive effects on the male and female reproductive systems have been identified too. Thus, PASS and PharmaExpert can be used to evaluate the pharmacological potential of complex pharmaceutical compositions containing natural products.
Assuntos
Produtos Biológicos , Plantas Medicinais , Humanos , Plantas Medicinais/química , Extratos Vegetais/farmacologia , Medicina Tradicional , Produtos Biológicos/farmacologia , ComputadoresRESUMO
Based on the prediction of biological activity spectra for several secondary metabolites of medicinal plants using the PASS computer program and validation in vitro of the predictions results the priority direction of the pharmaceutical composition Phytoladaptogene (PLA) development was determined. PLA is a complex of structurally diverse small organic compounds including biologically active substances of phytoadaptogenes (ginsenosides from Panax ginseng, rhodionin from Rhodiola rosea and others) compiled considering previously developed pharmaceutical compositions. Two variants of the pharmaceutical composition were studied: - the major and minor variants included 22 and 13 compounds, respectively. The probability of activity exceeds the probability of inactivity for 1400 out of 1945 pharmacological effects and mechanisms predicted by PASS for the major variant of PLA. The wide range of predicted activities is mainly due to the low structural similarity of constituent compounds. An in silico prediction indicates the possibilities of antitumor properties against bladder, stomach, colon, ovarian and cervical cancers both for minor and major PLA compositions. It was found that the highest probability values of activity were predicted for three mechanisms: apoptosis agonist, caspase-3 stimulant, and transcription factor NF-κB inhibitor. According to the PharmaExpert program they are associated with the antitumor effect against bladder cancer. Experimental validation was using the human bladder cancer cell line RT-112. The results of the MTT test have shown that the cytotoxicity of the major PLA variant is higher than that of the minor PLA variant. In vitro experiments performed using two methods (double staining with annexin V and propidium iodide and detection of active caspase-3 in cells) confirmed that the death of bladder cancer cells occurred via the apoptotic mechanism. The data obtained correspond to the results of the prediction and indicate advantages of the major PLA composition. Thus, PLA can become the basis for the development of a drug with the antitumor activity against bladder cancer. The antitumor activity predicted by PASS for other cancers may be the subject of further studies.
Assuntos
Antineoplásicos , Neoplasias da Bexiga Urinária , Antineoplásicos/farmacologia , Apoptose , Linhagem Celular Tumoral , Simulação por Computador , Humanos , Extratos Vegetais/farmacologia , Neoplasias da Bexiga Urinária/tratamento farmacológicoRESUMO
We studied the influence of nontoxic phytoadaptogen complex on the lifespan and somatic status (body weight, coat state, and motor activity) of CBA mice predisposed to spontaneous hepatomas. Administration of the complex phytoadaptogen during the first month of postnatal ontogeny increased mean animal lifespan by 17.1% (p<0.001) and median of survival by 25.6% (p<0.001) and promoted maintenance of satisfactory physical status of CBA mice during spontaneous hepatocarcinogenesis.
Assuntos
Anticarcinógenos/farmacologia , Antineoplásicos Fitogênicos/farmacologia , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Panax/química , Rhodiola/química , Animais , Anticarcinógenos/isolamento & purificação , Antineoplásicos Fitogênicos/isolamento & purificação , Peso Corporal/efeitos dos fármacos , Carcinogênese/efeitos dos fármacos , Carcinogênese/patologia , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Suscetibilidade a Doenças , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Masculino , Camundongos , Camundongos Endogâmicos CBA , Extratos Vegetais/química , Análise de SobrevidaRESUMO
Treatment of CBA mice predisposed to cancer with a complex phytoadaptogen in the therapeutic and preventive modes led to the appearance of moderate and low-differentiation hepato-cellular carcinomas infiltrated by leukocytes. Destructive signs were detected in tumor tissue.
Assuntos
Anticarcinógenos/farmacologia , Carcinoma Hepatocelular/prevenção & controle , Neoplasias Hepáticas Experimentais/prevenção & controle , Extratos Vegetais/farmacologia , Animais , Carcinoma Hepatocelular/patologia , Avaliação Pré-Clínica de Medicamentos , Fígado/efeitos dos fármacos , Fígado/patologia , Neoplasias Hepáticas Experimentais/patologia , Masculino , Camundongos Endogâmicos CBARESUMO
The incidence, size, and number of hepatocarcinomas decreased in cancer-prone male CBA mice under the effect of preventive and therapeutic treatment with a complex phytoadaptogen.
Assuntos
Anticarcinógenos/farmacologia , Carcinogênese/efeitos dos fármacos , Carcinoma Hepatocelular/prevenção & controle , Neoplasias Hepáticas/prevenção & controle , Extratos Vegetais/química , Administração Oral , Animais , Anticarcinógenos/isolamento & purificação , Carcinogênese/patologia , Carcinoma Hepatocelular/patologia , Suscetibilidade a Doenças , Esquema de Medicação , Neoplasias Hepáticas/patologia , Masculino , Camundongos , Camundongos Endogâmicos CBA , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/farmacologia , Carga Tumoral/efeitos dos fármacosRESUMO
The present review describes a hypothesis for a critical role of cell adhesive interactions in tumorigenesis. Dysregulation of tissue cell-cell interactions initiates first of all local (in the tissue) and then general (in whole body) conditions for tumor growth. Otherwise imbalance of tissue-specific adhesion factor at the very beginning of carcinogenesis is considered to trigger a cascade of pathological reactions responsible for more severe adhesive disorders that are in turn critical for the "totalitarian" behavior of a tumor and its "colonization" of other tissues and organs. Impaired disturbance is likely to be the key mechanism of carcinogenesis since it is significantly associated with the main features of a tumor: tissue proliferation control loss, anaplasia, invasion, metastasis, and immune surveillance deficit. The hypothesis is supported by evolutionary, biological, histological, immunological, and clinical arguments whose combination does not characterize any other known mechanisms of oncogenesis. The concept of adhesiveness opens new possibilities for the diagnosis, prevention, and treatment of tumors and also improves a strategy for designing.
Assuntos
Carcinogênese/metabolismo , Moléculas de Adesão Celular/metabolismo , Animais , Carcinogênese/patologia , Adesão Celular , Moléculas de Adesão Celular/genética , HumanosRESUMO
The expression of leukocyte integrins LFA-1 and Mac-1 and cytokines IL-6 and IL-10 was studied in mice predisposed to spontaneous hepatocarcinomas. The efficacy of a phytoadaptogen in correcting these parameters was evaluated. The role of adhesive interactions between immune cells and target cells in the recovery of antitumor regulatory mechanisms was estimated.
Assuntos
Interleucina-10/sangue , Interleucina-6/sangue , Antígeno-1 Associado à Função Linfocitária/metabolismo , Antígeno de Macrófago 1/metabolismo , Extratos Vegetais/farmacologia , Animais , Adesão Celular/efeitos dos fármacos , Hepatoblastoma/sangue , Hepatoblastoma/metabolismo , CamundongosRESUMO
The aim of the work was to elucidate the radioprotective activity of multyphytoadaptogene (MPA) in mice in various conditions of gamma radiation and MPA application. Males of CBA x C57BL/6 F1 mice were given 15% MPA solution with drinking water 2 weeks before the radiating (preventive application), 2 weeks before and 2 weeks after the radiating (preventive and therapeutic application) and also 2 weeks after the radiating only (therapeutic application). Animals of control groups received radiation or were given 5% ethanol solution in drinking water in the same application schemes. MPA increased the mice survival in preventive, preventive and therapeutic as well as therapeutic applications after 7.5 Gy radiation (66.7: 66.4 and 40.2% correspondingly). After 11.0 Gy radiation MPA increased the mice survival in preventive as well as preventive and therapeutic applications (75.0 and 76.9% correspondingly). MPA administration improved the somatic state, weight of animals, quality of life. MPA has no side effects. The data suggest the radioprotective activity of MPA.
Assuntos
Raios gama , Extratos Vegetais/uso terapêutico , Protetores contra Radiação/uso terapêutico , Irradiação Corporal Total , Animais , Etanol/uso terapêutico , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Lesões por Radiação/tratamento farmacológico , Lesões por Radiação/prevenção & controleRESUMO
The purpose of the work was to elucidate the radioprotective efficacy of multyphytoadaptogene (MPA) in dogs in various conditions of gamma radiation and MPA application. Dogs were given 15% MPA solution with drinking water in 3,6 ml/kg dose per day 2 weeks before the radiating (preventive application), 2 weeks before and 2 weeks after the radiating (preventive and therapeutic application) as well as 2 weeks after the radiating only (therapeutic application). Animals of control groups received radiation. Dogs were exposed to 3,5 Cy acute radiation and 8,0 Gy prolonged radiation. There were no survived dogs in control groups. At the same time MPA increased dogs survival in preventive, preventive and therapeutic as well as therapeutic applications after 3,5 Gy acute radiation and after 8,0 Gy prolonged radiation. MPA improved the somatic state, interfere with leukocytes amount in blood. The data obtained suggest the radioprotective efficacy of MPA.
Assuntos
Síndrome Aguda da Radiação/tratamento farmacológico , Raios gama , Extratos Vegetais/uso terapêutico , Lesões Experimentais por Radiação/tratamento farmacológico , Protetores contra Radiação/uso terapêutico , Síndrome Aguda da Radiação/prevenção & controle , Animais , Estudos de Casos e Controles , Cães , Avaliação Pré-Clínica de Medicamentos , Lesões Experimentais por Radiação/prevenção & controleRESUMO
Multiphytoadaptogene (MPA) consists of plant extracts components including adaptogenes. Genotoxicity analysis revealed the antimutagenic activity of MPA. MPA decreased the direct mutations frequency in ADE4-ADE8 loci induced by UV radiation and nitrous acid by 3.7 and 33 times, respectively. The lethal effect of UV radiation was inhibited when the preparation was used. MPA had no effect on replicative mutagenesis. At the same time it depressed mutagenesis caused by repair errors. The data obtained suggest the antimutagenic activity of multiphytoadaptogene is associated with postreplicative repair activation.
Assuntos
Antimutagênicos/farmacologia , Taxa de Mutação , Extratos Vegetais/farmacologia , Saccharomyces cerevisiae/genética , Dano ao DNA , Reparo do DNA , Ácido Nitroso/toxicidade , Saccharomyces cerevisiae/efeitos dos fármacos , Saccharomyces cerevisiae/efeitos da radiação , Proteínas de Saccharomyces cerevisiae/genética , Raios UltravioletaRESUMO
Therapeutic efficacy of the plant neuroprotector Phytomix-40 in Parkinson's disease was demonstrated. This preparation consists of the components from extracts of 40 plants, including some adaptogens (ginseng, eleutherococcus, Rhodiola rosea, etc.). The preparation normalized immune, antioxidant, and hormonal parameters in patients. The neuroprotective plant adaptogen can be used in complex therapy for Parkinson's disease for improving its efficacy.
Assuntos
Fármacos Neuroprotetores/uso terapêutico , Doença de Parkinson/prevenção & controle , Extratos Vegetais/uso terapêutico , Adulto , Idoso , Estudos de Casos e Controles , Humanos , Pessoa de Meia-IdadeRESUMO
The efficiency of treatment of diffuse stomach cancer can be improved by using a complex phytoadaptogen. In groups receiving phytoadaptogen, the level of tumor marker CA 19-9 decreased and the mean life span of patients increased by 2.5 times. The drug exhibited immunomodulating (including interferonogenic and adhesiogenic), antioxidant, and hormone-modulating effects.
Assuntos
Antineoplásicos Fitogênicos/uso terapêutico , Neoplasias Gástricas/tratamento farmacológico , Terapia Combinada , Humanos , Interferons/biossíntese , Pessoa de Meia-Idade , Neoplasias Gástricas/imunologia , Neoplasias Gástricas/cirurgiaRESUMO
The article describes results of research devoted to Phytomix-40, a mixture of plant adaptogens. It focuses on immunobiological criteria for its formulation, chemical composition and manufacture procedures, biological standartization tests, in vitro and in vivo preclinical studies, clinical trials in patients with non-malignant tumours (benign prostatic hyperplasia), precancer (oral leukoplakia), advanced cancer (malignant gastric cancer), and age-related neurodegenerative disease (parkinsonism). Prospects for the development of other plant preparations for non-toxic prevention and treatment of cancer and prolongation of life span of the affected subjects are discussed.
Assuntos
Geriatria/métodos , Oncologia/métodos , Neoplasias/prevenção & controle , Doenças Neurodegenerativas/prevenção & controle , Extratos Vegetais/farmacologia , Adjuvantes Imunológicos/farmacologia , HumanosRESUMO
Current state of phytoadaptogen research is discussed with special reference to the protective action of these agents in the organism, such as anticarcinogenic activity. The concept of correction of the body's defensive systems by phytoadaptogen complexes is formulated with a view to creation of an immunobiological basis for non-toxic prevention and therapy of cancer and age-related diseases.
Assuntos
Adjuvantes Imunológicos/farmacologia , Oncologia/métodos , Neoplasias/prevenção & controle , Extratos Vegetais/farmacologia , Animais , HumanosRESUMO
In the article the authors demonstrated that phytoadaptogens (Panax ginseng, Eleutherococcus senticosus, Rhodiola rosea) take part in protecting brain neurons from various injuries. Ability of phytoadaptogens to have influence on neurodegenerative mechanisms at Parkinson's disease is discussed. Phytoadaptogens should be proposed for study or use as therapeutic modulators in neurodegenerative disorders including Parkinson's disease.
Assuntos
Fármacos Neuroprotetores/farmacologia , Fitoterapia , Eleutherococcus , HumanosRESUMO
Oral administration of 10% solution of Phytomix-40 (multicomponent plant phytoadaptogen) to C57Bl/6 mice with MPTP-induced Parkinson's syndrome alleviated symptoms (oligokinesia and muscle rigidity), compensated for the deficiency of dopamine and its metabolites (DOPAC and homovanillic acid), and reduced the level of lipid peroxides in the striatum. In vitro Phytomix-40 in a concentration of 3.3 x 10(-2) g/liter exhibited a pronounced antioxidant effect (5-fold decreased MDA level in mouse brain homogenate in Fe(2+)-ascorbate-dependent LPO).
Assuntos
Transtornos Parkinsonianos/tratamento farmacológico , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Ácido 3,4-Di-Hidroxifenilacético/metabolismo , Animais , Cromatografia Líquida de Alta Pressão , Corpo Estriado/metabolismo , Dopamina/metabolismo , Ácido Homovanílico/metabolismo , Peróxidos Lipídicos/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Atividade Motora/efeitos dos fármacos , Rigidez Muscular/tratamento farmacológico , Rigidez Muscular/patologia , Transtornos Parkinsonianos/patologia , Serotonina/metabolismoRESUMO
Correction of hormonal, immune, interferon, and antioxidant status and genetic abnormalities with a complex phytoadaptogen leads to positive clinical effects in elderly patients with benign prostatic hyperplasia.
Assuntos
Extratos Vegetais/uso terapêutico , Próstata/patologia , Hiperplasia Prostática/tratamento farmacológico , Idoso , Análise de Variância , Antígenos de Superfície/análise , Análise Citogenética , Relação Dose-Resposta a Droga , Hormônios Esteroides Gonadais/sangue , Humanos , Técnicas Imunoenzimáticas , Linfócitos/efeitos dos fármacos , Masculino , Tamanho do Órgão , Extratos Vegetais/farmacologia , Próstata/efeitos dos fármacos , Hiperplasia Prostática/imunologia , Hiperplasia Prostática/metabolismo , Hiperplasia Prostática/patologia , Qualidade de VidaRESUMO
Today leukoplakia of the buccal mucosa is regarded as a typical pre-tumorous condition, both in medicine in general and in dentistry, in particular. Leukoplakia is in fact resistant to conservative treatment, and therefore search for new approaches to therapy of this disease is a pressing problem. Phytomix-40 (PM-40) is a mixture of natural extracts of 40 medicinal plants developed for practical oncology. PM was used in combined therapy of patients with leukoplakia with good results.
Assuntos
Leucoplasia Oral/tratamento farmacológico , Fitoterapia , Extratos Vegetais/uso terapêutico , Vitamina A/uso terapêutico , Adulto , Quimioterapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do TratamentoRESUMO
Leukoplakia of the oral mucosa is characterized by impairment of the epithelial differentiation program. The use of complex phytoadaptogen in the treatment of patients with leukoplakia normalized expression of Fas-APO-1 antigen and keratin 17; increased expression of CD54 attested to activation of immune effectors. The clinical effect manifested in involution or shrinkage and loosening of the pathological focus and complete epithelialization of erosive surfaces. The phytopreparation exhibited adaptogenic effects normalizing the immune and IFN status and improving the state of adaptation systems in the body.
Assuntos
Leucoplasia/tratamento farmacológico , Leucoplasia/fisiopatologia , Extratos Vegetais/uso terapêutico , Adulto , Moléculas de Adesão Celular/fisiologia , Feminino , Imunofluorescência , Humanos , Leucoplasia/imunologia , Masculino , Pessoa de Meia-IdadeRESUMO
A system of in vitro immunobiological tests is developed for screening of phytopreparations intended for the use as immunomodulators in oncology. Proliferative activity of human tumor cells decreased after treatment with complex phytoadaptogen. The immunomodulatory effect of this phytoadaptogen on immunocompetent cells of cancer patients and its nonspecific interferonogenic effect were detected. The composition of adaptogenic complex for preventive oncology is determined.