In Silico Identification of Protein Targets for Drug-like Compounds from Epicarp Extract of Cola rostrata K. Shum

Fruit epicarp has been found to contain several bioactive compounds which are useful for herbal treatment of several ailments and diseases. The phytochemicals present in C. rostrata epicarp as well as their potential to bind to human proteins and modify their function have not been investigated. This study, therefore, identified the top protein targets of drug-like components of C. rostrata epicarp extract in humans as well as the disease conditions associated with the targets. The identities of constituents of methanol and n-hexane fractions of absolute ethanol extract of C. rostrata epicarp were determined via GCMS analysis. Druglikeness (adherence to Lipinski, Ghose, Veber, Egan, and Muegge filters) and the protein targets of drug-like constituents were determined using SwissADME and SwissTargetPrediction web tools. GCMS analyses revealed the presence of 49 compounds in the n-hexane and methanol fractions. Corynan-16-carboxylic acid, 16,17-didehydro-9,17-dimethoxy-, methyl ester, (16E)-, a yohimbine derivative, was abundant (13.33%) in the methanol fraction. The n-hexane fraction was rich in odd-chain fatty acids and phytosterols. Four drug-like compounds were identified in the fractions: (1) Azelaic acid, monoethyl ester; (2) 3-(2-Methoxymethoxyethylidene)-2,2 dimethylbicyclo[2.2.1]heptane; (3) Cyclododecanol, 1-aminomethyl-, and (4) Corynan-16-carboxylic acid, 16,17-didehydro-9,17-dimethoxy-, methyl ester, (16E)-. The predicted top protein targets of the drug-like compounds include carbonic anhydrase II, protein-tyrosine phosphatase 1B, sphingosine kinase 1, maltase-glucoamylase, adenosine A2b receptor, P2X purinoceptor 7, MAP kinase p38 alpha, δ-opioid receptor, and alpha-2 adrenergic receptors. Findings show that C. rostrata epicarp contains drug-like phytochemicals with potential against cancer, diabetes, pain and inflammatory diseases, and the extract could have aphrodisiac potential

Cola rostrata K. Schum. constituents induce cytotoxicity through reactive oxygen species generation and mitochondrial membrane depolarisation

Aim: While the traditional use of Cola rostrata in treating illnesses and diseases has not been reported, the presence of cytotoxic principles has been reported in phylogenetically and biogeographically related species within the Cola genus. This study, therefore, evaluated the cytotoxic potential of extracts of the plant, and the associated cellular and molecular mechanisms. Methods: Activity-based fractionation of the extracts was carried out and cytotoxicity was assessed in the human cervical cancer cell line, HeLa, and the transformed human lung cell line, MRC5-SV2, using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay complemented with brightfield imaging. The 2ʼ,7ʼ-dichlorofluorescein diacetate (DCFDA) assay was used to assess induction of cellular reactive oxygen species (ROS), while flow cytometry of 5,5ʼ,6,6ʼ-tetrachloro-1,1ʼ,3,3ʼ-tetraethyl-imidacarbocyanine iodide (JC-1)-stained cells assessed the loss of mitochondrial membrane potential (∆ΨM). Gas chromatography-mass spectrometry (GC-MS) analysis was carried out on an active fraction. Results: Extracts of the fruit epicarp and leaf were cytotoxic against the cell lines. Half-maximal inhibitory concentration (IC50) values for the 48 h cytotoxicity of the ethanol extract of the epicarp against HeLa and MRC5-SV2 cells were 48.0 μg/mL ± 12.1 μg/mL and 40.4 μg/mL ± 7.2 μg/mL, respectively, while fractions from second-level partitioning of the hexane fraction of the leaf extract elicited cytotoxicity with IC50 values ranging from 12.8 μg/mL ± 1.0 μg/mL to 39.6 μg/mL ± 7.2 μg/mL in both cell lines, following 48 h treatment. GC-MS revealed the presence of seventeen compounds in a hexane fraction of the leaf extract, including even- and odd-chain fatty acids, the most abundant of which were n-hexadecanoic acid, decanoic acid 10-(2-hexylcyclopropyl); and octadecanoic acid. The mechanisms of cytotoxicity of most active fractions involved generation of ROS and mitochondrial membrane depolarisation. Conclusions: The findings show that C. rostrata is rich in cytotoxic phytochemicals which could be isolated for developing new anti-cancer agents

Influence of ethanolic extract of Allium sativum on TP53 gene and its anticancer potential in N-Nitrosodiethylamine (NDEA)-induced hepatocellular carcinoma in male albino rats

Objective(s): Cancer is a group of genetic disorders in which the behavior of the cell is disturbed by mutation and other abnormalities thereby posing as the leading cause of morbidity and mortality globally. Hepatocellular Carcinoma (HCC) is the most common form of liver cancer, highly aggressive with high mortality and incidence rate; and has limited therapeutic options. Most of the conventional cancer chemotherapeutics are associated with undesirable side effects, toxicity, chemoresistance, and high treatment cost, driving the need for a safer and more effective treatment alternative. Medicinal plants and herbs have shown very promising anti-cancer properties which are important for cancer treatment due to their multiple chemical compounds. Materials and Methods: Qualitative screening of the ethanolic extractof Allium sativum was conducted showing the different phytochemicalspresent. The levels of liver function and hematological parameters wasdetermined via spectrophotometric analysis. Polymerase Chain Reaction techniquewas used to assess the gene patterns of Tumorsuppressor p53 (TP53). Results: Phytochemical analysis revealed that Allium sativum has properties that antagonize the proliferating process of carcinogenesis in the liver. The NDEA-group showed significant distortion in the liver architecture characterized by vascular congestion of blood sinusoids, cirrhosis, and congestive hepatopathy while the treated groups showed a reduction in the abnormalities and malignant formation. The treated group showed a significant (P<0.05) increase and restored activities of Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Alkaline phosphatase (ALP), Bilirubin and hematological parameters (RBCs, WBCs, and Platelets). TP53 gene amplification was significantly (P<0.05) visible after treatment. Conclusion: Ethanolic plant extract of A. sativum demonstrates its anticancer properties by improving the liver architecture, increasing the antioxidant defense systems, and activation of the tumor suppressor (TP53) gene. Garlic extract has anti-proliferating properties and can be used as an alternative mode of treatment and prevention for hepatocellular carcinoma

"Vivendo o SUS": uma experiência prática no cenário da atenção básica

O projeto "Vivendo o SUS", realizado com a participação dos alunos do primeiro ano do curso de Medicina da PUC/SP, visou introduzir os estudantes no contexto das ações do sistema público de saúde e suas relações com a população local, no município de Sorocaba. Posteriormente, com a reforma curricular do curso de Medicina, foi construído o Módulo de Prática em Atenção à Saúde (PAS), com desenvolvimento nos seis anos do curso. A realização desse projeto foi importante para estimular e nortear o processo de mudança curricular, por meio da execução de uma atividade que propiciou exercícios de reflexão sobre a experiência vivenciada pelo estudante de Medicina, estimulando a percepção de situações como o cuidado e a organização do processo de trabalho na atenção básica, as relações na equipe de saúde e as informações como ferramentas para o planejamento. Atualmente, o ensino médico, inserido no espaço da Atenção Básica, contribui na produção de conhecimentos para o aprimoramento do sistema de saúde local e, intervindo na realidade, forma um profissional mais habilitado e comprometido com a comunidade