Isolation and Structural Characterization of Bioactive Molecules on Prostate Cancer from Mayan Traditional Medicinal Plants.
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ABSTRACT: Prostate cancer is the most common cancer in men around the world. It is a complex and heterogeneous disease in which androgens and their receptors play a crucial role in the progression and development. The current treatment for prostate cancer is a combination of surgery, hormone therapy, radiation and chemotherapy. Therapeutic agents commonly used in the clinic include steroidal and non-steroidal anti-androgens, such as cyproterone acetate, bicalutamide and enzalutamide. These few agents have multiple adverse effects and are not 100% effective. Several plant compounds and mixtures, including grape seed polyphenol extracts, lycopene and tomato preparations, soy isoflavones, and green tea extracts, have been shown to be effective against prostate cancer cell growth. In vivo activity of some isolated compounds like capsaicin and curcumin was reported in prostate cancer murine models. We prepared a library of plant extracts from traditional Mayan medicine. These plants were selected for their use in the contemporaneous Mayan communities for the treatment of different diseases. The extracts were assessed in a phenotypic screening using LNCaP prostate cancer androgen sensitive cell line, with a fixed dose of 25 μg/mL. MTT assay identified seven out of ten plants with interesting anti-neoplastic activity. Extracts from these plants were subjected to a bioguided fractionation to study their major components. We identified three compounds with anti-neoplastic effects against LNCaP cells, one of which shows selectivity for neoplastic compared to benign cells.
Project description:BackgroundNeorautanenia mitis, Hydnora abyssinica, and Senna surattensis are medicinal plants with a variety of traditional uses. In this study, we sought to isolate the bioactive compounds responsible for some of these activities, and to uncover their other potential medicinal properties.MethodsThe DCM and ethanol extracts of the roots of N. mitis and H. abyssinica, and the leaves of S. surattensis were prepared and their phytochemical components were isolated and purified using chromatographic methods. These extracts and their pure phytochemical components were evaluated in in-vitro models for their inhibitory activities against Plasmodium falciparum, Trypanosoma brucei rhodesiense, Mycobacterium tuberculosis, α-amylase (AA), and α-glucosidase (AG).ResultsRautandiol B had significant inhibitory activities against two strains of Plasmodium falciparum showing a high safety ratio (SR) and IC50 values of 0.40 ± 0.07 μM (SR - 108) and 0.74 ± 0.29 μM (SR - 133) against TM4/8.2 and K1CB1, respectively. While (-)-2-isopentenyl-3-hydroxy-8-9-methylenedioxypterocarpan showed the highest inhibitory activity against T. brucei rhodesiense with an IC50 value of 4.87 ± 0.49 μM (SR > 5.83). All crude extracts showed inhibitory activities against AA and AG, with three of the most active phytochemical components; rautandiol A, catechin, and dolineon, having only modest activities against AG with IC50 values of 0.28 mM, 0.36 mM and 0.66 mM, respectively.ConclusionThese studies have led to the identification of lead compounds with potential for future drug development, including Rautandiol B, as a potential lead compound against Plasmodium falciparum. The relatively higher inhibitory activities of the crude extracts against AG and AA over their isolated components could be due to the synergistic effects between their phytochemical components. These crude extracts could potentially serve as alternative inhibitors of AG and AA and as therapeutics for diabetes.
Project description:Traditional medicinal plants have been cultivated to treat various human illnesses and avert numerous infectious diseases. They display an extensive range of bene?cial pharmacological and health effects for humans. These plants generally synthesize a diverse range of bioactive compounds which have been established to be potent antimicrobial agents against a wide range of pathogenic organisms. Various research studies have demonstrated the antimicrobial activity of traditional plants scientifically or experimentally measured with reports on pathogenic microorganisms resistant to antimicrobials. The antimicrobial activity of medicinal plants or their bioactive compounds arising from several functional activities may be capable of inhibiting virulence factors as well as targeting microbial cells. Some bioactive compounds derived from traditional plants manifest the ability to reverse antibiotic resistance and improve synergetic action with current antibiotic agents. Therefore, the advancement of bioactive-based pharmacological agents can be an auspicious method for treating antibiotic-resistant infections. This review considers the functional and molecular roles of medicinal plants and their bioactive compounds, focusing typically on their antimicrobial activities against clinically important pathogens.
Project description:In traditional folklore, medicinal herbs play a vital role in the prevention and treatment of microbial diseases. In the present study, the phenolic profiles of the medicinal plants Asparagus aethiopicus L., Citrullus colocynthis L., Senna alexandrina L., Kalanchoe delagoensis L., Gasteria pillansii L., Cymbopogon citratus, Brassica juncea, and Curcuma longa L. were determined by high-performance liquid chromatography with a diode-array detector method. The results revealed rich sources of important compounds such as robinin in the fruits and leaves of A. aethiopicus; caffeic acid in the tubers of A. aethiopicus and quercitrin in the leaves of G. pillansii. Further, relatively high antioxidant, antibacterial, and antifungal activities were observed in C. colocynthis fruit coat, S. alexandrina pods, and A. aethiopicus leaves, respectively. The relatively higher the bioactivities of plants extracts associated with the phenols in these plants, in particular, the more abundant the phenols. Therefore, it was concluded that the fruit coat of C. colocynthis, pods of S. alexandrina, and leaves of A. aethiopicus might be excellent sources of natural products. These plant extracts also have a wide spectrum of antimicrobial activities that could be used in the pharmaceutical industries and to control diseases.
Project description:BackgroundThere are handful hypothesis-driven ethnobotanical studies in Nepal. In this study, we tested the non-random medicinal plant selection hypothesis using national- and community-level datasets through three different types of regression: linear model with raw data, linear model with log-transformed data and negative binomial model.MethodsFor each of these model, we identified over-utilized families as those with highest positive Studentized residuals and underutilized families with highest negative Studentized residuals. The national-level data were collected from online databases and available literature while the community-level data were collected from Baitadi and Darchula districts.ResultsBoth dataset showed larger variance (national dataset mean 6.51 < variance 156.31, community dataset mean 1.16 < variance 2.38). All three types of regression were important to determine the medicinal plant species selection and use differences among the total plant families, although negative binomial regression was most useful. The negative binomial showed a positive nonlinear relationship between total plant family size and number of medicinal species per family for the national dataset (β1 = 0.0160 ± 0.0009, Z1 = 16.59, p < 0.00001, AIC1 = 1181), and with similar slope and stronger performance for the community dataset (β2 = 0.1747 ± 0.0199, Z2 = 8.76, p < 0.00001, AIC2 = 270.78). Moraceae and Euphorbiaceae were found over-utilized while Rosaceae, Cyperaceae and Caryophyllaceae were recorded as underutilized.ConclusionsAs our datasets showed larger variance, negative binomial regression was found the most useful for testing non-random medicinal plant selection hypothesis. The predictions made by non-random selection of medicinal plants hypothesis holds true for community-level studies. The identification of over-utilized families is the first step toward sustainable conservation of plant resources and it provides a baseline for pharmacological research that might be leading to drug discovery.
Project description:The rationale of the present study was to isolate and identify endophytic fungi from endemic medicinal plants in Eastern Ghats and screened for antimicrobial potential of isolated fungal crude extracts. A total of 329 endophytic strains were isolated from 600 infected leaves and stem cuttings of endemic plants. The diversity and species richness was analyzed statistically and found to be higher in leaf segments than in stem segments. From isolated fungal strains, Cladosporium delicatulum was identified using molecular identification methods and selected as the most potent plumbagin-producing endophytic strain. Further the isolation and structural characterization of endophytic fungal plumbagin (5-hydroxyl-2-methylnaptalene-1,4-dione) was purified and confirmed through spectroscopy analysis. The molecular weight was determined as m/z 188 in positive mode by ESI-MS, which confirmed to be plumbagin which potentially inhibited all tested pathogens, therefore the endophytic fungal plumbagin from the current study possesses important biological activities against pathogens.
Project description:Aim. The present study was designed to investigate the cytotoxicity of a panel of 280 Korean medicinal plants belonging to 73 families and 198 species against human CCRF-CEM leukemia cells. Selected phytochemicals were investigated in more detail for their mode of action. Methods. The resazurin assay was used to determine cytotoxicity of the plant extracts. Microarray-based mRNA expression profiling, COMPARE, and hierarchical cluster analyses were applied to identify which genes correlate with sensitivity or resistance to selected phytochemicals of the Korean plants. Results. The results of the resazurin assay showed that cytotoxicity extracts tested at 10? ? g/mL from 13 samples inhibited proliferation more than 50% (IC50 < 10? ? g/mL) and the most active plants are Sedum middendorffianum (15.33%) and Lycoris radiata (17.61%). Out of 13 selected phytochemicals from these plants, hopeaphenol and deoxynarciclasine were the most cytotoxic ones. Genes from various functional groups (transcriptional or translational regulation, signal transduction, cellular proliferation, intracellular trafficking, RNA metabolism, endoplasmic/sarcoplasmic reticulum function, etc.) were significantly correlated with response of tumor cell lines to these two compounds. Conclusion. The results provide evidence on the possible use of selected Korean medicinal plants and chemical constituents derived from them for the treatment of tumors.
Project description:The worldwide botanical and medicinal culture diversity are astonishing and constitute a Pierian spring for innovative drug R&D. Here, the latest awareness and the perspectives of pharmacophylogeny and pharmacophylogenomics, as well as their expanding utility in botanical drug R&D, are systematically summarized and highlighted. Chemotaxonomy is based on the fact that closely related plants contain the same or similar chemical profiles. Correspondingly, it is better to combine morphological characters, DNA markers and chemical markers in the inference of medicinal plant phylogeny. Medicinal plants within the same phylogenetic groups may have the same or similar therapeutic effects, thus forming the core of pharmacophylogeny. Here we systematically review and comment on the versatile applications of pharmacophylogeny in (1) looking for domestic resources of imported drugs, (2) expanding medicinal plant resources, (3) quality control, identification and expansion of herbal medicines, (4) predicting the chemical constituents or active ingredients of herbal medicine and assisting in the identification and determination of chemical constituents, (5) the search for new drugs sorting out, and (6) summarizing and improving herbal medicine experiences, etc. Such studies should be enhanced within the context of deeper investigations of molecular biology and genomics of traditional medicinal plants, phytometabolites and metabolomics, and ethnomedicine-based pharmacological activity, thus enabling the sustainable conservation and utilization of traditional medicinal resources.
Project description:The Severe Acute Respiratory Syndrome-related Coronavirus 2 (SARS-CoV-2) or novel coronavirus (COVID-19) infection has been declared world pandemic causing a worrisome number of deaths, especially among vulnerable citizens, in 209 countries around the world. Although several therapeutic molecules are being tested, no effective vaccines or specific treatments have been developed. Since the COVID-19 outbreak, different traditional herbal medicines with promising results have been used alone or in combination with conventional drugs to treat infected patients. Here, we review the recent findings regarding the use of natural products to prevent or treat COVID-19 infection. Furthermore, the mechanisms responsible for this preventive or therapeutic effect are discussed. We conducted literature research using PubMed, Google Scholar, Scopus, and WHO website. Dissertations and theses were not considered. Only the situation reports edited by the WHO were included. The different herbal products (extracts) and purified molecules may exert their anti-SARS-CoV-2 actions by direct inhibition of the virus replication or entry. Interestingly, some products may block the ACE-2 receptor or the serine protease TMPRRS2 required by SARS-CoV-2 to infect human cells. In addition, natural products were shown to inhibit the SARS-CoV-2 life-cycle related proteins such as papain-like or chymotrypsin-like proteases. In conclusion, we suggest that natural products could be used alone or in combination as alternative medicines to treat/prevent COVID-19 infection. Moreover, their structures may offer clues for the development of anti-SARS-CoV-2 drugs.
Project description:Aim. In the present study, we investigated the antiangiogenic properties of 59 plants used in traditional Korean medicine. Selected phytochemicals were investigated in more detail for their modes of action. Methods. A modified chicken-chorioallantoic-membrane (CAM) assay using quail eggs was applied to test for antiangiogenic effects of plant extracts. A molecular docking in silico approached the binding of plant constituents to the vascular endothelial growth factor receptors 1 and 2 (VEGFR1, VEGFR2). Microarray-based mRNA expression profiling was employed to correlate the 50% inhibition concentrations (IC50) of a panel of 60 NCI cell lines to these phytochemicals. Results. Extracts from Acer mono leaves, Reynoutria sachalniensis fruits, Cinnamomum japonicum stems, Eurya japonica leaves, Adenophora racemosa whole plant, Caryopteris incana leaves-stems, and Schisandra chinensis stems inhibited angiogenesis more than 50% in quail eggs. Selected phytochemicals from Korean plants were analyzed in more detail using microarray-based mRNA expression profiles and molecular docking to VEGFR1 and VEGFR2. These results indicate multifactorial modes of action of these natural products. Conclusion. The antiangiogenic activity of plants used in traditional Korean medicine implicates their possible application for diseases where inhibition of blood vessel formation is desired, for example, cancer, macular degeneration, diabetic retinopathy and others.
Project description:Essential oils are promising as environmentally friendly and safe sources of pesticides for human use. Furthermore, they are also of interest as aromatherapeutic agents in the treatment of Alzheimer's disease, and inhibition of the enzyme acetylcholinesterase (AChE) has been evaluated as an important mechanism. The essential oils of some species in the genera Callicarpa, Premna, Vitex and Karomia of the family Lamiaceae were evaluated for inhibition of electric eel AChE using the Ellman method. The essential oils of Callicarpa candicans showed promising activity, with IC50 values between 45.67 and 58.38 μg/mL. The essential oils of Callicarpa sinuata, Callicarpa petelotii, Callicarpa nudiflora, Callicarpa erioclona and Vitex ajugifolia showed good activity with IC50 values between 28.71 and 54.69 μg/mL. The essential oils Vitex trifolia subsp. trifolia and Callicarpa rubella showed modest activity, with IC50 values of 81.34 and 89.38, respectively. trans-Carveol showed an IC50 value of 102.88 µg/mL. Molecular docking and molecular dynamics simulation were performed on the major components of the studied essential oils to investigate the possible mechanisms of action of potential inhibitors. The results obtained suggest that these essential oils may be used to control mosquito vectors that transmit pathogenic viruses or to support the treatment of Alzheimer's disease.