scholarly journals In Vitro and In Vivo Antitrypanosomal Activities of Methanol Extract of Echinops kebericho Roots

2020 ◽  
Vol 2020 ◽  
pp. 1-6
Author(s):  
Debela Abdeta ◽  
Nigatu Kebede ◽  
Mirutse Giday ◽  
Getachew Terefe ◽  
Solomon Mequanente Abay
Keyword(s):  
Body Weight ◽  
Neglected Tropical Diseases ◽  
Field Isolate ◽  
Parasite Load ◽  
Phytochemical Analysis ◽  
Isolation And Purification ◽  
Discovery Research ◽  
Drug Discovery Research

Microbial resistance to the few conventional antitrypanosomal drugs, increasing resistance of vectors to insecticides, lack of effective vaccines, and adverse effects of the existing antitrypanosomal drugs justify the urgent need for effective, tolerable, and affordable drugs. We assessed antitrypanosomal effects of the hydromethanolic extract of Echinops kebericho Mesfin roots against Trypanosoma congolense field isolate using in vitro and in vivo techniques. Parasite load, packed cell volume (PCV), body weight, and rectal temperature in Swiss albino mice were assessed. This finding is part of the outcomes of drug discovery research for neglected tropical diseases. The extract arrested the motility of trypanosomes within 40 min at 4 and 2 mg/mL concentration, whereas in the untreated control, motility continued for more than 160 min. The extract also reduced parasitemia and prevented drop in PCV and body weight significantly (p<0.05), as compared to control. Phytochemical analysis showed the presence of flavonoids, triterpenes, steroids, saponins, glycosides, tannins, and alkaloids. It is observed that this extract has activity against the parasite. Isolation and purification of specific compounds are required to identify hit compounds responsible for the antitrypanosomal activity of the studied medicinal plant.

scholarly journals In vitro and in vivo antitrypanosomal activities of Echinops kebericho root extract

2019 ◽  
Author(s):  
Debela Abdeta ◽  
Nigatu Kebede ◽  
Mirutse Giday ◽  
Getachew Terefe ◽  
Solomon Mequanente Abay
Keyword(s):  
Body Weight ◽  
Neglected Tropical Diseases ◽  
Field Isolate ◽  
Phytochemical Analysis ◽  
Root Extract ◽  
Isolation And Purification ◽  
Discovery Research ◽  
Drug Discovery Research

Abstract Objective: Microbial resistance to the few conventional antitrypanosomal drugs, increasing resistance of vectors to insecticides, lack of effective vaccines and adverse effects of the existing antitrypanosomal drugs justifies the urgent need for effective, tolerable and affordable drugs. We assessed antitrypanosomal effect of hydromethanolic extract of Echinops kebericho Mesfin roots against Trypanosoma congolense field isolate using in vitro and in vivo techniques. Parasite load, packed cell volume (PCV), body weight and rectal temperature in Swiss albino mice were assessed. This finding is part of the outcomes of drug discovery research for neglected tropical diseases. Result: The extract ceased motility of the trypanosomes within 40 min at 4 and 2 mg/ml concentration whereas in the untreated control motility continued for more than 160 min. The extract also reduced parasitemia, prevented drop in PCV and body weight significantly (p<0.05), as compared to control. Phytochemical analysis showed the presence of flavonoids, triterpines, steroids, saponins, glycosides, tannins and alkaloids. It is observed that this extract has activity against the parasite. Isolation and purification of specific compounds are required to identify hit compounds responsible for the antitrypanosomal activity of the studied medicinal plant.

scholarly journals Pharmacologic Characterization of a Kinetic In Vitro Human Co-Culture Angiogenesis Model Using Clinically Relevant Compounds

2013 ◽  
Vol 18 (10) ◽  
pp. 1234-1245 ◽  
Author(s):  
Ashley Wolfe ◽  
Belinda O’Clair ◽  
Vincent E. Groppi ◽  
Dyke P. McEwen
Keyword(s):  
Growth Factor ◽  
Umbilical Vein ◽  
Dermal Fibroblasts ◽  
Tube Length ◽  
Endothelial Cell Proliferation ◽  
Discovery Research ◽  
Drug Discovery Research ◽  
Angiogenesis Model

Angiogenesis, the formation of new vessels from preexisting vessels, involves multiple cell types acting in concert to cause endothelial cell proliferation, migration, and differentiation into microvascular arrays. Under pathologic conditions, microenvironment changes result in altered blood vessel production. Historically, in vitro angiogenesis assays study individual aspects of the process and tend to be variable, difficult to quantify, and limited in clinical relevance. Here, we describe a kinetic, quantitative, co-culture angiogenesis model and demonstrate its relevance to in vivo pharmacology. Similar to in vivo angiogenesis, a co-culture of human umbilical vein endothelial cells with normal human dermal fibroblasts remains sensitive to multiple cytokines, resulting in a concentration-dependent stimulation of tube formation over time. Treatment with axitinib, a selective vascular endothelial growth factor (VEGF) antagonist, inhibited VEGF-mediated tube length and branch point formation and was selective for inhibiting VEGF over basic fibroblast growth factor (bFGF), similar to previous studies. Conversely, an FGFR-1 selective compound, PD-161570, was more potent at inhibiting bFGF-mediated angiogenesis. These results demonstrate the cytokine dynamics, selective pharmacology, and translational application of this model system. Finally, combining quantitative angiogenic biology with kinetic, live-content imaging highlights the importance of using validated in vitro models in drug discovery research.

scholarly journals In vitro and in vivo anti-trypanosomal potentials of Afrormosia laxiflora and Khaya senegalensis against Trypanosoma brucei brucei

2018 ◽  
Vol 39 (3) ◽  
pp. 269-284
Author(s):  
G.D. Chechet ◽  
J Yahaya ◽  
A.J. Nok
Keyword(s):  
Body Weight ◽  
Trypanosoma Brucei ◽  
Post Infection ◽  
Methanol Extract ◽  
Control Group ◽  
Phytochemical Analysis ◽  
Trypanosoma Brucei Brucei ◽  
Khaya Senegalensis

Animal African trypanosomiasis (AAT) also known as Nagana is a resurgent disease in Africa. Medicinal plants are being used in less developed countries for the treatment of various diseases including trypanosomiasis, due to the high cost of currently available drugs. Most of these plants have been useful sources of treatment of various diseases based on information obtained from folk medicine but have not been scientifically certified. Here, we investigated the in vitro and in vivo anti-trypanosomal potentials of the methanol extract of Aformorsia laxiflora and Khaya senegalensis against T. b. brucei. Phytochemical screening as well as LD50 of the plant extracts was carried out following standard procedures. Parasitemia was monitored daily while Packed Cell Volume was determined at three time points (days 1, 4 and 7) during the course of the infection. The phytochemical analysis showed the presence of saponins, alkaloids, flavonoids, antraquinones, resins and tanins. However, steriods/terpenoids were absent in K. senegalensis but present in A. laxiflora. The toxicity of methanol extract of both A. laxiflora and K. senegalensis was above 5000mg/kg body weight. Methanol extracts of A. laxiflora (leaves) and K. senegalensis (stem bark) showed promising trypanocidal potential in vitro against T. b. brucei at concentrations of 10, 15, 25mg/ml and 40 and 20mg/ml respectively. At these concentrations, both extracts immobilized the parasites within 55mins post-incubation. In general, A. laxiflora leaf extract demonstrated prophylactic activity against T. b. brucei in vivo at a dose of 500mg/Kg body weight particularly in group C animals where a delayed pre-patent period (6 days post-infection), extended survival (14 days post-infection) and significant (P<0.05) reduction in the parasite burden confirmed by an absence of anemia (PCV 47.00±0.8 %) was observed when compared to the infected untreated control group. K. senegalensis extract on the other hand did not show anti-trypanosomal activity in the treated groups (1, 2, and 3). Based on these observations, it was therefore deduced that the methanol extract of leaves of A. laxiflora possessed the ability to ameliorate the burden of the disease and could be a plausible candidate for drug development against the disease.Keywords: Trypanosoma brucei brucei, Afromosia laxiflora, Khaya senegalensis, anti-trypanosomal, in vitro, in vivo

Current Progress on the Genomics of Schistosomiasis for Drug Discovery and Diagnostics

2020 ◽  
Vol 20 (5) ◽  
pp. 598-610
Author(s):  
Nileshkumar Meghani ◽  
Beom-Jin Lee ◽  
Hardik Amin ◽  
Behzad Nili-Ahmadabadi ◽  
Saraswathy Nagendran
Keyword(s):  
Drug Discovery ◽  
Early Stage ◽  
Diagnostic Tools ◽  
Discovery Research ◽  
Drug Discovery Research ◽  
Tremendous Progress ◽  
Significant Research ◽  
Structural Insights

For a number of decades, schistosomiasis has remained a public threat and an economic burden in a number of countries, directly impacting over 200 million people. The past 15 years have seen tremendous progress in the development of high-throughput methods for targeting or compound selection that are vital to early-stage schistosome drug discovery research. Genomewide approaches to analyze gene expression at the transcriptional and other -omic levels have helped immensely for gaining insight into the pathways and mechanisms involved in the schistosomiasis and it is expected to revolutionize the drug discovery as well as related diagnostics. This review discusses the most recent progress of pharmacology and genomics concerning schistosomiasis with a focus on drug discovery and diagnostic tools. It also provides chemical structural insights of promising targets along with available in vitro and/or in vivo data. Although significant research has been done to identify new molecules for the treatment and new methods for diagnosis, the necessity of new options for the sustainable control of schistosomiasis remains a great challenge.

scholarly journals Preparation of Three-dimensional (3-D) Human Liver (HepaRG) Cultures for Histochemical and Immunohistochemical Staining and Light Microscopic Evaluation

2018 ◽  
Vol 46 (6) ◽  
pp. 653-659 ◽  
Author(s):  
Natasha P. Clayton ◽  
Alanna Burwell ◽  
Heather Jensen ◽  
Barbara F. Williams ◽  
Quashana D. Brown ◽  
...  
Keyword(s):  
Immunohistochemical Staining ◽  
Human Liver ◽  
Three Dimensional ◽  
Culture Systems ◽  
Discovery Research ◽  
Glass Slides ◽  
Drug Discovery Research ◽  
Microscopic Evaluation

The use of three-dimensional (3-D) in vitro culture systems (spheroids, organoids) in biomolecular and drug discovery research has become increasingly popular. The popularity is due, in part, to a diminished reliance on animal bioassays and a desire to develop physiologically relevant cell culture systems that simulate the in vivo tissue microenvironment. Most evaluations of 3-D cultures are by confocal microscopy and high-content imaging; however, these technologies do not allow for detailed cellular morphologic assessments or permit basic hematoxylin and eosin histologic evaluations. There are few studies that have reported detailed processes for preparing 3-D cultures for paraffin embedding and subsequent use for histochemical or immunohistochemical staining. In an attempt to do so, we have developed a protocol to paraffin-embed human liver spheroids that can be sectioned with a microtome and mounted onto glass slides for routine histochemical and immunohistochemical staining and light microscopic evaluations.

scholarly journals Antileishmanial Activity of Ziziphus spina-christi Leaves Extract and Its Possible Cellular Mechanisms

2021 ◽  
Vol 9 (10) ◽  
pp. 2113
Author(s):  
Aishah Albalawi
Keyword(s):  
Plasma Membrane ◽  
Membrane Permeability ◽  
Leishmania Major ◽  
Parasite Load ◽  
Phytochemical Analysis ◽  
No Production ◽  
Cellular Mechanisms ◽  
Plasma Membrane Permeability

This experimental investigation was designed to assess the in vitro and in vivo antileishmanial effects of Z. spina-christi methanolic extract (ZSCME) and also aims to assess some of the antileishmanial mechanisms such as the NO production, apoptosis, and plasma membrane permeability. We assessed the in vitro leishmanicidal effects of ZSCME (10–200 µg/mL) against intracellular amastigote stage of the Leishmania major (MRHO/IR/75/ER) and, then, in vivo examined male BALB/c mice infected by L. major. In addition, the rate of infectivity, Caspase 3 activity, nitric oxide (NO) production, the plasma membrane permeability, and the cytotoxic effects of ZSCME were studied. The primary phytochemical analysis of ZSCME revealed the existence of high amounts of flavonoids, tannins, glycosides, alkaloids, and saponin in this plant. The findings exhibited that ZSCME meaningfully (p < 0.001) reduced the viability of amastigotes of L. major, whereas it prompted the creation and release of NO, apoptosis, and the plasma membrane permeability (p < 0.05) and indicated no cytotoxicity in macrophage cells. The in vivo results also demonstrated that ZSCME significantly decreased the parasite load and the diameter of the lesions in the infected mice. Our results demonstrate the promising in vitro and in vivo antileishmanial effects of ZSCME against of L. major. Although the findings of the present study showed some possible antileishmanial mechanisms of ZSCME, such as stimulating NO production, apoptosis, and increasing plasma membrane permeability, additional investigations are required to confirm these results.

scholarly journals Chemical toxicity prediction based on semi-supervised learning and graph convolutional neural network

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Jiarui Chen ◽  
Yain-Whar Si ◽  
Chon-Wai Un ◽  
Shirley W. I. Siu
Keyword(s):  
Neural Network ◽  
Supervised Learning ◽  
Superior Performance ◽  
Chemical Toxicity ◽  
Animal Testing ◽  
Toxicity Prediction ◽  
Discovery Research ◽  
Drug Discovery Research

AbstractAs safety is one of the most important properties of drugs, chemical toxicology prediction has received increasing attentions in the drug discovery research. Traditionally, researchers rely on in vitro and in vivo experiments to test the toxicity of chemical compounds. However, not only are these experiments time consuming and costly, but experiments that involve animal testing are increasingly subject to ethical concerns. While traditional machine learning (ML) methods have been used in the field with some success, the limited availability of annotated toxicity data is the major hurdle for further improving model performance. Inspired by the success of semi-supervised learning (SSL) algorithms, we propose a Graph Convolution Neural Network (GCN) to predict chemical toxicity and trained the network by the Mean Teacher (MT) SSL algorithm. Using the Tox21 data, our optimal SSL-GCN models for predicting the twelve toxicological endpoints achieve an average ROC-AUC score of 0.757 in the test set, which is a 6% improvement over GCN models trained by supervised learning and conventional ML methods. Our SSL-GCN models also exhibit superior performance when compared to models constructed using the built-in DeepChem ML methods. This study demonstrates that SSL can increase the prediction power of models by learning from unannotated data. The optimal unannotated to annotated data ratio ranges between 1:1 and 4:1. This study demonstrates the success of SSL in chemical toxicity prediction; the same technique is expected to be beneficial to other chemical property prediction tasks by utilizing existing large chemical databases. Our optimal model SSL-GCN is hosted on an online server accessible through: https://app.cbbio.online/ssl-gcn/home.

scholarly journals Chemical Toxicity Prediction Based on Semi-supervised Learning and Graph Convolutional Neural Network

2021 ◽  
Author(s):  
Jiarui Chen ◽  
Yain-Whar Si ◽  
Chon-Wai Un ◽  
Shirley W. I. Siu
Keyword(s):  
Neural Network ◽  
Supervised Learning ◽  
Superior Performance ◽  
Chemical Toxicity ◽  
Animal Testing ◽  
Toxicity Prediction ◽  
Discovery Research ◽  
Drug Discovery Research

Abstract As safety is one of the most important properties of drugs, chemical toxicology prediction has received increasing attentions in the drug discovery research. Traditionally, researchers rely on in vitro and in vivo experiments to test the toxicity of chemical compounds. However, not only are these experiments time consuming and costly, but experiments that involve animal testing are increasingly subject to ethical concerns. While traditional machine learning (ML) methods have been used in the field with some success, the limited availability of annotated toxicity data is the major hurdle for further improving model performance. Inspired by the success of semi-supervised learning (SSL) algorithms, we propose a Graph Convolution Neural Network (GCN) to predict chemical toxicity and trained the network by the Mean Teacher (MT) SSL algorithm. Using the Tox21 data, our optimal SSL-GCN models for predicting the twelve toxicological endpoints achieve an average ROC-AUC score of 0.757 in the test set, which is a 6% improvement over GCN models trained by supervised learning and conventional ML methods. Our SSL-GCN models also exhibit superior performance when compared to models constructed using the built-in DeepChem ML methods. This study demonstrates that SSL can increase the prediction power of models by learning from unannotated data. The optimal unannotated to annotated data ratio ranges between 1:1 and 4:1. This study demonstrates the success of SSL in chemical toxicity prediction; the same technique is expected to be beneficial to other chemical property prediction tasks by utilizing existing large chemical databases.

scholarly journals Phytochemistry PREPARATION OF DIFFERENT CRUDE EXTRACT AND ANTIMICROBIAL STUDIES OF SPIROGYRA RHIZOPUS

2019 ◽  
pp. 271-274
Author(s):  
DANIEL E ◽  
GIRMA T ◽  
VENKATESAN JAYAKUMAR S
Keyword(s):  
Green Algae ◽  
Crude Extract ◽  
Diffusion Method ◽  
Phytochemical Analysis ◽  
Bacterial Strains ◽  
Discovery Research ◽  
Crude Extracts ◽  
Drug Discovery Research ◽  
Pharmacologically Active

Objective: The importance of this work is to prepare the crude extracts of Spirogyra rhizopus and to study the biological activity of crude extract against four bacterial strains. Materials and Methods: Spirogyra algae collected from Jimma town, and crude extracts were prepared by cold percolation method and sonication method and further analyzed for qualitative phytochemical analysis. The efficacy of crude extracts is tested for bacterial activity by disc-diffusion method. Results: The maximum zone of inhibition shown by the crude extract is compared to standard and control. Among the four extracts, chloroform extract displayed the promising inhibitory action against four bacterial strains. Conclusions: The preliminary study concludes that green algae S. rhizopus is a potential source of pharmacologically active lead molecules. In vitro screening of crude extracts of green algae S. rhizopus shows promising activity against bacterial strains and thus suggests its application in drug discovery research.

Identification of Therapeutically Active Molecules against Anthrax through Structure and Ligand based Drug Design

2019 ◽  
Vol 18 (27) ◽  
pp. 2294-2312
Author(s):  
Sisir Nandi ◽  
Mridula Saxena ◽  
Anil Kumar Saxena
Keyword(s):  
Drug Design ◽  
Protective Antigen ◽  
Structural Features ◽  
Anthrax Toxin ◽  
Biological Warfare ◽  
Discovery Research ◽  
Drug Discovery Research ◽  
Pathogenic Viruses

Background: People suffer from fatal diseases which are responsible for mortality. Potent devices and medicines are being developed to fight diseases caused by the microorganism for saving the lives of individuals. Highly pathogenic viruses and bacteria are being incorporated into biological warfare, which has become a major threat to mankind and causes the destruction of lives in a short span of time. Objective: The pathogen Bacillus anthracis, which is the causative of anthrax, is used in bioterrorism. Efforts are therefore being made to study the progress of biodefense drug discovery research in combating anthrax-based bioterrorism. Methods: This review describes the present status of the studies ontherapeutic measurement of anthrax toxin inhibitors towards inhibition of protective antigen, lethal and edema factors using chemometric and drug design tools to explore essential structural features for further design of active congeneric compounds. Results: The inhibitors estimated to show high activity through different models may be proposed for further synthesis and testing of biological activity in terms of anthrax toxin inhibition and cytotoxicity testing by in vitro and in vivo assays. Conclusion: Such an attempt is an insight of biodefense drug design against the dreadful threat to the nation due to anthrax-based terrorism and biological warfare.

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