scholarly journals In Silico Investigation of Propolis Compounds as Potential Neuroprotective Agent

2021 ◽  
Vol 12 (6) ◽  
pp. 8285-8306
Keyword(s):  
Binding Affinity ◽  
In Silico ◽  
Neuronal Apoptosis ◽  
Neurodegenerative Disorder ◽  
Huperzine A ◽  
Docking Analysis ◽  
Tnf Α ◽  
Low Levels ◽  
New Treatment ◽  
Better Than

Alzheimer's disease is a neurodegenerative disorder caused by several factors, namely neuroinflammation, neuronal apoptosis, and low levels of neurotransmitter Acetylcholine. MAPK14, TNF-α, IL-1β, and NF-KB are proteins that are directly involved in the neuroinflammatory signaling pathway. Caspase3 is involved in neuronal apoptosis, and AChE act as a neurotransmitter breakdown catalyst. In this study, docking analysis of propolis compounds was successfully done against six proteins related neurodegenerative. The results show that 18 compounds of propolis have a better binding affinity than standard drugs (donepezil, huperzine A, fostamatinib, and amrinone). For AChE, only isoetin has a lower binding affinity than donepezil. Isoetin was also observed to inhibit the Caspase3, MAPK14, NF-kB, and TNF-α. In silico prediction of the blood-brain barrier (BBB) permeant revealed that three propolis compounds could pass the BBB, they are isoetin; 5,7,8,3′,4′-pentamethoxy flavone; and flavenochromane C. 5,7,8,3′,4′-pentamethoxy flavone can strongly bind to NF-kB and TNF-α, while Flavenochromane C potentially inhibits MAPK14, NF-kB, and TNF-α better than standard drugs. These compounds are firstly reported as neuroprotective agents. They can be further explored and could be used as a backbone molecule to develop a new treatment for neurodegenerative diseases.

Discovery of novel compounds targeting DJ-1 as neuroprotectants for Parkinson’s disease by virtual screening and in silico method

2020 ◽  
Vol 16 ◽  
Author(s):  
Swati Sharan ◽  
Pravir Kumar ◽  
Rashmi K Ambasta
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
In Silico ◽  
Dopaminergic Neurons ◽  
Simulation Analysis ◽  
Neurodegenerative Disorder ◽  
Neuroprotective Effect ◽  
Docking Analysis ◽  
Neuroprotective Agent ◽  
Zinc Database

Aim: To screen zinc database for structurally similar molecules to compound 23 that targets DJ1 for use as a neuroprotective agent for Parkinson’s disease. Background: Parkinson’s disease (PD), the second most common chronic neurodegenerative disorder characterized by progressive loss of dopaminergic neurons of the substantia nigra. To date, several proteins account for the recessive familial PD-forms, namely, Parkin, PINK-1, DJ-1, SNCA, PARK2, and LRRK2 Genes. DJ1 is one of the important central points that may be targeted for PD therapy. Recently, Compound 23 has been observed to exert the neuroprotective effect against neurodegeneration in PD model, but due to its toxic substructure, the hunt for better nontoxic compound continues. Objective: The overall objective of our work is to apply in silico approaches to screen structure similar compounds that interacts potentially with DJ1 and may serve as a good therapeutic molecule for PD. Method: Initial data mining was done from zinc database and then screened compounds were additionally screened with toxicity checker, carcinopred, ADMET analysis and docking analysis. Results: The basic screening of database for structurally similar chemicals to compound 23 resulted in 50 compounds, which were further screened to twenty-three and finally seven compounds have been screened based on the toxicity and carcinopred test. Later, the seven compounds were docked and analysed for its docking efficiency with DJ1. Our result of molecular docking and molecular simulation analysis highlights Molecule 42(SS2), to exhibit best binding affinity against DJ-1 protein target and can be proposed to be used as a therapeutic agent to modulate neurodegenerative proteins. Conclusion: Therefore, we conclude discovery of novel, non-toxic, non-carcinogenic; ADMET investigated capable of crossing BB barrier but structurally similar compounds of Compound-23, specifically molecule 42(SS2) and potentially molecule 34(SS1) to be used as a neuroprotective agent for Parkinson’s disease.

scholarly journals Huperzine A - An Interesting Anticholinesterase Compound from the Chinese Herbal Medicine

1998 ◽  
Vol 41 (4) ◽  
pp. 155-157 ◽  
Author(s):  
Jiří Patočka
Keyword(s):  
Herbal Medicine ◽  
Chinese Herbal Medicine ◽  
High Selectivity ◽  
Neurodegenerative Disorder ◽  
Huperzine A ◽  
Pharmacological Properties ◽  
Strong Inhibitor ◽  
Chinese Herbal ◽  
Attractive Candidate ◽  
Better Than

Huperzine A, alkaloid from the Chinese herbal medicine Qian Ceng Ta, which is prepared from the moss Huperzia serrata, has been used in China for centuries to treat fever and inflammation. Huperzine A is a strong inhibitor of cholinesterases with high selectivity to acetylcholinesterase and in China is developed as therapeutic against Alzheimer's disease. May be that huperzine A will be better than other centrally active anticholinesterases in treating this neurodegenerative disorder. Huperzine A appears to have additional pharmacological properties that make it an attractive candidate therapy for clinical trials.

In silico Study of the Active Compounds of Lindera aggregata (Sims) Kosterm. as Anti-coronavirus

2020 ◽  
Vol 16 ◽  
Author(s):  
Elok R. Firdiana ◽  
Elga Renjana ◽  
Linda W. Ningrum ◽  
Melisnawati H. Angio ◽  
Muhamad Nikmatullah ◽  
...  
Keyword(s):  
Binding Affinity ◽  
In Silico ◽  
Chinese Government ◽  
Docking Analysis ◽  
Target Proteins ◽  
Rate Of Spread ◽  
Inhibitory Mechanisms ◽  
In Silico Study ◽  
New Type ◽  
Coronavirus Infection

Background: Covid-19, caused by a new type of coronavirus named SARS-CoV-2, has become a pandemic. Together with SARS-CoV and MERS-CoV, Covid-19 is a large global outbreak of coronavirus infection; however, its rate of spread is much higher. Since the vaccines and anti-SARS-CoV-2 have not been found, a faster control mechanism is needed. Traditional herbs have shown the potential for this purpose, as has been demonstrated by the Chinese Government with a high success rate. One of the herbs used was Lindera aggregata, which is part of the collection in Purwodadi Botanic Garden. Objectives: Through in silico study, this research aims to reveal the secondary metabolites contained in L. aggregata that have the potential to serve as anti-SARS-CoV-2 medication as well as showcase their inhibitory mechanisms. Methods: The research was conducted through molecular docking analysis of terpenoids and alkaloids contained in the root of L. aggregata, with target proteins 3CLpro, PLpro, Spike, and ACE 2 playing a role in SARS-CoV-2 infection. Result: All analyzed compounds tended to interact with all four target proteins with different binding affinity values, but the interaction seemed stronger with 3CLpro and Spike. Terpenoids, linderane and linderalactone, had the strongest interaction tendency with 3CLpro, PLpro, and Spike; the compound norboldine, an alkaloid, had the strongest interaction with ACE 2, with a binding affinity value of -8.2 kcal/mol. Conclusion: Terpenoids and alkaloids contained in the root of L. aggregata, which caused inhibition of adsorption and replication of SARS-CoV-2, could serve as anti-SARS-CoV-2.

EFFECTS OF LANGUAGE AND PRIOR KNOWLEDGE LEVELS ON HYPERTEXT READING COMPREHENSION

2020 ◽  
Author(s):  
Kshema Jose
Keyword(s):  
Reading Comprehension ◽  
Prior Knowledge ◽  
Language Proficiency ◽  
Language Competence ◽  
Additional Information ◽  
Reading Order ◽  
Low Levels ◽  
Online Texts ◽  
Characteristic Features ◽  
Better Than

<p>This study observed how two hypertext features – absence of a linear or author-specified order and availability of multiple reading aids – influence reading comprehension processes of ESL readers. Studies with native or highly proficient users of English, have suggested that readers reading hypertexts comprehend better than readers reading print texts. This was attributed to (i) presence of hyperlinks that provide access to additional information that can potentially help overcome comprehension obstacles and (ii) the absence of an author-imposed reading order that helps readers exercise cognitive flexibility. An aspect that remains largely un-researched is how well readers with low language competence comprehend hypertexts. This research sought to initiate research in the area by exploring the question: Do all ESL readers comprehend a hypertext better than a print text?</p> <p>Keeping in mind the fact that a majority of readers reading online texts in English can be hindered by three types of comprehension deficits – low levels of language proficiency, non-availability of prior knowledge, or both – this study investigated how two characteristic features of hypertext, viz., linking to additional information and non-linearity in presentation of information, affect reading comprehension of ESL readers. </p> <p>Two types of texts that occur in the electronic medium – linear or pre-structured texts and non-linear or self-navigating texts, were used in this study. Based on a comparison of subjects’ comprehension outcomes and free recalls, text factors and reader factors that can influence hypertext reading comprehension of ESL readers are identified. </p> Contradictory to what many researchers believe, results indicate that self-navigating hypertexts might not promote deep comprehension in all ESL readers.

In silico screening of pyridoxine carbamates for Anti-Alzheimer’s activities

2020 ◽  
Vol 20 ◽  
Author(s):  
Dnyaneshwar Baswar ◽  
Abha Sharma ◽  
Awanish Mishra
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
In Silico ◽  
Neurodegenerative Disorder ◽  
Biological Activities ◽  
Cholinergic Neurons ◽  
In Silico Screening ◽  
In Silico Studies ◽  
Bbb Permeability ◽  
Ld50 Value

Background: Alzheimer’s disease (AD), an irreversible complex neurodegenerative disorder, is most common type of dementia, with progressive loss of cholinergic neurons. Based on the multi- factorial etiology of Alzheimer’s disease, novel ligands strategy appears as up-coming approach for the development of newer molecules against AD. This study is envisaged to investigate anti-Alzheimer’s potential of 10 synthesized compounds. The screening of compounds (1-10) was carried out using in silico techniques. Methods: For in silico screening of physicochemical properties of compounds molinspiration property engine v.2018.03, Swiss ADME online web-server and pkCSM ADME were used. For pharmacodynamic prediction PASS software while toxicity profile of compounds were analyzed through ProTox-II online software. Simultaneously, molecular docking analysis was performed on mouse AChE enzyme (PDB ID:2JGE, obtained from RSCB PDB) using Auto Dock Tools 1.5.6. Results: Based on in silico studies, compound 9 and 10 have been found to have better drug likeness, LD50 value, and better anti-Alzheimer’s, nootropic activities. However, these compounds had poor blood brain barrier (BBB) permeability. Compound 4 and 9 were predicted with better docking score for AChE enzyme. Conclusion: The outcome of in silico studies have suggested, out of various substitutions at different positions of pyridoxine-carbamate, compound 9 have shown promising drug likeness, with better safety and efficacy profile for anti-Alzheimer’s activity. However, BBB permeability appears as one the major limitation of all these compounds. Further studies are required to confirm its biological activities.

scholarly journals Biomimetic nanotherapy: core–shell structured nanocomplexes based on the neutrophil membrane for targeted therapy of lymphoma

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Qiangqiang Zhao ◽  
Duanfeng Jiang ◽  
Xiaoying Sun ◽  
Qiuyu Mo ◽  
Shaobin Chen ◽  
...  
Keyword(s):  
Mesoporous Silica Nanoparticles ◽  
Treatment Options ◽  
Inflammatory Factors ◽  
Main Method ◽  
Tnf Α ◽  
Good Biocompatibility ◽  
Inflammatory Drugs ◽  
Anti Inflammatory ◽  
New Treatment ◽  
Lymphoma Therapy

Abstract Background Non-Hodgkin’s lymphoma (NHL) is a malignant disease of lymphoid tissue. At present, chemotherapy is still the main method for the treatment of NHL. R-CHOP can significantly improve the survival rate of patients. Unfortunately, DOX is the main cytotoxic drug in R-CHOP and it can lead to adverse reactions. Therefore, it is particularly important to uncover new treatment options for NHL. Results In this study, a novel anti-tumor nanoparticle complex Nm@MSNs-DOX/SM was designed and constructed in this study. Mesoporous silica nanoparticles (MSNs) loaded with Doxorubicin (DOX) and anti-inflammatory drugs Shanzhiside methylester (SM) were used as the core of nanoparticles. Neutrophil membrane (Nm) can be coated with multiple nanonuclei as a shell. DOX combined with SM can enhance the anti-tumor effect, and induce apoptosis of lymphoma cells and inhibit the expression of inflammatory factors related to tumorigenesis depending on the regulation of Bcl-2 family-mediated mitochondrial pathways, such as TNF-α and IL-1β. Consequently, the tumor microenvironment (TME) was reshaped, and the anti-tumor effect of DOX was amplified. Besides, Nm has good biocompatibility and can enhance the EPR effect of Nm@MSNs-DOX/SM and increase the effect of active targeting tumors. Conclusions This suggests that the Nm-modified drug delivery system Nm@MSNs-DOX/SM is a promising targeted chemotherapy and anti-inflammatory therapy nanocomplex, and may be employed as a specific and efficient anti-Lymphoma therapy.

scholarly journals Hypoxia-Induced S100A8 Expression Activates Microglial Inflammation and Promotes Neuronal Apoptosis

2021 ◽  
Vol 22 (3) ◽  
pp. 1205
Author(s):  
Ji Sun Ha ◽  
Hye-Rim Choi ◽  
In Sik Kim ◽  
Eun-A Kim ◽  
Sung-Woo Cho ◽  
...  
Keyword(s):  
Calcium Binding ◽  
Neuronal Apoptosis ◽  
Microglial Cells ◽  
Molecular Pattern ◽  
Extracellular Signal ◽  
Tnf Α ◽  
Cox 2 ◽  
Necrosis Factor ◽  
Microglial Inflammation ◽  
Tlr4 Receptor

S100 calcium-binding protein A8 (S100A8), a danger-associated molecular pattern, has emerged as an important mediator of the pro-inflammatory response. Some S100 proteins play a prominent role in neuroinflammatory disorders and increase the secretion of pro-inflammatory cytokines in microglial cells. The aim of this study was to determine whether S100A8 induced neuronal apoptosis during cerebral hypoxia and elucidate its mechanism of action. In this study, we reported that the S100A8 protein expression was increased in mouse neuronal and microglial cells when exposed to hypoxia, and induced neuroinflammation and neuronal apoptosis. S100A8, secreted from neurons under hypoxia, activated the secretion of tumor necrosis factor (TNF-α) and interleukin-6 (IL-6) through phosphorylation of extracellular-signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) in microglia. Also, phosphorylation of ERK via the TLR4 receptor induced the priming of the NLRP3 inflammasome. The changes in Cyclooxygenase-2 (COX-2) expression, a well-known inflammatory activator, were regulated by the S100A8 expression in microglial cells. Knockdown of S100A8 levels by using shRNA revealed that microglial S100A8 expression activated COX-2 expression, leading to neuronal apoptosis under hypoxia. These results suggested that S100A8 may be an important molecule for bidirectional microglia-neuron communication and a new therapeutic target for neurological disorders caused by microglial inflammation during hypoxia.

scholarly journals In Silico Screening of Natural Products Isolated from Mexican Herbal Medicines against COVID-19

Biomolecules ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 216
Author(s):  
Nadia A. Rivero-Segura ◽  
Juan C. Gomez-Verjan
Keyword(s):  
Natural Products ◽  
In Silico ◽  
Herbal Medicines ◽  
In Silico Screening ◽  
Docking Analysis ◽  
Physiologically Based Pharmacokinetic ◽  
Important Challenge ◽  
Emodin Anthrone ◽  
Therapeutic Tools ◽  
Vaccine Distribution

The COVID-19 pandemic has already taken the lives of more than 2 million people worldwide, causing several political and socio-economic disturbances in our daily life. At the time of publication, there are non-effective pharmacological treatments, and vaccine distribution represents an important challenge for all countries. In this sense, research for novel molecules becomes essential to develop treatments against the SARS-CoV-2 virus. In this context, Mexican natural products have proven to be quite useful for drug development; therefore, in the present study, we perform an in silico screening of 100 compounds isolated from the most commonly used Mexican plants, against the SARS-CoV-2 virus. As results, we identify ten compounds that meet leadlikeness criteria (emodin anthrone, kaempferol, quercetin, aesculin, cichoriin, luteolin, matricin, riolozatrione, monocaffeoyl tartaric acid, aucubin). According to the docking analysis, only three compounds target the key proteins of SARS-CoV-2 (quercetin, riolozatrione and cichoriin), but only one appears to be safe (cichoriin). ADME (absorption, distribution, metabolism and excretion) properties and the physiologically based pharmacokinetic (PBPK) model show that cichoriin reaches higher lung levels (100 mg/Kg, IV); therefore, it may be considered in developing therapeutic tools.

Sign in / Sign up

Export Citation Format

Share Document