scholarly journals The potency of blumeatin and luteolin as caspase-1 inhibitor by molecular docking

2022 ◽  
Vol 2 (1) ◽  
pp. 22
Author(s):  
I Putu Ari Anggara Catur Pratama ◽  
I Made Harimbawa Putra ◽  
Luh Wayan Sita Pujasari ◽  
Komang Dian Merta Sari Dewi ◽  
Ni Putu Linda Laksmiani
Keyword(s):  
Molecular Docking ◽  
Amino Acid Residues ◽  
Caspase 1 ◽  
Protocol Validation ◽  
Docking Protocol ◽  
Tnf Α ◽  
Docking Approach ◽  
Ifn Γ ◽  
Anti Inflammation ◽  
Native Ligand

COVID-19 infection induces inflammation by increasing cytokines such as IL-1b, IL-6, IL-18, IFN-γ, and TNF-α. IL-1b is generated by the involvement of caspase-1. Therefore, caspase-1 inhibitor can be potential for inflammation therapy caused by COVID-19 infection. This study aims to determine the potential of blumeatin and luteolin as anti-inflammatory agents by inhibiting caspase-1 using a molecular docking approach. This study was carried out by caspase-1 (PDB ID: 1RWK) preparation, blumeatin and luteolin structure optimization, docking protocol validation, and docking of blumeatin and luteolin on caspase-1. Bluematin and luteolin had a binding affinity of -5,63 kcal/mol and -5,93 kcal/mol, lower than Q158 native ligand (-3.92 kcal/mol). Similar amino acid residues in hydrogen bonds interaction were observed between Q158 native ligand, blumeatin, and luteolin with caspase-1 (GLN 283 and ARG 179). Blumeatin and luteolin are potentially anti-inflammation agents through the inhibition of the caspase-1 in silico.

scholarly journals Molecular docking of gallic acid as anti-photoaging in silico

2021 ◽  
Vol 1 (2) ◽  
pp. 18
Author(s):  
Ni Kadek Diah Parwati Dewi ◽  
Kadek Dinda Suryadewi ◽  
Diah Mawarni Fitriari ◽  
Kadek Lia Andini ◽  
Ni Putu Linda Laksmiani
Keyword(s):  
Molecular Docking ◽  
Gallic Acid ◽  
In Silico ◽  
Potential Effect ◽  
Skin Aging ◽  
Amino Acid Residues ◽  
Docking Protocol ◽  
Skin Photoaging ◽  
In Silico Molecular Docking ◽  
Native Ligand

Skin aging caused by excessive exposure to ultraviolet is known as photoaging. The mechanism underlying skin photoaging relates to collagen degradation in the extracellular matrix (ECM) by overexpression of matrix metalloproteinases-1 (MMP-1). Gallic acid is a phenolic antioxidant found in many types of plants and can be used as an anti-photoaging agent due to its antioxidant activity. This study aims to determine the potential effect of gallic acid as an anti-photoaging against MMP-1 using in silico molecular docking. The stages included gallic acid structure optimization using the HyperChem 8, preparation of protein target MMP-1 (PDB ID: 966C) using the Chimera1.10.1, validation the molecular docking protocol, and docking gallic acid on MMP-1 with the Autodock 1.5.6. The results showed that gallic acid had an affinity for MMP-1 with a binding energy of -6.0 kcal/mol. There are similar amino acid residues in hydrogen bonds between the native ligand RS2 with MMP-1 and gallic acid with MMP-1, namely ALA 182, LEU 181, and HIS 218. The results suggest that gallic acid has the potential as the anti-photoaging agent through the inhibition of the MMP-1 enzyme.

scholarly journals Myrtenal and β-caryophyllene oxide screened from Liquidambaris Fructus suppress NLRP3 inflammasome components in rheumatoid arthritis

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Wen-xuan Li ◽  
Ping Qian ◽  
Yi-tong Guo ◽  
Li Gu ◽  
Jessore Jurat ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Molecular Docking ◽  
Nlrp3 Inflammasome ◽  
Network Pharmacology ◽  
Caryophyllene Oxide ◽  
Active Ingredients ◽  
Caspase 1 ◽  
Tnf Α ◽  
Cartilage Erosion ◽  
And Cartilage

Abstract Background Liquidambaris Fructus (LF) is the infructescence of Liquidambar formosana. In Traditional Chinese Medicine, LF has been used to treat joint pain, a common symptom of arthritis and rheumatism; however, a lack of pharmacological evidence has limited its applications in modern clinics. Therefore, this study aims to explore the protective effect of LF on rheumatoid arthritis (RA) and to identify its active ingredients. Methods Rats with adjuvant-induced arthritis (AIA) were divided into 4 groups and administered petroleum ether extract of LF (PEL), ethyl acetate extract of LF (EEL), water extract of LF (WEL), or piroxicam (PIR) respectively for 3 weeks. Two additional groups were used as normal control (NC) and model control (MC) and administered distilled water as a placebo. The clinical scores for arthritis, bone surface, synovial inflammation and cartilage erosion were used to evaluate the therapeutic efficacy of each treatment. The serum IL-1β and TNF-α level and the expression of NLRP3, IL-1β and caspase-1 p20 in the synovial tissue of AIA rats were evaluated by ELISA and Western blot. The active ingredients of LF were investigated using network pharmacology and molecular docking methods, and their inhibition of NLRP3 inflammasome activation was verified in the human rheumatoid arthritis fibroblast-like synovial cells (RA-FLS) model. Results PEL could alleviate paw swelling, bone and joint destruction, synovial inflammation and cartilage erosion in the AIA rats, with significantly superior efficacy to that of EEL and WEL. PEL reduced IL-1β and TNF-α serum levels, and attenuated the upregulation of NLRP3, IL-1β and caspase-1 p20 expression in the synovial tissue of AIA rats. Network pharmacology and molecular docking results indicated that myrtenal and β-caryophyllene oxide were the main two active ingredients of PEL, and these two compounds showed significant inhibition on TNF-α, NLRP3, IL-1β and caspase-1 p20 expression in RA-FLS. Conclusions Myrtenal and β-caryophyllene oxide screened from PEL could suppress the activation of NLRP3 inflammasome, thereby alleviating RA symptoms.

scholarly journals Qingwenzhike Prescription Alleviates Acute Lung Injury Induced by LPS via Inhibiting TLR4/NF-kB Pathway and NLRP3 Inflammasome Activation

2021 ◽  
Vol 12 ◽  
Author(s):  
Cai Zhang ◽  
Xinran Wang ◽  
Chunguo Wang ◽  
Cheng He ◽  
Quantao Ma ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Inflammasome Activation ◽  
Chemical Compositions ◽  
Alveolar Wall ◽  
Protective Effects ◽  
Caspase 1 ◽  
Nlrp3 Inflammasome Activation ◽  
Tnf Α ◽  
Ifn Γ ◽  
Underlying Mechanisms

Background: Acute lung injury (ALI) is characterized by dysfunction of the alveolar epithelial membrane caused by acute inflammation and tissue injury. Qingwenzhike (QWZK) prescription has been demonstrated to be effective against respiratory viral infections in clinical practices, including coronavirus disease 2019 (COVID-19) infection. So far, the chemical compositions, protective effects on ALI, and possible anti-inflammatory mechanisms remain unknown.Methods: In this study, the compositions of QWZK were determined via the linear ion trap/electrostatic field orbital trap tandem high-resolution mass spectrometry (UHPLC-LTQ-Orbitrap MS). To test the protective effects of QWZK on ALI, an ALI model induced by lipopolysaccharide (LPS) in rats was used. The effects of QWZK on the LPS-induced ALI were evaluated by pathological changes and the number and classification of white blood cell (WBC) in bronchoalveolar lavage fluid (BALF). To investigate the possible underlying mechanisms, the contents of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), monocyte chemoattractant protein (MCP-1), interleukin-1β (IL-1β), interleukin-18 (IL-18), and immunoregulatory-related factors interferon-γ (IFN-γ) were detected by ELISA. Furthermore, the expression of Toll-like receptor 4 (TLR4), p-IKKα/β, IKKα, IKKβ, p-IκBα, IκBα, p-NF-κB, nuclear factor-κB (NF-κB), NOD-like receptor family pyrin domain containing 3 (NLRP3), cleaved caspase-1, pro-caspase-1, apoptosis-associated speck-like protein containing CARD (ASC), and β-actin were tested by Western blot.Results: A total of 99 compounds were identified in QWZK, including 33 flavonoids, 23 phenolic acids, 3 alkaloids, 3 coumarins, 20 triterpenoids, 5 anthraquinones, and 12 others. ALI rats induced by LPS exhibited significant increase in neutrophile, significant decrease in lymphocyte, and evidently thicker alveolar wall than control animals. QWZK reversed the changes in WBC count and alveolar wall to normal level on the model of ALI induced by LPS. ELISA results revealed that QWZK significantly reduced the overexpression of proinflammatory factors IL-6, TNF-α, MCP-1, IL-1β, IL-18, and IFN-γ induced by LPS. Western blot results demonstrated that QWZK significantly downregulated the overexpression of TLR4, p-IKKα/β, p-IκBα, p-NF-κB, NLRP3, cleaved caspase-1, and ASC induced by LPS, which suggested that QWZK inhibited TLR4/NF-κB signaling pathway and NLRP3 inflammasomes.Conclusions: The chemical compositions of QWZK were first identified. It was demonstrated that QWZK showed protective effects on ALI induced by LPS. The possible underlying mechanisms of QWZK on ALI induced by LPS was via inhibiting TLR4/NF-kB signaling pathway and NLRP3 inflammasome activation. This work suggested that QWZK is a potential therapeutic candidate for the treatments of ALI and pulmonary inflammation.

scholarly journals Herbal Compounds from Syzygium aromaticum and Cassia acutifolia as a Shield against SARS-CoV-2 Mpro: a Molecular Docking Approach

2021 ◽  
Vol 11 (6) ◽  
pp. 14853-14865
Keyword(s):  
Molecular Docking ◽  
Docking Studies ◽  
New Drugs ◽  
In Vivo Studies ◽  
Syzygium Aromaticum ◽  
Amino Acid Residues ◽  
Ligand Interaction ◽  
Docking Approach ◽  
Novel Coronavirus

Novel coronavirus (severe acute respiratory syndrome coronavirus 2; SARS-CoV-2) was first identified in China in December 2019. Currently, the novel coronavirus disease 2019 (COVID-19) is the most infectious disease worldwide. In the absence of a vaccine or drug, herbal compounds may be used to treat or control this disease. To explore novel potent inhibitors that suppress this virus's growth, we performed molecular docking studies on SARS-CoV-2 Mpro using 17 effective herbal compounds, along with three reference drugs. Docking results showed that crategolic acid from Syzygium aromaticum (clove) had the highest binding affinity with SARS-CoV-2 Mpro protease, followed by sennoside (A, B, C, and D) compounds from Cassia acutifolia (Sana Makki). Crategolic acid and sennoside (A, B, C, and D) contain amino acid residues and hydrogen bonds involved in the protein-ligand interaction. The present study confirms that crategolic acid and sennoside represent the strongest potential inhibitors of SARS-CoV-2 Mpro. This study's results may help in vivo studies validate the usefulness of compounds from clove and Sana Makki in preparing herbal medicine for the treatment of COVID-19. This analysis supports the production of new drugs for the treatment and control of COVID-19.

scholarly journals Hepatoprotective Activity of Pirdot Leaves (Saurauia vulcani Korth) Ethanol Extract in Laboratory Rats (Rattus norvegicus) and Characterization of Bioactive Compounds Using a Molecular Docking Approach

2021 ◽  
Vol 9 (A) ◽  
pp. 1265-1270
Author(s):  
Erlintan Sinaga ◽  
Syafruddin Ilyas ◽  
Salomo Hutahaean ◽  
Panal Sitorus
Keyword(s):  
Molecular Docking ◽  
Binding Affinity ◽  
Bioactive Compounds ◽  
Ethanol Extract ◽  
Treated Group ◽  
Hepatoprotective Activity ◽  
Tnf Α ◽  
Pomolic Acid ◽  
Docking Approach ◽  
Cox 2

AIM: The hepatoprotective activities of  bioactive compounds Pirdot were investigated in vivo and in silico. METHODS: In this study, the completely randomized design non-factorial was experimentally to assess the value of SGPT and SGOT and twenty four adult male rats were divided into four groups : group G0, control group; group G1, a treated group received 0.1 ml sheep red blood cell; group G2, a treated group received 500 mg ethanol extract Pirdot; group G3, a group treated received 500 mg ethanol extract Pirdot and 0,1 ml sheep red blood cell. On thirty one days of treatment, the blood of all rats group were taken to value SGPT and SGOT using DiaLab kit. Furthermore, the molecular docking study was done to analyse molecular interaction that COX-2 and  TNF-α were the primary target protein of bioactive compounds of Pirdot associated with hepatoprotective activities. In addition, it tends to be the target of non-steroidal anti-inflammatory drugs such as Ibuprofen. RESULTS: The results show SGOT and SGPT value significantly [p<0.05] decreased on Group G2 and G3. Moreover, the bioactive compounds of Pirdot, such as Pomolic acid and Ursolic acid tend to be the potential compound on liver protection. Moreover, Pomolic acid has a good binding affinity -14.6 kcal mol-1 with COX-2 Protein and the binding affinity of cis-3-O-p-hydroxycinnamoyl Ursolic acid was -15.1 kcal mol-1 associated with TNF-α Protein. CONLUSION:  Pirdot Leaves (Saurauia vulcani Korth.)  Ethanol Extract showed Hepatoprotective activity in rats (Rattus norvegicus). Molecular docking approach showed that pomolic acid has a good binding affinity with COX-2 Protein and TNF-α Protein.

scholarly journals Inhibitory Effect of Paquinimod on a Murine Model of Neutrophilic Asthma Induced by Ovalbumin with Complete Freund’s Adjuvant

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Jong-Uk Lee ◽  
Jong Sook Park ◽  
Ji Ae Jun ◽  
Min Kyung Kim ◽  
Hun Soo Chang ◽  
...  
Keyword(s):  
Murine Model ◽  
Complete Freund’S Adjuvant ◽  
Dependent Manner ◽  
Neutrophilic Inflammation ◽  
Caspase 1 ◽  
Tnf Α ◽  
Ifn Γ ◽  
Freund’S Adjuvant ◽  
Complete Freund's Adjuvant ◽  
Freund's Adjuvant

Background. Quinoline-3-carboxamides have been used to treat autoimmune/inflammatory diseases in humans because they inhibit the functions of S100 calcium-binding protein A9 (S100A9), which participates in the development of neutrophilic inflammation in asthmatics and in an animal model of neutrophilic asthma. However, the therapeutic effects of these chemicals have not been evaluated in asthma. The purpose of this study was to evaluate the effect of paquinimod, one of the quinoline-3-carboxamides, on a murine model of neutrophilic asthma. Methods. Paquinimod was orally administered to 6-week-old C57BL/6 mice sensitized and challenged with ovalbumin (OVA)/complete Freund’s adjuvant (CFA) and OVA. Lung inflammation and remodeling were evaluated using bronchoalveolar lavage (BAL) and histologic findings including goblet cell count. S100A9, caspase-1, IL-1β, MPO, IL-17, IFN-γ, and TNF-α were measured in lung lysates using western blotting. Results. Paquinimod restored the enhancement of airway resistance and the increases in numbers of neutrophils and macrophages of BAL fluids and those of goblet cells in OVA/CFA mice toward the levels of sham-treated mice in a dose-dependent manner (0.1, 1, 10, and 25 mg/kg/day, p.o.). Concomitantly, p20 activated caspase-1, IL-1β, IL-17, TNF-α, and IFN-γ levels were markedly attenuated. Conclusion. These data indicate that paquinimod effectively inhibits neutrophilic inflammation and remodeling in the murine model of neutrophilic asthma, possibly via downregulation of IL-17, IFN-γ, and IL-1β.

scholarly journals Myricetin Inhibits SARS-CoV-2 Viral Replication by Targeting Mpro and Ameliorates Pulmonary Inflammation

2021 ◽  
Vol 12 ◽  
Author(s):  
Ting Xiao ◽  
Mengqi Cui ◽  
Caijuan Zheng ◽  
Ming Wang ◽  
Ronghao Sun ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Pulmonary Inflammation ◽  
Inflammatory Cells ◽  
Symptomatic Treatment ◽  
Binding Pocket ◽  
New Drugs ◽  
Potent Effect ◽  
Docking Method ◽  
Tnf Α ◽  
Ifn Γ

The coronavirus disease 2019 (COVID-19) has spread widely around the world and has seriously affected the human health of tens of millions of people. In view of lacking anti-virus drugs target to SARS-CoV-2, there is an urgent need to develop effective new drugs. In this study, we reported our discovery of SARS-CoV-2 Mpro inhibitors. We selected 15 natural compounds, including 7 flavonoids, 3 coumarins, 2 terpenoids, one henolic, one aldehyde and one steroid compound for molecular docking and enzymatic screening. Myricetin were identified to have potent inhibit activity with IC50 3.684 ± 0.076 μM in the enzyme assay. The binding pose of Myricetin with SARS-CoV-2 Mpro was identified using molecular docking method. In the binding pocket of SARS-CoV-2 Mpro, the chromone ring of Myricetin interacts with His41 through π-π stacking, and the 3’-, 4’- and 7-hydroxyl of Myricetin interact with Phe140, Glu166and Asp187 through hydrogen bonds. Significantly, our results showed that Myricetin has potent effect on bleomycin-induced pulmonary inflammation by inhibiting the infiltration of inflammatory cells and the secretion of inflammatory cytokines IL-6, IL-1α, TNF-α and IFN-γ. Overall, Myricetin may be a potential drug for anti-virus and symptomatic treatment of COVID-19.

scholarly journals ELUCIDATION THE TOXICITY MECHANISM OF ZINC OXIDE NANOPARTICLE USING MOLECULAR DOCKING APPROACH WITH PROTEINS

2018 ◽  
Vol 11 (3) ◽  
pp. 441
Author(s):  
Krishna Pal Singh ◽  
Anupam Dhasmana ◽  
Qamar Rahman
Keyword(s):  
Zinc Oxide ◽  
Molecular Docking ◽  
Amino Acid ◽  
Computational Models ◽  
Toxicity Assessment ◽  
Alternative Methods ◽  
Amino Acid Residues ◽  
Zinc Oxide Nanoparticle ◽  
Docking Approach ◽  
Oxide Nanoparticle

 Objective: At present, toxicological tests are resource-intensive, time-consuming and require a large pool of animal models for toxicity assessment. To speed up the toxicity evaluation and to reduce animal suffering during toxicity assessment, the use of alternative methods including computational models is in high demand. The computational toxicity prediction methods are very helpful for the regulatory bodies to quickly assess the health impact of nanomaterial materials. In the present work, we have examined the mechanism of zinc oxide nanoparticle (ZnO-NP)-proteins interaction and their effect of surface chemistries of ZnO-NP on the bioactive conformation of chemokines and other cytological proteins using in silico molecular docking approaches.Methods: Molecular docking study was conducted using AutoDock 4.0 version and the visualization result using Discover Studio 4.0.Results: In the present study, we observed that ZnO-NP has high binding affinity with the mitogen-activated protein kinases (P-38), nuclear factor kappa-light-chain-enhancer of activated B cell (NF-kB) proteins, and matrix metallopeptidase-9 with docking energies −8.81, −7.64, and −7.27 Kcal/ Mol, respectively, involving with hydrogen, metal acceptor, and electrostatic interaction. The top interacting amino acid residues with ZnO-NP are GLY, PHE, ARG, ASP, GLN, and ASN.Conclusion: Thus, based on the molecular docking studies, we determine that the ZnO-NP is strongly interacting with the chemokines and other cytological proteins thus responsible for blocking of the activation stimuli for these proteins to initiate the biological signals for the proper functioning. The important interaction pattern ZnO-NP with the surface-enriched amino acid residues of chemokines and cytological proteins using molecular docking approach.

scholarly journals Rational design of multi epitope-based subunit vaccine by exploring MERS-COV proteome: Reverse vaccinology and molecular docking approach

PLoS ONE ◽  
2021 ◽  
Vol 16 (2) ◽  
pp. e0245072
Author(s):  
Usman Ali Ashfaq ◽  
Saman Saleem ◽  
Muhammad Shareef Masoud ◽  
Matloob Ahmad ◽  
Nazia Nahid ◽  
...  
Keyword(s):  
Molecular Docking ◽  
T Cell ◽  
Middle East ◽  
Rational Design ◽  
Rna Virus ◽  
Structural Proteins ◽  
Cell Responses ◽  
Docking Approach ◽  
Ifn Γ ◽  
Antiviral Mechanism

Middle East respiratory syndrome (MERS-COV), first identified in Saudi Arabia, was caused by a novel strain of coronavirus. Outbreaks were recorded from different regions of the world, especially South Korea and the Middle East, and were correlated with a 35% mortality rate. MERS-COV is a single-stranded, positive RNA virus that reaches the host by binding to the receptor of dipeptidyl-peptides. Because of the unavailability of the vaccine available for the protection from MERS-COV infection, the rapid case detection, isolation, infection prevention has been recommended to combat MERS-COV infection. So, vaccines for the treatment of MERS-COV infection need to be developed urgently. A possible antiviral mechanism for preventing MERS-CoV infection has been considered to be MERS-CoV vaccines that elicit unique T-cell responses. In the present study, we incorporated both molecular docking and immunoinformatic approach to introduce a multiepitope vaccine (MEP) against MERS-CoV by selecting 15 conserved epitopes from seven viral proteins such as three structural proteins (envelope, membrane, and nucleoprotein) and four non-structural proteins (ORF1a, ORF8, ORF3, ORF4a). The epitopes, which were examined for non-homologous to host and antigenicity, were selected on the basis of conservation between T-cell, B-cell, and IFN-γ epitopes. The selected epitopes were then connected to the adjuvant (β-defensin) at the N-terminal through an AAY linker to increase the immunogenic potential. Structural modelling and physiochemical characteristic were applied to the vaccine construct developed. Afterwards the structure has been successfully docked with antigenic receptor, Toll-like receptor 3 (TLR-3) and in-silico cloning ensures that its expression efficiency is legitimate. Nonetheless the MEP presented needs tests to verify its safety and immunogenic profile.

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