scholarly journals Identification of Anti-Inflammatory and Anti-Proliferative Neolignanamides from Warburgia ugandensis Employing Multi-Target Affinity Ultrafiltration and LC-MS

2021 ◽  
Vol 14 (4) ◽  
pp. 313
Author(s):  
Xiao-Cui Zhuang ◽  
Yong-Li Zhang ◽  
Gui-Lin Chen ◽  
Ye Liu ◽  
Xiao-Lan Hu ◽  
...  
Keyword(s):  
Medicinal Plant ◽  
Binding Affinity ◽  
Proliferative Activity ◽  
Topoisomerase I ◽  
Drug Targets ◽  
Spectroscopic Method ◽  
Incidence And Mortality ◽  
Medicinal Plant Extracts ◽  
Cox 2 ◽  
Anti Inflammatory

Previous reports have illustrated that the incidence and mortality of cancer are increasing year by year worldwide. In addition, the occurrence, development, recurrence and metastasis of cancer are closely related to inflammation, which is a kind of defensive response of human body to various stimuli. As an important medicinal plant in Africa, Warburgia ugandensis has been reported to have certain anti-inflammatory and anti-proliferative activities, but its specific components and mechanisms of action remain elusive. To tackle this challenge, affinity ultrafiltration with drug targets of interest coupled to high-performance liquid chromatography-mass spectrometry (AUF-HPLC-MS/MS) could be utilized to quickly screen out bioactive constituents as ligands against target enzymes from complex extracts of this plant. AUF-HPLC-MS/MS with four drug targets, i.e., cyclooxygenase-2 (COX-2), 5-lipoxygenase (5-LOX), topoisomerase I (Top I) and topoisomerase II (Top II) were used to rapidly screen and characterize the anti-inflammatory and anti-proliferative natural ligands from W. ugandensis, and the resulting potential active compounds as ligands with specific binding affinity to COX-2, 5-LOX, Top I and Top II, were isolated with modern separation and purification techniques and identified with spectroscopic method like NMR, and then their antiinflammatory and anti-proliferative activities were tested to verify the screening results from AUF-HPLC-MS/MS. Compounds 1 and 2, which screened out and identified from W. ugandensis showed remarkable binding affinity to COX-2, 5-LOX, Top I and Top II with AUF-HPLC-MS/MS. In addition, 1 new compound (compound 3), together with 5 known compounds were also isolated and identified from W. ugandensis. The structure of compound 3 was elucidated by extensive 1D, 2D NMR data and UPLC-QTOF-MS/MS. Furthermore, compounds 1 and 2 were further proved to possess both anti-inflammatory and anti-proliferative activities which are in good agreement with the screening results using AUF-HPLC-MS/MS. This work showcased an efficient method for quickly screening out bioactive components with anti-inflammatory and anti-proliferative activity from complex medicinal plant extracts using AUF-HPLC-MS/MS with target enzymes of interest, and also demonstrated that neolignanamides (compounds 1 and 2) from W. ugandensis would be the active components responsible for its anti-inflammatory and anti-proliferative activity with the potential to treat cancer and inflammation.

scholarly journals 3D QSAR AND DOCKING STUDY OF INDOLE DERIVATIVES AS SELECTIVE COX-2 INHIBITORS

2019 ◽  
pp. 84-92
Author(s):  
Rajashree Chavan ◽  
HARINATH MORE
Keyword(s):  
Binding Affinity ◽  
Correlation Coefficient ◽  
3D Qsar ◽  
Docking Study ◽  
Field Analysis ◽  
Indole Derivatives ◽  
K Nearest Neighbor ◽  
Qsar Study ◽  
Cox 2 ◽  
Anti Inflammatory

Objective: Non-steroidal anti-inflammatory agents (NSAIDs) continue to be one of the most widely used groups of therapeutic agents. QSAR (quantitative structure-activity relationship) approach is a very useful and widespread technique for drug design. 3D QSAR facilitates evaluation of three-dimensional molecular fields around molecules and generates a relationship of these fields' values with the activity. Methods: 3D QSAR study was performed on selected twenty-four compounds from synthesized indole derivatives using the stepwise variable selection k-nearest neighbor (kNN) molecular field analysis approach for indicating the contribution of the steric and electronic field for activity. The docking study was performed to further confirm the binding affinity of synthesized molecules (ligands) to COX-2 enzyme as well as to study binding nature. Results: Statistically significant model was generated using VLife Molecular Design Suite 3.5 software with cross-validated correlation coefficient q2 of 0.9461 and high predictive correlation coefficient (Pred_r2) of 0.8782 indicating that the model is robust. The results of docking study suggest that the synthesized compounds have a comparable binding affinity with the COX-2 enzyme. Conclusion: The present study may prove to be helpful in the development and optimization of existing indole derivatives as anti-inflammatory agents with selective COX-2 inhibition.

Anti-inflammatory effects of 4 medicinal plant extracts in lipopolysaccharide-induced RAW 264.7 cells

2013 ◽  
Vol 22 (S1) ◽  
pp. 213-220 ◽  
Author(s):  
Mi Jang ◽  
Seung-Weon Jeong ◽  
Somi K. Cho ◽  
Kwang-Seok Ahn ◽  
Bum-Keun Kim ◽  
...  
Keyword(s):  
Medicinal Plant ◽  
Plant Extracts ◽  
Raw 264.7 Cells ◽  
Raw 264.7 ◽  
Medicinal Plant Extracts ◽  
Anti Inflammatory

In vitro antioxidant and anti-proliferative activity of Ethiopian medicinal plant extracts

2015 ◽  
Vol 74 ◽  
pp. 671-679 ◽  
Author(s):  
Jan Tauchen ◽  
Ivo Doskocil ◽  
Cecilia Caffi ◽  
Ermias Lulekal ◽  
Petr Marsik ◽  
...  
Keyword(s):  
Medicinal Plant ◽  
Plant Extracts ◽  
Proliferative Activity ◽  
Medicinal Plant Extracts

scholarly journals Potential Anti-Proliferative, Anti-Inflammatory and Anti-Viral Components from Sinopodophyllum Hexandrum Explored Using Bio-Affinity Ultrafiltration with Multiple Drug Targets

2021 ◽  
Author(s):  
Huixia Feng ◽  
Guilin Chen ◽  
Yongli Zhang ◽  
Mingquan Guo
Keyword(s):  
Molecular Docking ◽  
Drug Targets ◽  
Multiple Drug ◽  
Inhibitory Effects ◽  
Bioactive Ligands ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
Topo Ii ◽  
Sinopodophyllum Hexandrum

Abstract Background: Sinopodophyllum hexandrum (S. hexandrum) is a typical Chinese herbal medicine with numerous components and remarkable pharmacological activities. However, the specific phytochemicals responsible for its anti-proliferative, anti-inflammatory and anti-viral effects remain unexplored.Methods: The integrated analytical strategy combining bio-affinity ultrafiltration with multiple drug targets was developed to rapidly screen and identify bioactive ligands from S. hexandrum. The in vitro anti-proliferative and COX-2 inhibitory assays of bioactive ligands screened were further verified by sulforhodamine B (SRB) cell proliferation and cytotoxicity detection and COX-2 inhibitor screening kits, respectively. Molecular docking analysis was also implemented by the AutoDockTools 1.5.6 software.Results: 10, 7, 9 and 9 phytochemicals were screened out and identified as the potential Topo I, Topo II, COX-2 and ACE2 ligands, respectively. Hereinto, podophyllotoxin and quercetin with higher EF values displayed strong inhibitory effects on A549 and HT-29 cells comparable with etoposide and 5-FU. Furthermore, compared with indomethacin at 0.73 ± 0.07 mM, podophyllotoxin and kaempferol with higher EF values exerted stronger inhibitory effects with IC50 values at 0.36 ± 0.02 mM and 10.49 ± 0.61 mM, respectively. Additionally, the optimal binding sites and mode of action between bioactive ligands and multiple drug targets were determined by molecular docking. Wherein, isorhamnetin showed a stronger affinity to ACE2 with the binding energy of -5.72 kcal/mol and the IC50 value at 63.95 mM, lower than MLN-4760 (-4.27 kcal/mol and 738.62 mM). Conclusions: The integrative strategy combining multiple drug targets and bio-affinity ultrafiltration LC-MS in the present study showed very promising potential for the quick screening and identifying bioactive ligands in S. hexandrum for Topo I, Topo II, COX-2 and ACE2, and some bioactive compounds screened out from this work were verified with other in vitro assays, and even better than those positive drugs of interest. Based on these findings, we then first constructed an interacting network among multi-components and multi-targets. In this way, we showcased a quick and reliable experimental strategy for uncovering the underlying mechanism of the empirical traditional applications of S. hexandrum which could also provide valuable information for better understanding the therapeutic targets and therapeutic ligands of other herbal medicines.

scholarly journals In Silico Molecular Docking Studies of Lichen Metabolites against Cyclooxygenase-2 Enzyme

2015 ◽  
Vol 18 (2) ◽  
pp. 90-96 ◽  
Author(s):  
Mohammad Firoz Khan ◽  
Sabreena Aleem Nabila ◽  
Ridwan Bin Rashid ◽  
Mohammad Sharifur Rahman ◽  
Abu Asad Chowdhury ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Binding Affinity ◽  
Usnic Acid ◽  
Cyclooxygenase 2 ◽  
Therapeutic Effects ◽  
Lichen Metabolites ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
Cox 2 Inhibitors

Cyclooxygenase-2 (COX-2) is an inducible enzyme that causes inflammation. COX-2 inhibitors are clinically effective anti-inflammatory agents with less gastrointestinal and renal toxicities. However, they lack anti-thrombotic activity and hence lead to increased incidences of adverse cardiovascular thrombotic events, including myocardial infarction. Therefore, there is still need to develop COX-2 inhibitors with better therapeutic effects and tolerability. The aim of the present study is to explore the anti-inflammatory activity of five lichen metabolites by conducting virtual screenings. In this regard, molecular docking simulations were carried out for the lichen metabolites namely atranorin, diffractic acid, lecanoric acid, salazinic acid and usnic acid with human COX-2 enzyme and the docked results were compared with the standard reference ligands (Celecoxib and Rofecoxib). Among all the docked ligands, the lecanoric acid demonstrated best binding affinity -9.83 kcal/mol followed by atranorin (-8.7 kcal/mol) and diffractic acid (-8.6 kcal/mol) which are comparable to the reference ligands celecoxib (-12.3 kcal/mol) and rofecoxib (-11.2 kcal/mol). The salazinic acid and usnic acid has shown binding affinity of -7.9 kcal/mol and -4.7 kcal/mol, respectively. Moreover, all the ligands except atranorin and diffractic acid satisfied Lipinski’s rule of 5. From the docking results it was revealed that the lichen metabolites might have inhibitory activity against COX-2 enzyme, and are expected to be useful in conducting in vivo anti-inflammatory screenings on animal model which may lead to the development of more effective and potent new chemical entities with anti-inflammatory properties.Bangladesh Pharmaceutical Journal 18(2): 90-96, 2015

scholarly journals In Vitro Evaluation of Anti-Rift Valley Fever Virus, Antioxidant and Anti-Inflammatory Activity of South African Medicinal Plant Extracts

Viruses ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 221
Author(s):  
Garland K. More ◽  
Raymond T. Makola ◽  
Gerhard Prinsloo
Keyword(s):  
Free Radicals ◽  
Medicinal Plant ◽  
Plant Extracts ◽  
Rift Valley ◽  
Rift Valley Fever ◽  
Rift Valley Fever Virus ◽  
Inflammatory Activity ◽  
Valley Fever ◽  
Medicinal Plant Extracts ◽  
Anti Inflammatory

Rift valley fever virus (RVFV) is a mosquito-borne virus endemic to sub-Saharan African countries, and the first sporadic outbreaks outside Africa were reported in the Asia-Pacific region. There are no approved therapeutic agents available for RVFV; however, finding an effective antiviral agent against RVFV is important. This study aimed to evaluate the antiviral, antioxidant and anti-inflammatory activity of medicinal plant extracts. Twenty medicinal plants were screened for their anti-RVFV activity using the cytopathic effect (CPE) reduction method. The cytotoxicity assessment of the extracts was done before antiviral screening using the MTT assay. Antioxidant and reactive oxygen/nitrogen species’ (ROS/RNS) inhibitory activity by the extracts was investigated using non-cell-based and cell-based assays. Out of twenty plant extracts tested, eight showed significant potency against RVFV indicated by a decrease in tissue culture infectious dose (TCID50) < 105. The cytotoxicity of extracts showed inhibitory concentrations values (IC50) > 200 µg/mL for most of the extracts. The antioxidant activity and anti-inflammatory results revealed that extracts scavenged free radicals exhibiting an IC50 range of 4.12–20.41 µg/mL and suppressed the production of pro-inflammatory mediators by 60–80% in Vero cells. This study demonstrated the ability of the extracts to lower RVFV viral load and their potency to reduce free radicals.

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