IN SILICO MOLECULAR DOCKING OF XANTHONE DERIVATIVES AS CYCLOOXYGENASE-2 INHIBITOR AGENTS

Objective: To demonstrate the potential ofdifferent xanthone derivatives as cyclooxygenase-2 (COX-2) inhibitor agents and their selectivity against cycloooxygenase-1 (COX-1) and COX-2 using molecular simulation.Methods: Nine novel xanthone derivatives (compounds A-I) were employed to dock against protein COX-2 (Protein Data Bank/PDB ID: 1CX2) and COX-1 (PDB ID: 3N8Z). Celecoxib, a selective COX-2 inhibitor, was chosen as a control compound. The free binding energy produced by the docking was scored using Protein-Ligand Ant System (PLANTS) and the hydrogen bonds (H-bonds) between ligands and enzymes were visualised using Pymol.Results: Molecular docking studies revealed that celecoxib docked to the active site of COX-2 enzyme, but not to COX-1; whereasxanthone derivatives docked to the active site of both COX-2 and COX-1. Free binding energy of xanthone derivatives ranged between-73,57 to-79,18 and between-73,06 to-79,25 against COX-2 and COX-1, respectively, and-78,13 against celecoxib. H-bonds in the molecule of xanthone derivatives and COX-2 protein were found in amino acid residues Arg120, Tyr355, Tyr385,and Ser353. There was an insignificant difference between the free binding energyof xanthone derivatives against COX-2 and against COX-1, suggesting that their inhibition was non-selective.Conclusion: In conclusion, in silico studies showed that xanthone derivatives could be effective as potential inhibitors against COX-2, although they are not selective.

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In silico study of anthocyanin and ternatin flavonoids for the treatment of inflammation-related diseases using molecular docking analysis

Food Research ◽

10.26656/fr.2017.4(3).378 ◽

2020 ◽

Vol 4 (3) ◽

pp. 780-785

Author(s):

Y.T. Wijaya ◽

A. Yulandi ◽

A.W. Gunawan ◽

Yanti

Keyword(s):

Molecular Docking ◽

Binding Energy ◽

Active Site ◽

In Silico ◽

Protein Crystal ◽

Drug Candidate ◽

Inflammatory Drugs ◽

Cox 2 ◽

Anti Inflammatory ◽

Cox 1

Inflammatory markers such as cyclooxygenase (COX)-2, inducible nitric oxide synthase (iNOS), myeloperoxidase (MPO), and prostaglandin (PEG) are widely known as major targets in discovering natural anti-inflammatory drugs for the treatment of inflammationrelated diseases. Non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen and aspirin are mostly used at present, however, some NSAIDS have been reported to cause gastrointestinal side effect due to ligand-protein interaction. Molecular docking is a promising tool to study such modes of interaction. In this study, we evaluated the potential use of anthocyanin and ternatin flavonoids as natural anti-inflammatory agents for treatment of inflammatory-related diseases using in silico molecular docking assay. Automated docking study using Protein-Ligand ANT System (PLANTS) and AutoDock Vina was performed with various ligand molecules, including ibuprofen, anthocyanin, and ternatin against the protein crystal structures of COX-1, COX-2, iNOS, and MPO. The in silico data demonstrated that ibuprofen bound effectively to the active site of COX-1 and MPO with minimum binding energy, yet the compound required more energy to bind the active site of COX-2. Ternatin flavonoid was bound to COX-2 and iNOS with minimum binding energy. In terms of binding energy, anthocyanin flavonoid was found to be effective for inhibiting COX-1, COX-2, and iNOS. These results suggested that anthocyanin and ternatin flavonoids may potentially be developed as anti-inflammatory drug candidate for the treatment of inflammatory-related diseases.

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In vitro and In Silico Studies on Curcumin and Its Analogues as Dual Inhibitors for cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2)

ITB journal of Sciences ◽

10.5614/itbj.sci.2012.44.1.5 ◽

2012 ◽

Vol 44 (1) ◽

pp. 51-66 ◽

Cited By ~ 2

Author(s):

Nunung Yuniarti ◽

Perdana Adhi Nugroho ◽

Aditya Asyhar ◽

Sardjiman Sardjiman ◽

Zullies Ikawati ◽

...

Keyword(s):

In Silico ◽

Cyclooxygenase 2 ◽

Cyclooxygenase 1 ◽

In Silico Studies ◽

Dual Inhibitors ◽

Cox 2 ◽

Cox 1

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POTENSI DAUN ASAM JAWA (Tamarindus indica L.) SEBAGAI ALTERNATIF ANTIINFLAMASI: STUDI IN SILICO

Jurnal Kefarmasian Akfarindo ◽

10.37089/jofar.v0i0.68 ◽

2019 ◽

pp. 42-50

Author(s):

Erma Yunita ◽

Siti Fatimah ◽

Deni Yulianto ◽

Vedy Trikuncahyo ◽

Zihan Khodijah

Keyword(s):

Molecular Docking ◽

Root Mean Square ◽

Root Mean Square Deviation ◽

In Silico ◽

Mean Square ◽

Mean Square Deviation ◽

Tamarindus Indica ◽

Protein Target ◽

Cox 2 ◽

Cox 1

Daun asam jawa (Tamarindus indica L.) merupakan tanaman yang memiliki banyak khasiat. Kandungan senyawa kimia yang terkandung salah satunya Kuersetin. Kuersetin merupakan senyawa flavonoid yang dapat digunakan sebagai anti inflamasi. Penelitian ini bertujuan untuk mengetahui potensi aktivitas Kuersetin dari daun asam jawa sebagai anti inflamasi terhadap protein COX-1 dan COX-2 secara in silico. Ekstrak daun asam jawa diperoleh dengan maserasi bertingkat menggunakan heksan dan etanol. Kadar Kuersetinnya dihitung secara spektrofotometri UVVis. Konfirmasi aktivitas antiinflamasi dilakukan secara in silico. Protein yang digunakan adalah 6COX, 3PGH, dan 1EQH. Kuersetin sebagai senyawa aktif sedangkan Aspirin digunakan sebagai zat pembanding. Preparasi ligan Kuersetin menggunakan MarvinSketch kemudian preparasi protein target 6COX, 1EQH, dan 3PGH menggunakan YASARA. Selanjutnya melakukan molecular docking menggunakan program PLANTS. Parameter evaluasi validasi dapat dilihat dari nilai Root Mean Square Deviation (RMSD), dimana nilai RMSD yang diterima adalah kurang dari 2Å. Kadar Kuersetin yang diperoleh dalam ekstrak dalam daun asam jawa sebesar 31,26 mg/g. Hasil docking menunjukkan bahwa Kuersetin mampu berinteraksi dengan 1EQH, 3PGH, dan 6COX dimana skor dockingnya masing-masing adalah -77,6195; -75,1344; dan -82,2454, sedangkan hasil docking Aspirin masing-masing adalah -69,8784; -75,2421; dan - 72,0884. Kuersetin memiliki potensi sebagai anti inflamasi yang lebih baik dibandingkan dengan Aspirin namun memiliki resiko lebih tinggi menyebabkan ulkus lambung dibanding Aspirin.

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Chemical Profiles and Pharmacological Properties with in Silico Studies on Elatostema papillosum Wedd

Molecules ◽

10.3390/molecules26040809 ◽

2021 ◽

Vol 26 (4) ◽

pp. 809 ◽

Cited By ~ 3

Author(s):

Md. Zia Uddin ◽

Arkajyoti Paul ◽

Ahmed Rakib ◽

Saad Ahmed Sami ◽

Shafi Mahmud ◽

...

Keyword(s):

Molecular Docking ◽

Binding Affinity ◽

Serotonin Receptor ◽

Computational Study ◽

Biological Activities ◽

Binding Affinities ◽

In Silico Studies ◽

Cox 2 ◽

Cox 1

The current study attempted, for the first time, to qualitatively and quantitatively determine the phytochemical components of Elatostema papillosum methanol extract and their biological activities. The present study represents an effort to correlate our previously reported biological activities with a computational study, including molecular docking, and ADME/T (absorption, distribution, metabolism, and excretion/toxicity) analyses, to identify the phytochemicals that are potentially responsible for the antioxidant, antidepressant, anxiolytic, analgesic, and anti-inflammatory activities of this plant. In the gas chromatography-mass spectroscopy analysis, a total of 24 compounds were identified, seven of which were documented as being bioactive based on their binding affinities. These seven were subjected to molecular docking studies that were correlated with the pharmacological outcomes. Additionally, the ADME/T properties of these compounds were evaluated to determine their drug-like properties and toxicity levels. The seven selected, isolated compounds displayed favorable binding affinities to potassium channels, human serotonin receptor, cyclooxygenase-1 (COX-1), COX-2, nuclear factor (NF)-κB, and human peroxiredoxin 5 receptor proteins. Phytol acetate, and terpene compounds identified in E. papillosum displayed strong predictive binding affinities towards the human serotonin receptor. Furthermore, 3-trifluoroacetoxypentadecane showed a significant binding affinity for the KcsA potassium channel. Eicosanal showed the highest predicted binding affinity towards the human peroxiredoxin 5 receptor. All of these findings support the observed in vivo antidepressant and anxiolytic effects and the in vitro antioxidant effects observed for this extract. The identified compounds from E. papillosum showed the lowest binding affinities towards COX-1, COX-2, and NF-κB receptors, which indicated the inconsequential impacts of this extract against the activities of these three proteins. Overall, E. papillosum appears to be bioactive and could represent a potential source for the development of alternative medicines; however, further analytical experiments remain necessary.

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Anti-Arthritic and Anti-Inflammatory Potential of Spondias mangifera Extract Fractions: An In Silico, In Vitro and In Vivo Approach

Plants ◽

10.3390/plants10050825 ◽

2021 ◽

Vol 10 (5) ◽

pp. 825

Author(s):

Mohammad Khalid ◽

Mohammed H. Alqarni ◽

Ambreen Shoaib ◽

Muhammad Arif ◽

Ahmed I. Foudah ◽

...

Keyword(s):

Molecular Docking ◽

In Silico ◽

Arthritis Score ◽

Beneficial Effects ◽

Tnf Α ◽

Cox 2 ◽

Anti Inflammatory ◽

Cox 1

The fruits of Spondias mangifera (S. mangifera) have traditionally been used for the management of rheumatism in the northeast region of India. The present study explores the probable anti-arthritis and anti-inflammatory potential of S. mangifera fruit extract’s ethanolic fraction (EtoH-F). To support this study, we first approached the parameters in silico by means of the active constituents of the plant (beta amyrin, beta sitosterol, oleonolic acid and co-crystallised ligands, i.e., SPD-304) via molecular docking on COX-1, COX-2 and TNF-α. Thereafter, the absorption, distribution, metabolism, excretion and toxicity properties were also determined, and finally experimental activity was performed in vitro and in vivo. The in vitro activities of the plant extract fractions were evaluated by means of parameters like 1,1-Diphenyl-2- picrylhydrazyl (DPPH), free radical-reducing potential, albumin denaturation, and protease inhibitory activity. The in vivo activity was evaluated using parameters like COX, TNF-α and IL-6 inhibition assay and arthritis score in Freund Adjuvant (CFA) models at a dose of 400 mg/kg b.w. per day of different fractions (hexane, chloroform, alcoholic). The molecular docking assay was performed on COX-1, COX-2 and TNF-α. The results of in vitro studies showed concentration-dependent reduction in albumin denaturation, protease inhibitors and scavenging activity at 500 µg/mL. Administration of the S. mangifera alcoholic fraction at the abovementioned dose resulted in a significant reduction (p < 0.01) in arthritis score, paw diameters, TNF-α, IL-6 as compared to diseased animals. The docking results showed that residues show a critical binding affinity with TNF-α and act as the TNF-α antagonist. The alcoholic fraction of S. mangifera extract possesses beneficial effects on rheumatoid arthritis as well as anti-inflammatory potential, and can further can be used as a possible agent for novel target-based therapies for the management of arthritis.

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Molecular Docking Studies of Phytochemicals of Allophylus serratus Against Cyclooxygenase-2 Enzyme

10.1101/866152 ◽

2019 ◽

Author(s):

Kero Jemal

Keyword(s):

Molecular Docking ◽

Binding Energy ◽

Cyclooxygenase 2 ◽

Molecular Docking Study ◽

Leaf Extracts ◽

Sulfurous Acid ◽

Lipinski’S Rule ◽

Phytochemical Compounds ◽

Cox 2 ◽

Anti Inflammatory

AbstractAllophylus serratus is a medicinal plant used traditionally as anti-inflammatory agent. The main objectives of this study are to identify phytochemical compounds that have anti-inflammatory properties from the leaf extracts of Allophylus serratus and to search for cyclooxygenase-2 (COX-2) enzyme inhibitors through molecular docking. From the GC-MS analysis of leaf extracts of this plant, various phytochemicals were identified. About 10of these phytochemical compounds were analyzed for their drug likeliness based on Lipinski’s rule of five and inhibitor property against the cyclooxygenase (COX-2) enzyme, a protein responsible for inflammation The phytochemical compounds which satisfy the Lipinski’s rule such as 1H-Benzocycloheptene, 2,4a,5,6,7,8-hexahydro-3,5,5,9-tetramethyl-,(R) and Sulfurous acid, dipentyl ester were subjected to docking experiments using AutoDock Vina. The results from molecular docking study revealed that 1H-Benzocycloheptene, 2,4a,5,6,7,8-hexahydro-3,5,5,9-tetramethyl-, (R)-, Sulfurous acid, dipentyl ester and 1,2-Benzenedicarboxylic acid, bis(2-methylpropyl) ester bind effectively to the active site region of COX-2 with a binding energy of −8.9, −8.4, and −7.9, respectively. The binding energy of the phyto-compounds were compared with the known antiinflammatory drug Diclofenac that inhibit COX-2 enzyme. It was found that the phytochemical compounds from leaf extracts of Allophylus serratus have strong inhibitory effect on COX-2 enzyme and as a result they have potential anti-inflammatory medicinal values. Thus the study puts forth experimental validation for traditional antidote and these phyto-compounds could be further promoted as potential lead molecule.

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Identifikasi Aktivitas Inhibitor Enzim Tirosinase Senyawa Turunan Flavonoid pada Kulit Buah Cokelat (Theobroma cacao L) secara In Silico

ALCHEMY Jurnal Penelitian Kimia ◽

10.20961/alchemy.17.2.45317.168-176 ◽

2021 ◽

Vol 17 (2) ◽

pp. 168

Author(s):

Sani Ega Priani ◽

Taufik Muhammad Fakih

Keyword(s):

Molecular Docking ◽

Binding Energy ◽

Active Site ◽

In Silico ◽

Background Color ◽

White Space ◽

Font Size ◽

Flavonoid Compounds ◽

Normal Text ◽

Cocoa Pod Husk

<span style="font-size: 8.5pt; font-family: 'Times New Roman'; color: #000000; background-color: transparent; font-weight: 400; font-style: normal; font-variant: normal; text-decoration: none; vertical-align: baseline; white-space: pre-wrap;">Limbah kulit buah cokelat diketahui mengandung berbagai senyawa aktif, termasuk di antaranya adalah golongan flavonoid. Senyawa flavonoid diketahui berpotensi memiliki aktivitas inhibitor enzim tirosinase, suatu enzim yang menstimulasi proses pembentukan melanin. Penelitian ini bertujuan untuk mengevaluasi interaksi antara senyawa flavonoid dari kulit buah cokelat dengan enzim tirosinase menggunakan metode penambatan molekuler secara <span style="font-size: 8.5pt; font-family: 'Times New Roman'; color: #000000; background-color: transparent; font-weight: 400; font-style: italic; font-variant: normal; text-decoration: none; vertical-align: baseline; white-space: pre-wrap;">in silico<span style="font-size: 8.5pt; font-family: 'Times New Roman'; color: #000000; background-color: transparent; font-weight: 400; font-style: normal; font-variant: normal; text-decoration: none; vertical-align: baseline; white-space: pre-wrap;">. Pengujian dilakukan dengan beberapa tahapan yakni preparasi makromolekul enzim, pemodelan molekul senyawa uji, identifikasi sisi aktif molekul enzim, identifikasi dan evaluasi penambatan molekuler, serta simulasi dinamika molekuler senyawa uji dengan molekul enzim. Hasil simulasi penambatan molekuler antara molekul enzim dengan ligan alaminya yakni tirosin memberikan energi ikatan sebesar -4,91 kkal/mol. Senyawa flavonoid dari kulit buah cokelat yakni apigenin, epikatekin, katekin, kaemferol, kuersetin, dan kuersitrin diketahui memiliki afinitas pada sisi aktif enzim tirosinase dengan energi ikatan berturut turut -6,14; -6,17; -6,01; -5,89; -6,13; -6,81 kkal/mol. Hasil simulasi dinamika molekuler menunjukkan kuersitrin memiliki stabilitas yang baik dengan nilai RMSD rata-rata dan nilai energi bebas ikatan MM/PBSA masing-masing sebesar ±1,73 Å dan -80,12 kJ/mol. Hasil penelitian menunjukkan bahwa senyawa turunan flavonoid tersebut mampu berikatan dengan sisi aktif enzim tirosinase dengan afinitas yang lebih baik dibandingkan dengan ligan alaminya diamati dari nilai energi ikatannya. Senyawa turunan flavonoid yang terkandung dalam kulit buah cokelat berpotensi menjadi inhibitor kompetitif dari enzim tirosinase.<span style="font-size: 8.5pt; font-family: 'Times New Roman'; color: #000000; background-color: transparent; font-weight: 400; font-style: normal; font-variant: normal; text-decoration: none; vertical-align: baseline; white-space: pre-wrap;"><span id="docs-internal-guid-99cc03b4-7fff-2cb3-0bd8-cbf26c857d04" style="font-size: 8.5pt; font-family: 'Times New Roman'; color: #000000; background-color: transparent; font-style: normal; font-variant: normal; text-decoration: none; vertical-align: baseline; white-space: pre-wrap;">Identification of In Silico Tyrosinase Inhibitory Activity of Flavonoid Derivative Compounds in Cocoa Pod Husk (<span style="font-size: 8.5pt; font-family: 'Times New Roman'; color: #000000; background-color: transparent; font-style: italic; font-variant: normal; text-decoration: none; vertical-align: baseline; white-space: pre-wrap;">Theobroma cacao <span style="font-size: 8.5pt; font-family: 'Times New Roman'; color: #000000; background-color: transparent; font-style: normal; font-variant: normal; text-decoration: none; vertical-align: baseline; white-space: pre-wrap;">L.). <span style="font-size: 8.5pt; font-family: 'Times New Roman'; color: #000000; background-color: transparent; font-weight: 400; font-style: normal; font-variant: normal; text-decoration: none; vertical-align: baseline; white-space: pre-wrap;">Cocoa pod husk was known to contain several active compounds, such as flavonoids. Flavonoid compounds are known to potentially have inhibitory activity of the tyrosinase, the enzyme which stimulates melanin synthesis.<span style="font-size: 8.5pt; font-family: 'Times New Roman'; color: #000000; background-color: transparent; font-weight: 400; font-style: normal; font-variant: normal; text-decoration: none; vertical-align: baseline; white-space: pre-wrap;">This study was conducted to evaluate the molecular interaction between flavonoids from cocoa pod husk with tyrosinase enzyme using in silico molecular docking method. The study was carried out through several stages, including preparation of enzyme macromolecules, modeling the molecule of the test compound, identifying the active site of the enzyme molecule, identifying and evaluating molecular docking, and molecular dynamics simulations of the test compound with the enzyme molecule. Molecular docking simulation between the enzyme and its natural ligand (tyrosine) produces binding energy of -4.91 kcal/mol. Flavonoid compounds from cocoa pod husk, including apigenin, epicatechin, catechin, kaempferol, quercetin, dan quercitrin, have an affinity on the active site of the enzyme with binding energy were -6.14; -6.17; -6.01; -5.89; -6.13; -6.81 kcal/mol, respectively. Then the molecular dynamics simulation shows quercitrin has good stability interaction with the average RMSD value and the MM/PBSA binding-free energy values of ±1.73 Å and -80.12 kJ/mol, respectively. The results showed that flavonoids of cocoa pod husc extract have an affinity to the active site of the enzyme, with a stronger binding energy than the original ligand. The flavonoid compounds of cocoa pod husk potential as a competitive inhibitor of the tyrosinase enzyme.

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The Active Compound of Bangle Essential Oil as Cyclooxygenase-2 (Cox-2) Inhibitor: In Silico Approach

Jurnal Kimia VALENSI ◽

10.15408/jkv.v6i2.16943 ◽

2020 ◽

Vol 6 (2) ◽

pp. 156-168

Author(s):

Richa Mardianingrum ◽

Ruswanto Ruswanto ◽

Gina Septiani Agustien ◽

Aas Nuraisah

Keyword(s):

Molecular Dynamics ◽

Molecular Docking ◽

Body Temperature ◽

In Silico ◽

Cyclooxygenase 2 ◽

The Body ◽

Cox 2 ◽

Amino Benzoic Acid ◽

Native Ligand ◽

Methyl Phenyl

Fever is a condition where the body temperature rises above normal or more than 37o C and also tend to be an initial clinical manifestation of the use of antipyretic drugs thatcause toxicity such as on the liver due to prolonged usage. Particularly, the bangle (Zingiber purpureum Roxb.) is one of the Zingiberaceae plants that contain essential oils used for the treatment of fever. Therefore, this researchaimed to identify active compounds which have antipyreticspotential with the in silico approach. The simulation of molecular docking showed 1,4-naphthalenedione-2-ethyl-3-hydroxy was able to attach to the binding site of cyclooxygenase-2 (COX-2) and interact withmain residues that constituted the active cavity of COX-2. While the simulation of molecular dynamics suggested thatthe bound compound was stable at 4 ns, that is the time taken. The binding free energiesexpected by the MM-PBSA method indicated the 1,4-naphthalenedione-2-ethyl-3-hydroxy had a higher affinity than a native ligand (2-[(2,6-dichloro-3-methyl-phenyl)-amino] benzoic acid, JMS) and paracetamol. This suggested its capacity for advancing as a new COX-2 inhibitor.

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In-silico molecular docking analysis of some plant derived molecules for anti-inflammatory inhibitory activity

Current Botany ◽

10.25081/cb.2021.v12.6583 ◽

2021 ◽

pp. 22-27

Author(s):

L. Thamaraiselvi ◽

T. Selvankumar ◽

E.G. Wesely ◽

N. Vinod Kumar

Keyword(s):

Molecular Docking ◽

Binding Energy ◽

In Silico ◽

Novel Drugs ◽

In Silico Study ◽

Low Toxicity ◽

Cox 2 ◽

Anti Inflammatory ◽

In Silico Molecular Docking ◽

Oxide Synthase

Herbs are essential resources for drug discovery. However, numerous challenges stand in front of the scientific community to discover novel drugs from herbs. To explore the validation behind the precious knowledge of traditional medicine, we focused on achieving virtual screening to detect the potential medicines from the herbs. Five bioactive compounds from known anti-inflammatory medicinal plants were examined through molecular docking against cyclooxygenase-2 (COX-2) and inducible Nitric Oxide Synthase (iNOS), using AutoDock 4.2. The docking of selected ligands with COX-2 showed the binding energy varying from -6.15 Kcal/mol to ‑11.24 Kcal/mol. The docking energies of identified ligands with iNOS were generated ranges from -3.85kcal/mol to -6.99 kcal/mol. Among the tested ligands, it was noted that 6 urs-12-en-24-oic acid showed the best binding energy than other compounds with the lowest binding energy and highest binding affinity with both anti-inflammatory target proteins COX-2 and iNOS. The in silico study validates the potential phytochemical compound of the medicinal herb that contribute to anti-inflammatory activity with low toxicity and minimal side effects.

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Pulmonaria obscura and Pulmonaria officinalis Extracts as Mitigators of Peroxynitrite-Induced Oxidative Stress and Cyclooxygenase-2 Inhibitors–In Vitro and In Silico Studies

Molecules ◽

10.3390/molecules26030631 ◽

2021 ◽

Vol 26 (3) ◽

pp. 631

Author(s):

Justyna Krzyżanowska-Kowalczyk ◽

Mariusz Kowalczyk ◽

Michał B. Ponczek ◽

Łukasz Pecio ◽

Paweł Nowak ◽

...

Keyword(s):

Oxidative Stress ◽

Blood Plasma ◽

In Silico ◽

Mononuclear Cells ◽

Blood Platelets ◽

Cyclooxygenase 2 ◽

Human Blood Plasma ◽

Peripheral Blood Mononuclear ◽

In Silico Studies ◽

Cox 2

The Pulmonaria species (lungwort) are edible plants and traditional remedies for different disorders of the respiratory system. Our work covers a comparative study on biological actions in human blood plasma and cyclooxygenase-2 (COX-2) -inhibitory properties of plant extracts (i.e., phenolic-rich fractions) originated from aerial parts of P. obscura Dumort. and P. officinalis L. Phytochemical profiling demonstrated the abundance of phenolic acids and their derivatives (over 80% of the isolated fractions). Danshensu conjugates with caffeic acid, i.e., rosmarinic, lithospermic, salvianolic, monardic, shimobashiric and yunnaneic acids were identified as predominant components. The examined extracts (1–100 µg/mL) partly prevented harmful effects of the peroxynitrite-induced oxidative stress in blood plasma (decreased oxidative damage to blood plasma components and improved its non-enzymatic antioxidant capacity). The cellular safety of the extracts was confirmed in experimental models of blood platelets and peripheral blood mononuclear cells. COX-2 inhibitor screening evidently suggested a stronger activity of P. officinalis (IC50 of 13.28 and 7.24 µg/mL, in reaction with synthetic chromogen and physiological substrate (arachidonic acid), respectively). In silico studies on interactions of main components of the Pulmonaria extracts with the COX-2 demonstrated the abilities of ten compounds to bind with the enzyme, including rosmarinic acid, menisdaurin, globoidnan A and salvianolic acid H.

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