scholarly journals Chemical Characterization and Anti-Inflammatory Activity of Phytoconstituents from Swertia alata

Plants ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 1109
Author(s):  
Sakshi Bajaj ◽  
Shivkanya Fuloria ◽  
Vetriselvan Subramaniyan ◽  
Dhanalekshmi Unnikrishnan Meenakshi ◽  
Sharad Wakode ◽  
...  
Keyword(s):  
Ethanolic Extract ◽  
Attenuated Total Reflection ◽  
Inflammatory Activity ◽  
Inhibition Activity ◽  
Ulcerogenic Activity ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
Cox 1

Swertia alata C.B Clarke (Gentianaceae) is a well-reported plant in the traditional system of medicine. The present study was intended to isolate the phytoconstituents from the ethanolic extract of the aerial parts of S. alata; and evaluate for in vitro COX-1/COX-2 inhibition activity, in vivo anti-inflammatory and ulcerogenic activity. Phytoisolation involved partitioning of S. alata ethanolic extract into petroleum ether and chloroform soluble fractions using silica gel-based column chromatography. The isolation afforded two phytoisolates, namely oleanolic acid (SA-1) and 3-hydroxylup-12-(13)-ene-17-carboxylic acid (SA-4). Phytoisolates structures were established by melting point, ultraviolet (UV), attenuated total reflection-Fourier-transform infrared (ATR-FTIR), nuclear magnetic resonance (1H-NMR, 13C-NMR and HMBC) and mass spectrometry. Phytoisolates were further evaluated for in vitro cyclooxygenase (COX-1/COX-2) inhibitory activity, in vivo anti-inflammatory and ulcerogenic activity. The study revealed SA-4 (COX-1/COX-2 inhibition activity of 104/61.68 µM with % inhibition of 61.36) to be more effective than SA-1 (COX-1/COX-2 inhibition activity of 128.4/87.25 µM, with % inhibition of 47.72). SA-1 and SA-4, when subjected to ulcerogenic study, exhibited significant gastric tolerance. The current study reports chromatographic isolation and spectrometric characterization of SA-1 and SA-4. The present study concludes that compound SA-4 possess significant anti-inflammatory activity and less irritant property over gastric mucosa with no significant ulcerogenicity in comparison to indomethacin.

Chemical characterization and anti-inflammatory activity of phytoconstituents from Swertia alata

2020 ◽  
Author(s):  
sakshi bajaj ◽  
Sharad Wakode ◽  
Avneet Kaur ◽  
Himangini Bansal ◽  
Satish Manchanda ◽  
...  
Keyword(s):  
Multiple Bond ◽  
Attenuated Total Reflection ◽  
Antiulcer Activity ◽  
Traditional System ◽  
Ulcerogenic Activity ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
Cox 1

Abstract Background: Swertia alata C.B Clarke (Gentianaceae) is well reported in Indian Traditional system of medicine and plant was known for its febrifuge, tonic, laxative and antimalarial properties.Objective: To isolate the phytoconstituents from the plant species S alata (Gentianaceae) and to study in vitro COX-1/COX-2, in vivo anti-inflammatory and ulcerogenic activity.Material and methods: With intent to explore newer phytoconstituents, the ethanolic extract of aerial parts of S. alata was partitioned into petroleum ether and chloroform soluble fractions. The isolation of phytoconstituents was performed using silica gel base column chromatography, afforded two phytoisolates (one new and one known) characterized as oleanolic acid (SA-1) and 3-hydroxylup-12-(13)-ene-17-carboxylic acid (SA-4). The structures of the isolated compounds were established based on melting point (MP), Ultraviolet (UV), Attenuated total reflection-Fourier-transform infrared spectroscopy (ATR-FTIR), 1D (1H NMR & 13C NMR) 2D Heteronuclear Multiple Bond Correlation (HMBC) Nuclear magnetic resonance (NMR) and Mass spectrometry. Pharmacological screening was performed to evaluate in vitro Cyclooxygenase (COX-1 /COX-2) inhibitory activity, in vivo anti-inflammatory and ulcerogenic activity.Results: Among the compounds, SA-4 (COX-1: COX-2 :: 104 : 61.68 µM, % inhibition = 61.36) found to be more effective than SA-1(COX-1:COX-2:: 128.4:87.25 µM, % inhibition = 47.72) Ulcerogenic study was also performed on the isolated compounds (SA-1 and SA-4) and found to possess significant gastric tolerance than indomethacin. Conclusion: Ayurvedic knowledge supported by modern science is necessary to isolate, characterize, and standardize the active constituents from herbal sources for anti-inflammatory and antiulcer activity.

scholarly journals Studies in 3,4-diaryl-1,2,5-oxadiazoles and their N-oxides: Search for better COX-2 inhibitors

2007 ◽  
Vol 57 (1) ◽  
pp. 13-30 ◽  
Author(s):  
Mange Yadav ◽  
Shrikant Shirude ◽  
Devendra Puntambekar ◽  
Pinkal Patel ◽  
Hetal Prajapati ◽  
...  
Keyword(s):  
Enzyme Inhibition ◽  
Docking Studies ◽  
Inflammatory Activity ◽  
Rat Paw Edema ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
Cox 2 Inhibitors ◽  
Cox 1

Studies in 3,4-diaryl-1,2,5-oxadiazoles and theirN-oxides: Search for better COX-2 inhibitorsA series of 3,4-diaryl-1,2,5-oxadiazoles and 3,4-diaryl-1,2,5-oxadiazoleN-oxides were prepared and evaluated for COX-2 and COX-1 binding affinityin vitroand for anti-inflammatory activity by the rat paw edema method.p-Methoxy (p-OMe) substituted compounds 9, 21, 34, 41, 42 showed COX-2 enzyme inhibition higher than that showed by compounds with other substituents. 3,4-Di(4-methoxyphenyl)-1,2,5-oxadiazoleN-oxide (42) showed COX-2 enzyme inhibition of 54% at 22 μmol L-1and COX-1 enzyme inhibition of 44% at 88 μmol L-1concentrations, but showed very lowin vivoanti-inflammatory activity. Its deoxygenated derivative (21) showed lower COX-2 enzyme inhibition (26% at 22 μmol L-1) and higher COX-1 enzyme inhibition (53% at 88 μmol L-1) but, markedin vivoanti-inflammatory activity (71% at 25 mg kg-1)vs.celecoxib (48% at 12.5 mg kg-1). Molecular modeling (docking) studies showed that the methoxy group is positioned in the vicinity of COX-2 secondary pocket and it also participates in hydrogen bonding interactions in the COX-2 active site. These preliminary studies suggest thatp-methoxy (p-OMe) group in one of benzene rings may give potentially active leads in this series of oxadiazole/N-oxides.

Design, Synthesis, Characterization and in silico molecular docking studies and in vivo anti-inflammatory Activity of Pyrazoline clubbed Thiazolinone Derivatives

2020 ◽  
Vol 17 ◽  
Author(s):  
Deepak Kumar Singh ◽  
Mayank Kulshreshtha ◽  
Yogesh Kumar ◽  
Pooja A Chawla ◽  
Akash Ved ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Biological Activities ◽  
Inflammatory Activity ◽  
Standard Drug ◽  
Docking Score ◽  
Chemical Structures ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
Cox 1

Background: The pyrazolines give the reactions of aliphatic derivatives, resembling unsaturated compounds in their behavior towards permanganate and nascent hydrogen. This nucleus has been associated with various biological activities including inflammatory. Thiazolinone is a heterocyclic compound that contains both sulfur and nitrogen atom with a carbonyl group in their structure.Thiazolinone and their derivatives have attracted continuing interest because of their various biological activities, such as anti-inflammatory, antimicrobial, anti-proliferative, antiviral, anticonvulsant etc. The aim of the research was to club pyrazoline nucleus with thiazolinone in order to have significantanti-inflammatory activity. The synthesized compounds were chemically characterized for the establishment of their chemical structures and to evaluate as anti-inflammatory agent. Method: In the present work, eight derivatives of substituted pyrazoline (PT1-PT8) were synthesized by a three step reaction.The compounds were subjected to spectral analysis by Infrared, Mass and Nuclear magnetic resonance spectroscopy and elemental analysis data. All the synthesized were evaluated for their in vivo anti-inflammatory activity. The synthesized derivatives were evaluated for their affinity towards target COX-1 and COX-2, using indomethacin as the reference compound molecular docking visualization through AutoDock Vina. Results: Compounds PT-1, PT-3, PT-4 and PT-8 exhibited significant anti-inflammatory activity at 3rd hour being 50.7%, 54.3%, 52.3% and 57% respectively closer to that of the standard drug indomethacin (61.9%).From selected anti-inflammatory targets, the synthesized derivatives exhibited better interaction with COX-1 and COX-2 receptor, where indomethacin showed docking score of -6.5 kJ/mol, compound PT-1 exhibited highest docking score of -9.1 kJ/mol for COX-1 and compound PT-8 having docking score of 9.4 kJ/mol for COX-2. Conclusion: It was concluded that synthesized derivatives have more interaction with COX-2 receptors in comparison to the COX-1 receptors because the docking score with COX-2 receptors were very good. It is concluded that the synthesized derivatives (PT-1 to PT-8) are potent COX-2 inhibitors.

scholarly journals Evaluation of antinociceptive, in-vivo & in-vitro anti-inflammatory activity of ethanolic extract of Curcuma zedoaria rhizome

2014 ◽  
Vol 14 (1) ◽  
Author(s):  
H M Arif Ullah ◽  
Sayera Zaman ◽  
Fatematuj Juhara ◽  
Lucky Akter ◽  
Syed Mohammed Tareq ◽  
...  
Keyword(s):  
Ethanolic Extract ◽  
Inflammatory Activity ◽  
Curcuma Zedoaria ◽  
Anti Inflammatory

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

Plants ◽  
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.

Synthesis of new hexahydropyrimido[1,2-a]azepine derivatives bearing functionalized aryl and heterocyclic moieties as anti-inflammatory agents

2021 ◽  
Author(s):  
Hassanein H Hassanein ◽  
Doaa E Abdel Rahman ◽  
Marwa A Fouad ◽  
Rehab F Ahmed
Keyword(s):  
Molecular Docking ◽  
Binding Sites ◽  
Docking Study ◽  
In Vivo Studies ◽  
Molecular Docking Study ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
Cox 1

New hexahydropyrimido[1,2- a]azepine derivatives bearing functionalized aryl and heterocyclic moieties were synthesized as anti-inflammatory agents with better safety profiles. All synthesized compounds were assessed in vitro for their COX-1 and COX-2 inhibition activities. The most selective compounds, 2f, 5 and 6, were further evaluated for their in vivo anti-inflammatory activity and PGE2 inhibitory activity. To rationalize their selectivity, molecular docking within COX-1 and COX-2 binding sites was performed. Their physicochemical properties and drug-like nature profile were also calculated. The good activity and selectivity of compounds 2f, 5 and 6 were rationalized using a molecular docking study and supported by in vivo studies. These promising findings are encouraging for performing future investigations of these derivatives.

Design, Synthesis and Pharmacological Evaluation of Gastro- Protective Anti-inflammatory Analgesic Agents based on Dual Oxidative Stress / Cyclooxygenase Inhibition

2020 ◽  
Vol 19 (3) ◽  
pp. 268-290 ◽  
Author(s):  
Monika Gaba ◽  
Sarbjot Singh ◽  
Chander Mohan ◽  
Richa Dhingra ◽  
Monika Chauhan ◽  
...  
Keyword(s):  
Antioxidant Activity ◽  
Inhibitory Activity ◽  
Frap Assay ◽  
Anti Oxidant ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
Analgesic Activities ◽  
Cox 1

Background: Non-steroidal anti-inflammatory drugs (NSAIDs) derived local generation of reactive oxygen species (ROS) plays a crucial role in the formation of gastric ulceration. Objective: Therefore, anti-inflammatory analgesics with potent antioxidant activity could be a potential therapeutic strategy for the treatment of pain and inflammatory disorders without gastrointestinal (GI) side effects. Methods: In an effort to develop gastroprotective analgesic and anti-inflammatory agents, a series of 2-methylamino-substituted-1H-benzo[d] imidazol-1-yl) (phenyl) methanone derivatives were synthesized and evaluated in vitro for cyclooxygenase (COX) inhibition as well as anti-oxidant potential by the FRAP assay. The compounds with significant in vitro COX-1/COX-2 inhibitory activity and antioxidant activity were further screened in vivo for their anti-inflammatory and analgesic activities. Moreover, the ulcerogenic potential of test compounds was also studied. To gain insight into the plausible mode of interaction of compounds within the active sites of COX-1 and COX-2, molecular docking simulations were performed. Results: Among the various synthesized molecules, most of the compounds showed good cyclooxygenase inhibitory activity and efficient antioxidant activity in FRAP assay. After preliminary and indicative in vitro assays, three compounds exhibited most significant antiinflammatory and analgesic activity with better gastric tolerability during their in vivo evaluation. Ligand interaction studies indicated highest dock score -43.05 of 1,2- disubstituted benzimidazole derivatives in comparison to the reference ligand -30.70. Overall studies provided us (2-((4-methoxyphenylamino) methyl) -1h-benzo [d] imidazol- 1-yl) (phenyl) methanone as a lead with potent gastro-protective anti-inflammatory and analgesic activities that can be used for future research. Conclusion: From the above results, it can be concluded that designing of multifunctional molecules with COX-1/COX-2 inhibitory and anti-oxidant activities could hold a great promise for further development of GI-safer NSAIDs.

scholarly journals Preliminary Assessment of the Anti-Inflammatory Activity of New Structural Honokiol Analogs with a 4′-O-(2-fluoroethyl) Moiety and the Potential of Their 18F-Labeled Derivatives for Neuroinflammation Imaging

Molecules ◽  
2021 ◽  
Vol 26 (21) ◽  
pp. 6630
Author(s):  
Daria D. Vaulina ◽  
Kira I. Stosman ◽  
Konstantin V. Sivak ◽  
Andrey G. Aleksandrov ◽  
Nikolai B. Viktorov ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Inflammatory Activity ◽  
Preliminary Evaluation ◽  
Moderate Increase ◽  
Biodistribution Studies ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
The Brain

Neolignans honokiol and 4′-O-methylhonokiol (MH) and their derivatives have pronounced anti-inflammatory activity, as evidenced by numerous pharmacological studies. Literature data suggested that cyclooxygenase type 2 (COX-2) may be a target for these compounds in vitro and in vivo. Recent studies of [11C]MPbP (4′-[11С]methoxy-5-propyl-1,1′-biphenyl-2-ol) biodistribution in LPS (lipopolysaccharide)-treated rats have confirmed the high potential of MH derivatives for imaging neuroinflammation. Here, we report the synthesis of four structural analogs of honokiol, of which 4′-(2-fluoroethoxy)-2-hydroxy-5-propyl-1, 1′-biphenyl (F-IV) was selected for labeling with fluorine-18 (T1/2 = 109.8 min) due to its high anti-inflammatory activity confirmed by enzyme immunoassays (EIA) and neuromorphological studies. The high inhibitory potency of F-IV to COX-2 and its moderate lipophilicity and chemical stability are favorable factors for the preliminary evaluation of the radioligand [18F]F-IV in a rodent model of neuroinflammation. [18F]F-IV was prepared with good radiochemical yield and high molar activity and radiochemical purity by 18F-fluoroethylation of the precursor with Boc-protecting group (15) with [18F]2-fluoro-1-bromoethane ([18F]FEB). Ex vivo biodistribution studies revealed a small to moderate increase in radioligand uptake in the brain and peripheral organs of LPS-induced rats compared to control animals. Pretreatment with celecoxib resulted in significant blocking of radioactivity uptake in the brain (pons and medulla), heart, lungs, and kidneys, indicating that [18F]F-IV is likely to specifically bind to COX-2 in a rat model of neuroinflammation. However, in comparison with [11C]MPbP, the new radioligand showed decreased brain uptake in LPS rats and high retention in the blood pool, which apparently could be explained by its high plasma protein binding. We believe that the structure of [18F]F-IV can be optimized by replacing the substituents in the biphenyl core to eliminate these disadvantages and develop new radioligands for imaging activated microglia.

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