scholarly journals Anti-Inflammatory and Analgesic Activities of 7-Chloro-4-(Piperazin-1-yl) Quinoline Derivative Mediated by Suppression of InflammatoryMediators Expression in Both RAW 264.7 and Mouse Models

2020 ◽  
Vol 27 (3) ◽  
pp. 326-338
Author(s):  
Mona Elsayed Aboutabl ◽  
Ahmed Ragab Hamed ◽  
Mohamed Farouk Hamissa ◽  
Emad Khairy Ahmed
Keyword(s):  
Gene Expression ◽  
Experimental Models ◽  
Quinoline Derivative ◽  
Inflammatory Activity ◽  
Raw 264.7 ◽  
Inos Protein Expression ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
Analgesic Activities

Background: 4-Aminoquinoline derivatives possess various potential biological properties.The introduction of additional piperazine heterocyclic pharmacophoric moiety tends to haveprofound impact in increasing the activity. The present work was undertaken to investigate thein-vitro and in-vivo anti-inflammatory activity as well as the peripheral and central analgesicactivities of compound 1-(4-(7-chloroquinoline-4-yl)piperazin-1-yl)-2-(4-phenylpiperazin-1-yl)ethanone (5) in experimental models. Methods: The percentage inhibition of the lipopolysaccharide induced NO release of 7-chloro-4-(piperazin-1-yl)quinoline derivatives 1-9 was determined in RAW 264.7 murine macrophagemodel. Western blot analysis was performed to evaluate the effect of compound 5 on proteinexpression of inducible nitric oxide synthase (iNOS). Gene expression of inflammatory markerswas evaluated using real-time polymerase chain reaction. The peripheral and central analgesicactivities of compound 5 were evaluated in mice using writhing and hot-plate tests, respectively.Anti-inflammatory activity was assessed using carrageenan-induced paw edema assay in miceand serum NO and COX-2 levels were measured. Results: Compound 5 demonstrated the highest NO inhibitory activity that was accompaniedby inhibition of iNOS protein expression and decreased gene expression levels of inflammatorymarkers. It revealed a potential peripheral analgesic effect through inhibition of abdominalwrithing in mice treated with doses of 15 and 30 mg/kg and its effect was comparable to diclofenacsodium. Compound 5 possessed an analgesic activity starting from 15 min post administrationand reached its peak at 45 min which was significantly higher than that of tramadol hydrochloridesuggesting its potential as central analgesic agent. It also showed percentage of inhibition ofedema of 34, 50 and 64% at 1, 2, and 3 h respectively, post carrageenan challenge together with asignificant decrease in serum NO and COX-2 levels. Conclusion: The remarkable anti-inflammatory and analgesic activities of compound 5 couldbe attributed to the advantageous introduction of the heterocyclic 7-chloro-4-(piperazin1-yl)quinoline scaffold incorporated with N-phenylpiperzine functional groups linked together withthe ethanone pharmacophoric chain.

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 A REVIEW ON IN VIVO AND IN VITRO EXPERIMENTAL MODELS TO INVESTIGATE THE ANTI-INFLAMMATORY ACTIVITY OF HERBAL EXTRACTS

2018 ◽  
Vol 11 (11) ◽  
pp. 29
Author(s):  
Inayat Kabir ◽  
Imtiyaz Ansari
Keyword(s):  
Reference Model ◽  
Experimental Models ◽  
Inflammatory Activity ◽  
Herbal Extracts ◽  
Double Positive ◽  
Arthritis Models ◽  
Inflammatory Drugs ◽  
Anti Inflammatory

The article emphasizes the anti-inflammatory effects of herbal extracts on different experimental models that are repeatedly used to test the in vivo anti-inflammatory activity of herbal components. Edema, granuloma and arthritis models are used to test the anti-inflammatory activity of plant extracts whereas formalin or acetic acid-induced writhing test and hot plate methods are the most repeatedly used to evaluate anti-nociceptive potentials of the herbal extracts. Although adjuvant-induced and collagen-induced arthritis models are also quite efficient, they have been used seldom to evaluate anti-inflammatory tendencies of the herbs. Here, we suggest a double positive reference model using both steroid and nonsteroidal anti-inflammatory drugs at the same time, instead of using only one of them either.

scholarly journals Anti-Inflammatory Activity of the Active Compounds of Sanguisorbae Radix In Macrophages and in Vivo Toxicity Evaluation in Zebrafish

Cosmetics ◽  
2019 ◽  
Vol 6 (4) ◽  
pp. 68
Author(s):  
Young-Ah Jang ◽  
Yong Hur ◽  
Jin-Tae Lee
Keyword(s):  
Target Genes ◽  
Inflammatory Activity ◽  
Dependent Manner ◽  
Active Components ◽  
Necrosis Factor Alpha ◽  
In Vivo Toxicity ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
Sanguisorbae Radix

Sanguisorbae Radix (SR) is the root of the Sanguisorba officinalis L., a plant native to Asian countries and used in traditional medicine. We isolated the active components of SR and investigated their anti-inflammatory potential. Quercetin (QC), (+)-catechin (CC), and gallic acid (GA) were isolated from acetone extracts of SR. To elucidate the molecular mechanism by which these compounds suppress inflammation, we analyzed the transcriptional up-regulation of inflammatory mediators, such as nuclear factor-kappa B (NF-κB) and its target genes, inducible NOS (iNOS), and cyclooxygenase (COX)-2, in lipopolysaccharide (LPS)-stimulated macrophage RAW264.7 cells. Notably, QC, CC, and GA were found to inhibit the production of nitric oxide, tumor necrosis factor-alpha, and prostaglandin in a dose-dependent manner. Western blot results indicate that the compounds decreased the expression of iNOS and COX-2 proteins. Furthermore, the compounds decreased phosphorylation of IKK, IκB, ERK, p-38, and JNK proteins in LPS-induced cells. The results support the notion that QC, CC, and GA can potently inhibit the inflammatory response, with QC showing the highest anti-inflammatory activity. In in vivo toxicity studies in zebrafish (Danio rerio), QC showed no toxicity up to 25 μg/mL. Therefore, QC has non-toxic potential as a skin anti-inflammatory biomaterial.

scholarly journals ANTI-INFLAMMATORY ACTIVITY OF KNEMA ATTENUATA (HOOK. F. AND THOMSON) WARB ETHANOLIC STEM BARK EXTRACT IN ALBINO WISTAR RATS

2019 ◽  
pp. 330-334
Author(s):  
SUPRIYA RAJA H
Keyword(s):  
Stem Bark ◽  
Inflammatory Activity ◽  
Assay Method ◽  
Bark Extract ◽  
Raw 264.7 ◽  
Myeloperoxidase Activity ◽  
Stem Bark Extract ◽  
Anti Inflammatory

Objective: Knema attenuata (Myristicaceae), popularly known as “wild nutmeg,” is an endemic tree species from Western Ghats, which has been used in folk medicine. Conventionally, the stem bark of K. attenuata is used for treating inflammatory conditions without any scientific information available for the same. The present study was undertaken to evaluate the anti-inflammatory activity of the ethanolic stem bark extract (ESBE) of K. attenuata using in vivo and in vitro screening models. Methods: The ethanolic extract of stem bark was prepared by soxhlation, and its cytotoxicity in RAW 264.7 cell line was assessed using MTT assay method. In vivo anti-inflammatory effect of extract was estimated in rats using carrageenan-induced paw edema model and cotton pellet-induced granuloma model. The in vitro anti-inflammatory activity of the extract was evaluated by cyclooxygenase and lipoxygenase inhibition assay, estimation of myeloperoxidase activity, and determination of cellular nitrite levels in lipopolysaccharide-stimulated RAW 264.7 macrophage cells. Results: Toxic symptoms were not observed for the ESBE. The extract demonstrated significant anti-inflammatory activity in both in vivo and in vitro models. The anti-inflammatory action exhibited by the extract was a result of the inhibition of leukocyte migration and nitric oxide pathway and partially by inhibition of mediators such as prostaglandins and leukotrienes. Conclusion: Findings from the study provide the evidence for the popular use of stem bark extract of K. attenuata as a potential anti-inflammatory agent.

scholarly journals Antioxidant, Anti-Inflammatory, and Analgesic Activities ofAgrimonia eupatoriaL. Infusion

2017 ◽  
Vol 2017 ◽  
pp. 1-13 ◽  
Author(s):  
Telmo N. Santos ◽  
Gustavo Costa ◽  
J. Pinto Ferreira ◽  
Joana Liberal ◽  
Vera Francisco ◽  
...  
Keyword(s):  
Antiradical Activity ◽  
Inflammatory Activity ◽  
No Production ◽  
Hot Plate ◽  
Edema Model ◽  
Anti Inflammatory ◽  
Analgesic Activities ◽  
First Time

Agrimony (Agrimonia eupatoriaL.) (Ae) is used in traditional medicine to treat inflammatory and oxidative related diseases. Therefore, this study focuses on the anti-inflammatory and analgesic potential of Ae infusion (AeI). Phenolic compounds characterization was achieved by HPLC-PDA-ESI/MSn. To evaluate antioxidant potential, 2,2-diphenyl-1-picrylhydrazyl (DPPH), superoxide anion, hydroxyl radical, and SNAP assays were used. In vitro anti-inflammatory activity of AeI was investigated in LPS-stimulated macrophages by measuring the NO production. In vivo anti-inflammatory activity was validated using the mouse carrageenan-induced paw edema model. Peripheral and central analgesic potential was evaluated using the acetic acid-induced writhing and hot-plate tests, respectively, as well as the formalin assay to assess both activities. The safety profile was disclosed in vitro and in vivo, using MTT and hematoxylin assays, respectively. Vitexin, quercetinO-galloyl-hexoside, and kaempferolO-acetyl-hexosyl-rhamnoside were referred to in this species for the first time. AeI and mainly AePF (Ae polyphenolic fraction) showed a significant antiradical activity against all tested radicals. Both AeI and AePF decreased NO levels in vitro, AePF being more active than AeI. In vivo anti-inflammatory and analgesic activities were verified for both samples at concentrations devoid of toxicity. Agrimony infusion and, mainly, AePF are potential sources of antiradical and anti-inflammatory polyphenols.

scholarly journals Secondary Metabolite Profiling, Anti-Inflammatory and Hepatoprotective Activity of Neptunia triquetra (Vahl) Benth

Molecules ◽  
2021 ◽  
Vol 26 (23) ◽  
pp. 7353
Author(s):  
Nasir Aziz Wagay ◽  
Shah Rafiq ◽  
Mohammad Aslam Rather ◽  
Younas Rasheed Tantray ◽  
Feng Lin ◽  
...  
Keyword(s):  
Total Protein ◽  
Ethanolic Extract ◽  
Liver Weight ◽  
Hepatoprotective Activity ◽  
Experimental Models ◽  
Inflammatory Activity ◽  
Albino Rats ◽  
Total Lipids ◽  
Anti Inflammatory

The present study aimed to analyze the phytoconstituents of Neptunia triquetra (Vahl) Benth. Anti-inflammatory and hepatoprotective activities of ethanol (EE), chloroform (CE) and dichloromethane (DCME) of stem extracts were evaluated using in vivo experimental models. The extracts were analyzed for phytoconstituents using GC-HRMS. Anti-inflammatory activity of CE, EE and DCME was accessed using carrageenan-induced paw oedema, cotton pellet-induced granuloma and the carrageenan-induced air-pouch model in Wistar albino rats. The hepatotoxicity-induced animal models were investigated for the biochemical markers in serum (AST, ALT, ALP, GGT, total lipids and total protein) and liver (total protein, total lipids, GSH and wet liver weight). In the in vivo study, animals were divided into different groups (six in each group) for accessing the anti-inflammatory and hepatoprotective activity, respectively. GC-HRMS analysis revealed the presence of 102 compounds, among which 24 were active secondary metabolites. In vivo anti-inflammatory activity of stem extracts was found in the order: indomethacin > chloroform extract (CE) > dichloromethane extract (DCME) > ethanolic extract (EE), and hepatoprotective activity of stem extracts in the order: CE > silymarin > EE > DCME. The results indicate that N. triquetra stem has a higher hepatoprotective effect than silymarin, however the anti-inflammatory response was in accordance with or lower than indomethacin.

Synthesis, Characterization and Preliminary Pharmacological Evaluation of Triazolothiadiazoles Derived from some NSAIDs and Thiocarbohydrazide

2018 ◽  
pp. 73-92
Keyword(s):  
Biological Activities ◽  
Enzyme Synthesis ◽  
Control Group ◽  
Paw Edema ◽  
H Nmr ◽  
Pharmacological Test ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
Analgesic Activities

The synthesis of new NSAIDs with improved efficacy and selectivity towards COX2, which encouraged by the various biological activities of 1,2,4-triazoles and 1,3,4-thiadiazoles. In this experiment, the production of 1,2,4-triazolothiadiazoles derivatives from Ibuprofen, Naproxen and Indomethacin. We have enhanced anti-inflammatory and analgesic activities by conventional method and microwave-assisted technique, and then compare the time consuming by reaction and yield percent of the product in both way, besides evaluation of anti-inflammatory action of the target compounds by pharmacological test with predictable selectivity towards COX-2 enzyme. Synthesis of the target compounds (P1a-3b, N1a-3b and I1a-3b) has been successfully accomplished by checking purity, characterization, also identification of the synthetic compounds which detected by estimation of physical properties, FT-IR and ¹H-NMR spectroscopy. In vivo potent anti-inflammatory activity of the ending compounds is evaluating in rats utilizing egg-white prompted edema model of inflammation. The experienced compounds (P1a-3b, N1a-3b and I1a-3b) and the reference drugs (Ibuprofen, Naproxen and Indomethacin) produced significant reduction in paw edema in compare to the effect of control group. Wholly tested compounds produced considerable decrease of paw edema in contrast to control group. However, compounds (P3b, N3b and I1b) have considerable more paw edema declining than Ibuprofen, Naproxen and Indomethacin. Intermediate and target compounds are synthesis by microwave method have better result by time and yield in compare with conventional way. The synthesized compounds (Pa1-3b and N1a-3b) may exhibit expected selectivity towards COX-2 enzyme properly due to their large size than its parent Ibuprofen, Naproxen.

Millettia pachycarpa Exhibits Anti-Inflammatory Activity Through the Suppression of LPS-Induced NO/iNOS Expression

2014 ◽  
Vol 42 (04) ◽  
pp. 949-965 ◽  
Author(s):  
Haoyu Ye ◽  
Caifeng Xie ◽  
Wenshuang Wu ◽  
Minli Xiang ◽  
Zhuowei Liu ◽  
...  
Keyword(s):  
Docking Simulation ◽  
Binding Pocket ◽  
Inflammatory Activity ◽  
Molecular Docking Simulation ◽  
Inos Activity ◽  
Inos Protein Expression ◽  
Edema Model ◽  
Anti Inflammatory

The present study was designed to investigate the in vitro and in vivo anti-inflammatory activity of flavonoids isolated from Millettia pachycarpa Benth. The seeds of M. pachycarpa Benth were extracted with ethanol and subjected to chromatographic separation for the isolation of bioactive compounds. Their structures were elucidated by spectroscopic methods. The anti-inflammatory activity of the compounds was investigated by evaluating the inhibition ability of NO production, iNOS activity and iNOS protein expression induced by LPS-stimulated RAW264.7 macrophages in vitro and the carrageenan-induced hind paw edema model in vivo. Molecular docking simulation was also employed to obtain the binding parameters in the binding pocket of iNOS. Thirteen compounds (1–13) were isolated from Chinese herbal medicine M. pachycarpa Benth. Among them, 4-hydroxylonchocarpin (6) and deguelin (7) exhibited remarkable inhibitory rates of 66.5% and 57.7%, respectively, compared with that of 52.5% of indomethacin in LPS-induced macrophages cells. 4-hydroxylonchocarpin (6) with low toxicity (IC50 > 100 μm) exhibited better inhibitory effects to positive control of 1400W on iNOS activity at the concentration of 10 μm. Western blot assay revealed that 4-hydroxylonchocarpin (6) inhibited iNOS protein expression in RAW264.7 cells and molecular docking simulation showed that 4-hydroxylonchocarpin (6) fit well into the binding pocket of iNOS. In the carrageenan-induced paw edema model, our data revealed that the anti-inflammatory potential of 4-hydroxylonchocarpin (6) at 10 mg/kg showed comparable inhibitory ability to indomethacin at 5 h while a higher concentration of 4-hydroxylonchocarpin (6) at 50 mg/kg showed higher inhibitory activity than indomethacin, which was further confirmed by plasma levels of nitrite. The overall results suggest that 4-hydroxylonchocarpin (6) might be used as a potential therapeutic agent for inflammation-associated disorders.

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