Gabapentin Antioxidant Derivatives with Anti-Inflammatory and Neuroprotective Potency

2021 ◽  
Vol 18 ◽  
Author(s):  
Georgios Papagiouvannis ◽  
Panagiotis Theodosis-Nobelos ◽  
Paraskevi Tziona ◽  
Antonios Gavalas ◽  
Panos N. Kourounakis ◽  
...  
Keyword(s):  
Structural Characteristics ◽  
Radical Scavenging Activity ◽  
Radical Scavenging ◽  
Protein Glycation ◽  
Inflammatory Activity ◽  
Biochemical Pathways ◽  
Rat Paw Edema ◽  
Anti Inflammatory ◽  
Effective Drugs

Aims: The aim of this work is to investigate the antioxidant and anti-inflammatory potency of novel gabapentin derivatives, which could be proven useful as neuroprotective agents. Background: Alzheimer’s Disease (AD) is one of the most common neurodegenerative disorders worldwide. Due to its multi-factorial character, no effective treatment has been obtained yet. In this direction, the multi-targeting compounds approach could be useful for the development of novel, more effective drugs against AD. Oxidative stress and inflammation are highly involved in the progression of neurodegeneration, while gabapentin has been investigated for the treatment of behavioral symptoms in AD. Objective: In this work, derivatives of cinnamic acid, trolox and 3,5-di-tertbutyl-4-hydroxybenzoic acid amidated with gabapentin methyl ester, were designed and studied. Compounds with these structural characteristics are expected to act in various biochemical pathways, affecting neurodegenerative processes. Methods: The designed compounds were synthesized with classical amidation methods, purified by flash column chromatography, and identified spectrometrically (1H-NMR and 13C-NMR). Their purity was determined by CHN elemental analysis. They were tested in vitro for their antioxidant and anti-inflammatory properties, and for their inhibitory effect on acetylcholinesterase. Their in vivo anti-inflammatory activity was also tested. Results: Those molecules incorporating an antioxidant moiety possessed inhibitory activity against rat microsomal membrane lipid peroxidation and oxidative protein glycation, as well as radical scavenging activity. Moreover, most of them presented moderate inhibition towards lipoxygenase (up to 51% at 100μΜ) and acetylcholinesterase (AchE) (IC50 up to 274μΜ) activities. Finally, all synthesized compounds presented in vivo anti-inflammatory activity, decreasing carrageenan-induced rat paw edema up to 53% and some of them could inhibit cyclooxygenase significantly. Conclusion: These results indicate that the designed compounds could be proven useful as multi-targeting molecules against AD, since they affect various biochemical pathways associated with neurodegeneration. Thus, more effective drugs can be obtained, and possible adverse effects of drug combination can be limited.

scholarly journals Anti-Inflammatory Potential Evaluation (In-Vitro and In-Vivo) of Arthrophytum scoparium Aerial Part

2020 ◽  
Vol 10 (5) ◽  
pp. 213-218
Author(s):  
Sabrina Manel Kaddour ◽  
Lekhmici Arrar ◽  
Abderrahmane Baghiani
Keyword(s):  
Protein Denaturation ◽  
Radical Scavenging Activity ◽  
Folk Medicine ◽  
Radical Scavenging ◽  
Inflammatory Activity ◽  
Traditional Use ◽  
Rat Paw Edema ◽  
Anti Inflammatory

Arthrophytum scoparium is plant commonly used in folk medicine in Algeria to treat numerous human diseases especially infectious, Rheumatism, diabetes and cancer. However, its anti-inflammatory activity and the underlying mechanisms have not been studied systematically. The present study aims to assess both the in vitro and in vivo anti-inflammatory potential and antioxidant activity of the plant. Results showed that A. scoparium chloroform extract (ChE) contains the largest amount of phenolic and flavonoid compounds. In-vitro bioassay consisted of investigating the effect of the plant extracts against protein denaturation (BSA and egg albumin). In-vivo anti-inflammatory activity was evaluated by measuring the percentage inhibition of carrageenan-induced rat paw edema after oral administration of the extracts. Results showed that inhibition of protein denaturation was maximum in case of A. scoparium crude extract (CrE) with dose dependant manner. Similarly in the in-vivo study, carrageenan induced inflammation was significantly antagonized by CrE with inhibition of 87.02% at 400 mg/kg. CrE extracts showed the highest scavenger effect against hydroxyl and hydrogen peroxide. The CrE showed potent anti-inflammatory activity in both the conditions in vivo and in vitro. In conclusion different A. scoparium extracts scavenged reactive oxygen species efficiently; it may be due to the presence of its flavonoids and polyphenols. These results support the traditional use of this plant. Keywords: Arthrophytum scoparium, polyphenols, anti-inflammatory activity, radical scavenging activity.

scholarly journals Bioactivity-Guided Investigation of the Anti-Inflammatory Activity of Hippophae rhamnoides Fruits

Planta Medica ◽  
2017 ◽  
Vol 84 (01) ◽  
pp. 26-33 ◽  
Author(s):  
Dóra Rédei ◽  
Norbert Kúsz ◽  
Nikoletta Jedlinszki ◽  
Gábor Blazsó ◽  
István Zupkó ◽  
...  
Keyword(s):  
Hippophae Rhamnoides ◽  
Inflammatory Activity ◽  
Hippophaë Rhamnoides ◽  
Rat Paw Edema ◽  
In Vivo Animal Models ◽  
Anti Inflammatory ◽  
Rat Paw ◽  
First Time ◽  
Peel Extract

AbstractAccording to modern ethnobotanical records, the fruit of Hippophae rhamnoides is effective in the treatment of different allergic symptoms. In order to obtain pharmacological evidence for this observation, the fruit was investigated for anti-inflammatory activity using in vivo animal models. Aqueous and 70% MeOH extracts were tested in 48/80-induced rat paw edema assay after oral administration, and it was found that the 70% MeOH extract (500 mg/kg) reduced significantly edema volume (0.660 ± 0.082 mL vs. control 0.935 ± 0.041 mL). Extracts of different parts of the fruit (pulp, peel, seed) were investigated in the same assay, and the peel extract was shown to exhibit maximum edema-reducing effect (0.470 ± 0.124 mL vs. control 0.920 ± 0.111 mL). This extract was used to elucidate the mode of action. Different inflammation inducers (serotonin, histamine, dextran, bradykinin, and carrageenan) were applied in the rat paw model, but the extract inhibited only the compound 48/80 elicited inflammation. The active extract was then fractionated by solvent-solvent partitioning and chromatographic methods with the guidance of the 48/80-induced anti-inflammatory assay, and the main compounds responsible for the activity were identified as ursolic acid and oleanolic acid. Our data suggest that the activity is most probably based on a membrane stabilizing effect caused by the inhibition of degranulation of mast cells. Moreover, previously unknown 2,5-bis-aryl-3,4-dimethyltetrahydrofuran lignans, nectandrin B, fragransin A2, and saucernetindiol were isolated and identified from H. rhamnoides for the first time.

scholarly journals Probiotic Cell-Free Supernatants Exhibited Anti-Inflammatory and Antioxidant Activity on Human Gut Epithelial Cells and Macrophages Stimulated with LPS

2018 ◽  
Vol 2018 ◽  
pp. 1-12 ◽  
Author(s):  
Stefania De Marco ◽  
Marzia Sichetti ◽  
Diana Muradyan ◽  
Miranda Piccioni ◽  
Giovanna Traina ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Lactobacillus Reuteri ◽  
Intestinal Inflammation ◽  
Radical Scavenging Activity ◽  
Radical Scavenging ◽  
Human Colon ◽  
Saccharomyces Boulardii ◽  
Inflammatory Activity ◽  
Industrialized Countries ◽  
Anti Inflammatory

The incidence of inflammatory bowel disease is increasing all over the world, especially in industrialized countries. The aim of the present work was to verify the anti-inflammatory activity of metabolites. In particular, cell-free supernatants ofLactobacillus acidophilus, Lactobacillus casei,Lactococcus lactis, Lactobacillus reuteri, andSaccharomyces boulardiihave been investigated. Metabolites produced by these probiotics were able to downregulate the expression of PGE-2 and IL-8 in human colon epithelial HT-29 cells. Moreover, probiotic supernatants can differently modulate IL-1β, IL-6, TNF-α, and IL-10 production by human macrophages, suggesting a peculiar anti-inflammatory activity. Furthermore, supernatants showed a significant dose-dependent radical scavenging activity. This study suggests one of the mechanisms by which probiotics exert their anti-inflammatory activity affecting directly the intestinal epithelial cells and the underlying macrophages. This study provides a further evidence to support the possible use of probiotic metabolites in preventing and downregulating intestinal inflammation as adjuvant in anti-inflammatory therapy.

In vitro and in vivo delivery of atorvastatin: A comparative study of anti-inflammatory activity of atorvastatin loaded copolymeric micelles

2017 ◽  
Vol 32 (8) ◽  
pp. 1127-1138 ◽  
Author(s):  
Sina Andalib ◽  
Pezhman Molhemazar ◽  
Hossein Danafar
Keyword(s):  
Inflammatory Responses ◽  
Inflammatory Activity ◽  
Lipid Lowering ◽  
Precipitation Method ◽  
Paw Edema ◽  
Scanning Calorimetry ◽  
Rat Paw Edema ◽  
Anti Inflammatory

Statins have been shown to exert ‘pleiotropic effects’ independent of their cholesterol lowering actions that include anti-inflammatory properties. In this study we synthesized mono methoxy poly (ethylene glycol)–poly (ε-caprolactone) (mPEG-PCL) di block copolymers. The structure of the copolymers was characterized by H nuclear magnetic resonance, Fourier-transform infrared spectroscopy, differential scanning calorimetry and gel permeation chromatography techniques. In this method, atorvastatin was encapsulated within micelles through a single-step nano-precipitation method, leading to the formation of atorvastatin-loaded mPEG-PCL (atorvastatin/mPEG-PCL) micelles. The resulting micelles were characterized further by various techniques such as dynamic light scattering and atomic force microscopy. In this study the anti-inflammatory activity of atorvastatin and atorvastatin/mPEG-PCL micelles on acute models of inflammation are analyzed, to compare the effect of indometacin in rats. Carrageenan induces rat paw edema; six animals of each group (10 groups) received indometacin, atorvastatin, and atorvastatin/mPEG-PCL micelles orally 1, 6, 12 and 24 h before carrageenan injection in paw. The paw edema thickness measured at 1, 2, 3 and 4 h after injection and percentage inhibition of edema in various groups were calculated. The results showed that the zeta potential of micelles was about −16.6 mV and the average size was 81.7 nm. Atorvastatin was encapsulated into mPEG-PCL micelles with loading capacity of 14.60 ± 0.96% and encapsulation efficiency of 62.50 ± 0.84%. Atorvastatin and atorvastatin/mPEG-PCL micelles showed significant anti-inflammatory activity in the present study. The anti-inflammatory activity of atorvastatin and atorvastatin/mPEG-PCL micelles was significant in comparison with indometacin. Atorvastatin/mPEG-PCL micelles showed more anti-inflammatory activity than atorvastatin. This study revealed the anti-inflammatory activity of atorvastatin and atorvastatin/mPEG-PCL micelles and suggested the statins have a potential inflammatory activity along with its lipid lowering properties. Contrary to anti-inflammatory effects, the pro-inflammatory responses are independent of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibition and can be mediated directly by atorvastatin.

scholarly journals Evaluation of Anti-Inflammatory and Analgesic Activities of Methanolic Extract of Aitchisonia Rosea in Albino Mice

2020 ◽  
Vol 8 (1) ◽  
pp. 31-36
Author(s):  
Shahid Rasool ◽  
Ambreen Malik Uttra ◽  
Mehreen Malik Uttra ◽  
Faheem Ahmed ◽  
Khizar Abbas
Keyword(s):  
Acetic Acid ◽  
Methanolic Extract ◽  
Radical Scavenging Activity ◽  
Radical Scavenging ◽  
Paw Edema ◽  
Egg Albumin ◽  
Inflammatory Conditions ◽  
Albino Mice ◽  
Anti Inflammatory

Objective:  Current analysis aims at in-vivo investigation of analgesic and anti-inflammatory activities of Aitchisonia rosea methanolic extract. Methods: Albino mice (20-30 g) were used in the study. Extract at 200, 400 and 800 mg/kg doses was tested against egg albumin and carrageenan induced mice paw edema along with formalin persuaded paw licking and acetic acid prompted writhing for analgesic activity. Results: Results depicted dose reliant and significant (p<0.001) inhibition of carrageenan as well as egg albumin brought paw edema, abdominal constrictions/ hind limb stretching tempted by acetic acid and formalin instigated paw licking. Capability of crude extract to halt inflammatory and analgesic response was akin to that of ibuprofen in all models. Conclusion: The current findings support the use of Aitchisonia rosea for inflammatory conditions, which might be attributed to its previously proven high alkaloid, flavonoids, phenol, tannins content and free radical scavenging activity.

scholarly journals CHEMICAL ANALYSIS, ANTIOXIDANT, ANTI-INFLAMMATORY AND ANTINOCICEPTIVE EFFECTS OF ACETONE EXTRACT OF ALGERIAN SOLENOSTEMMA ARGEL (DELILE) HAYNE LEAVES

2020 ◽  
pp. 72-81
Author(s):  
DAOUIA KELTOUM BENMAAROUF ◽  
DIANA C. G. A. PINTO ◽  
BERNARD CHINA ◽  
SAFIA ZENIA ◽  
KHEIRA BOUZID BENDESARI ◽  
...  
Keyword(s):  
Acetic Acid ◽  
Radical Scavenging Activity ◽  
Radical Scavenging ◽  
Granuloma Formation ◽  
Paw Edema ◽  
Oral Toxicity ◽  
Traditional Use ◽  
Anti Inflammatory ◽  
Dose Dependent

Objective: To investigate the qualitative composition of the acetonic extract from leaves of S. argel (AESA) and their anti-inflammatory and analgesic properties in vivo. Methods: AESA profile was established by UHPLC/DAD/ESI-MS2. AESA was subjected to the acute oral toxicity study according to the OECD-420 method. Antioxydant activity of AESA was performed by DPPH radical scavenging assay. Anti-inflammatory effects of AESA were determined in two animal models: carrageenan-induced paw edema in rats and cotton pellet-induced granuloma formation in rats. Further, anti-nociceptives activities of AESA were assessed by hot plate test, acetic acid-induced abdominal writhing test and formalin test. Results: The in vivo AESA toxicity was low. AESA expresses a maximum radical scavenging activity with a IC50 value of 36,05 μg/ml. The AESA at 250 and 400 mg/kg significantly reduced carrageen an induced paw edema by 70.09% and 85.53% 6h after carrageenan injection, respectively. AESA produced significant dose-dependent anti-inflammatory effect against cotton pellets-induced granuloma formation in rats. In addition, AESA at 250 and 400 mg/kg significantly reduced acetic acid-induced writhing by 56.83 and 80.41%, respectively. Oral administration of 250 and 400 mg/kg of AESA caused a significant dose dependent anti-nociceptive effect in both neurogenic and inflammatory phases of formalin-induced licking. AESA also impacted the pain latency in the hot plat test. Conclusion: These data suggest that AESA possesses antioxidant, anti-inflammatory and anti-nociceptive effects. These results support the traditional use of S. argel to cure pain and inflammatory diseases in the Algerian Sahara.

scholarly journals Unravelling the Anti-Inflammatory and Antioxidant Potential of the Marine Sponge Cliona celata from the Portuguese Coastline

Marine Drugs ◽  
2021 ◽  
Vol 19 (11) ◽  
pp. 632
Author(s):  
Joana Alves ◽  
Helena Gaspar ◽  
Joana Silva ◽  
Celso Alves ◽  
Alice Martins ◽  
...  
Keyword(s):  
Marine Sponge ◽  
Radical Scavenging Activity ◽  
Radical Scavenging ◽  
Marine Sponges ◽  
Inflammatory Activity ◽  
Raw 264.7 Cells ◽  
Protective Effects ◽  
Antioxidant Power ◽  
Anti Inflammatory ◽  
Cliona Celata

Inflammation is a double-edged sword, as it can have both protective effects and harmful consequences, which, combined with oxidative stress (OS), can lead to the development of deathly chronic inflammatory conditions. Over the years, research has evidenced the potential of marine sponges as a source of effective anti-inflammatory therapeutic agents. Within this framework, the purpose of this study was to evaluate the antioxidant and the anti-inflammatory potential of the marine sponge Cliona celata. For this purpose, their organic extracts (C1–C5) and fractions were evaluated concerning their radical scavenging activity through 2,2-diphenyl-1-picrylhydrazyl radical (DPPH), ferric reducing antioxidant power (FRAP), oxygen radical absorbance capacity (ORAC), and anti-inflammatory activity through a (lipopolysaccharides (LPS)-induced inflammation on RAW 264.7 cells) model. Compounds present in the two most active fractions (F5 and F13) of C4 were tentatively identified by gas chromatography coupled to mass spectrometry (GC-MS). Even though samples displayed low antioxidant activity, they presented a high anti-inflammatory capacity in the studied cellular inflammatory model when compared to the anti-inflammatory standard, dexamethasone. GC-MS analysis led to the identification of n-hexadecanoic acid, cis-9-hexadecenal, and 13-octadecenal in fraction F5, while two major compounds, octadecanoic acid and cholesterol, were identified in fraction F13. The developed studies demonstrated the high anti-inflammatory activity of the marine sponge C. celata extracts and fractions, highlighting its potential for further therapeutic applications.

scholarly journals In- vitro antioxidant and In vivo Anti-inflammatory Potentials of Marantochloa Leucantha (Marantaceae) Extracts and Fractions

2019 ◽  
Vol 18 (2) ◽  
pp. 233-240
Author(s):  
Wilfred O Obonga ◽  
Charles O Nnadi ◽  
Chinonye C Chima ◽  
Sunday N Okafor ◽  
Edwin O Omeje
Keyword(s):  
Antioxidant Activity ◽  
Radical Scavenging ◽  
Paw Edema ◽  
Frap Assay ◽  
Rat Paw Edema ◽  
Etoac Fraction ◽  
High Antioxidant Activity ◽  
Anti Inflammatory

This study evaluated the antioxidant and anti-inflammatory properties of Marantochloa leucantha (Marantaceae). The in vitro antioxidant activity of the extracts and solvent fractions was evaluated by 1,1-diphenyl- 2-picrylhydrazyl (DPPH) radical scavenging and ferric reducing antioxidant potential (FRAP) assay models and in vivo anti-inflammatory activity by the rat paw edema model. The phytochemical screening indicated the presence of tannins, terpenoids, steroids, flavonoids, reducing sugar and phenolics. The antioxidant assay showed that all the extracts exhibited high antioxidant activity comparable with ascorbic and gallic acid controls. In DPPH model, a 250 μg/ml EtOAc fraction of the leaves showed antioxidant activity of 93.9 ± 1.7 % (EC50 0.82 μg/ml) and a 1000 μg/ml of same stem fraction produced 91.9 ± 0.3 % activity (EC50 1.38 μg/ml). In the FRAP model, EtOAc fraction exhibited 31.1±0.7 and 92.0 ± 2.2 μM Fe2+/g of dried leaves and stem, respectively at 1000 μg/ml FeSO4 equivalent. The anti-inflammatory potential of the plant showed that the crude stem extract and fractions at 200 - 600 mg/kg exhibited significant (p < 0.01) dose-related inhibition of paw edema in rats. A 200 mg/kg EtOAc fraction showed 18.8 % inhibition compared to 31 % observed in diclofenac-treated rats in 2 h post albumin challenge. These findings validated the folkloric use of this plant in the treatment of diseases associated to the oxidative stress and could further provide promising lead compounds with potent antioxidant and anti-inflammatory activities Dhaka Univ. J. Pharm. Sci. 18(2): 233-240, 2019 (December)

Inhibition of iNOS by Benzimidazole Derivatives: Synthesis, Docking, and Biological Evaluations

2021 ◽  
Vol 17 ◽  
Author(s):  
Richa Minhas ◽  
Yogita Bansal
Keyword(s):  
Inflammatory Activity ◽  
Benzimidazole Derivatives ◽  
Critical Study ◽  
Paw Edema ◽  
Rat Paw Edema ◽  
Anti Inflammatory ◽  
Inos Inhibitors ◽  
Rat Paw

Background: Inducible nitric Oxide Synthase (iNOS) plays a key role in the progression of inflammatory diseases by accelerating the production of NO, which makes it an intriguing target to treat inflammation in complex diseases. Therefore, the search is on to develop molecules as selective iNOS inhibitors. Objective: The present work was aimed to design, synthesize and evaluate benzimidazole-coumarin coupled molecules as anti-iNOS agents through in silico and pharmacological studies. Methods: A critical study of literature reports on iNOS inhibitors led to the selection of a (un)substituted coumarin nucleus, 2-aminobenzimidazole, and a 4-atom linker as important structural components for iNOS inhibition. Two series of compounds (7-16 and 17-26) were designed and synthesized by coupling these components. The compounds were subjected to docking using iNOS (1QW4) and nNOS (1QW6) as targets. All compounds were evaluated for NO and iNOS inhibitory activities in vitro. The selected compound was finally evaluated for anti-inflammatory activity in vivo using the carrageenan-induced rat paw edema model. Results : All compounds showed moderate to good inhibition of NO and iNOS in vitro. Compound 12 was the most potent inhibitor of NO and iNOS. Hence, it was evaluated in vivo for toxicity and anti-inflammatory activity. It was found to be safe in acute toxicity studies, and effective in reducing the rat paw edema significantly. Its anti-inflammatory behaviour was similar to that of aminoguanidine, which is a selective iNOS inhibitor. Conclusion: The newly synthesized benzimidazole-coumarin hybrids may serve as potential leads for the development of novel anti-iNOS agents.

scholarly journals IN VITRO ANTIOXIDANT AND ANTI-INFLAMMATORY ACTIVITIES OF ALCHORNEA CORDIFOLIA (SCHUMACH AND THONN.) MULL. ARG. AND ANTROCARYON KLAINEANUM PIERRE EXTRACTS

2020 ◽  
pp. 129-135
Author(s):  
ROSETTE CHRISTELLE NDJIB ◽  
STEVE VALDI DJOVA ◽  
CHRISTELLE WAYOUE KOM ◽  
AGBOR GABRIEL AGBOR ◽  
AMINA MAMAT ◽  
...  
Keyword(s):  
Concentration Level ◽  
Radical Scavenging Activity ◽  
Radical Scavenging ◽  
Dry Weight ◽  
Inflammatory Activity ◽  
Phytochemical Screening ◽  
Reducing Activity ◽  
Anti Inflammatory ◽  
Β Carotene

Objective: This study aims to evaluate the in vitro antioxidant, anti-inflammatory activities of the aqueous and hydroethanolic extracts recipe of Alchornea cordifolia and Antrocaryon klaineanum. A preliminary phytochemical screening was carried out. Methods: The total phenols content was determined by the Folin Ciocalteu reagent method, while the antioxidant activity of both extracts was characterized by the 2-2diphenyl-1-picrilhidrazil (DPPH) and β-carotene assays. The anti-inflammatory activity of the extracts was evaluated as the inhibition of Bovine Serum Albumin (BSA) denaturation and antiproteinase activity. Results: The aqueous extracts of Alchornea cordifolia and Antrocaryon klaineanum contained more polyphenols [270 mg Ascorbic acid equivalent (AAE)/g dry weight (dw)] than the hydroethanolic recipe extract (262.41 mg AAE/g dw) at the same concentration level. On the other hand, the aqueous and hydroethanolic recipe extract had the same radical scavenging activity with the antiradical power of 0.851 and 0.830, respectively. Similarly, the recipe extract had the same reducing activity with reducing the power of 94.2±2.03 mg EAA/g dw and 97.4±4.16 mg EAA/g dw for the aqueous and hydroethanolic recipe extract of Alchornea cordifolia and Antrocaryon klaineanum respectively. For the anti-inflammatory activity it was observed that both extracts possess the same activity as Diclofenac® with an IC50 of 50.21 μg/ml. The phytochemical screening of the extracts revealed the presence of alkaloids, flavonoids, carbohydrates, phenols and tannins, which may account for their activities. Conclusion: The plant recipe extract studied possess antioxidant and anti-inflammatory potentials, which may be beneficiary to its consumers.

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