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.

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 Development, Optimisation and Evaluation of Ketoprofen Lipospheres

2020 ◽  
Vol 11 (SPL4) ◽  
pp. 1853-1863
Author(s):  
Shubhra Rai ◽  
Gopal Rai ◽  
Ashish Budhrani
Keyword(s):  
Drug Delivery ◽  
Particle Size ◽  
Research Work ◽  
Extended Period ◽  
Entrapment Efficiency ◽  
Inflammatory Activity ◽  
Scanning Calorimetry ◽  
Anti Inflammatory

Lipospheres represent a novel type of fat-based encapsulation system produced for the topical drug delivery of bioactive compounds. The goal of this research work was to develop lipospheres, including ketoprofen applied for topical skin drug delivery. Ketoprofen lipospheres were formulated by melt emulsification method using stearic acid and Phospholipon® 90G. The lipospheres were analysed in terms of particle size and morphology, entrapment efficiency, Differential scanning calorimetry, In-vitro drug release, In-vivo (Anti-inflammatory activity). Outcomes of research revealed that particle size was found to be 9.66 µm and entrapment efficiency 86.21 ± 5.79 %. In-vivo, the study of ketoprofen loaded lipospheres formulation shows a higher plain formulation concentration in plasma (5.61 mg/mL). For dermis, ketoprofen retention was 27.02 ± 5.4 mg/mL for the lipospheres formulation, in contrast to that of the plain formulation group (10.05 ± 2.8 mg/mL). The anti-inflammatory effect of liposphere drug delivery systems was assessed by the xylene induced ear oedema technique and compared with marketed products. Finally, it seems that the liposphere drug delivery system possesses superior anti-inflammatory activity as compared to the marketed product gel consistencies. Liposphere may be capable of entrapping the medicament at very high levels and controlling its release over an extended period. Liposphere furnishes a proper size for topical delivery as well as is based on non-irritating and non-toxic lipids; it’s a better option for application on damaged or inflamed skin.

scholarly journals SYNTHESIS, ANTIOXIDANT AND ANTI-INFLAMMATORY ACTIVITIES OF ETHYL 2-(2-CYANO-3- (SUBSTITUTED PHENYL)ACRYLAMIDO)-4,5-DIMETHYLTHIOPHENE-3-CARBOXYLATES

2017 ◽  
Vol 10 (7) ◽  
pp. 95 ◽  
Author(s):  
Madhavi K ◽  
Sree Ramya G
Keyword(s):  
Antioxidant Activity ◽  
Free Radical ◽  
Antioxidant Properties ◽  
Inflammatory Activity ◽  
Paw Edema ◽  
Standard Drug ◽  
Rat Paw Edema ◽  
Anti Inflammatory ◽  
Rat Paw

Objective: Objective of the study was to synthesize and evaluate a series of novel compounds, ethyl 2-(2-cyano-3-(substituted phenyl)acrylamido)- 4,5-dimethylthiophene-3-carboxylates, for in vitro antioxidant and in vivo anti-inflammatory activities.Methods: Ethyl 2-(2-cyano-3-(substituted phenyl)acrylamido)-4,5-dimethylthiophene-3-carboxylates were synthesized by knoevenagel condensation of active methylene group of ethyl 2-(2-cyanoacetamido)-4,5-dimethylthiophene-3-carboxylate with substituted benzaldehydes. The synthesized compounds were evaluated for their in vitro antioxidant properties in three different models, viz., reduction of 1,1-diphenyl-2-pycrylhydrazyl free radical, scavenging of nitric oxide free radical, and ferric ion-induced lipid peroxidation using rat brain homogenate. Few selected compounds with good antioxidant properties were pharmacologically evaluated for anti-inflammatory activity by carrageenan-induced rat paw edema model.Results: Clean and efficient synthetic procedure was used for the preparation of series of compounds. The structures of synthesized compounds were confirmed by infrared, 1H nuclear magnetic resonance and mass spectra. The antioxidant activity data revealed that the compounds of ethyl 2-(2-cyano-3-(substituted phenyl)acrylamido)-4,5-dimethylthiophene-3-carboxylate containing phenolic substitution showed greater antioxidant activity. Hence, the active compounds were evaluated for anti-inflammatory activity and found to possess good activity. The percentage inhibition of rat paw edema obtained for the evaluated compounds was in the range of 70.2-83.1, comparable to the standard drug diclofenac (85.0%).Conclusion: The use of inexpensive, eco-friendly and readily available reagents, easy work-up and high purity of products makes the procedure a convenient and robust method for the synthesis of title compounds. The compounds of ethyl 2-(2-cyano-3-(substituted phenyl)acrylamido)-4,5- dimethylthiophene-3-carboxylate containing phenolic substitution showed greater antioxidant and anti-inflammatory activities.

scholarly journals EFFECT OF TERPENES AS PENETRATION ENHANCERS ON THE RELEASE AND PERMEATION KINETICS OF MELOXICAM GELS FORMULATIONS

2020 ◽  
pp. 1-5
Author(s):  
Raj Kumari ◽  
Pallavi Matta ◽  
Meenakshi Sharma ◽  
Madhu Verma
Keyword(s):  
Penetration Enhancers ◽  
Peppermint Oil ◽  
Clove Oil ◽  
Paw Edema ◽  
Rat Paw Edema ◽  
Lemongrass Oil ◽  
Anti Inflammatory ◽  
Rat Paw

Introduction: The transdermal route of administration has been extensively accepted as one of the potential route for the local and systemic delivery of drugs. The greatest obstacle in drug absorption is the highly organized stratum corneum (SC), which hinder drug transport. The probable solution leads to inclusion of penetration enhancers for reversibly disorganizing the barrier characteristic of stratum corneum. Objective: The main objective of the research work was to study the influence of peppermint oil, lemongrass oil, clove oil and turpentine oil as penetration enhancers on the percutaneous absorption of Meloxicam (ME) from a Carbopol 934 based gel formulation. Materials and Methods: ME gel sample was divided into 5 batches i.e., F1, F2, F3, F4, F5. Except F1, all other batches were incorporated with penetration enhancers (5% w/w) namely peppermint oil, clove oil, lemongrass oil and turpentine oil. The formulations were further evaluated for in-vitro drug release studies using a standard cellophane membrane at 37± 0.5˚ C in phosphate buffer pH 7.4 and a comparative anti-inflammatory activity was conducted using rat paw edema method. Result and Discussion: In-vitro permeation studies using a standard cellophane membrane showed that the rank order of enhancement ratio (ERflux) for Meloxicam as peppermint oil (1.414) > clove oil (1.353) > lemongrass oil (1.326) > turpentine oil (1.272) proving peppermint oil as the most competent penetration enhancer for Meloxicam. Further In- vivo anti-inflammatory activity were carried out using the standard rat paw edema method. The in vivo studies revealed that gel containing peppermint, clove, lemongrass and turpentine exhibited 2.53, 2.0, 1.9 and 1.38 times higher anti-inflammatory effect as compared to meloxicam (standard). Conclusion: It can be concluded from the study that all the 4 terpenes significantly increases the permeation of meloxicam gels and can be used as effective penetration enhancers.

scholarly journals A Glycosaminoglycan-Rich Fraction from Sea Cucumber Isostichopus badionotus Has Potent Anti-Inflammatory Properties In Vitro and In Vivo

Nutrients ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 1698
Author(s):  
Leticia Olivera-Castillo ◽  
George Grant ◽  
Nuvia Kantún-Moreno ◽  
Hirian A. Barrera-Pérez ◽  
Jorge Montero ◽  
...  
Keyword(s):  
Sea Cucumber ◽  
Inflammatory Responses ◽  
Ethanol Extract ◽  
Inflammatory Activity ◽  
Bioactive Constituents ◽  
Mouse Ear ◽  
Health Promoting ◽  
Anti Inflammatory

Sea cucumber body wall contains several naturally occurring bioactive components that possess health-promoting properties. Isostichopus badionotus from Yucatan, Mexico is heavily fished, but little is known about its bioactive constituents. We previously established that I. badionotus meal had potent anti-inflammatory properties in vivo. We have now screened some of its constituents for anti-inflammatory activity in vitro. Glycosaminoglycan and soluble protein preparations reduced 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced inflammatory responses in HaCaT cells while an ethanol extract had a limited effect. The primary glycosaminoglycan (fucosylated chondroitin sulfate; FCS) was purified and tested for anti-inflammatory activity in vivo. FCS modulated the expression of critical genes, including NF-ĸB, TNFα, iNOS, and COX-2, and attenuated inflammation and tissue damage caused by TPA in a mouse ear inflammation model. It also mitigated colonic colitis caused in mice by dextran sodium sulfate. FCS from I. badionotus of the Yucatan Peninsula thus had strong anti-inflammatory properties in vivo.

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)

Evaluation of Biological Activity of Derivatives of 1,3,4 Thiadiazole, 1,3,4-Oxadiazole and 1,2,4-Triazole

2020 ◽  
Vol 20 ◽  
Author(s):  
Gaurav M. Doshi ◽  
Mayuresh U. Bansode ◽  
Rakesh R. Somani
Keyword(s):  
Erythrocyte Membrane ◽  
Paw Edema ◽  
Toxic Dose ◽  
Rat Paw Edema ◽  
Maximum Decrease ◽  
Inhibitory Activities ◽  
Anti Inflammatory ◽  
Rat Paw

Objectives: 1,3,4-thiadiazole (A), 1,3,4-oxadiazole (B) and 1,2,4-triazole (C) derivatives have been known for their immense pharmacotherpaeutic potential. The current research article attempts to further explore and understand the probable biochemical mechanism related to anti-inflammatory activity of derivatives. Methods: The screened A, B and C derivatives were investigated for both in-vitro (Erythrocyte Membrane stabilization activity, Proteinase enzyme inhibitory activities) and in-vivo correlation using acute and chronic anti-inflammatory potential by carrageenan induced rats paw edema and cotton pellet granuloma methods respectively. The activity was studied after interpreting acute toxicity studies results. Results: In vitro studiesin the case of Erythrocyte Membrane stability and Proteinase enzyme inhibitory activities exhibited by A, B, and C at 100 ppm were found to be 48.89%, 51.08% and 50.08% and 66.78%, 76.91% and 57.41% respectively. The maximum toxic dose was found to be 2000 mg/kg. The derivatives were studied for two-dose levels viz; Lower (100 mg/kg) and higher dose (200 mg/kg). In rat paw edema maximum decrease was obtained for A (50.05%), B (50.05%) and C (51.06%) at lower and higher dose at 68.76%, 55.61%, and 65.26% respectively for effect up to 24 h. In the chronic model of cotton pelletgranuloma viz; higher and lower doses of A, B and C exhibited 38.15%, 33.19% and 30.25 % and 19.45%, 18.55% and 17.55 % respectively. Conclusion: The studied models depicted that derivatives A, B and C have the probable potential as anti-inflammatory agents. Further studies need to undertaken to explore their potential in the different therapeutic areas.

scholarly journals The Dietary Flavonoid Kaempferol Mediates Anti-Inflammatory Responses via the Src, Syk, IRAK1, and IRAK4 Molecular Targets

2015 ◽  
Vol 2015 ◽  
pp. 1-15 ◽  
Author(s):  
Shi Hyoung Kim ◽  
Jae Gwang Park ◽  
Jongsung Lee ◽  
Woo Seok Yang ◽  
Gye Won Park ◽  
...  
Keyword(s):  
Inflammatory Responses ◽  
Molecular Targets ◽  
Peritoneal Macrophages ◽  
Cellular Adhesion ◽  
Inflammatory Activity ◽  
Prostaglandin E ◽  
Genes Encoding ◽  
Anti Inflammatory

Even though a lot of reports have suggested the anti-inflammatory activity of kaempferol (KF) in macrophages, little is known about its exact anti-inflammatory mode of action and its immunopharmacological target molecules. In this study, we explored anti-inflammatory activity of KF in LPS-treated macrophages. In particular, molecular targets for KF action were identified by using biochemical and molecular biological analyses. KF suppressed the release of nitric oxide (NO) and prostaglandin E2(PGE2), downregulated the cellular adhesion of U937 cells to fibronectin (FN), neutralized the generation of radicals, and diminished mRNA expression levels of inflammatory genes encoding inducible NO synthase (iNOS), TNF-α, and cyclooxygenase- (COX-) 2 in lipopolysaccharide- (LPS-) and sodium nitroprusside- (SNP-) treated RAW264.7 cells and peritoneal macrophages. KF reduced NF-κB (p65 and p50) and AP-1 (c-Jun and c-Fos) levels in the nucleus and their transcriptional activity. Interestingly, it was found that Src, Syk, IRAK1, and IRAK4 responsible for NF-κB and AP-1 activation were identified as the direct molecular targets of KF by kinase enzyme assays and by measuring their phosphorylation patterns. KF was revealed to havein vitroandin vivoanti-inflammatory activity by the direct suppression of Src, Syk, IRAK1, and IRAK4, involved in the activation of NF-κB and AP-1.

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.

scholarly journals Anti-allergic and anti-inflammatory activities of black cumin extracts in in vitro and in vivo model systems

2021 ◽  
Author(s):  
Nazma Shaheen ◽  
Afiatul Azam ◽  
Amlan Ganguly ◽  
Saeed Anwar ◽  
Md Sorwer Alam Parvez ◽  
...  
Keyword(s):  
Acetic Acid ◽  
Paw Edema ◽  
Writhing Test ◽  
Black Cumin ◽  
Rat Paw Edema ◽  
Anti Inflammatory ◽  
Rat Paw ◽  
Dose Dependent

Black cumin (Nigella sativa) is a widely used ingredient of traditional medicine for its broad-spectrum pharmacological actions, including anti-allergic, bronchial asthma, and anti-inflammatory properties. We sought to evaluate BC extracts' efficacy for their anti-allergic and anti-inflammatory properties using a comprehensive in vitro, in vivo, and silico experimental setup. To investigate whether BC extract has anti-inflammatory, anti-allergic, and analgesic therapeutic potentials in vitro and in vivo. The activity of BC was assessed through anti-allergic activity on rat basophilic leukemia-2H3 cell line, anti-inflammatory activity on J774.1A cell line, anti-inflammatory activity by carrageenan-induced rat paw edema, analgesic activity by acetic acid-induced writhing test, and ingenuity analysis of the BC extracts in inflammation control. BC exerted potent anti-allergic activity by inhibiting antigen-induced degranulation. An anti-inflammatory effect is shown by inhibiting TNF-α pro-duction. The acetic acid-induced writhing test shown a dose-dependent reduction of writhing number following BC administration. Rat paw edema test shown the dose-dependent reduction of paw edema volume following BC administration. Ingenuity Pathway Analysis (IPA) suggested BC extracts containing ferulic acid, p-coumaric acid, kaempferol, and quercetin can inhibit inflammation. This study suggests that bioactive compounds in BC extract act as an anti-allergic and anti-inflammatory agent by regulating several downstream and upstream inflammation pathways.

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