Improved Pharmacokinetic Profile and Anti-Inflammatory Property of a Novel Curcumin Derivative, A50

Chronic inflammation is considered as one of the challenging diseases, and overproduction of reactive oxygen species (ROS) is strongly related to the onset of chronic inflammation. Therefore, antioxidant and anti-inflammatory approaches are particularly becoming suitable treatment and prevention of inflammation. Curcumin (CUR), a main component of turmeric extract, is well known as an effective agent in both antioxidant and anti-inflammatory activities; however, there are still some limitations of its use including poor water solubility, low bioavailability, and oxidation by ROS. Nanotechnology has been used as a drug delivery system, which is a promising approach in overcoming the aforementioned drawbacks of CUR; hence, it improves the antioxidant and anti-inflammatory effects of conventional medications. In this research, silica-containing redox nanoparticles (siRNP) were designed with the size of several tens of nanometers, prepared by self-assembly of an amphiphilic block copolymer consisting of drug absorptive silica moiety and ROS-scavenging nitroxide radical moiety in the hydrophobic segment. CUR was simply encapsulated into siRNP through the dialysis method, creating CUR-loaded siRNP (CUR@siRNP), which significantly improved the water solubility of CUR. The efficient antioxidant activity and anti-inflammatory effect of CUR@siRNP in vitro were also improved via 2,2-diphenyl-1-picrylhydrazyl assay and lipopolysaccharide-induced macrophage cell line activation, respectively. Oral administration of CUR@siRNP showed improvement in pharmacokinetic profile in vivo including AUC and Cmax values as compared to free CUR. Furthermore, the anti-inflammatory effect of nanoformulation was investigated in the colitis mouse model induced by dextran sodium sulfate.

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ANTI-INFLAMMATORY ACTIVITY AND PHARMACOKINETIC PROFILE OF A NEW PARENTERAL FORMULATION OF NIMESULIDE

Pharmacological Research ◽

10.1006/phrs.1998.0417 ◽

1999 ◽

Vol 39 (2) ◽

pp. 137-141 ◽

Cited By ~ 11

Author(s):

S.K. GUPTA ◽

R.K. BHARDWAJ ◽

P. TYAGI ◽

S. SENGUPTA ◽

T. VELPANDIAN

Keyword(s):

Pharmacokinetic Profile ◽

Inflammatory Activity ◽

Parenteral Formulation ◽

Anti Inflammatory

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Preclinical Pharmacokinetics and Acute Toxicity in Rats of 5-{[(2E)-3-Bromo-3-carboxyprop-2-enoyl]amino}-2-hydroxybenzoic Acid: A Novel 5-Aminosalicylic Acid Derivative with Potent Anti-Inflammatory Activity

Molecules ◽

10.3390/molecules26226801 ◽

2021 ◽

Vol 26 (22) ◽

pp. 6801

Author(s):

Mara Gutiérrez-Sánchez ◽

Aurelio Romero-Castro ◽

José Correa-Basurto ◽

Martha Cecilia Rosales-Hernández ◽

Itzia Irene Padilla-Martínez ◽

...

Keyword(s):

Acute Toxicity ◽

Pharmacokinetic Profile ◽

Hplc Method ◽

Maximum Plasma ◽

Hydroxybenzoic Acid ◽

Aminosalicylic Acid ◽

Preclinical Pharmacokinetics ◽

Anti Inflammatory

Compound 5-{[(2E)-3-bromo-3-carboxyprop-2-enoyl]amino}-2-hydroxybenzoic acid (C1), a new 5-aminosalicylic acid (5-ASA) derivative, has proven to be an antioxidant in vitro and an anti-inflammatory agent in mice. The in vivo inhibition of myeloperoxidase was comparable to that of indomethacin. The aim of this study was to take another step in the preclinical evaluation of C1 by examining acute toxicity with the up-and-down OECD method and pharmacokinetic profiles by administration of the compound to Wistar rats through intravenous (i.v.), oral (p.o.), and intraperitoneal (i.p.) routes. According to the Globally Harmonized System, C1 belongs to categories 4 and 5 for the i.p. and p.o. routes, respectively. An RP-HPLC method for C1 quantification in plasma was successfully validated. Regarding the pharmacokinetic profile, the elimination half-life was approximately 0.9 h with a clearance of 24 mL/min after i.v. administration of C1 (50 mg/kg). After p.o. administration (50 mg/kg), the maximum plasma concentration was reached at 33 min, the oral bioavailability was about 77%, and the compound was amply distributed to all tissues evaluated. Therefore, C1 administered p.o. in rats is suitable for reaching the colon where it can exert its effect, suggesting an important advantage over 5-ASA and indomethacin in treating ulcerative colitis and Crohn’s disease.

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Effects of FM0807, a novel curcumin derivative, on lipopolysaccharide-induced inflammatory factor release via the ROS/JNK/p53 pathway in RAW264.7 cells

Bioscience Reports ◽

10.1042/bsr20180849 ◽

2018 ◽

Vol 38 (5) ◽

Cited By ~ 3

Author(s):

Yilong Wu ◽

Zhiwei Liu ◽

Weifang Wu ◽

Su Lin ◽

Nanwen Zhang ◽

...

Keyword(s):

Signaling Pathway ◽

Inflammatory Activity ◽

Raw 264.7 Cells ◽

Raw 264.7 ◽

Inflammatory Factor ◽

P53 Signaling ◽

Anti Inflammatory ◽

P53 Signaling Pathway ◽

Curcumin Derivative

Purpose: Sepsis is a systemic inflammatory response caused by infection. Curcumin is known to have antioxidant and anti-inflammatory activities. FM0807, a curcumin derivative, was investigated in the present study to determine its effect on cytokines and the possible molecular mechanism. Main methods: The experiments were carried out in lipopolysaccharide (LPS)-induced RAW 264.7 cells. Cell viability was measured by MTT assay. ELISA, Griess assays, fluorescence-based quantitative PCR, flow cytometric analysis, 2′,7′-dichlorodihydrofluorescein diacetate (DCFH-DA) experiments, and Western blotting were carried out to assess the potential effects of FM0807 on LPS-induced RAW 264.7 cells. Significant findings: FM0807 had no cytotoxic effects on RAW 264.7 cells. Furthermore, pretreatment with FM0807 inhibited the inflammatory factor tumor necrosis factor-α (TNF-α), interleukin (IL) 1β (IL-1β), IL-6, and inducible nitric oxide synthase (iNOS) at the protein and gene levels. FM0807 also inhibited the production of reactive oxygen species (ROS) and apoptosis. In addition, the activation of the ROS/JNK (c-jun NH2-terminal kinase)/p53 signaling pathway was inhibited by FM0807 in RAW 264.7 cells in vitro. Conclusion: FM0807 has anti-inflammatory activity in vitro, which suggests a potential clinical application in sepsis. The anti-inflammatory activity of FM0807 may be mediated by the ROS/JNK/p53 signaling pathway.

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The Anti-Inflammatory Mechanism of Action of a Water Soluble Curcumin Derivative and Mscs in Alzheimer Disease Induced In Rats

Bulletin of Egyptian Society for Physiological Sciences ◽

10.21608/besps.2013.35244 ◽

2013 ◽

Vol 33 (2) ◽

pp. 127-144

Author(s):

MT Abdel Aziza ◽

Ameen Rizk ◽

HH Ahmed ◽

LA Rashed ◽

M Sohier ◽

...

Keyword(s):

Alzheimer Disease ◽

Mechanism Of Action ◽

Water Soluble ◽

Inflammatory Mechanism ◽

Anti Inflammatory ◽

Curcumin Derivative

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Sterols from Jatropha tanjorensis leaves exhibit anti-inflammatory potential: in vitro and in silico studies

Bulletin of the National Research Centre ◽

10.1186/s42269-021-00658-z ◽

2021 ◽

Vol 45 (1) ◽

Author(s):

Damilola Alex Omoboyowa

Keyword(s):

Molecular Docking ◽

In Silico ◽

Diclofenac Sodium ◽

Ethanol Extract ◽

Pharmacokinetic Profile ◽

Gas Chromatography Mass Spectrometry ◽

Toxicity Screening ◽

In Silico Studies ◽

Anti Inflammatory

Abstract Background Inflammation has continued to raise global challenges and Jatropha tanrogenesis (JT) is used traditionally for its management. In this study, the in silico and in vitro anti-inflammatory potential of bioactive sterols were investigated. The active compounds of ethanol extract of JT leaves were identified using Gas chromatography-mass spectrometry (GC.MS) followed by molecular docking against COX-1 and COX-2 using maestro Schrödinger and pharmacokinetic profile prediction using webserver tools. The in vitro anti-inflammatory and anti-oxidantive potentials were investigated using standard protocols. Results GC–MS analysis of ethanol extract of JT leaves revealed the presence of eight (8) compounds, the molecular docking analysis of these compounds demonstrated varying degrees of binding affinities against the target proteins. The extract exhibit concentration dependent anti-oxidant activity with IC50 of 106.383 and 6.00 Fe2+E/g for DPPH and FRAP respectively. The extract showed significant (P < 0.05) reduction in percentage inhibition of hemolysis at 200 µg/ml while non-significant (P > 0.05) increase was observed at 600 and 1000 µg/ml compared to 200 µg/ml of diclofenac sodium. At lower concentration of 25 and 50 µg/ml, percentage inhibition of albumin denaturation was significantly (P < 0.05) higher compared to 200 µg/ml of diclofenac sodium. Drug likeness prediction and ADME/toxicity screening showed that the bioactive compounds possess no side effects. Conclusion The results obtained in this study suggested that, JT leaves possess anti-inflammatory activity and could be used as a source of new drug.

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