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Diacetylcurcumin: Its Potential Antiarthritic Effect on a Freund's Complete Adjuvant-Induced Murine Model.

ABSTRACT: The present study aims to evaluate the antiarthritic activity of diacetylcurcumin (DAC), a synthetic derivative where the free phenolic groups of curcumin are derivatized by acetylation, thereby conferring greater lipophilicity to the parent molecule and partially overcoming the limited systemic bioavailability of curcumin. Antiarthritic activity was evaluated on a Freund's complete adjuvant (FCA)-induced murine model of arthritis. Oral administration of DAC (60 and 120 mg/kg) resulted in a significant inhibition of inflammation in the acute and chronic phases, respectively, demonstrating an improved and sustained anti-inflammatory effect, comparable to that of curcumin (150 mg/kg) in the chronic stage at a lower dose. Phenylbutazone (80 mg/kg) was used as a reference drug. The pharmacological consequence of DAC or curcumin treatment is the prevention of secondary lesions commonly associated with this biological model.

SUBMITTER: Escobedo-Martinez C

PROVIDER: S-EPMC6680498 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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Diacetylcurcumin: Its Potential Antiarthritic Effect on a Freund's Complete Adjuvant-Induced Murine Model.

Escobedo-Martínez Carolina C Guzmán-Gutiérrez Silvia Laura SL Carrillo-López María Isabel MI Deveze-Álvarez Martha Alicia MA Trujillo-Valdivia Alfonso A Meza-Morales William W Enríquez Raúl G RG

Molecules (Basel, Switzerland) 20190721 14

The present study aims to evaluate the antiarthritic activity of diacetylcurcumin (DAC), a synthetic derivative where the free phenolic groups of curcumin are derivatized by acetylation, thereby conferring greater lipophilicity to the parent molecule and partially overcoming the limited systemic bioavailability of curcumin. Antiarthritic activity was evaluated on a Freund's complete adjuvant (FCA)-induced murine model of arthritis. Oral administration of DAC (60 and 120 mg/kg) resulted in a sign ...[more]

PMID: 31330908

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Project description:Naringin (NAR), a naturally occurring essential flavonoid, present in grapefruit and Chinese herbal medicines, creates great interest in researchers due to its diverse biological and pharmacological activities. However, further development of NAR is hindered due to its poor water solubility and dissolution rates in GIT. To address these limitations, in this study, we report polymeric nanoparticles (NPs) of NAR (NAR-PLGA-NPs) for enhancing the oral NAR efficiency, with a biodegradable polymer (PLGA) to improve its absorption and bioavailability. NAR-PLGA-NPs were fabricated by a modified solvent emulsification-evaporation technique. Physicochemical properties were evaluated by SEM, particle size distribution, entrapment efficiency, Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), and differential scanning calorimetry (DSC). In vitro drug release and ex vivo permeation studies were carried out in phosphate buffer (pH 6.8) for 24 h. Furthermore, in vivo anti-arthritic studies were performed on a mouse model, and the results were compared with free NAR. The modulation of inflammatory mediators was also evidently supported by docking studies. Optimized nanoformulation FN4 (NAR-PLGA-NPs) prepared with acetone-ethanol (2:1) as a solvent system in a combination of stabilizers, i.e., poloxamer-188 and sodium deoxylate (1:1), along with 2% PVA solution, was prepared. From size characterization studies, it was observed that nanoformulations possessed a low particle size (179.7 ± 2.05 nm), a low polydispersity index (0.206 ± 0.001), and a negative zeta potential (-9.18 ± 0.78 mV) with a maximum entrapment efficiency (74 ± 3.61%). The drug release followed a Korsmeyer-Peppas release kinetic model (anomalous non-Fickian diffusion), providing greater NAR release after lyophilization (82.11 ± 3.65%) drug release in pH 6.8 phosphate buffer for 24 h. Ex vivo permeation analysis through an isolated goat intestinal membrane revealed 80.02 ± 3.69% drug release in 24 h. Encapsulation of a drug into PLGA is well described by the results of FTIR, DSC, and XRD. Finally, the therapeutic efficacy of optimized FN4 (NAR-PLGA-NPs) and its possible application on RA were further confirmed in a Freund's complete adjuvant-induced rat arthritic model as against free NAR at a dose of 20 mg/kg body wt. Our findings demonstrate that sustained action of NAR from optimized FN4 NPs with a rate-controlling polymeric carrier system exhibited prolonged circulation time and reduced arthritic inflammation, hence indicating the possibility as a novel strategy to secure the unpropitious biological interactions of hydrophobic NAR in a gastric environment.

Project description:BackgroundMigraine is a neurovascular primary headache disorder, which causes significant socioeconomic problems worldwide. The pathomechanism of disease is enigmatic, but activation of the trigeminovascular system (TS) appears to be essential during the attack. Migraine research of recent years has focused on neuropeptides, such as calcitonin gene-related peptide (CGRP) and pituitary adenylate cyclase-activating polypeptide 1-38 (PACAP1-38) as potential pathogenic factors and possible therapeutic offensives. The goal of present study was to investigate the simultaneous expression of CGRP and precursor of PACAP1-38 (preproPACAP) in the central region of the TS in a time-dependent manner following TS activation in rats.MethodsThe right whisker pad of rats was injected with 50 μl Complete Freund's Adjuvant (CFA) or saline. A mechanical allodynia test was performed with von Frey filaments before and after treatment. Transcardial perfusion of the animals was initiated 24, 48, 72 and 120 h after injection, followed by the dissection of the nucleus trigeminus caudalis (TNC). After preparation, the samples were stored at - 80 °C until further use. The relative optical density of CGRP and preproPACAP was analyzed by Western blot. One-way ANOVA and Kruskal-Wallis followed by Tukey post hoc test were used to evaluate the data. Regression analysis was applied to explore the correlation between neuropeptides expression and hyperalgesia.ResultsOrofacial CFA injection resulted in significant CGRP and preproPACAP release in the TNC 24, 48, 72 and 120 h after the treatment. The level of neuropeptides reached its maximum at 72 h after CFA injection, corresponding to the peak of facial allodynia. Negative, linear correlation was detected between the expression level of neuropeptides and value of mechanonociceptive threshold.ConclusionThis is the first study which suggests that the expression of CGRP and preproPACAP simultaneously increases in the central region of activated TS and it influences the formation of mechanical hyperalgesia. Our results contribute to a better understanding of migraine pathogenesis and thereby to the development of more effective therapeutic approaches.

Dataset Information

Diacetylcurcumin: Its Potential Antiarthritic Effect on a Freund's Complete Adjuvant-Induced Murine Model.

Publications

Diacetylcurcumin: Its Potential Antiarthritic Effect on a Freund's Complete Adjuvant-Induced Murine Model.

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