Curcumin-loaded lipid-core nanocapsules attenuates the immune challenge LPS-induced in rats: Neuroinflammatory and behavioral response in sickness behavior

doi:10.1016/j.jneuroim.2020.577270

Journal of Neuroimmunology

Volume 345, 15 August 2020, 577270

https://doi.org/10.1016/j.jneuroim.2020.577270 Get rights and content

Highlights

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CUR-LNC treatment abrogated sickness behavior in rats.
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CUR-LNC had neuroimmunomodulatory action in immune challenge LPS-induced.
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CUR-LNC treatment attenuated neurobehavioral changes in sickness behavior model.

Abstract

The purpose of current study was to evaluate the effect of curcumin (CUR) loaded lipid-core nanocapsules (CUR-LNC) treatment on neuroinflammatory and behavioral alterations in a model of sickness behavior induced by lipopolysaccharide (LPS) in rats. Rats were treated with CUR-LNC and CUR daily for 14 days. After the last treatments, sickness behavior was induced with LPS. Sickness behavior LPS-induced was confirmed by behavioral tests, an increase in levels of proinflammatory cytokines, decrease in levels of IL-10, overexpression of IDO-1 and IDO-2. In conclusion, CUR-LNC treatment attenuated the neuroinflammatory and behavioral changes caused in sickness behavior model.

Graphical abstract

Introduction

When the organism is infected by a pathogen either occasionally or accidentally, immune system activation occurs. In response to this activation there are changes mediated by central nervous system (CNS) such as lethargy, reduction in locomotor and exploratory activity, increase in proinflammatory cytokines levels, fever, fatigue, cognitive impairment and inability to derive pleasure from otherwise enjoyable situations (Dantzer and Kelley, 2007; Dantzer et al., 2008; Hennessy et al., 2014). This set of neurochemical and behavioral changes in response to activation of immune system is known as sickness behavior (Dantzer et al., 2008).

Sickness behavior is easily induced in rodents by peripheral administration of lipopolysaccharide (LPS) (Kelley et al., 2003). LPS is an endotoxin, component of the outer cell wall of gram-negative bacteria (Raetz and Whitfield, 2002). The mechanism of action of LPS is via the increase of proinflammatory cytokines such as tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) in CNS (Dantzer et al., 2008; Dantzer, 2009). This increase in CNS proinflammatory cytokine levels leads to activation of the kynurenine pathway (KP) mediated by induction of enzyme indoleamine-2,3-dioxygenase (IDO), causing neuroinflammation (Rana et al., 2016).

In view of the above, the search for compounds with anti-inflammatory activity and few side effects emerges as an alternative for treatment of sickness behavior (De Gomes et al., 2018a). In this context, curcumin (CUR) is a bioactive compound present in turmeric (Curcuma longa). CUR is commonly used as a spice and food-coloring agent (Saber et al., 2019). Some studies have already shown that curcumin has antioxidant, anti-inflammatory and neuroprotective activity (Gazal et al., 2014; Zhang et al., 2015; Yu et al., 2018). CUR action is limited due to low solubility, bioavailability and is highly unstable when exposed to light and certain pH conditions (Zhang et al., 2015). Also, it has a short lifetime in blood circulation, poor absorption and rapid metabolism in the gastrointestinal tract (Mahmood et al., 2015).

In this sense, nanotechnology emerges as an innovative solution to the problems presented earlier. Lipid-core nanocapsules (LNC) have been shown to increase bioavailability of drug and bioactive compound (Meloxicam and CUR) (Nakama et al., 2020), with the ability to carry and deliver the compound moderately to the active site/target tissue (brain tissue) (Giacomeli et al., 2019), besides having the ability to cross the blood-brain barrier (BBB) (via transport in favor of concentration gradient, due to its size) (Carreño et al., 2016).

Thus, the purpose of present study was to evaluate the effect of CUR loaded LNC treatment on neuroinflammatory and behavioral alterations in a model of sickness behavior LPS-induced in rats.

Section snippets

Chemicals

The caprylic/capric triglyceride oil, poly (ɛ-caprolactone) (PCL), sorbitan monostearate (Span 60®), Polysorbate 80 (P80), CUR and LPS (extracted from Escherichia coli, serotype 127:B8, L3129) were purchased from Sigma-Aldrich (Brazil). All chemicals used were of analytical grade.

Formation, physicochemical characterization of LNC and CUR solution

CUR-loaded LNC by preformed polymer interfacial deposition (Jäger et al., 2009). The concentrations of chemical compounds used to form the LNC are described below (Concentration used for a nanoformulation with a final

Physicochemical characterization of LNC

CUR-LNC and Blank-LNC were macroscopically homogeneous presented a Tyndall effect. For physicochemical characterization of CUR-LNC and Blank-LNC the following analysis were performed: Mean diameter distribution (297 and 397 nm, respectively), span (1.4 and 2.0), zeta potential (−29.59 and − 23.56), pH (6.2 and 6.1), drug content (92.3%) and encapsulation rate (91.0%) (Table 2).

Sickness behavior measurement

Statistical analysis of BW and LA showed a significant CUR × LPS interaction (F_2,48 = 5.23; P < 0.04 and F_2,48 = 6.69; P

Discussion

In the current study, was demonstrated in a pioneering manner, the protective effect of CUR loaded LNC treatment in a model of sickness behavior LPS-induced. Treatment with CUR-LNC was able to block behavioral changes caused by the immune challenge to animals. Still, CUR-LNC modulated the levels of proinflammatory and anti-inflammatory cytokines, attenuating the neuroinflammation, characteristic in sickness behavior model. In addition, the levels of CUR-LNC were higher in brain of rats, when

Conclusion

In the present scientific investigation, we evaluated the effect of CUR-LNC treatment on neuroinflammatory and behavioral changes in sickness behavior model LPS-induced in rats. In general manner, CUR-LNC exercising pharmacological effects upper to free CUR, probably because it arrives in greater amount in CNS. Moreover, CUR-LNC blocked the increase in levels of proinflammatory cytokines, modulated the levels of IL-10, prevented the increase in expression of IDO, avoiding overactivation of KP

Declaration of Competing Interest

The authors report no conflicts of interest.

Acknowledgements

This study was financed in part by the Coordination for the Improvement of Higher Education Personnel - Brazil (CAPES) – Finance Code 001. M.G.G thanks CAPES and Postgraduate Program in Pharmaceutical Sciences of Federal University of Pampa for the postdoctoral research fellowship. We also acknowledged S.E.H for the support to carry out the study.

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Curcumin-loaded lipid-core nanocapsules attenuates the immune challenge LPS-induced in rats: Neuroinflammatory and behavioral response in sickness behavior

Highlights

Abstract

Graphical abstract

Introduction

Section snippets

Chemicals

Formation, physicochemical characterization of LNC and CUR solution

Physicochemical characterization of LNC

Sickness behavior measurement

Discussion

Conclusion

Declaration of Competing Interest

Acknowledgements

Pharmacol. Rep.

Int. J. Pharm.

Brain Behav. Immun.

Eur. J. Pharm. Sci.

Immunol. Allergy Clin. N. Am.

Life Sci.

Brain Behav. Immun.

Psychoneuroendocrinology

J. Nut. Biochem.

Chem. Biol. Interact.

J. Neuroimmunol.

Behav. Brain Res.

Brain Behav. Immun.

Neuroscience

Eur. J. Pharmacol.

Brain Res.

Behav. Brain Res.

Brain Res.

Brain Behav. Immun.

Brain Behav. Immun.

Neurobiol. Learn Mem.

Brain Res.

Brain Behav. Immun.

Trends Pharmacol.

Methods

Int. J. Biol. Macromol.

Behav. Brain Res.

Arab. J. Chem.

Life Sci.

J. Neuroimmunol.

Ecotoxicol. Environ. Saf.

J. Psychiatr. Res.