Micronized Resveratrol Shows Anticonvulsant Properties in Pentylenetetrazole-Induced Seizure Model in Adult Zebrafish

Almeida, Emilia Rodrigues; Lima‐Rezende, Cássia Alves; Schneider, Sabrina Ester; Garbinato, Cristiane; Pedroso, Jefferson; Decui, Laura; Aguiar, Gean Pablo S.; Müller, Liz Girardi; Oliveira, J. Vladimir; Siebel, Anna Maria

doi:10.1007/s11064-020-03158-0

Cited by 22 publications

(10 citation statements)

References 40 publications

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“…The micronization of curcumin (Bertoncello et al, 2018), N-acetylcysteine (Aguiar et al, 2017), trans-resveratrol (Aguiar et al, 2018, 2016; Almeida et al, 2021; Decui et al, 2020), methotrexate (Chen et al, 2012), phenylbutazone (Moribe et al, 2005), Panax notoginseng saponins (Liang et al, 2021), etoposide (Cheng et al, 2016), ellagic acid (Li et al, 2015), taxifolin (Zu et al, 2012) atorvastatin calcium (Zhang et al, 2009) and ibuprofen (Han et al, 2011; Sosna et al, 2018) by the SEDS technique have shown a reduction in particle size, an increase in the dissolution rate, an increase in the solubility, as well as a modification of the crystalline structure of the compound when compared with non-micronized composts. Recently, the micronization of Panax notoginseng saponins changed the pharmacokinetic parameters of these compounds in rats, showing significantly higher values in plasma powders with smaller particle sizes than the larger particle sizes (Liang et al, 2021).…”

Section: Resultsmentioning

confidence: 99%

Curcumin micronization by supercritical fluid:in vitroandin vivobiological relevance

Sachett

Gallas‐Lopes

Benvenutti

et al. 2021

Preprint

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Curcumin, a polyphenol extracted from the rhizome of Curcuma longa L. (Zingiberaceae), is shown to have antioxidant, anti-inflammatory, neuroprotective, anxiolytic, and antidepressant properties in both preclinical and clinical studies. However, its low bioavailability is a limitation for its potential adoption as a therapeutic agent. The process of micronization can overcome this barrier by reducing the particle size and increasing the dissolution rate, potentially improving the bioavailability of the compounds of interest. In this study, we compared the in vitro antioxidant effects of curcumin (CUR) and micronized curcumin (MC) and studied their effects on behavioral and neurochemical parameters in zebrafish submitted to unpredictable chronic stress (UCS). MC (1 g/L) presented higher antioxidant activity in vitro as compared to CUR, as measured by iron-reducing antioxidant power (FRAP), 1,1-diphenyl-2-2-picyryl-hydrazyl radical removal (DPPH), and deoxyribose tests. UCS increased total distance traveled in the social interaction test (SI), while decreased crossings, time, and entries to the top area in the novel tank test (NTT). No effects of UCS were observed in the open tank test (OTT). The behavioral effects induced by UCS were not blocked by any curcumin preparation. UCS also decreased non-protein thiols (NPSH) levels, while increased glutathione reductase (GR) activity and thiobarbituric acid reactive substances (TBARS) levels on zebrafish brain. MC presented superior antioxidant properties than CUR in vivo, blocking the stress-induced neurochemical effects. Although this study did not measure the concentration of curcumin on the zebrafish brain, our results suggest that micronization increases the bioavailability of curcumin, potentiating its antioxidant activity both in vitro and in vivo. Our study also demonstrates that counteracting the oxidative imbalance induced by UCS is not sufficient to block its behavioral effects.

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Section: Resultsmentioning

confidence: 99%

Curcumin micronization by supercritical fluid:in vitroandin vivobiological relevance

Sachett

Gallas‐Lopes

Benvenutti

et al. 2021

Preprint

Self Cite

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“…It has shown anticonvulsive activity against various models, for example, pentylenetetrazole (PTZ)-induced seizure, electroconvulsions, and kainic-acid-induced seizures . Thus, most studies published in the recent past − show that resveratrol positively affects seizures. Some studies, such as Tomaciello et al, did not find significant protection with resveratrol in their seizure models (but did not exclude the possibility of protection with chronic treatment).…”

Section: Introductionmentioning

confidence: 99%

Resveratrol-Loaded Glutathione-Coated Collagen Nanoparticles Attenuate Acute Seizures by Inhibiting HMGB1 and TLR-4 in the Hippocampus of Mice

Siddiqui

Asad

Akhter

et al. 2022

ACS Chem. Neurosci.

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Epilepsy is a relatively complicated neurological disorder that results in seizures. The use of resveratrol in treating seizures has been reported in recent studies. However, the low bioavailability of resveratrol and the difficulty of reaching the targeted location in the brain reduce its efficacy considerably. The side effects due to the higher concentration of drugs are another matter of concern. The purpose of the present study is to enhance the antiepileptic potential of resveratrol by delivering it to the brain's targeted location by encapsulating it in glutathione-coated collagen nanoparticles. The collagen nanoparticles increase the bioavailability of resveratrol, while the transport of resveratrol to its target location in the brain is facilitated by glutathione. By encapsulating resveratrol in glutathione-coated collagen nanoparticles, the concentration also substantially decreases. Resveratrol encapsulated in synthesized nanoparticles is referred to as nanoresveratrol. In the present study, nanoresveratrol effectiveness was studied through PTZ-induced seizures (PTZ-IS) and the increasing current electroshock (ICES) test. The efficacy of nanoresveratrol was further established using biochemical analysis, histopathological examinations, ELISA and real-time-PCR tests, and immunohistochemistry examination of the hippocampus of mice. Hence, this study is unique in the sense that it synthesized nanoresveratrol by using glutathione-coated collagen nanoparticles, followed by its application to treating seizures. On the basis of the study results, nanoresveratrol was found to be effective in preventing cognitive impairment in the mice and controlling epilepsy seizures to a greater extent than resveratrol. The proposed nanoformulation also reduces the concentration of resveratrol considerably. The present study results show that even 0.4 mg/kg of nanoresveratrol outperforms 40 mg/kg of resveratrol.

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“…Our group has shown that micronization decreased the minimum effective concentration of N-acetylcysteine (NAC) required to exert an anxiolytic effect in zebrafish (Aguiar et al, 2017). Also, micronized curcumin and resveratrol, but not non-micronized compounds, showed similar effects as the antiepileptic drugs diazepam and valproate, reducing seizure occurrence and slowing seizure progression in the PTZ-induced seizure model in zebrafish (Almeida et al, 2021;Bertoncello et al, 2018;Decui et al, 2020).…”

Section: Introductionmentioning

confidence: 99%

Curcumin micronization by supercritical fluid: In vitro and in vivo biological relevance

Sachett

Gallas‐Lopes

Benvenutti

et al. 2022

Industrial Crops and Products

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Micronized Resveratrol Shows Anticonvulsant Properties in Pentylenetetrazole-Induced Seizure Model in Adult Zebrafish

Cited by 22 publications

References 40 publications

Curcumin micronization by supercritical fluid:in vitroandin vivobiological relevance

Curcumin micronization by supercritical fluid:in vitroandin vivobiological relevance

Resveratrol-Loaded Glutathione-Coated Collagen Nanoparticles Attenuate Acute Seizures by Inhibiting HMGB1 and TLR-4 in the Hippocampus of Mice

Curcumin micronization by supercritical fluid: In vitro and in vivo biological relevance

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