In Vitro Neuroprotective and Anti-Inflammatory Activities of Natural and Semi-Synthetic Spirosteroid Analogues

García-Pupo, Laura; Zaldo-Castro, Armando; Exarchou, Vassiliki; Tacoronte-Morales, Juan Enrique; Pieters, Luc; Berghe, Wim Vanden; Nuñez-Figueredo, Yanier; Hernández, René Delgado

doi:10.3390/molecules21080992

Cited by 6 publications

(5 citation statements)

References 63 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In this sense, we recently studied a steroidal sapogenin derivative (S15) which exerts neuroprotective effects in stroke-related models. In vitro, the non-estrogenic S15 compound counteracts glutamate-induced excitotoxicity while diosgenin did not improve the viability of damaged cells ( Garcia-Pupo et al. 2016 , 2017 ).…”

Section: Saponins As Immunomodulators and Regulators Of Cell Death In Strokementioning

confidence: 93%

Emerging immune and cell death mechanisms in stroke: Saponins as therapeutic candidates

García-Pupo

San

Hernández

et al. 2020

Brain, Behavior, & Immunity - Health

Self Cite

View full text Add to dashboard Cite

The complexity of the ischemic cascade is based on the integrated crosstalk of every cell type in the neurovascular unit. Depending on the features of the ischemic insult, several cell death mechanisms are triggered, such as apoptosis, necroptosis, ferroptosis/oxytosis, ETosis or pyroptosis, leading to reactive astrogliosis. However, emerging evidence demonstrates a dual role for the immune system in stroke pathophysiology, where it exerts both detrimental and also beneficial functions. In this review, we discuss the relevance of several cell death modalities and the dual role of the immune system in stroke pathophysiology. We also provide an overview of some emerging immunomodulatory therapeutic strategies, amongst which saponins, which are promising candidates that exert multiple pharmacological effects.

show abstract

Section: Saponins As Immunomodulators and Regulators Of Cell Death In Strokementioning

confidence: 93%

Emerging immune and cell death mechanisms in stroke: Saponins as therapeutic candidates

García-Pupo

San

Hernández

et al. 2020

Brain, Behavior, & Immunity - Health

Self Cite

View full text Add to dashboard Cite

show abstract

“…In-vitro studies also revealed the ability of the said combination to increase cell viability of PTZ-treated HEK-293 cells by 267%. Various studies in the literature have refuted the relationship of cell viability with neuroprotective efficacy [ 92 , 93 , 94 ]. HEK 293 cells were initially derived in 1973 from a kidney [ 95 ].…”

Section: Discussionmentioning

confidence: 99%

Trio-Drug Combination of Sodium Valproate, Baclofen and Thymoquinone Exhibits Synergistic Anticonvulsant Effects in Rats and Neuro-Protective Effects in HEK-293 Cells

Pottoo

Salahuddin

Khan

et al. 2022

CIMB

View full text Add to dashboard Cite

Epilepsy is a chronic brain disorder, with anti-epileptic drugs (AEDs) providing relief from hyper-excitability of neurons, but largely failing to restrain neurodegeneration. We investigated a progressive preclinical trial in rats, whereby the test drugs; sodium valproate (SVP; 150 and 300 mg/kg), baclofen (BFN; 5 and 10 mg/kg), and thymoquinone (THQ; 40 and 80 mg/kg) were administered (i.p, once/day for 15 days) alone, and as low dose combinations, and subsequently tested for antiseizure and neuroprotective potential using electrical stimulation of neurons by Maximal electroshock (MES). The seizure stages were monitored, and hippocampal levels of m-TOR, IL-1β, IL-6 were measured. Hippocampal histopathology was also performed. Invitro and Insilco studies were run to counter-confirm the results from rodent studies. We report the synergistic effect of trio-drug combination; SVP (150 mg/kg), BFN (5 mg/kg) and THQ (40 mg/kg) against generalized seizures. The Insilco results revealed that trio-drug combination binds the Akt active site as a supramolecular complex, which could have served as a delivery system that affects the penetration and the binding to the new target. The potential energy of the ternary complex in the Akt active site after dynamics simulation was found to be −370.426 Kcal/mol, while the supramolecular ternary complex alone was −38.732 Kcal/mol, with a potential energy difference of −331.694 Kcal/mol, which favors the supramolecular ternary complex at Akt active site binding. In addition, the said combination increased cell viability by 267% and reduced morphological changes induced by Pentylenetetrazol (PTZ) in HEK-293 cells, which indicates the neuroprotective property of said combination. To conclude, we are the first to report the anti-convulsant and neuroprotective potential of the trio-drug combination.

show abstract

“…The primary neurons were isolated from the cortices of rat embryos as previously described [34][35][36]. The cells were cultured in a 96-well plate in complete neurobasal medium for 7 days and then challenged with 100 ng/mL of a lipopolysaccharide and apocynin-free drug or apocynin nanoconjugate for 48 h, after which the cell viability was measured with an MTT assay.…”

Section: Mtt Assaymentioning

confidence: 99%

Transferrin-Grafted Albumin Nanoparticles for the Targeted Delivery of Apocynin and Neuroprotection in an In Vitro Model of the BBB

Perumal

Ravula

Agas

et al. 2023

Micro

View full text Add to dashboard Cite

Traumatic brain injury (TBI) is a major cause of morbidity and mortality worldwide, affecting over 10 million people annually, with an estimated cost of $76.5 billion. Although apocynin freely transverses the blood–brain barrier (BBB), its application is limited due to its rapid elimination, low terminal half-life (t1/2 = 6.7 min), narrow dose–response relationship, and cytotoxicity, thereby requiring repeated dosages. With this study, we aimed to develop transferrin-functionalized nanoparticles encapsulating apocynin to treat neuroinflammation for targeted drug delivery to sites of brain injury. As a preliminary approach, we endeavored to optimize the formulation parameters of apocynin-loaded albumin nanoparticles prepared through the desolvation method. The nanoparticles were characterized for their size, polydispersity, surface charge, drug loading and in vitro drug release. In this study, we also investigated the anti-inflammatory and neuroprotective effects of free apocynin and nanoparticle-loaded apocynin in neuronal cells. We show that the developed formulation displayed monodispersed, nanosized particles with higher entrapment efficiency, loading, stability, and sustained release profiles. The permeability of the nanoparticles across HBMECs reached the maximum at 67%. The in vivo evaluation revealed the enhanced uptake of transferrin-anchored nanoparticles in the brain tissues when compared with unmodified nanoparticles after I.V. administration. In vivo nanoparticle localization studies using a blast TBI (bTBI) model and confocal fluorescence microscopy have shown that tf-apoANPs are successful in delivering relatively high amounts of nanoparticles to the brain parenchyma and glial cells compared to non-targeted nanoparticles. We also establish that targeted nanoparticles accumulate in the brain. In conclusion, tf-apoANPs are efficacious carriers for targeted delivery across the blood–brain barrier to potentially treat neuroinflammation in brain injury and other diseases.

show abstract

In Vitro Neuroprotective and Anti-Inflammatory Activities of Natural and Semi-Synthetic Spirosteroid Analogues

Cited by 6 publications

References 63 publications

Emerging immune and cell death mechanisms in stroke: Saponins as therapeutic candidates

Emerging immune and cell death mechanisms in stroke: Saponins as therapeutic candidates

Trio-Drug Combination of Sodium Valproate, Baclofen and Thymoquinone Exhibits Synergistic Anticonvulsant Effects in Rats and Neuro-Protective Effects in HEK-293 Cells

Transferrin-Grafted Albumin Nanoparticles for the Targeted Delivery of Apocynin and Neuroprotection in an In Vitro Model of the BBB

Contact Info

Product

Resources

About