Pinocembrin Protects from AGE-Induced Cytotoxicity and Inhibits Non-Enzymatic Glycation in Human Insulin

Borriello, Margherita; Iannuzzi, Clara

doi:10.3390/cells8050385

Cited by 25 publications

(23 citation statements)

References 61 publications

(101 reference statements)

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“…Oxidative stress, disrupted energy homeostasis, neuroinflammation, and apoptosis are commonly seen in the brain after TBI, as well as in other brain diseases [22], which, in turn, can compromise the normal cellular function of the brain [54]. Oxidative stress has been considered the earliest pathological event in several diseases [55]. More specifically, the cortex and hippocampus of the brain are more susceptible to oxidative stress, which ultimately results in memory problems [56].…”

Section: Discussionmentioning

confidence: 99%

Neurological Enhancement Effects of Melatonin against Brain Injury-Induced Oxidative Stress, Neuroinflammation, and Neurodegeneration via AMPK/CREB Signaling

Rehman

Ikram

Ullah

et al. 2019

Cells

146

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Oxidative stress and energy imbalance strongly correlate in neurodegenerative diseases. Repeated concussion is becoming a serious public health issue with uncontrollable adverse effects in the human population, which involve cognitive dysfunction and even permanent disability. Here, we demonstrate that traumatic brain injury (TBI) evokes oxidative stress, disrupts brain energy homeostasis, and boosts neuroinflammation, which further contributes to neuronal degeneration and cognitive dysfunction in the mouse brain. We also demonstrate that melatonin (an anti-oxidant agent) treatment exerts neuroprotective effects, while overcoming oxidative stress and energy depletion and reducing neuroinflammation and neurodegeneration. Male C57BL/6N mice were used as a model for repetitive mild traumatic brain injury (rmTBI) and were treated with melatonin. Protein expressions were examined via Western blot analysis, immunofluorescence, and ELISA; meanwhile, behavior analysis was performed through a Morris water maze test, and Y-maze and beam-walking tests. We found elevated oxidative stress, depressed phospho-5′AMP-activated protein kinase (p-AMPK) and phospho- CAMP-response element-binding (p-CREB) levels, and elevated p-NF-κB in rmTBI mouse brains, while melatonin treatment significantly regulated p-AMPK, p-CREB, and p-NF-κB in the rmTBI mouse brain. Furthermore, rmTBI mouse brains showed a deregulated mitochondrial system, abnormal amyloidogenic pathway activation, and cognitive functions which were significantly regulated by melatonin treatment in the mice. These findings provide evidence, for the first time, that rmTBI induces brain energy imbalance and reduces neuronal cell survival, and that melatonin treatment overcomes energy depletion and protects against brain damage via the regulation of p-AMPK/p-CREB signaling pathways in the mouse brain.

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Section: Discussionmentioning

confidence: 99%

Neurological Enhancement Effects of Melatonin against Brain Injury-Induced Oxidative Stress, Neuroinflammation, and Neurodegeneration via AMPK/CREB Signaling

Rehman

Ikram

Ullah

et al. 2019

Cells

146

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“…Intracellular ROS were detected by means of an oxidation-sensitive fluorescent probe 2′,7′-dichlorofluorescin diacetate (DCFH-DA) as previously reported [ 41 ]. Cells were grown in 12-well plates (2.5 × 10 6 cell/well), pre-incubated with DCFH-DA for 30 min and then incubated with protein samples for 24 h. Control experiments were performed using untreated cells and cells exposed to a 0.001-M H 2 O 2 .…”

Section: Methodsmentioning

confidence: 99%

Vanillin Prevents Doxorubicin-Induced Apoptosis and Oxidative Stress in Rat H9c2 Cardiomyocytes

et al. 2020

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Doxorubicin (doxo) is an effective anticancer compound in several tumor types. However, as a consequence of oxidative stress induction and ROS overproduction, its high cardiotoxicity demands urgent attention. Vanillin possesses antioxidant, antiproliferative, antidepressant and anti-glycating properties. Therefore, we investigated the potential vanillin protective effects against doxo-induced cardiotoxicity in H9c2 cells. Using multiparametric approach, we demonstrated that vanillin restored both cell viability and damage in response to doxo exposure. Contextually, vanillin decreased sub-G1 appearance and caspase-3 and PARP1 activation, reducing the doxo-related apoptosis induction. From a mechanistic point of view, vanillin hindered doxo-induced ROS accumulation and impaired the ERK phosphorylation. Notably, besides the cardioprotective effects, vanillin did not counteract the doxo effectiveness in osteosarcoma cells. Taken together, our results suggest that vanillin ameliorates doxo-induced toxicity in H9c2 cells, opening new avenues for developing alternative therapeutic approaches to prevent the anthracycline-related cardiotoxicity and to improve the long-term outcome of antineoplastic treatment.

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“…Human insulin 4 mg/mL was dissolved in ultrapure milliQ water at pH 2.0 and the concentration was estimated by absorbance (ε 275 = 4560 M −1 cm −1 ). Insulin was then diluted at 2 mg/mL concentration in a phosphate buffer of 50 mM, pH 7.0 [69]. HT was dissolved in ultrapure milliQ water at 100 mM concentration.…”

Section: Insulin Preparation and Amyloid Aggregationmentioning

confidence: 99%

Hydroxytyrosol Inhibits Protein Oligomerization and Amyloid Aggregation in Human Insulin

Sirangelo

Borriello

Vilasi

2020

IJMS

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Hydroxytyrosol (HT), one of the main phenolic components of olive oil, has attracted considerable interest for its biological properties, including a remarkable antioxidant and anti-inflammatory power and, recently, for its ability to interfere with the amyloid aggregation underlying several human diseases. We report here a broad biophysical approach and cell biology techniques that allowed us to characterize the molecular mechanisms by which HT affects insulin amyloid aggregation and the related cytotoxicity. Our data show that HT is able to fully inhibit insulin amyloid aggregation and this property seems to be ascribed to the stabilization of the insulin monomeric state. Moreover, HT completely reverses the toxic effect produced by amyloid insulin aggregates in neuroblastoma cell lines by fully inhibiting the production of toxic amyloid species. These findings suggest that the beneficial effects of olive oil polyphenols, including HT, may arise from multifunctional activities and suggest possible a application of this natural compound in the prevention or treatment of amyloid-associated diseases.

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Pinocembrin Protects from AGE-Induced Cytotoxicity and Inhibits Non-Enzymatic Glycation in Human Insulin

Cited by 25 publications

References 61 publications

Neurological Enhancement Effects of Melatonin against Brain Injury-Induced Oxidative Stress, Neuroinflammation, and Neurodegeneration via AMPK/CREB Signaling

Neurological Enhancement Effects of Melatonin against Brain Injury-Induced Oxidative Stress, Neuroinflammation, and Neurodegeneration via AMPK/CREB Signaling

Vanillin Prevents Doxorubicin-Induced Apoptosis and Oxidative Stress in Rat H9c2 Cardiomyocytes

Hydroxytyrosol Inhibits Protein Oligomerization and Amyloid Aggregation in Human Insulin

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