Negletein as a neuroprotectant enhances the action of nerve growth factor and induces neurite outgrowth in PC12 cells

Phan, Chia Wei; Sabaratnam, Vikineswary; Bovicelli, Paolo; Righi, Giuliana; Saso, Luciano

doi:10.1002/biof.1296

Cited by 7 publications

(5 citation statements)

References 33 publications

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“…Some flavonoids, such as MOS and NEG, have been extensively studied mainly due to their promising antimicrobial, antitumor, and neuroprotective activity [20,23,32]. However, little information is available on other molecules, despite their structural relation to MOS and NEG; for example, few studies have been done on 5,6-dihydroxy-flavone 7 [26,27].…”

Section: Discussionmentioning

confidence: 99%

“…The first two compounds are present in some plants used in folk medicine, such as Centaurea clementei (Boiss) (negletein) [21], and Desmos chinensis (Lour.) (mosloflavone) [22], their antioxidant characteristics are well known and several studies have found that they have beneficial effects on human health [23]. MOS and NEG were obtained by a simple synthesis starting from the 7-methyl ether of crysin, similarly to what was described in Righi et al [24].…”

Section: Introductionmentioning

confidence: 99%

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Role of Some Food-Grade Synthesized Flavonoids on the Control of Ochratoxin A in Aspergillus carbonarius

et al. 2019

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Ochratoxin A (OTA) is a mycotoxin with a serious impact on human health. In Mediterranean countries, the black Aspergilli group, in particular Aspergillus carbonarius, causes the highest OTA contamination. Here we describe the synthesis of three polyphenolic flavonoids: 5-hydroxy-6,7-dimethoxy-flavone (MOS), 5,6-dihydroxy-7-methoxy-flavone (NEG), and 5,6 dihydroxy-flavone (DHF), as well as their effect on the prevention of OTA biosynthesis and lipoxygenase (LOX) activity in A. carbonarius cultured in a conducive liquid medium. The best control effect on OTA biosynthesis was achieved using NEG and DHF. In fungal cultures treated with these compounds at 5, 25, and 50 μg/mL, OTA biosynthesis significantly decreased throughout the 8-day experiment. NEG and DHF appear to have an inhibiting effect also on the activity of LOX, whereas MOS, which did not significantly inhibit OTA production, had no effect on LOX activity. The presence of free hydroxyls in catecholic position in the molecule appears to be a determining factor for significantly inhibiting OTA biosynthesis. However, the presence of a methoxy group in C-7 in NEG could slightly lower the molecule’s reactivity increasing OTA inhibition by this molecule at 5 μg/mL. Polyphenolic flavonoids present in edible plants may be easily synthesized and used to control OTA biosynthesis.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Role of Some Food-Grade Synthesized Flavonoids on the Control of Ochratoxin A in Aspergillus carbonarius

et al. 2019

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“…PC12 cells originate from the pheochromocytoma of the rat adrenal medulla and are widely established as a neuronal model [18, 19] in differentiated [20, 21] or undifferentiated [22, 23] form.…”

Section: Introductionmentioning

confidence: 99%

Differential Effects of Silibinin A on Mitochondrial Function in Neuronal PC12 and HepG2 Liver Cells

Esselun

Bruns

Hagl

et al. 2019

Oxidative Medicine and Cellular Longevity

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The Mediterranean plant Silybum marianum L., commonly known as milk thistle, has been used for centuries to treat liver disorders. The flavonolignan silibinin represents a natural antioxidant and the main bioactive ingredient of silymarin (silybin), a standard extract of its seeds. Mitochondrial dysfunction and the associated generation of reactive oxygen/nitrogen species (ROS/RNS) are involved in the development of chronic liver and age-related neurodegenerative diseases. Silibinin A (SIL A) is one of two diastereomers found in silymarin and was used to evaluate the effects of silymarin on mitochondrial parameters including mitochondrial membrane potential and ATP production with and without sodium nitroprusside- (SNP-) induced nitrosative stress, oxidative phosphorylation, and citrate synthase activity in HepG2 and PC12 cells. Both cell lines were influenced by SIL A, but at different concentrations. SIL A significantly weakened nitrosative stress in both cell lines. Low concentrations not only maintained protective properties but also increased basal mitochondrial membrane potential (MMP) and adenosine triphosphate (ATP) levels. However, these effects could not be associated with oxidative phosphorylation. On the other side, high concentrations of SIL A significantly decreased MMP and ATP levels. Although SIL A did not provide a general improvement of the mitochondrial function, our findings show that SIL A protects against SNP-induced nitrosative stress at the level of mitochondria making it potentially beneficial against neurological disorders.

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“…The kinase c-Jun N-terminal kinase 1/2, downstream of ASK1, may phosphorylate and activate FoxO1 protein, resulting in cell apoptosis (41). On the other hand, Phan et al (42) had reported that negletein together with NGF enhanced the phosphorylation of AKT and CREB, helping to protect neurons from cell death and promoting neuritogenesis in serum-deprived PC12 cells. In the present study, the increased expression levels of ASK1 and FoxO1 were observed in RGCs exposed to 40, 60 and 80 mmHg HP.…”

Section: Discussionmentioning

confidence: 99%

High hydrostatic pressure induces apoptosis of retinal ganglion cells via regulation of the NGF signalling pathway

Liu

Wang

et al. 2019

Mol Med Report

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High pressure is the most important factor inducing retinal ganglion cell (RGC) apoptosis. However, the underlying mechanisms remain obscure. The present study investigated the effects of different levels of hydrostatic pressure (HP) on RGCs and the potential mechanisms involved. Primary cultured rat RGCs were exposed to five levels of HP (0, 20, 40, 60 and 80 mmHg) for 24 h. Morphological changes in RGCs were observed. The viability and apoptosis rate of RGCs were detected using a Cell Counting Kit-8 assay and Annexin V-fluorescein isothiocyanate/propidium iodide flow cytometry, respectively. Western blotting, reverse transcription-quantitative polymerase chain reaction and immunofluorescence were used to detect the expression and mRNA levels of nerve growth factor (NGF), protein kinase B (AKT), apoptosis signal-regulating kinase 1 (ASK1), forkhead box O1 (FoxO1) and cAMP response element binding protein (CREB). In the 0- and 20-mmHg groups, there were no apoptotic morphological changes. In the 40 mmHg group, parts of the cell were shrunken or disrupted. In the 60 mmHg group, neurite extension was weakened and parts of the cells were disintegrating or dying. In the 80 mmHg group, the internal structures of the cells were not visible at all. The apoptosis rates of RGCs were significantly higher and the viability rates significantly lower under 40, 60 and 80 mmHg compared with under 0 or 20 mmHg (all P<0.01). The expression and mRNA levels of NGF, AKT and CREB decreased in a dose-dependent manner in the 40-, 60- and 80-mmHg groups (all P<0.05), but those of ASK1 and FoxO1 increased in a dose-dependent manner (all P<0.05). Interestingly, the alterations to the expression and mRNA levels of CREB were significantly larger compared with the changes in ASK1 or FoxO1 in the 40-, 60- and 80-mmHg groups (all P<0.01). The results of the present study demonstrate that elevated HP of 40, 60 or 80 mmHg reduces viability and induces apoptosis in RGCs, which may occur through effects on the NGF/ASK1/FoxO1 and NGF/AKT/CREB pathways, of which the latter is more strongly affected.

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Negletein as a neuroprotectant enhances the action of nerve growth factor and induces neurite outgrowth in PC12 cells

Cited by 7 publications

References 33 publications

Role of Some Food-Grade Synthesized Flavonoids on the Control of Ochratoxin A in Aspergillus carbonarius

Role of Some Food-Grade Synthesized Flavonoids on the Control of Ochratoxin A in Aspergillus carbonarius

Differential Effects of Silibinin A on Mitochondrial Function in Neuronal PC12 and HepG2 Liver Cells

High hydrostatic pressure induces apoptosis of retinal ganglion cells via regulation of the NGF signalling pathway

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