Vitamin C deficiency induces hypoglycemia and cognitive disorder through S-nitrosylation-mediated activation of glycogen synthase kinase 3β

Shu, Yingying; Zou, Chaochun; Cai, Yuqing; He, Qiong; Wu, Xiaowei; Zhu, Hai‐Bin; Qv, Meiyu; Chao, Yunqi; Xu, Chengyun; Tang, Lanfang; Wu, Ximei

doi:10.1016/j.redox.2022.102420

Cited by 6 publications

(6 citation statements)

References 45 publications

(53 reference statements)

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“…MS/MS spectra of sugar esters hydroxybensoyl-hexose (5), vanillyl-hexose (11), and syringoyl-hexose (13) were acquired. In contrast to the analogous hexosides, the precursor ions afforded fragment ions resulting from the hexose cross ring cleavages as 0.4 Hex (−60 Da), 0.3 Hex (−90 Da), and 0.2 Hex (−120 Da) [18] (Figure 3).…”

Section: Hydroxybenzoic Hydroxycinnamic Acids and Their Derivativesmentioning

confidence: 99%

“…In (-) ESI mode, the precursor ions provided the relevant ions at m/z 317.030 (myricetin), 301.035/300.028 (quercetin), 285.040 (luteolin and kaempferol), 331.046 (patuletin), 329.066 (jaceosidin), 315.047 (nepetin and isorhamnetin), and 299.056 (hispidulin). A 6-methoxylated flavonoid skeleton was discernable by the RDA ions at m/z 165.990 ( 1,3 A -CH 3 ), 164.982 ( 1,3 A -CH 4 ), 163.002 ( 1,3 A -H 2 O), and 136.987 ( 1,3 A − -CH 4 -CO) [13,14]. In addition, a low abundant ion at 181.013 ( 1,3 A − ) was registered in the fragmentation pattern of patuletin and 6-methoxykaempferol.…”

Section: Flavonoidsmentioning

confidence: 99%

“…As antioxidants are substances that are efficient to scavenge ROS and decrease oxidative damage, these compounds have been studied for therapeutic approaches to many different diseases. Moreover, a deficiency of antioxidants such as vitamins C and E has been associated with cognitive disorders [13]. Therefore, many natural products, especially polyphenols with antioxidant properties could be useful in cognitive decline or neurodegenerative diseases such as Alzheimer's disease [14].…”

Section: Introductionmentioning

confidence: 99%

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Phytochemical Profiling, Antioxidant and Cognitive-Enhancing Effect of Helichrysum italicum ssp. italicum (Roth) G. Don (Asteraceae)

Gevrenova

Kostadinova

Stefanova

et al. 2023

Plants

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This study aimed at the evaluation of the antioxidant and cognitive-enhancing effect of methanol–aqueous extract from Helichrysum italicum ssp. italicum aerial parts. Significant radical scavenging activity (110.33 ± 3.47 and 234.70 ± 5.21 mg TE/g for DPPH and ABTS) and reducing power (354.23 ± 17.51 and 210.24 ± 8.68 mg TE/g for CUPRAC and FRAP) were observed. The extract showed average acetylcholinesterase and low butyrylcholinesterase inhibitory potential. H. italicum extract (200 mg/kg/po) administered in combination with galantamine (3 mg/kg/po) for 12 days significantly improved the memory and learning process compared with galantamine alone in the passive avoidance test. The effect was comparable to that of Ginkgo biloba extract (100 mg/kg/po). In deep secondary metabolite annotation of the extract by UHPLC-HRMS, more than 90 hydroxybenzoic and hydroxicinnamic acid-glycosides, phenylethanoid glycosides, a series of acylquinic and caffeoylhexaric acids, methoxylated derivatives of scutellarein, quercetagetin and 6-hydroxyluteolin, and prenylated phloroglucinol-α-pyrones were reported for the first time in H. italicum. Fragmentation patterns of four subclasses of heterodimer-pyrones were proposed. In-depth profiling of the pyrones revealed 23 compounds undescribed in the literature. Pyrones and acylphloroglucinols together with acylquinic acids could account for memory improvement. The presented research advanced our knowledge of H. italicum, highlighting the species as a rich source of secondary metabolites with cognitive-enhancing potential.

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Section: Hydroxybenzoic Hydroxycinnamic Acids and Their Derivativesmentioning

confidence: 99%

Section: Flavonoidsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Phytochemical Profiling, Antioxidant and Cognitive-Enhancing Effect of Helichrysum italicum ssp. italicum (Roth) G. Don (Asteraceae)

Gevrenova

Kostadinova

Stefanova

et al. 2023

Plants

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“…As antioxidants are substances that are efficient to trap ROS and decrease oxidative damage, these products have been studied for therapeutic approaches to many different diseases. On the other hand, a deficiency of antioxidants such as vitamins C and E has been associated with cognitive disorders [ 77 ]. In literature, many natural products and pharmacological compounds have antioxidant properties [ 73 , 78 ].…”

Section: Oxidative Stressmentioning

confidence: 99%

Antioxidant Intervention to Improve Cognition in the Aging Brain: The Example of Hydroxytyrosol and Resveratrol

Terracina

Petrella

Francati

et al. 2022

IJMS

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Both physiological and pathological aging processes induce brain alterations especially affecting the speed of processing, working memory, conceptual reasoning and executive functions. Many therapeutic approaches to reduce the impact of brain aging on cognitive functioning have been tested; unfortunately, there are no satisfactory results as a single therapy. As aging is partly contributed by free radical reactions, it has been proposed that exogenous antioxidants could have a positive impact on both aging and its associated manifestations. The aim of this report is to provide a summary and a subsequent review of the literature evidence on the role of antioxidants in preventing and improving cognition in the aging brain. Manipulation of endogenous cellular defense mechanisms through nutritional antioxidants or pharmacological compounds represents an innovative approach to therapeutic intervention in diseases causing brain tissue damage, such as neurodegeneration. Coherently with this notion, antioxidants, especially those derived from the Mediterranean diet such as hydroxytyrosol and resveratrol, seem to be able to delay and modulate the cognitive brain aging processes and decrease the occurrence of its effects on the brain. The potential preventive activity of antioxidants should be evaluated in long-term exposure clinical trials, using preparations with high bioavailability, able to bypass the blood-brain barrier limitation, and that are well standardized.

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“…C57BL/6 mice were from Shanghai SLAC Laboratory Animal Co. (Shanghai, China) and ODS rats were from CLEA Japan, Inc. (Tokyo, Japan). L-gulono-γ-lactone oxidase (Gulo −/− ) global knockout mice with C57BL/6 genetic background were generated as described previously [25,34,47]. Gulo −/− mice were maintained with daily prepared tap water containing VC at 4 g/L (Sigma, St. Louis, MO) and ODS rats were maintained with daily prepared tap water containing VC at 1 g/L [27].…”

Section: Animalsmentioning

confidence: 99%

Vitamin C inactivates c-Jun N-terminal kinase to stabilize heart and neural crest derivatives expressed 1 in regulating placentation and pregnant maintenance

Ruan

Zhu

Luo

et al. 2023

Preprint

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Vitamin C (VC) is an essential nutrient for anti-oxidation, metabolic reaction, and stem cell differentiation. However, the precise role of VC in placentation and pregnant maintenance remains unknown. Here, we demonstrate that physiological concentration of VC stabilizes the Hand1, a bHLH transcription factor crucial for the development of trophoblast giant cell (TGC) lineage, to promote the differentiation of trophoblast stem cells into TGCs. The role of VC depends on the inactivation of JNK kinase, which directly phosphorylates Hand1 at Ser48 and thereby induces Hand1 proteasomal degradation, whereas loss-of-function mutation of Ser48 on Hand1 robustly decreases not only the basal but also VC-induced Hand1 stabilization. As a result, VC deficiency, lentiviral knockdown of JNK or overexpression of Hand1 mutants in trophectoderm significantly affects the differentiation of primary and secondary TGCs in E8.5 mouse placentas. VC deficiency causes a severe defect in the differentiation of diverse TGCs and the formation of vascular network of labyrinth in mature mouse placentas and thereby fails to maintain the pregnancy. Thus, these results uncover JNK inactivation and subsequent Hand1 stabilization as a hitherto uncharacterized mechanism controlling VC-mediated placentation and perhaps pregnant maintenance.

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Vitamin C deficiency induces hypoglycemia and cognitive disorder through S-nitrosylation-mediated activation of glycogen synthase kinase 3β

Cited by 6 publications

References 45 publications

Phytochemical Profiling, Antioxidant and Cognitive-Enhancing Effect of Helichrysum italicum ssp. italicum (Roth) G. Don (Asteraceae)

Phytochemical Profiling, Antioxidant and Cognitive-Enhancing Effect of Helichrysum italicum ssp. italicum (Roth) G. Don (Asteraceae)

Antioxidant Intervention to Improve Cognition in the Aging Brain: The Example of Hydroxytyrosol and Resveratrol

Vitamin C inactivates c-Jun N-terminal kinase to stabilize heart and neural crest derivatives expressed 1 in regulating placentation and pregnant maintenance

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