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Protective Effect of Flavonoids against Methylglyoxal-Induced Oxidative Stress in PC-12 Neuroblastoma Cells and Its Structure-Activity Relationships.

ABSTRACT: Methylglyoxal-induced oxidative stress and cytotoxicity are the main factors causing neuronal death-related, diabetically induced memory impairment. Antioxidant and anti-apoptotic therapy are potential intervention strategies. In this study, 25 flavonoids with different substructures were assayed for protecting PC-12 cells from methylglyoxal-induced damage. A structure-activity relationship (SAR) analysis indicated that the absence of the double bond at C-2 and C-3, substitutions of the gallate group at the 3 position, the pyrogallol group at the B-ring, and the R configuration of the 3 position enhanced the protection of flavan-3-ols, and a hydroxyl substitution at the 4' and meta-positions were important for the protection of flavonol. These SARs were further confirmed by molecular docking using the active site of the Keap1-Nrf2 complex as the receptor. The mechanistic study demonstrated that EGCG with the lowest EC₅₀ protected the PC-12 cells from methylglyoxal-induced damage by reducing oxidative stress via the Nrf2/Keap1/HO-1 and Bcl-2/Bax signaling pathways. These results suggested that flavan-3-ols might be a potential dietary supplement for protection against diabetic encephalopathy.

SUBMITTER: Zhang D

PROVIDER: S-EPMC9693184 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature

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Protective Effect of Flavonoids against Methylglyoxal-Induced Oxidative Stress in PC-12 Neuroblastoma Cells and Its Structure-Activity Relationships.

Zhang Danyang D Li Xia X He Xiaoshi X Xing Yan Y Jiang Bo B Xiu Zhilong Z Bao Yongming Y Dong Yuesheng Y

Molecules (Basel, Switzerland) 20221112 22

Methylglyoxal-induced oxidative stress and cytotoxicity are the main factors causing neuronal death-related, diabetically induced memory impairment. Antioxidant and anti-apoptotic therapy are potential intervention strategies. In this study, 25 flavonoids with different substructures were assayed for protecting PC-12 cells from methylglyoxal-induced damage. A structure-activity relationship (SAR) analysis indicated that the absence of the double bond at C-2 and C-3, substitutions of the gallate ...[more]

PMID: 36431904

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Project description:BackgroundHericium erinaceus is a culinary and medicinal mushroom in Traditional Chinese Medicines. It has numerous pharmacological effects including immunomodulatory, anti-tumour, anti-microbial, anti-aging and stimulation of nerve growth factor (NGF) synthesis, but little is known about its potential role in negating the detrimental effects of oxidative stress in depression. The present study investigated the neuroprotective effects of H. erinaceus standardised aqueous extract (HESAE) against high-dose corticosterone-induced oxidative stress in rat pheochromocytoma (PC-12) cells, a cellular model mimicking depression.MethodsPC-12 cells was pre-treated with HESAE for 48 h followed by 400 μM corticosterone for 24 h to induce oxidative stress. Cells in complete medium without any treatment or pre-treated with 3.125 μg/mL desipramine served as the negative and positive controls, respectively. The cell viability, lactate dehydrogenase (LDH) release, endogenous antioxidant enzyme activities, aconitase activity, mitochondrial membrane potentials (MMPs), intracellular reactive oxygen species (ROS) levels and number of apoptotic nuclei were quantified. In addition, HESAE ethanol extract was separated into fractions by chromatographic methods prior to spectroscopic analysis.ResultsWe observed that PC-12 cells treated with high-dose corticosterone at 400 μM had decreased cell viability, reduced endogenous antioxidant enzyme activities, disrupted mitochondrial function, and increased oxidative stress and apoptosis. However, pre-treatment with HESAE ranging from 0.25 to 1 mg/mL had increased cell viability, decreased LDH release, enhanced endogenous antioxidant enzyme activities, restored MMP, attenuated intracellular ROS and protected from ROS-mediated apoptosis. The neuroprotective effects could be attributed to significant amounts of adenosine and herierin III isolated from HESAE.ConclusionsHESAE demonstrated neuroprotective effects against high-dose corticosterone-induced oxidative stress in an in vitro model mimicking depression. HESAE could be a potential dietary supplement to treat depression.

Dataset Information

Protective Effect of Flavonoids against Methylglyoxal-Induced Oxidative Stress in PC-12 Neuroblastoma Cells and Its Structure-Activity Relationships.

Publications

Protective Effect of Flavonoids against Methylglyoxal-Induced Oxidative Stress in PC-12 Neuroblastoma Cells and Its Structure-Activity Relationships.

Similar Datasets

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