Next Article in Journal
Unification of Opposites between Two Antioxidant Transcription Factors Nrf1 and Nrf2 in Mediating Distinct Cellular Responses to the Endoplasmic Reticulum Stressor Tunicamycin
Next Article in Special Issue
Optimization of the Extraction of Bioactive Compounds from Walnut (Juglans major 209 x Juglans regia) Leaves: Antioxidant Capacity and Phenolic Profile
Previous Article in Journal
Intrarenal Transplantation of Hypoxic Preconditioned Mesenchymal Stem Cells Improves Glomerulonephritis through Anti-Oxidation, Anti-ER Stress, Anti-Inflammation, Anti-Apoptosis, and Anti-Autophagy
Previous Article in Special Issue
Grown to be Blue—Antioxidant Properties and Health Effects of Colored Vegetables. Part I: Root Vegetables
Open AccessArticle

3,3′-Diindolylmethane Promotes BDNF and Antioxidant Enzyme Formation via TrkB/Akt Pathway Activation for Neuroprotection against Oxidative Stress-Induced Apoptosis in Hippocampal Neuronal Cells

1
Department of Food and Nutrition, Chungnam National University, Daejeon 34134, Korea
2
Korean Medicine-Application Center, Korea Institute of Oriental Medicine, Daegu 41062, Korea
3
Korean Medicine R&D Team 1, National Institute for Korean Medicine Development, Gyeongsan 38540, Korea
4
College of Pharmacy, Chungnam National University, Daejeon 34134, Korea
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Antioxidants 2020, 9(1), 3; https://doi.org/10.3390/antiox9010003
Received: 15 November 2019 / Revised: 6 December 2019 / Accepted: 16 December 2019 / Published: 18 December 2019
3,3′-Diindolylmethane (DIM), a metabolite of indole-3-carbinol present in Brassicaceae vegetables, possesses various health-promoting effects. Nonetheless, the effect of DIM on neurodegenerative diseases has not been elucidated clearly. In this study, we hypothesized DIM may protect neuronal cells against oxidative stress-induced apoptosis by promoting the formation of brain-derived neurotrophic factor (BDNF) and antioxidant enzymes through stabilizing the activation of the tropomyosin-related kinase receptor B (TrkB) cascade and we investigated the effect of DIM on oxidative stress-mediated neurodegenerative models. DIM protected neuronal cells against oxidative stress-induced apoptosis by regulating the expression of apoptosis-related proteins in glutamate-treated HT-22 cells. Additionally, DIM improved the expression of BDNF and antioxidant enzymes, such as heme oxygenase-1, glutamate-cysteine ligase catalytic subunit, and NAD(P)H quinine oxidoreductase-1, by promoting the activation of the TrkB/protein kinase B (Akt) pathway in the cells. Consistent with in vitro studies, DIM attenuated memory impairment by protecting hippocampal neuronal cells against oxidative damage in scopolamine-treated mice. Conclusionally, DIM exerted neuroprotective and antioxidant actions through the activation of both BDNF production and antioxidant enzyme formation in accordance with the TrkB/Akt pathway in neuronal cells. Such an effect of DIM may provide information for the application of DIM in the prevention of and therapy for neurodegenerative diseases. View Full-Text
Keywords: 3,3′-diindolylmethane; antioxidant enzymes; brain-derived neurotrophic factor; hippocampal neuronal cells; neurodegenerative disease 3,3′-diindolylmethane; antioxidant enzymes; brain-derived neurotrophic factor; hippocampal neuronal cells; neurodegenerative disease
Show Figures

Graphical abstract

MDPI and ACS Style

Lee, B.D.; Yoo, J.-M.; Baek, S.Y.; Li, F.Y.; Sok, D.-E.; Kim, M.R. 3,3′-Diindolylmethane Promotes BDNF and Antioxidant Enzyme Formation via TrkB/Akt Pathway Activation for Neuroprotection against Oxidative Stress-Induced Apoptosis in Hippocampal Neuronal Cells. Antioxidants 2020, 9, 3.

Show more citation formats Show less citations formats
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop