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.

You BR, et al. Nutr Res Pract. 2019 Jun;13(3):189-195. https://doi.org/10.4162/nrp.2019.13.3.189

Enteromorpha prolifera, a green alga, has long been used in food diets as well as traditional remedies in East Asia. Our preliminary study demonstrated that an ethyl acetate extract of Enteromorpha prolifera (EAEP) exhibited the strongest antioxidant activity compared to ethanol or water extracts. Nonetheless, there has been no report on the effect of EAEP on memory impairment due to oxidative damage. This study investigated whether EAEP could attenuate memory deficits in an oxidative stress-induced mouse model. EAEP was orally administered (50 or 100 mg/kg body weight (b.w.)) to mice and then scopolamine was administered. The oral administration of EAEP at 100 mg/kg b.w. significantly restored memory impairments induced by scopolamine, as evaluated by the Morris water maze test, and the passive avoidance test. Further, EAEP upregulated the protein expression of BDNF, p-CREB, p-TrkB, and p-Akt. Moreover, EAEP downregulated the expression of amyloid-β, tau, and APP. The regulation of cholinergic marker enzyme activities and the protection of neuronal cells from oxidative stress-induced cell death in the brain of mice via the downregulation of amyloid-β and the upregulation of the BDNF/TrkB pathway by EAEP suggest its potential as a pharmaceutical candidate to prevent neurodegenerative diseases.

In this study, we found that E. prolifera extract (EAEP) exhibits neuroprotective effects in oxidative stress-induced neuronal cells. EAEP improved cell viability as well as attenuated the formation of intracellular reactive oxygen species (ROS) and apoptotic bodies in glutamate-treated hippocampal neuronal cells (HT-22). Furthermore, EAEP improved the expression of brain-derived neurotrophic factor (BDNF) and antioxidant enzymes such as heme oxygenase-1 (HO-1), NAD(P)H quinine oxidoreductase-1 (NQO-1), and glutamate–cysteine ligase catalytic subunit (GCLC) via the tropomyosin-related kinase receptor B/ protein kinase B (TrkB/Akt) signaling pathway. In contrast, the pre-incubation of K252a, a TrkB inhibitor, or MK-2206, an Akt-selective inhibitor, ameliorated the neuroprotective effects of EAEP in oxidative stress-induced neuronal cells. These results suggest that EAEP protects neuronal cells against oxidative stress-induced apoptosis by upregulating the expression of BDNF and antioxidant enzymes via the activation of the TrkB/Akt pathway. In conclusion, such an effect of EAEP, which is rich in carotenoid-derived compounds, may justify its application as a food supplement in the prevention and treatment of neurodegenerative disorders.

Objectives: Although mulberry fruit possesses some biological activities, it is not known how it protects neuronal cells in neurodegenerative diseases. Here, we examined whether mulberry fruit extract (MFE) protected neuronal cells against oxidative stress-induced neurodegeneration. Methods: In this experiments, glutamate challenged hippocampal neuronal HT-22 cell lines as an in vitro model and scopolamine-induced memoty-impairment mice model were used. Results: MFE improved cell viability and glutathione level as well as reducing reactive oxygen species level in glutamate-treated HT-22 cells. Additionally, MFE suppressed apoptotic bodies and mitochondrial depolarization through regulating expression of apoptosis-related proteins. Furthermore, MFE elevated expression of p-TrkB, p-Akt, p-CREB, BDNF, and antioxidant enzymes as well as nuclear translocation of Nrf2. In contrast, the inclusion of K252a, a TrkB inhibitor, or MK-2206, an Akt selective inhibitor, neutralized the neuroprotective actions of MFE. Separately, MFE attenuated scopolamine-induced amnesia via regulating the activities of enzymes related with cholinergic function and the antioxidant system in mice. Additionally, MFE protected neuronal cells in the hippocampal CA1 and CA3 regions in brain of mice. Conclusions: MFE protects neuronal cells against oxidative stress-induced apoptosis through upregulating the expression of BDNF and antioxidant enzymes by stabilizing the activation of the TrkB/Akt pathway. Such an effect of MFE, which includes rich polyphenols, may provide information for its application as a food supplement for the prevention and treatment of neurodegenerative diseases.

In recent years, growth hormone deficiency in children has been treated with hormone therapy despite the possible significant side effects. Therefore, it was deemed beneficial to develop functional foods or dietary supplements for safely improving children’s growth. Spirulina platensis is known for its high antioxidant, anti-aging, anti-cancer, and immunity-enhancing properties, as well as its high digestibility and high protein content, but little has been reported about its influence on bone development in children with a normal supply of protein. In this study, we evaluated the effects of spirulina on the bone metabolism and antioxidant profiles of three-week-old growing male rats. The animals were divided into four groups (n = 17 per group) and were fed AIN93G diets with 0% (control), 30% (SP30), 50% (SP50), and 70% (SP70) of casein protein replaced by spirulina, respectively, for seven weeks. We observed that spirulina enhanced bone growth and bone strength by stimulating parathyroid hormone and growth hormone activities, as well its increased antioxidant activity. These results indicate that spirulina provides a suitable dietary supplement and alternative protein source with antioxidant benefits for growth improvement in early developmental stages.