• Biomolecules & Therapeutics
• /
• v.31 no.3
• /
• pp.285-297
• /
• 2023

Alzheimer's disease (AD) is a neurodegenerative disease with progressive memory loss and the cognitive decline. AD is mainly caused by abnormal accumulation of misfolded amyloid β (Aβ), which leads to neurodegeneration via a number of possible mechanisms such as down-regulation of brain-derived neurotrophic factor-tropomyosin-related kinase B (BDNF-TRKB) signaling pathway. 7,8-Dihydroxyflavone (7,8-DHF), a TRKB agonist, has demonstrated potential to enhance BDNF-TRKB pathway in various neurodegenerative diseases. To expand the capacity of flavones as TRKB agonists, two natural flavones quercetin and apigenin, were evaluated. With tryptophan fluorescence quenching assay, we illustrated the direct interaction between quercetin/apigenin and TRKB extracellular domain. Employing Aβ folding reporter SH-SY5Y cells, we showed that quercetin and apigenin reduced Aβ-aggregation, oxidative stress, caspase-1 and acetylcholinesterase activities, as well as improved the neurite outgrowth. Treatments with quercetin and apigenin increased TRKB Tyr516 and Tyr817 and downstream cAMP-response-element binding protein (CREB) Ser133 to activate transcription of BDNF and BCL2 apoptosis regulator (BCL2), as well as reduced the expression of pro-apoptotic BCL2 associated X protein (BAX). Knockdown of TRKB counteracted the improvement of neurite outgrowth by quercetin and apigenin. Our results demonstrate that quercetin and apigenin are to work likely as a direct agonist on TRKB for their neuroprotective action, strengthening the therapeutic potential of quercetin and apigenin in treating AD.

• Fisheries and Aquatic Sciences
• /
• v.26 no.1
• /
• pp.24-34
• /
• 2023

Reactive oxygen species (ROS) at high concentrations induce oxidative stress, an imbalanced redox state that is a prevalent cause of neurodegenerative disorders. This study aimed to investigate the protective effect of Capsosiphon fulvescens (CF) extract on oxidative stress-induced impairment of cognitive function in models of neurodegenerative diseases. CF was extracted with subcritical water and several solvents and H₂O₂ (0.25 mM) or aluminum chloride (AlCl₃; 25 µM) as an inducer of ROS was treated in PC12 neuronal cells and zebrafish larvae. All statistical analyses were performed using one-way analysis of variance and Dunnett's test using GraphPad Prism. H₂O₂ and AlCl₃ were found to significantly induce ROS production in PC12 neuronal cells and zebrafish larvae. In addition, they strongly affected intracellular Ca²⁺ levels, antioxidant enzyme activity, brain-derived neurotrophic factor (BDNF) and tropomyosin receptor kinase B (TrkB) signaling, acetylcholinesterase (AChE) activity, and hallmarks of Alzheimer's disease. However, treatment of H₂O₂-induced PC12 cells or AlCl₃-induced zebrafish larvae with CF subcritical water extract at 90℃ and CF water extract effectively regulated excessive ROS production, intracellular Ca²⁺ levels, and mRNA expression of superoxide dismutase, glutathione peroxide, glycogen synthase kinase-3 beta, β-amyloid, tau, AChE, BDNF, and TrkB. Our study suggested that CF extracts can be a potential source of nutraceuticals that can improve the impairment of cognitive function and synaptic plasticity by regulating ROS generation in neurodegenerative diseases.

• Korean Journal of Exercise Nutrition
• /
• v.16 no.2
• /
• pp.73-84
• /
• 2012

Thyroid hormones are important for the development of the brain including the cerebellum. In the present study, we investigated the effect of treadmill exercise on the survival of Purkinje neurons and the activation of astrocytes in the cerebellar vermis of hypothyroidism-induced rat pups. On the day of perinatal 14, pregnant rats were divided into two groups (n = 5 in each group): the pregnant control group and the pregnantmethimazole (MMI)-treated group. For the induction of hypothyroidism in the rat pups, MMI was added to the drinking water (0.02% wt/vol), from the day of perinatal 14 to postnatal 49. After delivery, male rat pups born from the pregnant control group were assigned to the control group. Male rat pups born from the MMI-treated group were divided into the hypothyroidism-induction group, the hypothyroidism-induction with treadmill exercise group, and the hypothyroidism-induction with thyroxine (T4) treatment group (n = 10 in each group). The rat pups in the exercise group were forced to run on a treadmill for 30 min once a day for 4 weeks, starting on postnatal day 22. In the hypothyroidism-induced rat pups, motor coordination was reduced and Purkinje cell death and reactive astrocytes in the cerebellar vermis were increased. Treadmill exercise enhanced motor coordination, increased the survival of Purkinje neurons, down-regulated reactive astrocytes, and enhanced brain-derived neurotrophic factor (BDNF) and receptor tyrosine kinase B (TrkB) expressions in the hypothyroidism-induced rat pups. These results suggest that treadmill exercise has beneficial effects in terms of protecting against thyroid dysfunction by increasing T3 and T4 and the related protein, BDNF, as well as TrkB, inhibition on astrocyte activation and the reduction of Purkinje cell loss regarding the cerebellum in hypothyroidism rat pups.

• Journal of Ginseng Research
• /
• v.48 no.1
• /
• pp.59-67
• /
• 2024

Background: Alzheimer's disease (AD) has memory impairment associated with aggregation of amyloid plaques and neurofibrillary tangles in the brain. Although anti-amyloid β (Aβ) protein antibody and chemical drugs can be prescribed in the clinic, they show adverse effects or low effectiveness. Therefore, the development of a new drug is necessarily needed. We focused on the cognitive function of Panax ginseng and tried to find active ingredient(s). We isolated panaxcerol D, a kind of glycosyl glyceride, from the non-saponin fraction of P. ginseng extract. Methods: We explored effects of acute or sub-chronic administration of panaxcerol D on cognitive function in scopolamine- or Aβ_25-35 peptide-treated mice measured by several behavioral tests. After behavioral tests, we tried to unveil the underlying mechanism of panaxcerol D on its cognitive function by Western blotting. Results: We found that pananxcerol D reversed short-term, long-term and object recognition memory impairments. The decreased extracellular signal-regulated kinases (ERK) or Ca²⁺/calmodulin-dependent protein kinase II (CaMKII) in scopolamine-treated mice was normalized by acute administration of panaxcerol D. Glial fibrillary acidic protein (GFAP), caspase 3, NF-kB p65, synaptophysin and brainderived neurotrophic factor (BDNF) expression levels in Aβ_25-35 peptide-treated mice were modulated by sub-chronic administration of panaxcerol D. Conclusion: Pananxcerol D could improve memory impairments caused by cholinergic blockade or Aβ accumulation through increased phosphorylation level of ERK or its anti-inflammatory effect. Thus, panaxcerol D as one of non-saponin compounds could be used as an active ingredient of P. ginseng for improving cognitive function.

• Biomedical Science Letters
• /
• v.30 no.1
• /
• pp.1-9
• /
• 2024

Although there have been several attempts to use virtual reality (VR) in the treatment of depression, the results have been inconsistent and existing studies have mostly relied on subjective measures to assess the effectiveness of VR in improving depression. The aim of this study was to investigate the effect of nature experience-based VR intervention on depressive symptoms in a young population using both subjective and objective measurements. The study population included 15 participants who had more than 14 identifiers of the Korean Beck Depression Inventory (K-BDI)-II. Participants received three weeks (four times per week) of VR intervention. The effectiveness of VR was assessed through changes in K-BDI-II scores and depression-related blood biomarkers. Nature experience-based VR intervention led to an approximately 50% reduction of K-BDI-II score (before 25.7±7.7 vs. after 12.5±8.3 (P<0.001)). Of these, loss of pleasure and fatigue showed the largest amount of improvement. However, levels of cortisol, brain-derived neurotrophic factor, and interleukin-6 did not differ from those at baseline. The findings of our pilot study suggest that nature experience-based VR can be a useful adjunctive treatment method for improving depressive symptoms in individuals who have difficulty accessing the real outside natural environment.

• Applied Microscopy
• /
• v.39 no.1
• /
• pp.1-7
• /
• 2009

Experimental induction of polycystic ovary (PCO) resembling some aspects of human PCO syndrome was produced using the long-acting compound estradiol valerate (EV). Our previous study on the role of Korean red ginseng total saponins (GTS) in a steroid-induced PCO rat model demonstrated that electro-acupuncture modulates nerve growth factor (NGF) concentration in the ovaries. In fact, the involvement of a neurogenic component in the pathology of PCO-related ovarian dysfunction is preceded by an increase in sympathetic outflow to the ovaries. In the present study, we tested the hypothesis that therapeutic GTS administration modulates sympathetic nerve activity in rats with PCO. This was done by analyzing NGF protein and NGF mRNA expression involved in the pathophysiological process underlying steroid-induced PCO. EV injection resulted in significantly higher ovarian NGF mRNA expression in PCO rats compared to control rats, and PCO ovaries were counteracted by GTS administration with significantly lower expression of NGF mRNA compared to EV treated ovaries. However, NGF protein was unaffected in both EV and GTS treated ovaries compared to control rats. These results indicate that EV modulates the neurotrophic state of the ovaries, which may be a component of the pathological process by which EV induces cyst formation and anovulation in rodents.

• The Korean Journal of Physiology and Pharmacology
• /
• v.21 no.4
• /
• pp.361-370
• /
• 2017

Previous reports have suggested that physical and psychological stresses may trigger fibromyalgia (FM). Stress is an important risk factor in the development of depression and memory impairments. Antidepressants have been used to prevent stress-induced abnormal pain sensation. Among various antidepressants, tianeptine has been reported to be able to prevent neurodegeneration due to chronic stress and reverse decreases in hippocampal volume. To assess the possible effect of tianeptine on FM symptoms, we constructed a FM animal model induced by restraint stress with intermittent cold stress. All mice underwent nociceptive assays using electronic von Frey anesthesiometer and Hargreaves equipment. To assess the relationship between tianeptine and expression levels of brain-derived neurotrophic factor (BDNF), cAMP response element-binding protein (CREB), and phosphorylated cAMP response element-binding protein (p-CREB), western blotting and immunohistochemistry analyses were performed. In behavioral analysis, nociception tests showed that pain threshold was significantly decreased in the FM group compared to that in the control group. Western blot and immunohistochemical analyses of medial prefrontal cortex (mPFC) and hippocampus showed downregulation of BDNF and p-CREB proteins in the FM group compared to the control group. However, tianeptine recovered these changes in behavioral tests and protein level. Therefore, this FM animal model might be useful for investigating mechanisms linking BDNF-CREB pathway and pain. Our results suggest that tianeptine might potentially have therapeutic efficacy for FM.

• The Korean Journal of Physiology and Pharmacology
• /
• v.17 no.5
• /
• pp.393-403
• /
• 2013

Baicalein (BA), a plant-derived active flavonoid present in the root of Scutellaria baicalensis, has been widely used for the treatment of stress-related neuropsychiatric disorders including depression. Previous studies have demonstrated that repeated restraint stress disrupts the activity of the hypothalamic-pituitary-adrenal (HPA) axis, resulting in depression. The behavioral and neurochemical basis of the BA effect on depression remain unclear. The present study used the forced swimming test (FST) and changes in brain neurotransmitter levels to confirm the impact of BA on repeated restraint stress-induced behavioral and neurochemical changes in rats. Male rats received 10, 20, or 40 mg/kg BA (i.p.) 30 min prior to daily exposure to repeated restraint stress (2 h/day) for 14 days. Activation of the HPA axis in response to repeated restraint stress was confirmed by measuring serum corticosterone levels and the expression of corticotrophin-releasing factor in the hypothalamus. Daily BA administration significantly decreased the duration of immobility in the FST, increased sucrose consumption, and restored the stress-related decreases in dopamine concentrations in the hippocampus to near normal levels. BA significantly inhibited the stress-induced decrease in neuronal tyrosine hydroxylase immunoreactivity in the ventral tegmental area and the expression of brain-derived neurotrophic factor (BDNF) mRNA in the hippocampus. Taken together, these findings indicate that administration of BA prior to the repeated restraint stress significantly improves helpless behaviors and depressive symptoms, possibly by preventing the decrease in dopamine and BDNF expression. Thus, BA may be a useful agent for the treatment or alleviation of the complex symptoms associated with depression.

• Nutrition Research and Practice
• /
• v.12 no.3
• /
• pp.191-198
• /
• 2018

BACKGROUD/OBJECTIVES: Neuroinflammation plays critical role in neurodegenerative disorders, such as Alzheimer's disease (AD). We investigated the effect of three licorice varieties, Glycyrhiza uralensis, G. glabra, and Shinwongam (SW) on a mouse model of inflammation-induced memory and cognitive deficit. MATERIALS/METHODS: C57BL/6 mice were injected with lipopolysaccharide (LPS; 2.5 mg/kg, intraperitoneally) and orally administrated G. uralensis, G. glabra, and SW extract (150 mg/kg/day). SW, a new species of licorice in Korea, was combined with G. uralensis and G. glabra. Behavioral tests, including the T-maze, novel object recognition and Morris water maze, were carried out to assess learning and memory. In addition, the expressions of inflammation-related proteins in brain tissue were measured by western blotting. RESULTS: There was a significant decrease in spatial and objective recognition memory in LPS-induced cognitive impairment group, as measured by the T-maze and novel object recognition test; however, the administration of licorice ameliorated these deficits. In addition, licorice-treated groups exhibited improved learning and memory ability in the Morris water maze. Furthermore, LPS-injected mice had up-regulated pro-inflammatory proteins, such as inducible nitric oxide synthase (iNOS), cyclooxygenase-2, interleukin-6, via activation of toll like receptor 4 (TLR4) and nuclear factor-kappa B ($NF{\kappa}B$) pathways in the brain. However, these were attenuated by following administration of the three licorice varieties. Interestingly, the SW-administered group showed greater inhibition of iNOS and TLR4 when compared with the other licorice varieties. Furthermore, there was a significant increase in the expression of brain-derived neurotrophic factor (BDNF) in the brain of LPS-induced cognitively impaired mice that were administered licorice, with the greatest effect following SW treatment. CONCLUSIONS: The three licorice varieties ameliorated the inflammation-induced cognitive dysfunction by down-regulating inflammatory proteins and up-regulating BDNF. These results suggest that licorice, in particular SW, could be potential therapeutic agents against cognitive impairment.

• Korean Journal of Food Science and Technology
• /
• v.53 no.6
• /
• pp.715-721
• /
• 2021

Cognitive impairment and Alzheimer's disease are serious social problems associated with the rising elderly population in Korea. 1,2,3,4,6-Penta-O-galloyl-β-ᴅ-glucopyranose (PGG) is a gallotannin isolated from medicinal plants such as Rhus chinensis. This study was performed to evaluate the effect of PGG on biomarkers related to cognitive function in human neuroblastoma SK-N-SH cells. Inhibition of acetylcholinesterase (AChE) activity is considered to be one of the main therapeutic strategies. PGG inhibited AChE activity in the test tube as well as in SK-N-SH cells. In addition, PGG induced protein and mRNA expression of brain-derived neurotrophic factor (BDNF), which is a mammalian neurotrophin that plays major roles in the development, maintenance, repair, and survival of neuronal populations. As one of the underlying molecular mechanisms that induce BDNF expression, PGG induced the activation of Ca²⁺/calmodulin (CaM)-dependent protein kinase II (CaMKII)-cAMP response element binding protein (CREB) pathway. In conclusion, PGG may be an useful material for improving cognitive function.