• Biomolecules & Therapeutics
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• v.20 no.2
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• pp.207-213
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• 2012

The present study examined the effects of krill-derived phosphatidylserine (Krill-PS) on the learning and memory function and the neural activity in rats with trimethyltin (TMT)-induced memory deficits. The rats were administered vehicle (medium-chain triglyceride: MCT) or Krill-PS (50, 100 mg/kg, p.o.) daily for 21 days. The cognitive improving efficacy of Krill-PS in TMT-induced amnesic rats was investigated by assessing the Morris water maze test and by performing choline acetyltransferase (ChAT), acetylcholinesterase (AChE) and cAMP responsive element binding protein (CREB) immunohistochemistry. The rats with TMT injection showed impaired learning and memory of the tasks and treatment with Krill-PS produced a significant improvement of the escape latency to find the platform in the Morris water maze at the $2^{nd}$ and $4^{th}$ day compared to that of the MCT group (p<0.05). In the retention test, the Krill-PS+MCT groups showed increased time spent around the platform compared to that of the MCT group. Consistent with the behavioral data, Krill-PS 50+MCT group significantly alleviated the loss of acetylcholinergic neurons in the hippocampus and medial septum compared to that of the MCT group. Treatment with Krill-PS significantly increased the CREB positive neurons in the hippocampal CA1 area as compared to that of the MCT group. These results suggest that Krill-PS may be useful for improving the cognitive function via regulation of cholinergic marker enzyme activity and neural activity.

• Journal of Oriental Neuropsychiatry
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• v.30 no.3
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• pp.199-207
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• 2019

Objectives: The purpose of this study was to evaluate the neuroprotective effects of donepezil and 33 kinds of herbal extract combinations in SH-SY5Y cells with $A{\beta}_{25-35}$ treatment. Methods: MTT assay was performed to measure the cell viability of each herbal extract combined with donepezil against $A{\beta}$-induced neurotoxicity. The most active extracts were then subjected to assess the effects on CREB phosphorylation and COX-2 expressions through the western blot analysis. Results: There were eight herbal extracts representing significant increase on the cell viability: 1) Erycibe obtusifolia, 2) Polygonum multiflorum, 3) Polygala tenuifolia, 4) Illicium verum, 5) Santalum album, 6) Loranthus parasticus, 7) Platycladus orientalis, and 8) Zanthoxylum piperitum. Especially, when Santalum album and donepezil were treated together, the phosphorylation of CREB significantly increased and COX-2 protein expression was significantly inhibited. Conclusions: Among the screened herbal extracts, combination treatment of each of the eight herbs and donepezil showed neuroprotective effects in SH-SY5Y cells. Additionally, the combination of Santalum album and donepezil suggested cognitive improvement by up-regulation of p-CREB and down-regulation of COX-2.

• Proceedings of the Zoological Society Korea Conference
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• 2000.10a
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• pp.239.3-240
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• 2000

No Abstract, See Full Text

• Proceedings of the Zoological Society Korea Conference
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• 2003.08a
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• pp.166.4-166
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• 2003

No Abstract, See Full Text

• Natural Product Sciences
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• v.26 no.3
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• pp.221-229
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• 2020

This study was undertaken to investigate the protective effect of rice bran oil (RBO) on amyloid β protein (Aβ) (25-35)-induced memory impairment and brain damage in an ICR mouse model. Memory impairment was produced by intracerebroventricular microinjection of 15 nmol Aβ (25-35) and assessed using the passive avoidance test. Treatment with RBO at 0.1, 0.5, or 1 mL/kg (p.o. daily for 8 days) protected against Aβ (25-35)-induced memory impairment. Furthermore, Aβ (25-35)-induced decreases in glutathione and increases in lipid peroxidation and cholinesterase activity in brain tissue were inhibited by RBO, and Aβ (25-35)-induced increases of phosphorylated mitogen-activated protein kinases (MAPKs) and inflammatory factors, and changes in the levels of apoptosis-related proteins were significantly inhibited by RBO. Furthermore, Aβ (25-35) suppressed the PI3K/Akt pathway and the phosphorylation of CREB, but increased phosphorylation of tau (p-tau) in mice brain; these effects were significantly inhibited by administration of RBO. These results suggest that RBO inhibits Aβ (25-35)-induced memory impairment by inducing anti-apoptotic and anti-inflammatory effects, promoting PI3K/Akt/CREB signaling, and thus, inhibiting p-tau formation.

• Biomolecules & Therapeutics
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• v.32 no.1
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• pp.65-76
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• 2024

Bortezomib (BTZ) is a proteasome inhibitor used to treat multiple myeloma (MM). However, the induction of peripheral neuropathy is one of the major concerns in using BTZ to treat MM. In the current study, we have explored the effects of BTZ (0.01-5 nM) on rat neural stem cells (NSCs). BTZ (5 nM) induced cell death; however, the percentage of neurons was increased in the presence of mitogens. BTZ reduced the B-cell lymphoma 2 (Bcl-2)/Bcl-2 associated X protein ratio in proliferating NSCs and differentiated cells. Inhibition of βIII-tubulin (TUBB3) degradation was observed, but not inhibition of glial fibrillary acidic protein degradation, and a potential PEST sequence was solely found in TUBB3. In the presence of growth factors, BTZ increased cAMP response element-binding protein (CREB) phosphorylation, brain-derived neurotrophic factor (Bdnf) transcription, BDNF expression, and Tubb3 transcription in NSCs. However, in the neuroblastoma cell line, SH-SY5Y, BTZ (1-20 nM) only increased cell death without increasing CREB phosphorylation, Bdnf transcription, or TUBB3 induction. These results suggest that although BTZ induces cell death, it activates neurogenic signals and induces neurogenesis in NSCs.

• Journal of Physiology & Pathology in Korean Medicine
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• v.24 no.6
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• pp.983-988
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• 2010

The present study aims to investigate a possible mechanism of electroacupuncture (EA) in the spinal dorsal horn that may underlie N-methyl-D-aspartate (NMDA) receptor-associated extracellular signal-regulated kinase (ERK) mitogen-activated protein kinase (MAPK) signaling pathways. The hot plate latency of the ipsilateral hindpaw of EA-treated rats was significantly decreased compared with complete Freund's adjuvant (CFA)-injected ones. The expressions of NR1 and NR2B subuint mRNA of NMDA receptor in the whole L4-5 segments are decreased by CFA treatment, but NR2B subunit was significantly recovered by EA treatment. When we detected the expression of ERK, there were no significant difference between normal and CFA-treated rats with EA or NMDA receptor antagonist MK801. But phosphorylated ERK expressions were markedly induced by CFA, but these inductions were significantly modulated by EA treatment. Although hosphorylation of ERK was also arrested by MK801, these inductions of CFA-injected rats was markedly inhibited only by co-treatment with EA and MK801. Phosphorylated cAMP response element-binding protein (CREB), ERK-related transcriptional factor, showed a significant increase in CFA-treated rats and this increase was slightly inhibited by EA and MK801 treatments. But immunoreaction for phosphorylated CREB were significantly increased by CFA treatment in the superficial laminae of the dorsal horn and these inductions were significantly arrested by co-treatment of EA and MK801. Consequently, the hyperalgesia induced by CFA are associated NMDA receptor and EA and MK801 may showed anti-hyperalgesia via same mechanism for inhibition of ERK and CREB phosphorylation in the dorsal horn.

• The Korean Journal of Physiology and Pharmacology
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• v.21 no.4
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• pp.377-384
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• 2017

Activation of protein kinase C (PKC) is closely linked with endothelial dysfunction. However, the effect of $PKC{\beta}II$ on endothelial dysfunction has not been characterized in cultured endothelial cells. Here, using adenoviral $PKC{\beta}II$ gene transfer and pharmacological inhibitors, the role of $PKC{\beta}II$ on endothelial dysfucntion was investigated in cultured endothelial cells. Phorbol 12-myristate 13-acetate (PMA) increased reactive oxygen species (ROS), p66shc phosphorylation, intracellular adhesion molecule-1, and monocyte adhesion, which were inhibited by $PKC{\beta}i$ (10 nM), a selective inhibitor of $PKC{\beta}II$. PMA increased the phosphorylation of CREB and manganese superoxide dismutase (MnSOD), which were also inhibited by $PKC{\beta}i$. Gene silencing of CREB inhibited PMA-induced MnSOD expression, suggesting that CREB plays a key role in MnSOD expression. Gene silencing of $PKC{\beta}II$ inhibited PMA-induced mitochondrial ROS, MnSOD, and ICAM-1 expression. In contrast, overexpression of $PKC{\beta}II$ using adenoviral $PKC{\beta}II$ increased mitochondrial ROS, MnSOD, ICAM-1, and p66shc phosphorylation in cultured endothelial cells. Finally, $PKC{\beta}II$-induced ICAM-1 expression was inhibited by Mito-TEMPO, a mitochondrial ROS scavenger, suggesting the involvement of mitochondrial ROS in PKC-induced vascular inflammation. Taken together, the results suggest that $PKC{\beta}II$ plays an important role in PMA-induced endothelial dysfunction, and that the inhibition of $PKC{\beta}II$-dependent p66shc signaling acts as a therapeutic target for vascular inflammatory diseases.

• Proceedings of the Korean Society of Life Science Conference
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• 2008.10a
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• pp.53.1-53.1
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• 2008

• Korean Journal of Food Science and Technology
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• v.51 no.1
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• pp.52-57
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• 2019

The objective of this study was to evaluate the anti-melanogenic effects of crude polysaccharide fractions from Annona muricata L. (ALP) in 3-isobutyl-1-methylxanthine (IBMX) stimulating hormone-induced mouse B16F10 melanoma cells. The inhibitory effect of ALP on tyrosinase activity was approximately $33.88{\pm}0.79%$ at 5 mg/mL. Additionally, the B16F10 cellular tyrosinase and melanin synthesis inhibition activities by ALP were $54.21{\pm}4.76$ and $56.74{\pm}6.97%$ at $250{\mu}g/mL$, respectively. Similarly, whitening-related protein tyrosinase, tyrosinase-related protein 1 (TRP-1) and TRP-2, and microphthalmia-associated transcription factor (MITF) were reduced by ALP treatment. These results indicated that ALP could be used as a functional cosmetic ingredient after confirming its whitening activity related to melanin content.