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Oh, Dool-Ri,Kim, Yujin,Choi, Eun-Jin,Jung, Myung-A,Oh, Kyo-Nyeo,Hong, Ji-Ae,Bae, Donghyuck,Kim, Kwangsu,Kang, Huwon,Kim, Jaeyong,Kim, Young Ran,Cho, Seung Sik,Choi, Chul-Young World Scientific Publishing Company 2018 The American journal of Chinese medicine Vol.46 No.2
<P>The fruit of <I>Vaccinium bracteatum</I> Thunb. (VBF) is commonly known as the oriental blueberry in Korea. The aim of this study was to evaluate the antidepressant-like effects of water VBF extract (VBFW) in a mouse model of chronic restraint stress (CRS) and to identify the underlying mechanisms of its action. The behavioral effects of VBFW were assessed in the forced swim test (FST) and open field test (OFT). The levels of serum corticosterone (CORT), brain monoamines, in addition to the extracellular signal-regulated kinases (ERKs)/protein kinase B (Akt) signaling pathway were evaluated. VBFW treatment significantly reduced the immobility time and increased swimming time in FST without altering the locomotor activity in unstressed mice. Furthermore, CRS mice treated with VBFW exhibited a significantly decreased immobility time in FST and serum CORT, increased locomotor activity in OFT, and enhanced brain monoamine neurotransmitters. Similarly, VBFW significantly upregulated the ERKs/Akt signaling pathway in the hippocampus and PFC. In addition, VBFW may reverse CORT-induced cell death by enhancing cyclic AMP-responsive element-binding protein expression through the up-regulation of ERKs/Akt signaling pathways. In addition, VBFW showed the strong antagonistic effect of the 5-HT<TEX>$ _{2\text{A}}$</TEX> receptor by inhibiting 5-HT-induced intracellular Ca<TEX>$ ^{2+}$</TEX> and ERK1/2 phosphorylation. Our study provides evidence that antidepressant-like effects of VBFW might be mediated by the regulation of monoaminergic systems and glucocorticoids, which is possibly associated with neuroprotective effects and antagonism of 5-HT<TEX>$ _{2\text{A}}$</TEX> receptor.</P>
Dool-Ri Oh,Yujin Kim,Kyo-Nyeo Oh,Eun-Jin Choi,Donghyuck Bae,Yonguk Kim,Chulyung Choi 한국식품영양과학회 2021 한국식품영양과학회 학술대회발표집 Vol.2021 No.10
Vaccinium bracteatum Thunb. (VB) are a component of traditional herbal medicines found in East Asia, specially, fruit is commonly known as the oriental blueberry in Korea. The present study aimed to evaluate the mechanisms underlying the antidepressant, preventing oxidative stress and insomnia of water extract of VB fruit (VBFW) using in vitro and in vivo models. First, since the serotonin neurotransmitter system is hypothesized to contribute to depression, we studied the effects of water extract from VBFW on the serotonin receptors (5-HTRs)-related activities in Chinese hamster ovary (CHO)-K1 cells transfected with the human 5-HT1, 5-HT2, 5-HT3, 5-HT4, 5-HT6, and 5-HT7 receptors. VBFW produced the antagonistic effects at the 5-HT2A receptors, and showed the agonistic effects at the 5-HT1A receptors, which could possibly produce antidepressant-like effects. Next, it was studied by using animal models predictive of antidepressant-like effects. The effects of VBFW were studied in normal and 4-Chloro-DL-phenylalanine methyl ester hydrochloride (PCPA)-induced serotonin-depleted mice. These results suggest that evidence of the antidepressant-like effects of VBFW includes the decreased immobility time during the forced swim test (FST) in mice that is caused by a decrease in the levels of serum corticosterone (CORT), as well as increased serotonergic neurotransmission. Moreover, this study provides an evidence that the antidepressant-like effects of VBFW in mice exposed to chronic restraint stress (CRS) exhibited significantly reduced immobility time and increased swimming times in the FST, and increased locomotor activity in the OFT. In addition, CRS mice treated with VBFW exhibited significantly decreased the hypothalamic-pituitary-adrenal (HPA) axis and oxidative stress (e.g., glutamate and MDA levels), but upregulated brain monoamine neurotransmitters (e.g., 5-HT, dopamine, norepinephrine) and the extracellular signal-regulated kinase (ERK) and protein kinase B (Akt) phosphorylation. Furthermore, since depression can lead to sleep problems, the sedative and hypnotic effects of VBFW in an animal model and alterations to the γ-aminobutyric acid (GABA)-ergic system were also studied. VBFW significantly reduced the sleep latency and increased the total sleep duration during pentobarbital-induced sleeping behaviors in mice, which are possibly associated with upregulation of the glutamate decarboxylase (GAD)65/67 protein and GABAA receptor subunits (α5, β1, and β2). In conclusion, the antidepressant effects of VBFW were possibly mediated by regulation monoamine neurotransmitters in basis of their effects on 5-HT2A and 5-HT1A receptors and ERK/Akt phosphorylation, and prevention of HPA axis dysfunction. Furthermore, VBFW induces sedative and hypnotic effects by regulating the serotonergic and GABAA-ergic systems. These results suggest that the VBFW might be an effective natural therapeutic agent for stress and depression disorder.
Estrogen Receptor α Regulates Dlx3-Mediated Osteoblast Differentiation
Lee, Sung Ho,Oh, Kyo-Nyeo,Han, Younho,Choi, You Hee,Lee, Kwang-Youl Korean Society for Molecular and Cellular Biology 2016 Molecules and cells Vol.39 No.2
Estrogen receptor ${\alpha}$ (ER-${\alpha}$), which is involved in bone metabolism and breast cancer, has been shown to have transcriptional targets. Dlx3 is essential for the skeletal development and plays an important role in osteoblast differentiation. Various osteogenic stimulators and transcription factors can induce the protein expression of Dlx3. However, the regulatory function of ER-${\alpha}$ in the Dlx3 mediated osteogenic process remains unknown. Therefore, we investigated the regulation of Dlx3 and found that ER-${\alpha}$ is a positive regulator of Dlx3 transcription in BMP2-induced osteoblast differentiation. We also found that ER-${\alpha}$ interacts with Dlx3 and increases its transcriptional activity and DNA binding affinity. Furthermore, we demonstrated that the regulation of Dlx3 activity by ER-${\alpha}$ is independent of the ligand (estradiol) binding domain. These results indicate that Dlx3 is a novel target of ER-${\alpha}$, and that ER-${\alpha}$ regulates the osteoblast differentiation through modulation of Dlx3 expression and/or interaction with Dlx3.