• Journal of Veterinary Science
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• v.22 no.6
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• pp.92.1-92.12
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• 2021

Background: Naringin and its aglycone naringenin are citrus-derived flavonoids with several pharmacological effects. On the other hand, the mechanism for the anti-diabetic effects of naringenin and naringin are controversial and remain to be clarified further. Objective: This study examined the relationship between glucose uptake and AMP-activated protein kinase (AMPK) phosphorylation by naringenin and naringin in high glucose-treated HepG2 cells. Methods: Glucose uptake was measured using the 2-NBDG fluorescent D-glucose analog. The phosphorylation levels of AMPK and GSK3β (Glycogen synthase kinase 3 beta) were observed by Western blotting. Molecular docking analysis was performed to evaluate the binding affinity of naringenin and naringin to the γ-subunit of AMPK. Results: The treatment with naringenin and naringin stimulated glucose uptake regardless of insulin stimulation in high glucose-treated HepG2 cells. Both flavonoids increased glucose uptake by promoting the phosphorylation of AMPK at Thr172 and increased the phosphorylation of GSK3β. Molecular docking analysis showed that both naringenin and naringin bind to the γ-subunit of AMPK with high binding affinities. In particular, naringin showed higher binding affinity than the true modulator, AMP with all three CBS domains (CBS1, 3, and 4) in the γ-subunit of AMPK. Therefore, both naringenin and naringin could be positive modulators of AMPK activation, which enhance glucose uptake regardless of insulin stimulation in high glucose-treated HepG2 cells. Conclusions: The increased phosphorylation of AMPK at Thr172 by naringenin and naringin might enhance glucose uptake regardless of insulin stimulation in high glucose treated HepG2 cells.

• Journal of Microbiology and Biotechnology
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• v.34 no.4
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• pp.812-827
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• 2024

Phloroglucinol (PG) is one of the abundant isomeric benzenetriols in brown algae. Due to its polyphenolic structure, PG exhibits various biological activities. However, the impact of PG on anagen signaling and oxidative stress in human dermal papilla cells (HDPCs) is unknown. In this study, we investigated the therapeutic potential of PG for improving hair loss. A non-cytotoxic concentration of PG increased anagen-inductive genes and transcriptional activities of β-Catenin. Since several anagen-inductive genes are regulated by β-Catenin, further experiments were performed to elucidate the molecular mechanism by which PG upregulates anagen signaling. Various biochemical analyses revealed that PG upregulated β-Catenin signaling without affecting the expression of Wnt. In particular, PG elevated the phosphorylation of protein kinase B (AKT), leading to an increase in the inhibitory phosphorylation of glycogen synthase kinase 3 beta (GSK3β) at serine 9. Treatment with the selective phosphoinositide 3-kinase/AKT inhibitor, LY294002, restored the increased AKT/GSK3β/β-Catenin signaling and anagen-inductive proteins induced by PG. Moreover, conditioned medium from PG-treated HDPCs promoted the proliferation and migration of human epidermal keratinocytes via the AKT signaling pathway. Subsequently, we assessed the antioxidant activities of PG. PG ameliorated the elevated oxidative stress markers and improved the decreased anagen signaling in hydrogen peroxide (H₂O₂)-induced HDPCs. The senescence-associated β-galactosidase staining assay also demonstrated that the antioxidant abilities of PG effectively mitigated H₂O₂-induced senescence. Overall, these results indicate that PG potentially enhances anagen signaling and improves oxidative stress-induced cellular damage in HDPCs. Therefore, PG can be employed as a novel therapeutic component to ameliorate hair loss symptoms.

• Proceedings of the Korean Society of Life Science Conference
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• 2007.10a
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• pp.77.2-77.2
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• 2007

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• Journal of Microbiology and Biotechnology
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• v.34 no.4
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• pp.985-986
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• 2024

• The Journal of Korean Obstetrics and Gynecology
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• v.19 no.3
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• pp.121-134
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• 2006

Purpose : Cuscuta chinensis Lam. is utilized extensively as important medicines for threatened abortion habitual abortion. However, objective data related to an embryo is not existed until now. Therefore, this study is focused to find out stability of Cuscuta chinensis Lam. about an embryo during pregnancy based on data related to stability of nerve cell and antioxydative effect by using neural cell line, PC 12 cell. Methods : Experimentation concerns cytotoxic effects and antioxydative effect through methods such as MTT ssay, western botting after abstracting an undiluted solution from domestic Cuscuta chinensis Lam. Results : 1. As a result of experimentation on MTT assay according to each magnification from Cuscuta chinensis Lam. extraction solution with different abstraction methods, cytotoxic effect is not observed to all extract except an undiluted solution which is abstracted from MeOH stiring. Also, an undiluted solution in stiring with MeOH could not confirm whether come from Cuscuta chinensis Lam. or not. 2. As a result of revelation of Bax and GSK-3${\beta}$ which is responsive to the first stage from general stress in order to observe antioxydative effects of Cuscuta chinensis Lam. revelation of Bax by Cuscuta chinensis Lam. appeared to decrease. Conclusion : Cytotoxic effects with Cuscuta chinensis Lam. about PC12 cell is not discovered and it assume that it would be anti apoptotic effect by ROS as Bax and GSK-3${\beta}$ inviable effect. In the future, this study could be used as basic data for additional research on Cuscuta chinensis Lam. and effect and stability of complicated prescriptions for keeping pregnancy.

• The Korean Journal of Physiology and Pharmacology
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• v.18 no.2
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• pp.155-161
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• 2014

Overexpression of amyloid precursor protein with the Swedish mutation causes abnormal hyperphosphorylation of the microtubule-associated protein tau. Hyperphosphorylated isoforms of tau are major components of neurofibrillary tangles, which are histopathological hallmarks of Alzheimer's disease. Protein phosphatase 2A (PP2A), a major tau protein phosphatase, consists of a structural A subunit, catalytic C subunit, and a variety of regulatory B subunits. The B subunits have been reported to modulate function of the PP2A holoenzyme by regulating substrate binding, enzyme activity, and subcellular localization. In the current study, we characterized regulatory B subunit-specific regulation of tau protein phosphorylation. We showed that the PP2A B subunit PPP2R2A mediated dephosphorylation of tau protein at Ser-199, Ser-202/Thr-205, Thr-231, Ser-262, and Ser-422. Down-regulation of PPP2R5D expression decreased tau phosphorylation at Ser-202/Thr-205, Thr-231, and Ser-422, which indicates activation of the tau kinase glycogen synthase kinase 3 beta ($GSK3{\beta}$) by PP2A with PPP2R5D subunit. The level of activating phosphorylation of the $GSK3{\beta}$ kinase Akt at Thr-308 and Ser-473 were both increased by PPP2R5D knockdown. We also characterized B subunit-specific phosphorylation sites in tau using mass spectrometric analysis. Liquid chromatography-mass spectrometry revealed that the phosphorylation status of the tau protein may be affected by PP2A, depending on the specific B subunits. These studies further our understanding of the function of various B subunits in mediating site-specific regulation of tau protein phosphorylation.

• Journal of Life Science
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• v.19 no.10
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• pp.1346-1351
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• 2009

Recent evidence has shown that many pluripotetic neural crest cells are fate-restricted and that different fate-restricted crest cells emigrate from the neural tube at different times. Jin et al. (2001) identified the expression patterns of Wnts and its antagonists at the time that neural crest cells were being specified and suggested that Wnt signaling was involved in the segregation/differentiation of neural crest cells in the trunk in vitro. In this study, we evaluated the effects of Wnt signaling in avian neural crest lineage segregation. To accomplish this, Wnt signaling was disturbed at the time of neural crest segregation and differentiation by grafting Wnt-3a expressing cells and conducting dominant negative glycogen synthase kinase (dnGSK) electroporation. Stimulation of Wnt signaling induced neural crest lineage segregation and melanoblast specification, and increased the expression levels of genes known to be involved in neural crest development such as cadherin 7 and Slug, which suggests that they are involved in Wnt-induced neural crest lineage differentiation into melanoblasts.

• Korean Journal of Plant Resources
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• v.30 no.6
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• pp.640-646
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• 2017

In this study, we elucidated anti-cancer activity and potential molecular mechanism of 70% ethanol extracts from Taxilli Ramulus (Taxillus chinensis (DC.) Danser) (TR-E70) against human colorectal cancer cells. Anti-cell proliferative effect of TR-E70 was evaluated by MTT assay. The effect of TR-E70 on the expression of cyclin D1 in the protein and mRNA level was evaluated by Western blot and RT-PCR, respectively. TR-E70 suppressed the proliferation of human colorectal cancer cell lines, HCT116 and SW480. Although TR-E70 decreased cyclin D1 expression in protein and mRNA level, decreased level of cyclin D1 protein by TR-E70 more dramatically occurred than that of cyclin D1 mRNA. Cyclin D1 downregulation by TR-E70 was attenuated in presence of MG132. In addition, TR-E70 phosphorylated threonine-286 (T286) of cyclin D1. TR-E70-mediated cyclin D1 degradation was blocked in presence of LiCl as an inhibitor $GSK3{\beta}$ but not PD98059 as an ERK1/2 inhibitor and SB203580 as a p38 inhibitor. Our results suggest that TR-E70 may downregulate cyclin D1 as one of the potential anti-cancer targets through $GSK3{\beta}$-dependent cyclin D1 degradation. From these findings, TR-E70 has potential to be a candidate for the development of chemoprevention or therapeutic agents for human colorectal cancer.

• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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• v.26 no.1
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• pp.1-18
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• 2013

Objective: Recently the demands for the effective and safe depigmentative and anti-aging agents of the skin have increased due to the medical, pharmaceutical and cosmetic reasons. The purpose of this study is to investigate the MKG(Methanol Extract of Kaempferia galanga) and their dermal bioactivity properties related to cosmeceuticals such as depigmentation. Methods: We assessed inhibitory effects of MKG on melanin production in B16/F10 melanoma cells, on mushroom tyrosinase activity, effects of MKG on the expression tyrosinase, TRP-1, TRP-2, GSK-$3{\beta}$, CREB, MITF in B16/F10 melanoma cells without cytotoxicity range. Cell viability was measured by MTT assay and tyrosinase activity was assessed using by DOPA staining, western-blot analysis. We measured inhibition of melanin synthesis and tyrosinase activity by down-regulation of melanogenic enzyme expressions in ${\alpha}$-MSH induced melanogenesis B16/F10 melanoma cells. Results: MKG inhibited tyrosinase-activity, total melanin contents and dendrite out-growth. MKG inhibited melanogenesis by down-regulation of tyorsinase, TRP-1, TRP-2, CREB, and MITF in B16/F10 cells. The treatment with MKG at the 12.5, $25{\mu}g/ml$ level significantly inhibited the melanin synthesis induced ${\alpha}$-MSH in B16/F10 melanoma cells compared with untreated control. Conclusion: These results suggest that MKG inhibit melanin biosynthesis which is involved in hyper-pigmentation. So MKG is considered to be used as a whitening components reducing cytotoxicity.

• Korean Journal of Veterinary Research
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• v.54 no.1
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• pp.21-26
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• 2014

Although benfotiamine has various beneficial anti-diabetic effects, the detailed mechanisms underlying the impact of this compound on the insulin signaling pathway are still unclear. In the present study, we evaluated the effects of benfotiamine on the hepatic insulin signaling pathway in Otsuka Long-Evans Tokushima Fatty (OLETF) rats, which are a type 2 diabetes mellitus model. OLETF rats treated with benfotiamine showed decreased body weight gain and reduced adipose tissue weight. In addition, blood glucose levels were lower in OLETF rats treated with benfotiamine. Following treatment with benfotiamine, the levels of Akt phosphorylation (S473/T308) in the OLETF groups increased significantly compared to the OLETF control group so that they were almost identical to the levels observed in the control group. Moreover, benfotiamine restored the phosphorylation levels of both glycogen synthase kinase (GSK)-$3{\alpha}/{\beta}$ (S21, S9) and glycogen synthase (GS; S641) in OLETF rats to nearly the same levels observed in the control group. Overall, these results suggest that benfotiamine can potentially attenuate type 2 diabetes mellitus in OLETF rats by restoring insulin sensitivity through upregulation of Akt phosphorylation and activation of two downstream signaling molecules, GSK-$3{\alpha}/{\beta}$ and GS, thereby reducing blood glucose levels through glycogen synthesis.