• Horticultural Science & Technology
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• v.31 no.6
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• pp.813-820
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• 2013

Monoterpenoids were recently found as main biologically active compounds which is responsible for various physiological effect in goat's beard (Aruncus dioicus). Ethyl acetate extract of A. dioicus (ADE) was treated to B16F10 melanoma cells for the examination of whitening activity. MTT assay was performed to evaluate cell toxicity and the result showed that slight cell toxicity (> 10%) by over $500{\mu}g{\cdot}mL^{-1}$. Thus, 0, 5, 10, or $50{\mu}g{\cdot}mL^{-1}$ ADE was used for further experiments. We found that tyrosinase activity was decreased according to ADE concentration, and the total melanin content was also dramatically reduced. Especially with $50{\mu}g{\cdot}mL^{-1}$ ADE treatment tyrosinase activity was reduced to 35.6%, and 58.8% of melanin content was lowered. In addition, whitening related proteins including tyrosinase, tyrosinase related protein 1 (TRP1), TRP2, microphthalmia associated transcription factor (MITF) and cAMP and protein kinase A (PKA) were reduced by ADE treatment. It caused decreased phosphorylation of cAMP response binding protein (CREB) but increased phosphorylation of extracellular signal related kinase (ERK). Therefore, in this paper we would like to suggest the potent usage of A. dioicus natively grown in Ulleungdo, Korea as materials of functional cosmetics by confirming whitening activity related with melanin content.

• Development and Reproduction
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• v.22 no.1
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• pp.95-104
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• 2018

CREBZF (cAMP-response element binding protein zhangfei) is a member of ATF/CREB family, and which regulates various cellular functions by suppressing major factors with direct interaction. In this study, we have examined the expression of CREBZF on mouse endometrium during uterus estrous cycles and estrogen (E2) treatment. In uterus, CREBZF mRNA expression was higher than other organs and mRNA and protein of CREBZF was increased in proestrus phase and decreased in estrus phase. The expression of CREBZF in 3-weeks old mouse uterus was reduced by E2 injection in endometrium. In addition, the expression of progesterone receptor, a marker of E2 in ovariectomized mice was found to be strongly expressed in stroma, while CREBZF was only expressed in epithelium. Also, we conformed that E2-suppressed CREBZF was restored by co-injection of ICI 182,780, an estrogen receptor antagonist. Overall, these results suggest that CREBZF is regulated by estrogen and involved in ER signaling pathway in mouse uterus.

• Journal of the Society of Cosmetic Scientists of Korea
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• v.46 no.1
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• pp.11-22
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• 2020

In this study, we investigated anti-pigmentation effect of a hexapeptide. The peptide significantly reduced melanin contents and inhibited tyrosinase activity in a dose-dependent manner, in which tyrosinase is a key enzyme in melanogenesis. The peptide also significantly reduced the expression levels of tyrosinase (TYR), tyrosinase-related protein 1 (TYRP1) and their upstream transcription factor, microphthalmia-associated transcription factor (MITF). Furthermore, the peptide suppressed the phosphorylation level of cAMP-response element binding protein (CREB), a transcription factor of MITF, and increased the phosphorylation level of extracellular signal-regulated kinase (ERK), a kinase mediates MITF phosphorylation and proteasomal degradation. The peptide significantly inhibited the expression of Rab27A, Melanophilin, and MyosinVa, the components of motor complex involved in intracellular movement of melanosome. These results suggest that Hexapeptide could be used as an effective whitening agent that has inhibitory effect on melanin production and melanosome transport by regulating expression and degradation of MITF in melanocytes.

• Journal of Ginseng Research
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• v.47 no.6
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• pp.714-725
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• 2023

Background: Our previous investigation indicated that the preparation of Panax ginseng Meyer (P. ginseng) inhibited melanogenesis. It comprised salicylic acid (SA), protocatechuic acid (PA), p-coumaric acid (p-CA), vanillic acid (VA), and caffeic acid (CA). In this investigation, the regulatory effects of P. ginseng phenolic acid monomers on melanin production were assessed. Methods: In vitro and in vivo impact of phenolic acid monomers were assessed. Results: SA, PA, p-CA and VA inhibited tyrosinase (TYR) to reduce melanin production, whereas CA had the opposite effects. SA, PA, p-CA and VA significantly downregulated the melanocortin 1 receptor (MC1R), cycle AMP (cAMP), protein kinase A (PKA), cycle AMP-response element-binding protein (CREB), microphthalmia-associated transcription factor (MITF) pathway, reducing mRNA and protein levels of TYR, tyrosinase-related protein 1 (TYRP1), and TYRP2. Moreover, CA treatment enhanced the cAMP, PKA, and CREB pathways to promote MITF mRNA level and phosphorylation. It also alleviated MITF protein level in α-MSH-stimulated B16F10 cells, comparable to untreated B16F10, increasing the expression of phosphorylation glycogen synthase kinase 3β (p-GSK3β), β-catenin, p-ERK/ERK, and p-p38/p38. Furthermore, the GSK3β inhibitor promoted p-GSK3β and p-MITF expression, as observed in CA-treated cells. Moreover, p38 and ERK inhibitors inhibited CA-stimulated p-p38/p38, p-ERK/ERK, and p-MITF increase, which had negative binding energies with MC1R, as depicted by molecular docking. Conclusion: P. ginseng roots' phenolic acid monomers can safely inhibit melanin production by bidirectionally regulating melanin synthase transcription. Furthermore, they reduced MITF expression via MC1R/cAMP/PKA signaling pathway and enhanced MITF post-translational modification via Wnt/mitogen-activated protein kinase signaling pathway.

• BMB Reports
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• v.56 no.4
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• pp.252-257
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• 2023

The hypoxia-inducible factor-1α (HIF-1α) is a key regulator of hypoxic stress under physiological and pathological conditions. HIF-1α protein stability is tightly regulated by the ubiquitin-proteasome system (UPS) and autophagy in normoxia, hypoxia, and the tumor environment to mediate the hypoxic response. However, the mechanisms of how the UPS and autophagy interplay for HIF-1α proteostasis remain unclear. Here, we found a HIF-1α species propionylated at lysine (K) 709 by p300/CREB binding protein (CBP). HIF-1α stability and the choice of degradation pathway were affected by HIF-1α propionylation. K709-propionylation prevented HIF-1α from degradation through the UPS, while activated chaperon-mediated autophagy (CMA) induced the degradation of propionylated and nonpropionylated HIF-1α. CMA contributed to HIF-1α degradation in both normoxia and hypoxia. Furthermore, the pan-cancer analysis showed that CMA had a significant positive correlation with the hypoxic signatures, whereas SIRT1, responsible for K709-depropionylation correlated negatively with them. Altogether, our results revealed a novel mechanism of HIF-1α distribution into two different degradation pathways.

• Biomolecules & Therapeutics
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• v.18 no.1
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• pp.39-47
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• 2010

Brain-derived neurotrophic factor (BDNF) is a neurotrophic factor involved in neuronal differentiation, plasticity, survival and regeneration. BDNF draws massive attention mainly due to the potential as a therapeutic target in neurological diseases such as depression and Alzheimer's disease. In a primary screening for the natural compounds enhancing BDNF release from cultured rat primary cortical neuron, we found that compounds such as baicalein, tanshinone IIa, cinnamic acid, epiberberine, genistein and wogonin among many others increased BDNF release. All the compounds at $0.1{\mu}M$ of concentration barely showed stimulatory effect on BDNF induction, however, their combination (mixture 1; baicalein, tanshinone IIa and cinnamic acid, mixture 2; epiberberine, genistein and wogonin) showed synergistic increase in BDNF release as well as mRNA and protein expression. The level of BDNF expression was comparable to the maximum BDNF stimulation attainable by a positive control oroxylin A ($20{\mu}M$) without cell toxicity as determined by MTT analysis. Both mixtures synergistically increased the phosphorylation of extracellular signal-regulated kinase (ERK) as well as cAMP response element binding protein (CREB), an immediate and essential regulator of BDNF expression. Similar to these results, mixture of these compounds synergistically inhibited the up-regulation of inducible nitric oxide synthase (iNOS) induced by lipopolysaccharide treatments in rat primary astrocytes. These results suggest that the combinatorial treatment of natural compounds in lower concentration might be a useful strategy to obtain sufficient BDNF stimulation in neurological disease condition such as depression, while minimizing potential side effects and toxicity of higher concentration of a single compound.

• Journal of Life Science
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• v.25 no.4
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• pp.473-480
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• 2015

The endoplasmic reticulum (ER) in the eukaryotic cells is the first compartment in the secretory pathway. Almost secretory proteins and membrane proteins are secreted through the ER, in which post-translational modifications occur via diverse signals from the ER lumen to the cytoplasm and nucleus. Only then are correctly-folded proteins secreted to the outside cells. Unfolded proteins that accumulate in the ER cause a kind of intracellular stress, ER stress, and activate an unfolded protein response (UPR) system. The 3 major transducers of the UPR are inositol requiring 1 (IRE1), PKR-like ER kinase (PERK) and activating transcription factor 6 (ATF6), all of which are ER transmembrane proteins. Recently, novel types of a new ATF6 family have been identified. Those commonly have an ER-transmembrane domain, a transcription-activation domain and a basic leucine zipper (bZIP) domain―Luman, OASIS, BBF2H7, CREBH and CREB4. Each factor functions by regulating the UPR in specific organs and tissues. Although the detailed molecular mechanisms of OASIS family members are unknown, in this study we comprehensively introduce these molecular signals.

• Proceedings of the PSK Conference
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• 2003.04a
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• pp.140.2-140.2
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• 2003

Sauchinone, a lignan isolated from Saururus chinensis (Saururaceae), is a diastereomeric lignan with cytoprotective and antioxidant activities in cultured hepatocytes. The effects of sauchinone on the iNOS, TNF-$\alpha$ and COX-2 gene expression and on the activation of transcription factors, NF-$\kappa$B, C/EBP, AP-1 and CREB were determined in Raw264.7 cells as part of the studies on its anti-inflammatory effects. (omitted)

• Journal of Ginseng Research
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• v.47 no.2
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• pp.349-351
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• 2023

• Microbiology and Biotechnology Letters
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• v.47 no.1
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• pp.148-157
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• 2019

A 70% ethanol extract of Erigeron annuus (L.) Pers. was investigated for its whitening activity for application as a functional ingredient in cosmetic products. At the E. annuus extract concentration of $100{\mu}g/ml$, the electron-donating ability was found to be 67.83%, the tyrosinase inhibitory effect (related to skin-whitening) was 69%, the elastase inhibitory effect (related to skin-wrinkling) was 69%, and the astringent effect was 80%. The $ABTS^+$ radical-scavenging ability was 87% at the $500{\mu}g/ml$ concentration. In the cell viability test measured on melanoma cells, 96% of the cells treated with $100{\mu}g/ml$ of the extract were viable. According to the western blot results, the protein expression of the microphthalmia-associated transcription factor (MITF), tyrosinase, tyrosinase-related protein (TRP)-1, and TRP-2 was decreased by 60.22%, 47.83%, 54.79%, and 67.88%, respectively, at the extract concentration of $100{\mu}g/ml$. The protein expression of phosphorylated extracellular signal regulated kinase (p-ERK) and phosphorylated cAMP response element-binding protein (p-CREB) was decreased with increasing concentrations of the extract. Reverse transcription-polymerase chain reaction of the extract showed that the mRNA expression of MITF, tyrosinase, TRP-1, and TRP-2 was decreased by 86.51%, 85.22%, 74.26%, and 66.66%, respectively, at $100{\mu}g/ml$ extract concentration. The findings suggest that the 70% ethanol extract from E. annuus (L.) Pers. has potential as a cosmeceutical ingredient with whitening effect.