• KSBB Journal
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• v.28 no.2
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• pp.137-145
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• 2013

In order to develop new skin whitening agents, we prepared the $CH_2Cl_2$ layer (NGC) and BuOH layer (NGB) of 75% EtOH extract of the Nelumbinis nucifera Gaertner. We measured their tyrosinase inhibitory activity in vitro and melanin synthesis inhibitory activity in B16-F1 melanoma cells. They did not show inhibitory activity against mushroom tyrosinase but showed melanin synthesis inhibitory activity in a dose-dependent manner. In a melanin synthesis inhibition assay, NGC and NGB suppressed melanin production up to 52% and 46% at a concentration of $100{\mu}g/mL$, respectively. To elucidate the mechanism of the inhibitory effects of NGC and NGB on melanogenesis, we measured the expression of melanogenesis-related proteins by western blot assay. As a result, NGC suppressed the expression of tyrosinase, tyrosinase related protein 1 (TRP-1), tyrosinase related protein 2 (TRP-2), phosphorylated cAMP responsive element binding (p-CREB) protein, and microphthalmia associated transcription factor (MITF). And NGB inhibited the protein expression of tyrosinase and MITF, but had no significant effect on TRP-1, TRP-2, and p-CREB expression. Moreover, NGB increased the expression of phosphorylated extracellular signal-regulated kinase (p-ERK). In addition, we examined the inhibitory effect on the glycosylation of tyrosinase. As a result, NGC and NGB inhibited the activity of ${\alpha}$-glucosidase in vitro and the glycosylation of tyrosinase in B16-F1 melanoma cells. From these results, we concluded that NGC and NGB could be used as active ingredients for skin whitening.

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

• 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.

• 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.

• Molecules and Cells
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• v.44 no.7
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• pp.493-499
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• 2021

Parkinson's disease (PD) is characterized by a progressive loss of dopamine-producing neurons in the midbrain, which results in decreased dopamine levels accompanied by movement symptoms. Oral administration of l-3,4-dihydroxyphenylalanine (L-dopa), the precursor of dopamine, provides initial symptomatic relief, but abnormal involuntary movements develop later. A deeper understanding of the regulatory mechanisms underlying dopamine homeostasis is thus critically needed for the development of a successful treatment. Here, we show that p21-activated kinase 4 (PAK4) controls dopamine levels. Constitutively active PAK4 (caPAK4) stimulated transcription of tyrosine hydroxylase (TH) via the cAMP response element-binding protein (CREB) transcription factor. Moreover, caPAK4 increased the catalytic activity of TH through its phosphorylation of S⁴⁰, which is essential for TH activation. Consistent with this result, in human midbrain tissues, we observed a strong correlation between phosphorylated PAK4^S474, which represents PAK4 activity, and phosphorylated TH^S40, which reflects their enzymatic activity. Our findings suggest that targeting the PAK4 signaling pathways to restore dopamine levels may provide a new therapeutic approach in PD.

• Journal of Ginseng Research
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• v.32 no.1
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• pp.1-7
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• 2008

Ginseng saponin has been shown to inhibit the development of dependence on morphine, cocaine, methamphetamine, but the antinarcotics effects of ginseng on nalbuphine remains still largely unknown. Ginseng administration attenuated the naloxone-induced jumping behavior on nalbuphine dependent mice. The development of morphine dependence was mediated through ${\mu}-opioid$ receptor, however, development of nalbuphine dependence was mediated through ${\kappa}-opioid$ receptor. However, it was found that the efficacy of analgesic antagonism of GTS was mediated through the serotonergic mechanism, not mediated through the opioid receptor. In addition, ginseng administration modulated cellular signal transduction in the brain. The increased NMDA receptor subunit (NR1, pNR1), phosphate extracellular signal regulated protein kinase (pERK), phosphate cAMP response element binding protein (pCREB) expression by nalbuphine was decreased by the administration of ginseng powder in cortex, hippocampus, striatum of rat brain. These results suggest that ginseng could be one of the targets of antinarcotic therapies to reduce the development of tolerance and dependence on nalbuphine as well as morphine.

• Natural Product Sciences
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• v.22 no.4
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• pp.246-251
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• 2016

This study investigated the effects of (-)-sesamin on memory deficits in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned mouse model of Parkinson's disease (PD). MPTP lesion (30 mg/kg/day, 5 days) in mice showed memory deficits including habit learning memory and spatial memory. However, treatment with (-)-sesamin (25 and 50 mg/kg) for 21 days ameliorated memory deficits in MPTP-lesioned mouse model of PD: (-)-sesamin at both doses improved decreases in the retention latency time of the passive avoidance test and the levels of dopamine, norepinephrine, 3,4-dihydroxyphenylacetic acid, and homovanillic acid, improved the decreased transfer latency time of the elevated plus-maze test, reduced the increased expression of N-methyl-D-aspartate (NMDA) receptor, and increased the reduced phosphorylation of extracellular signal-regulated kinase (ERK1/2) and cyclic AMP-response element binding protein (CREB). These results suggest that (-)-sesamin has protective effects on both habit learning memory and spatial memory deficits via the dopaminergic neurons and NMDA receptor-ERK1/2-CREB system in MPTP-lesioned mouse model of PD, respectively. Therefore, (-)-sesamin may serve as an adjuvant phytonutrient for memory deficits in PD patients.

• Journal of Physiology & Pathology in Korean Medicine
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• v.28 no.3
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• pp.337-345
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• 2014

The present study examined the effects of soybean-derived phosphatidylserine (SB-PS) on the learning and memory function and the neural activity in rats with trimethyltin (TMT)-induced memory deficits. The cognitive improving efficacy of SB-PS on the amnesic rats, which was induced by TMT, was investigated by assessing the Morris water maze test and by performing cholineacetyl transferase (ChAT), acetylcholinesterase (AChE) and cAMP responsive element binding protein (CREB) immunohistochemistry. A positron emission tomography (PET) scanning the rat brain was by performed administer 18F-Fluorodeoxy-glucose (18F-FDG). The rats with TMT injection showed impaired learning and memory of the tasks and treatment with SB-PS produced a significant improvement of the escape latency to find the platform in the Morris water maze at the 2nd day compared to that of the MCT group. In the retention test, the SB-PS group showed increased time spent around the platform compared to that of the MCT group. Consistent with the behavioral data, SB-PS 50 group significantly alleviated the loss of acetyl cholinergic neurons in the hippocampus compared to that of the MCT group. Treatment with SB-PS significantly increased the CREB positive neurons in the hippocampus as compared to that of the MCT group. In addition, SB-PS groups increased the glucose uptake in the hippocampus and SB-PS 50 group increased the glucose uptake in the frontal lobe, as compared to that of the MCT group. These results suggest that SB-PS may be useful for improving the cognitive function via regulation of cholinergic marker enzyme activity and neural activity.

• Journal of Life Science
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• v.32 no.5
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• pp.331-339
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• 2022

Melanin is a pigment produced by melanocytes to protect the skin from external stimuli, mainly ultraviolet (UV) rays. However, abnormal and excessive production of melanin causes hyperpigmentation disorders, such as freckles, age spots, and discoloration. Natural cosmeceuticals are a new trend for treating or preventing hyperpigmentation due to fewer side effects and biocompatibility. In this context, the current study focused on Cnidium japonicum, a halophyte with several uses in folk medicine, to evaluate its potential as a skin-whitening agent. The effect of C. japonicum extract (CJE) on melanin production was analyzed in melanogenesis-stimulated B16F10 melanoma cells. The results showed that CJE successfully inhibited the oxidation of tyrosine and L-DOPA by tyrosinase and subsequently decreased the production of the key enzymes responsible for melanin production: tyrosinase, tyrosinase-related protein-1, and protein-2. This effect was confirmed by decreased intracellular and extracellular melanin levels in B16F10 melanoma cells after CJE treatment. Further experiments to elucidate the action mechanism revealed that CJE treatment suppressed melanin production by inhibiting the activation of glycogen synthase kinase 3 β (GSKβ)/β-catenin and protein kinase A (PKA)/cAMP-response element binding protein (CREB) pathways, which are the upstream activators of melanogenesis. In conclusion, the present study suggests that C. japonicum is a potential natural source of bioactive substances for the development of novel cosmeceuticals that can act against hyperpigmentation.

• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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• v.24 no.1
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• pp.25-35
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• 2011

Objective : The present study was designed to assess the potential inhibitory activity of an ethanol extract of Belamcandae Rhizoma (EBR) on the alpha-melanocyte stimulating hormone (${\alpha}$-MSH)-induced melanogenesis signal pathway in B16F10 melanoma cells. Methods : Several experiments were performed in B16F10 melanoma cells. We studied tyrosinase activity, melanin content, cell-free tyrosinase activity and DOPA stain, and performed Western blots and RT-PCR for proteins and mRNA involved in melanogenesis. Results : ${\alpha}$-MSH-induced tyrosinase activity and melanin content were inhibited significantly by EBR. EBR markedly suppressed the protein expression level of tyrosinase in B16F10 melanoma cells. On the other hand, the expression of tyrosinase-related protein-1 (TRP-1) and -2 (TRP-2; DCT) were not affected by EBR. To elucidate the mechanism of the depigmenting property of EBR, we examined the involvement EBR in cAMP response element binding (CREB) protein phosphorylation and microphthalmia-associated transcription factor (MITF) signalling induced by ${\alpha}$-MSH. EBR did not regulate CREB phosphorylation and MITF expression by ${\alpha}$-MSH. Nevertheless, the mRNA expression of tyrosinase was significantly attenuated by EBR treatment without changes in the expression of TRP-1 and -2 mRNA. Conclusion : Our study suggested that EBR inhibits ${\alpha}$-MSH-induced melanogenesis by suppressing tyrosinase mRNA.