• Journal of Applied Biological Chemistry
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• v.62 no.4
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• pp.425-431
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• 2019

Platelet activation is essential for hemostatic process on blood vessel damage. However, excessive platelet activation can cause some cardiovascular diseases including atherosclerosis, thrombosis, and myocardial infarction. Scoparone is commonly encountered in the roots of genus Artemisia or Scopolia, and has been studied for its potential pharmacological properties including immunosuppression and vasorelaxation, but antiplatelet effects of scoparone have not been reported yet. We investigated the effect of scoparone on human platelet activation prompted by an analogue of thromboxane A₂, U46619. As the results, scoparone dose-dependently increased cyclic adenosine monophosphate (cAMP) levels as well as cyclic guanosine monophosphate (cGMP) levels, both being aggregation-inhibiting molecules. In addition, scoparone strongly phosphorylated inositol 1, 4, 5-triphosphate receptor (IP3R) and vasodilator-stimulated phosphoprotein (VASP), substrates of cAMP dependent kinase and cGMP dependent kinase. Phosphorylation of IP₃R by scoparone resulted in inhibition of Ca²⁺ mobilization in calcium channels in a dense tubular system, and phosphorylation of VASP by scoparone led to an inability of fibrinogen being able to bind to αIIb/β3. Finally, scoparone inhibited thrombin-induced fibrin clotting, thereby reducing thrombus formation. Therefore, we suggest that scoparone has a strong antiplatelet effect and is highly probable to prevent platelet-derived vascular disease.

• Proceedings of the Plant Resources Society of Korea Conference
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• 2022.09a
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• pp.104-104
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• 2022

Dendropanax morbiferus H. Lev has been reported to have some pharmacologic activities and also interested in functional cosmetics. We found that the water extract of D. morbiferus leaves significantly inhibited tyrosinase activity and melanin formation in α-melanocyte stimulating hormone (MSH)-induced B16-F10 cells. D. morbiferus reduced melanogenesis-related protein levels, such as microphthalmia? associated transcription factor (MITF), TRP-1, and TRP-2, without any cytotoxicity. Two active ingredients of D. morbiferus, (10E)-9,16-dihydroxyoctadeca-10,17-dien-12,14-diynoate (DMW-1) and (10E)-(?)-10,17-octadecadiene-12,14-diyne-1,9,16-triol (DMW-2) were identified by testing the anti-melanogenic effects and then by liquid chromatography-tandem mass spectrometry (LC/MS/MS) analysis. DMW-1 and DMW-2 significantly inhibited melanogenesis by the suppression of protein kinase A (PKA)/cyclic AMP (cAMP)-responsive binding protein (CREB) and p38 MAPK phosphorylation. DMW-1 showed a better inhibitory effect than DMW-2 in α-MSH-induced B16-F10 cells. D. morbiferus and its active component DMW-1 inhibited melanogenesis through the downregulation of cAMP, p-PKA/CREB, p-p38, MITF, TRP-1, TRP-2, and tyrosinase. These results indicate that D. morbiferus and DMW-1 may be useful ingredients for cosmetics and therapeutic agents for skin hyperpigmentation disorders.

• BMB Reports
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• v.45 no.12
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• pp.724-729
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• 2012

In this study, we evaluated the anti-melanogenesis effects of Caffeoylserotonin (CaS) in B16 melanoma cells. Treatment with CaS reduced the melanin content and tyrosinase (TYR) activity in B16 melanoma cells in a dose-dependent manner. CaS inhibited the expression of melanogenesis-related proteins, including microphthalmia-associated transcription factor (MITF), TYR, and tyrosinase-related protein-1 (TRP-1), but not TRP-2. ${\alpha}$-MSH is known to interact with melanocortin 1 receptor (MC1R) thus activating adenylyl cyclase and increasing intracellular cyclic AMP (cAMP) levels. Furthermore, cAMP activates extracellular signal-regulated kinase 2 (ERK2) via phosphorylation, which phosphorylates MITF, thereby targeting the transcription factor to proteasomes for degradation. The CaS reduced intracellular cAMP levels to unstimulated levels and activated ERK phosphorylation within 30 min. The ERK inhibitor PD98059 abrogated the suppressive effect of CaS on ${\alpha}$-MSH-induced melanogenesis. Based on this study, the inhibitory effects of CaS on melanogenesis are derived from the downregulation of MITF signaling via the inhibition of intracellular cAMP levels, as well as acceleration of ERK activation.

• Journal of Ginseng Research
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• v.38 no.2
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• pp.83-88
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• 2014

The adenosine monophosphate (AMP)-activated protein kinase (AMPK) is a key sensor of cellular energy. Once activated, it switches on catabolic pathways generating adenosine triphosphate (ATP), while switching off biosynthetic pathways consuming ATP. Pharmacological activation of AMPK by metformin holds a therapeutic potential to reverse metabolic abnormalities such as type 2 diabetes and nonalcoholic fatty liver disease. In addition, altered metabolism of tumor cells is widely recognized and AMPK is a potential target for cancer prevention and/or treatment. Panax ginseng is known to be useful for treatment and/or prevention of cancer and metabolic diseases including diabetes, hyperlipidemia, and obesity. In this review, we discuss the ginseng extracts and ginsenosides that activate AMPK, we clarify the various mechanisms by which they achieve this, and we discuss the evidence that shows that ginseng or ginsenosides might be useful in the treatment and/or prevention of metabolic diseases and cancer.

• Biomedical Science Letters
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• v.23 no.4
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• pp.402-405
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• 2017

Vinegar has been widely produced for a variety of industrial and domestic use as well as medicinal use. For sale of the commercial vinegar with herbal extracts, we produced an experimental black vinegar through sequential fermentation of alcohol, followed by acetic acid according to the manufacturer's procedure. To investigate the effect of anti-obesity of black vinegar on biochemical values, we evaluated enzyme activities via acetyl-CoA carboxylase (ACC), which plays a critical role in the lipid metabolism. We found that increased phosphorylated adenosine monophosphate (AMP) activated protein kinase (AMPK) and ACC in L6 mouse muscle cells treated with the manufactured vinegar. Based on the results, supplementation of experimental herbal black vinegar inactivates ACC, enhancing the phosphorylation of AMPK. Thus, the lipid oxidation and inhibitory effect of fatty acid synthesis by the black vinegar expects to facilitate the anti-obesity activity.

• Journal of the Korean Magnetic Resonance Society
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• v.16 no.1
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• pp.1-10
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• 2012

A new scalaran class sesterterpenoid with five known ones was isolated from a marine sponge Smenospongia species collected from the Gageo island, Korea. Chemical structure of all of compounds was determined on the basis of a combination of extensive 1D and 2D NMR experiments and MS data. The new compound exhibited a new functional group on a common scalaran sesterterpene skeleton, identified as 12-deacetoxy-23-deacetoxyscalarin. The compound 1 moderately showed the effect of the activation of AMP-activated protein kinase (AMPK) in L6 myoblast cell.

• Biomedical Science Letters
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• v.13 no.4
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• pp.305-311
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• 2007

cAMP-dependent protein kinase A (PKA) is the best-characterized protein kinases and has served as a model of the structure and regulation of cAMP-binding protein as well as of protein kinases. To determine the function of PKA in development, we employed the yeast two-hybrid system to screen for catalytic subunit of PKA $(C\alpha)$ interacting partners in a cDNA library from mouse embryo. A Testis-brain RNA-binding protein (TB-RBP), specifically bound to $C\alpha$. This interaction was verified by several biochemical analysis. Our findings indicate that $C\alpha$ can modulate nucleic acid binding proteins of TB-RBP and provide insights into the diverse role of PKA.

• Korean Journal of Biological Psychiatry
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• v.18 no.4
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• pp.189-196
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• 2011

Major depressive disorder is characterized by cellular and molecular alterations resulting in the depressive behavioral phenotypes. Preclinical and clinical studies have demonstrated the deficits, including cell atrophy and loss, in limbic and cortical regions of patients with depression, which is restored with antidepressants by reestablishing proper molecular changes. These findings have implicated the involvement of relevant intracellular signaling pathways in the pathogenetic and therapeutic mechanisms of depressive disorders. This review summarizes the current knowledge of the signal transduction mechanisms related to depressive disorders, including cyclic-AMP, mitogen-activated protein kinase, Akt, and protein translation initiation signaling cascades. Understanding molecular components of signaling pathways regulating neurobiology of depressive disorders may provide the novel targets for the development of more efficacious treatment modalities.

• Mycobiology
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• v.39 no.3
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• pp.143-150
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• 2011

The basidiomycete fungus Cryptococcus neoformans is an important pathogen of immunocompromised people. The ability of the fungus to sense its environment is critical for proliferation and the generation of infectious propagules, as well as for adaptation to the mammalian host during infection. The conserved cAMP/protein kinase A pathway makes an important contribution to sensing, as demonstrated by the phenotypes of mutants with pathway defects. These phenotypes include loss of the ability to mate and to elaborate the key virulence factors capsule and melanin. This review summarizes recent work that reveals new targets of the pathway, new phenotypic consequences of signaling defects, and a more detailed understanding of connections with other aspects of cryptococcal biology including iron regulation, pH sensing, and stress.

• Mycobiology
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• v.47 no.3
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• pp.346-349
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• 2019

AMP-activated protein kinase sucrose non-fermenting 1 (Snf1) is a representative regulator of energy status that maintains cellular energy homeostasis. In addition, Snf1 is involved in the mediation of environmental stress such as salt stress. Snf1 regulates metabolic enzymes such as acetyl-CoA carboxylase, indicating a possible role for Snf1 in metabolic regulation. In this article, we performed nuclear magnetic resonance (NMR) spectroscopy to profile the metabolic changes induced by Snf1 under environmental stress. According to our NMR data, we suggest that Snf1 plays a role in regulating cellular concentrations of a variety of metabolites during environmental stress responses.