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Rosa davurica Pall., is mainly distributed in Korea, Japan, northeastern China, southeastern Siberia, and eastern Asia. It has been extensively used to treat various kinds of diseases by reason of the significant antioxidant, antiviral and anti-inflammatory activities. However, the pharmacological mechanism of Rosa davurica Pall. in atopic dermatitis (AD) is still ill defined and poorly understood. This study was to examine the anti-inflammatory effects and its mechanism on AD of Rosa davurica Pall. leaves (RDL). To evaluate the therapeutic potential of RDL against AD, we have investigated the effects of RDL on the inflammatory reactions and the productions of inflammatory chemokines and cytokines that were induced by tumor necrosis factor-α (TNF-α)/interferon-γ (IFN-γ) in HaCaT cells. Futhermore, we examined the effects of RDL on the signaling pathways of mitogen-activated protein kinase (MAPK) and nuclear factor-kappa B (NF-κB). For the in-vivo studies, RDL extract was topically applied to the dinitrochlorobenzene (DNCB)-induced AD mice, then its therapeutic effect was evaluated physiologically and morphologically. After the stimulation of HaCaT cells with TNF-α/IFN-γ, RDL considerably reduced the release of inflammatory mediators such as nitric oxide (NO), PEG2 and other cytokines. RDL also reduced the phosphorylations of MAPK and NF-κB in TNF-α/IFN-γ-stimulated HaCaT cells. In vivo topical application of RDL to DNCB-induced AD mice significantly reduced the dorsal skin and ear thickness, clinical dermatitis severity, and mast cells. Treatment with RDL also markedly decreased the levels of serum IgE, IL-6 and the number of WBCs in the blood. Our studies indicate that RDL inhibits the AD-like skin lesions by modulating skin inflammation. Consequently, these results suggest that RDL may be served as a possible alternative therapeutic treatment for skin disorder such as AD.
Du Hyeon Hwang; Phil-Ok Koh; Changkeun Kang; Euikyung Kim. Rosa davurica Pall. improves DNCB-induced atopic dermatitis in mice and regulated TNF-Alpa/IFN-gamma-induced skin inflammatory responses in HaCaT cells. Phytomedicine 2021, 91, 153708 .
AMA StyleDu Hyeon Hwang, Phil-Ok Koh, Changkeun Kang, Euikyung Kim. Rosa davurica Pall. improves DNCB-induced atopic dermatitis in mice and regulated TNF-Alpa/IFN-gamma-induced skin inflammatory responses in HaCaT cells. Phytomedicine. 2021; 91 ():153708.
Chicago/Turabian StyleDu Hyeon Hwang; Phil-Ok Koh; Changkeun Kang; Euikyung Kim. 2021. "Rosa davurica Pall. improves DNCB-induced atopic dermatitis in mice and regulated TNF-Alpa/IFN-gamma-induced skin inflammatory responses in HaCaT cells." Phytomedicine 91, no. : 153708.
Jellyfish venom is well known for its local skin toxicities and various lethal accidents. The main symptoms of local jellyfish envenomation include skin lesions, burning, prickling, stinging pain, red, brown, or purplish tracks on the skin, itching, and swelling, leading to dermonecrosis and scar formation. However, the molecular mechanism behind the action of jellyfish venom on human skin cells is rarely understood. In the present study, we have treated the human HaCaT keratinocyte with Nemopilema nomurai jellyfish venom (NnV) to study detailed mechanisms of actions behind the skin symptoms after jellyfish envenomation. Using two-dimensional gel electrophoresis (2-DE) and matrix-assisted laser desorption-ionization time-of-flight mass spectrometry (MALDI-TOF/MS), cellular changes at proteome level were examined. The treatment of NnV resulted in the decrease of HaCaT cell viability in a concentration-dependent manner. Using NnV (at IC50), the proteome level alterations were determined at 12 h and 24 h after the venom treatment. Briefly, 70 protein spots with significant quantitative changes were picked from the gels for MALDI-TOF/MS. In total, 44 differentially abundant proteins were successfully identified, among which 19 proteins were increased, whereas 25 proteins were decreased in the abundance levels comparing with their respective control spots. DAPs involved in cell survival and development (e.g., Plasminogen, Vinculin, EMILIN-1, Basonuclin2, Focal adhesion kinase 1, FAM83B, Peroxisome proliferator-activated receptor-gamma co-activator 1-alpha) decreased their expression, whereas stress or immune response-related proteins (e.g., Toll-like receptor 4, Aminopeptidase N, MKL/Myocardin-like protein 1, hypoxia up-regulated protein 1, Heat shock protein 105 kDa, Ephrin type-A receptor 1, with some protease (or peptidase) enzymes) were up-regulated. In conclusion, the present findings may exhibit some possible key players during skin damage and suggest therapeutic strategies for preventing jellyfish envenomation.
Indu Choudhary; Duhyeon Hwang; Jinho Chae; Wonduk Yoon; Changkeun Kang; Euikyung Kim. Proteomic Changes during the Dermal Toxicity Induced by Nemopilema nomurai Jellyfish Venom in HaCaT Human Keratinocyte. Toxins 2021, 13, 311 .
AMA StyleIndu Choudhary, Duhyeon Hwang, Jinho Chae, Wonduk Yoon, Changkeun Kang, Euikyung Kim. Proteomic Changes during the Dermal Toxicity Induced by Nemopilema nomurai Jellyfish Venom in HaCaT Human Keratinocyte. Toxins. 2021; 13 (5):311.
Chicago/Turabian StyleIndu Choudhary; Duhyeon Hwang; Jinho Chae; Wonduk Yoon; Changkeun Kang; Euikyung Kim. 2021. "Proteomic Changes during the Dermal Toxicity Induced by Nemopilema nomurai Jellyfish Venom in HaCaT Human Keratinocyte." Toxins 13, no. 5: 311.
This article reports data associated with Prakash et al. [1]. Nemopilema nomurai jellyfish venom (NnV) can lead to neurotoxicity in zebrafish (Danio rerio) model. In the present study, zebrafish were treated with NnV by intraperitoneal injection and the swimming behavior of each fish was evaluated using a score scale. The dose of NnV in each treatment group was based on the protein concentration of NnV. Swimming is the main locomotory movements in the fishes. NnV modulated the swimming behavior of Danio rerio in a dose-dependent manner. In this article provided data are directly related to the previously published research article – “Danio rerio as an alternative vertebrate model for jellyfish venom study: the toxinological aspects of Nemopilema nomurai venom” [1] where the downregulation of acetylcholinesterase activity as well as histopathological alterations were observed from the brain of Danio rerio treated with NnV. Here we provide datasets, including mortality rate table, swimming behavior graph, and videos of zebrafish after NnV envenomation.
Ramachandran Loganathan Mohan Prakash; Du Hyeon Hwang; Il-Hwa Hong; Jinho Chae; Changkeun Kang; Euikyung Kim. Dataset of Swimming behavioral alterations in Danio rerio by Nemopilema nomurai jellyfish venom. Data in Brief 2021, 34, 106721 .
AMA StyleRamachandran Loganathan Mohan Prakash, Du Hyeon Hwang, Il-Hwa Hong, Jinho Chae, Changkeun Kang, Euikyung Kim. Dataset of Swimming behavioral alterations in Danio rerio by Nemopilema nomurai jellyfish venom. Data in Brief. 2021; 34 ():106721.
Chicago/Turabian StyleRamachandran Loganathan Mohan Prakash; Du Hyeon Hwang; Il-Hwa Hong; Jinho Chae; Changkeun Kang; Euikyung Kim. 2021. "Dataset of Swimming behavioral alterations in Danio rerio by Nemopilema nomurai jellyfish venom." Data in Brief 34, no. : 106721.
Ramachandran Loganathan Mohan Prakash; Du Hyeon Hwang; Il-Hwa Hong; Jinho Chae; Changkeun Kang; Euikyung Kim. Corrigendum to “Danio rerio as an alternative vertebrate model for jellyfish venom study: The toxinological aspects of Nemopilema nomurai venom” [Toxicol. Lett. 335 (2020) 91-97]. Toxicology Letters 2020, 339, 20 -22.
AMA StyleRamachandran Loganathan Mohan Prakash, Du Hyeon Hwang, Il-Hwa Hong, Jinho Chae, Changkeun Kang, Euikyung Kim. Corrigendum to “Danio rerio as an alternative vertebrate model for jellyfish venom study: The toxinological aspects of Nemopilema nomurai venom” [Toxicol. Lett. 335 (2020) 91-97]. Toxicology Letters. 2020; 339 ():20-22.
Chicago/Turabian StyleRamachandran Loganathan Mohan Prakash; Du Hyeon Hwang; Il-Hwa Hong; Jinho Chae; Changkeun Kang; Euikyung Kim. 2020. "Corrigendum to “Danio rerio as an alternative vertebrate model for jellyfish venom study: The toxinological aspects of Nemopilema nomurai venom” [Toxicol. Lett. 335 (2020) 91-97]." Toxicology Letters 339, no. : 20-22.
Nemopilema nomurai venom (NnV) is severely toxic to many organisms. However, the mechanism of its poisoning has not been properly understood yet. The present work demonstrates that zebrafish (Danio rerio) is an alternative vertebrate model for studying NnV jellyfish venom for the first time. In this model, NnV appears to cause severe hemorrhage and inflammation in cardiopulmonary regions of zebrafish. NnV also altered the swimming behavior of zebrafish accompanied by a significant downregulation of acetylcholinesterase (AChE) activity in brain tissues. Histopathological changes observed for various organs of D. rerio caused by NnV corresponded to an increase in lactate dehydrogenase (LDH) activity in tissues. NnV also significantly altered glutathione S-transferase (GST) activity in cardiopulmonary and brain tissues of D. rerio. SDS-PAGE revealed many protein bands of NnV of various sizes after silver staining. Taken together, these results indicate that Danio rerio can be a useful alternative animal model for jellyfish venom toxicology studies. Findings of the present study also suggest that Danio rerio could be used to develop an effective treatment strategy and discover the mechanism of action of jellyfish venom envenomation.
Ramachandran Loganathan Mohan Prakash; Du Hyeon Hwang; Il-Hwa Hong; Jinho Chae; Changkeun Kang; Euikyung Kim. Danio rerio as an alternative vertebrate model for jellyfish venom study: The toxinological aspects of Nemopilema nomurai venom. Toxicology Letters 2020, 335, 91 -97.
AMA StyleRamachandran Loganathan Mohan Prakash, Du Hyeon Hwang, Il-Hwa Hong, Jinho Chae, Changkeun Kang, Euikyung Kim. Danio rerio as an alternative vertebrate model for jellyfish venom study: The toxinological aspects of Nemopilema nomurai venom. Toxicology Letters. 2020; 335 ():91-97.
Chicago/Turabian StyleRamachandran Loganathan Mohan Prakash; Du Hyeon Hwang; Il-Hwa Hong; Jinho Chae; Changkeun Kang; Euikyung Kim. 2020. "Danio rerio as an alternative vertebrate model for jellyfish venom study: The toxinological aspects of Nemopilema nomurai venom." Toxicology Letters 335, no. : 91-97.
Jellyfish stingings are currently raising serious public health concerns around the world. Hence, the search for an effective first aid reagent for the envenomation has been the goal of many investigators in the field. There have been a few previous reports of in vivo as well as in vivo studies suggesting the metalloproteinase activity of scyphozoan jellyfish venom, such as N. nomurai venom (NnV), plays a major role in the pathogenesis. These results have inspired us to develop a metalloproteinase inhibitor as a candidate for the treatment of Scyphozoan jellyfish envenomation. It has been previously demonstrated that the major polyphenol component in green tea, epigallocatechin-3-gallate (EGCG), can inhibit metalloproteinase activity of snake venoms. In fact, plant polyphenols as potential therapeutics have been shown to exert positive effects on neutralizing snake venoms and toxins. In the present study, we found that EGCG significantly inhibits the toxic proteases of NnV in a concentration-dependent manner. Human keratinocyte (HaCaT) and Human dermal fibroblast (HDF) cell culture studies showed that EGCG treatment can protect the cells from NnV-induced cytotoxicity which has been accompanied by the down-regulation of human matrix metalloproteinase (MMP)-2 and -9. Simulated rat NnV envenomation study disclosed that topical treatments with EGCG considerably ameliorated the progression of the dermonecrotic lesions caused by NnV. EGCG also reduced the activitions of tissue MMP-2 and MMP-9, which seem to be crucial players in the dermal toxic responses induced by NnV. Therefore, we propose that EGCG might be an effective therapeutic agent for the treatment of cutaneoous jellyfish symptoms.
Du Hyeon Hwang; Hyunkyoung Lee; Indu Choudhary; Changkeun Kang; Jinho Chae; Euikyung Kim. Protective effect of epigallocatechin-3-gallate (EGCG) on toxic metalloproteinases-mediated skin damage induced by Scyphozoan jellyfish envenomation. Scientific Reports 2020, 10, 1 -10.
AMA StyleDu Hyeon Hwang, Hyunkyoung Lee, Indu Choudhary, Changkeun Kang, Jinho Chae, Euikyung Kim. Protective effect of epigallocatechin-3-gallate (EGCG) on toxic metalloproteinases-mediated skin damage induced by Scyphozoan jellyfish envenomation. Scientific Reports. 2020; 10 (1):1-10.
Chicago/Turabian StyleDu Hyeon Hwang; Hyunkyoung Lee; Indu Choudhary; Changkeun Kang; Jinho Chae; Euikyung Kim. 2020. "Protective effect of epigallocatechin-3-gallate (EGCG) on toxic metalloproteinases-mediated skin damage induced by Scyphozoan jellyfish envenomation." Scientific Reports 10, no. 1: 1-10.
Acne, also known as acne vulgaris, is a common disorder of human skin involving the sebaceous gland and Propionibacterium acnes (P. acnes). Although there are a number of treatments suggested for acne, many of them have limitations in their safety and have efficacy issues. Therefore, there is a high demand to develop safe and effective novel acne treatments. In the present study, we demonstrate the protective effects of Rosa davurica Pall. leaves (RDL) extract against P. acnes-induced inflammatory responses in vitro and in vivo. The results showed that RDL dose-dependently inhibited the growth of skin bacteria, including P. acnes (KCTC3314) and aerobic Staphylococcus aureus (KCTC1621) or Staphylococcus epidermidis (KCTC1917). The downregulation of proinflammatory cytokines by RDL appears to be mediated by blocking the phosphorylations of mitogen-activated protein kinase (MAPK) and subsequent nuclear factor-kappa B (NF-κB) pathways in P. acnes-stimulated HaCaT cells. In a mouse model of acne vulgaris, histopathological changes were examined in the P. acnes-induced mouse ear edema. The concomitant intradermal injection of RDL resulted in the reduction of ear swelling in mice along with microabscess but exerted no cytotoxic effects for skin cells. Instrumental analysis demonstrated there were seven major components in the RDL extract, and they seemed to have important roles in the anti-inflammatory and antimicrobial effects of RDL. Conclusively, our present work showed for the first time that RDL has anti-inflammatory and antimicrobial effects against P. acnes, suggesting RDL as a promising novel strategy for the treatment of acne, including natural additives in anti-acne cosmetics or pharmaceutical products.
Du Hyeon Hwang; Dong Yeol Lee; Phil-Ok Koh; Hye Ryeon Yang; Changkeun Kang; Euikyung Kim. Rosa davurica Pall. Improves Propionibacterium acnes-Induced Inflammatory Responses in Mouse Ear Edema Model and Suppresses Pro-Inflammatory Chemokine Production via MAPK and NF-κB Pathways in HaCaT Cells. International Journal of Molecular Sciences 2020, 21, 1717 .
AMA StyleDu Hyeon Hwang, Dong Yeol Lee, Phil-Ok Koh, Hye Ryeon Yang, Changkeun Kang, Euikyung Kim. Rosa davurica Pall. Improves Propionibacterium acnes-Induced Inflammatory Responses in Mouse Ear Edema Model and Suppresses Pro-Inflammatory Chemokine Production via MAPK and NF-κB Pathways in HaCaT Cells. International Journal of Molecular Sciences. 2020; 21 (5):1717.
Chicago/Turabian StyleDu Hyeon Hwang; Dong Yeol Lee; Phil-Ok Koh; Hye Ryeon Yang; Changkeun Kang; Euikyung Kim. 2020. "Rosa davurica Pall. Improves Propionibacterium acnes-Induced Inflammatory Responses in Mouse Ear Edema Model and Suppresses Pro-Inflammatory Chemokine Production via MAPK and NF-κB Pathways in HaCaT Cells." International Journal of Molecular Sciences 21, no. 5: 1717.
Several eradication programs have been developed and executed to curb alien invasive species that tend to damage the ecological environments they colonize; however, only few studies have evaluated the utilization of carcasses of these species after eradication. Nutria (Myocastor coypus) is an invasive rodent species targeted by eradication programs in many countries. We noted that nutria produce large amounts of ursodeoxycholic acid (UDCA) in their bile. UDCA is a unique component responsible for the anti-inflammatory and hepatoprotective effects exerted by bear bile. Therefore, we sought to examine the medicinal utility of nutria carcasses by investigating the hepatoprotective effect of their bile in mice. C57BL/6 mice were injected with thioacetamide (TAA), which induced liver damage by increasing Kupffer cell infiltration. Administration of nutria bile reduced hepatic inflammation, improved hepatic function, and increased the levels of senescence marker protein 30 (an indicator of hepatocyte viability). Our results show that nutria bile exerts protective effects against TAA-induced liver injury in mice, suggesting that nutria carcasses may be used for the treatment of liver injuries.
Joo-Yeon Kong; Seong-Chan Yeon; Hu Jang Lee; Changkeun Kang; Jin-Kyu Park; Kyu-Shik Jeong; Il-Hwa Hong. Protective Effects of Nutria Bile against Thioacetamide-Induced Liver Injury in Mice. Evidence-Based Complementary and Alternative Medicine 2019, 2019, 6059317 -10.
AMA StyleJoo-Yeon Kong, Seong-Chan Yeon, Hu Jang Lee, Changkeun Kang, Jin-Kyu Park, Kyu-Shik Jeong, Il-Hwa Hong. Protective Effects of Nutria Bile against Thioacetamide-Induced Liver Injury in Mice. Evidence-Based Complementary and Alternative Medicine. 2019; 2019 ():6059317-10.
Chicago/Turabian StyleJoo-Yeon Kong; Seong-Chan Yeon; Hu Jang Lee; Changkeun Kang; Jin-Kyu Park; Kyu-Shik Jeong; Il-Hwa Hong. 2019. "Protective Effects of Nutria Bile against Thioacetamide-Induced Liver Injury in Mice." Evidence-Based Complementary and Alternative Medicine 2019, no. : 6059317-10.
Nowadays, proliferation of jellyfish has become a severe matter in many coastal areas around the world. Jellyfish Nemopilema nomurai is one of the most perilous organisms and leads to significant deleterious outcomes such as harm to the fishery, damage the coastal equipment, and moreover, its envenomation can be hazardous to the victims. Till now, the components of Nemopilema nomurai venom (NnV) are unknown owing to scant transcriptomics and genomic data. In the current research, we have explored a proteomic approach to identify NnV components and their interrelation with pathological effects caused by the jellyfish sting. Altogether, 150 proteins were identified, comprising toxins and other distinct proteins that are substantial in nematocyst genesis and nematocyte growth by employing two-dimensional gel electrophoresis and matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI/TOF/MS). The identified toxins are phospholipase A2, phospholipase D Li Sic Tox beta IDI, a serine protease, putative Kunitz-type serine protease inhibitor, disintegrin and metalloproteinase, hemolysin, leukotoxin, three finger toxin MALT0044C, allergens, venom prothrombin activator trocarin D, tripeptide Gsp 9.1, and along with other toxin proteins. These toxins are relatively well characterized in the venoms of other poisonous species to induce pathogenesis, hemolysis, inflammation, proteolysis, blood coagulation, cytolysis, hemorrhagic activity, and type 1 hypersensitivity, suggesting that these toxins in NnV can also cause similar deleterious consequences. Our proteomic works indicate that NnV protein profile represents valuable source which leads to better understanding the clinical features of the jellyfish stings. As one of the largest jellyfish in the world, Nemopilema nomurai sting is considered to be harmful to humans due to its potent toxicity. The identification and functional characterization of its venom components have been poorly described and are beyond our knowledge. Here is the first report demonstrating the methodical overview of NnV proteomics research, providing significant information to understand the mechanism of NnV envenomation. Our proteomics findings can provide a platform for novel protein discovery and development of practical ways to deal with jellyfish stings on human beings.
Indu Choudhary; Du Hyeon Hwang; Hyunkyoung Lee; Won Duk Yoon; Jinho Chae; Chang Hoon Han; Seungshic Yum; Changkeun Kang; Euikyung Kim. Proteomic Analysis of Novel Components of Nemopilema nomurai Jellyfish Venom: Deciphering the Mode of Action. Toxins 2019, 11, 153 .
AMA StyleIndu Choudhary, Du Hyeon Hwang, Hyunkyoung Lee, Won Duk Yoon, Jinho Chae, Chang Hoon Han, Seungshic Yum, Changkeun Kang, Euikyung Kim. Proteomic Analysis of Novel Components of Nemopilema nomurai Jellyfish Venom: Deciphering the Mode of Action. Toxins. 2019; 11 (3):153.
Chicago/Turabian StyleIndu Choudhary; Du Hyeon Hwang; Hyunkyoung Lee; Won Duk Yoon; Jinho Chae; Chang Hoon Han; Seungshic Yum; Changkeun Kang; Euikyung Kim. 2019. "Proteomic Analysis of Novel Components of Nemopilema nomurai Jellyfish Venom: Deciphering the Mode of Action." Toxins 11, no. 3: 153.
Rumex japonicus Houtt. (RJ) is traditionally used in folk medicines to treat patients suffering from skin disease in Korea and other parts of East Asia. However, the beneficial effect of RJ extract on atopic dermatitis (AD) has not been thoroughly examined. Therefore, this study aimed to investigate the anti-inflammatory effects of RJ on AD in vitro and in vivo. Treatment with RJ inhibited the phosphorylation of mitogen-activated protein kinase (MAPK) as well as the activation of nuclear factor-kappa B (NF-κB) in tumor necrosis factor-α (TNF-α) stimulated in HaCaT cells. The five-week-old Balb/c mice were used as an AD-like mouse model by treating them with 1-chloro-2, 4-dinitrobenzene (DNCB). Topical administration of RJ to DNCB-treated mice significantly reduced clinical dermatitis severity, epidermal thickness, and decreased mast cell and eosinophil infiltration into skin and ear tissue. These results suggest that RJ inhibits the development of AD-like skin lesions by regulating the skin inflammation responses in HaCaT cells and Balb/c mice. Thus, RJ may be a potential therapeutic agent for AD.
Hye Ryeon Yang; Hyunkyoung Lee; Jong-Hyun Kim; Il-Hwa Hong; Du Hyeon Hwang; Il Rae Rho; Gon Sup Kim; Euikyung Kim; Changkeun Kang. Therapeutic Effect of Rumex japonicus Houtt. on DNCB-Induced Atopic Dermatitis-Like Skin Lesions in Balb/c Mice and Human Keratinocyte HaCaT Cells. Nutrients 2019, 11, 573 .
AMA StyleHye Ryeon Yang, Hyunkyoung Lee, Jong-Hyun Kim, Il-Hwa Hong, Du Hyeon Hwang, Il Rae Rho, Gon Sup Kim, Euikyung Kim, Changkeun Kang. Therapeutic Effect of Rumex japonicus Houtt. on DNCB-Induced Atopic Dermatitis-Like Skin Lesions in Balb/c Mice and Human Keratinocyte HaCaT Cells. Nutrients. 2019; 11 (3):573.
Chicago/Turabian StyleHye Ryeon Yang; Hyunkyoung Lee; Jong-Hyun Kim; Il-Hwa Hong; Du Hyeon Hwang; Il Rae Rho; Gon Sup Kim; Euikyung Kim; Changkeun Kang. 2019. "Therapeutic Effect of Rumex japonicus Houtt. on DNCB-Induced Atopic Dermatitis-Like Skin Lesions in Balb/c Mice and Human Keratinocyte HaCaT Cells." Nutrients 11, no. 3: 573.
Nemopilema nomurai is a giant jellyfish that blooms in East Asian seas. Recently, N. nomurai venom (NnV) was characterized from a toxicological and pharmacological point of view. A mild dose of NnV inhibits the growth of various kinds of cancer cells, mainly hepatic cancer cells. The present study aims to identify the potential therapeutic targets and mechanism of NnV in the growth inhibition of cancer cells. Human hepatocellular carcinoma (HepG2) cells were treated with NnV, and its proteome was analyzed using two-dimensional gel electrophoresis, followed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI/TOF/MS). The quantity of twenty four proteins in NnV-treated HepG2 cells varied compared to non-treated control cells. Among them, the amounts of fourteen proteins decreased and ten proteins showed elevated levels. We also found that the amounts of several cancer biomarkers and oncoproteins, which usually increase in various types of cancer cells, decreased after NnV treatment. The representative proteins included proliferating cell nuclear antigen (PCNA), glucose-regulated protein 78 (GRP78), glucose-6-phosphate dehydrogenase (G6PD), elongation factor 1γ (EF1γ), nucleolar and spindle-associated protein (NuSAP), and activator of 90 kDa heat shock protein ATPase homolog 1 (AHSA1). Western blotting also confirmed altered levels of PCNA, GRP78, and G6PD in NnV-treated HepG2 cells. In summary, the proteomic approach explains the mode of action of NnV as an anticancer agent. Further characterization of NnV may help to unveil novel therapeutic agents in cancer treatment.
Indu Choudhary; Hyunkyoung Lee; Min Jung Pyo; Yunwi Heo; Jinho Chae; Seung Shic Yum; Changkeun Kang; Euikyung Kim. Proteomic Investigation to Identify Anticancer Targets of Nemopilema nomurai Jellyfish Venom in Human Hepatocarcinoma HepG2 Cells. Toxins 2018, 10, 194 .
AMA StyleIndu Choudhary, Hyunkyoung Lee, Min Jung Pyo, Yunwi Heo, Jinho Chae, Seung Shic Yum, Changkeun Kang, Euikyung Kim. Proteomic Investigation to Identify Anticancer Targets of Nemopilema nomurai Jellyfish Venom in Human Hepatocarcinoma HepG2 Cells. Toxins. 2018; 10 (5):194.
Chicago/Turabian StyleIndu Choudhary; Hyunkyoung Lee; Min Jung Pyo; Yunwi Heo; Jinho Chae; Seung Shic Yum; Changkeun Kang; Euikyung Kim. 2018. "Proteomic Investigation to Identify Anticancer Targets of Nemopilema nomurai Jellyfish Venom in Human Hepatocarcinoma HepG2 Cells." Toxins 10, no. 5: 194.
Because jellyfish are capable of provoking envenomation in humans, they are considered hazardous organisms. Although the effects of their toxins are a matter of concern, information on the venom components, biological activity and pathological mechanisms are still scarce. Therefore, the aim of the present study was to investigate a serine protease component of Nemopilema nomurai jellyfish venom (NnV) and unveil its characteristics. To determine the relationship between fibrinolytic activity of NnV and the serine protease, fibrin zymography was performed using metalloprotease and serine protease inhibitors. The biochemical characterization of serine proteases of NnV were determined by the amidolytic assay. Fractions with fibrinolytic activity were obtained by DEAE cation exchange column. NnV displayed fibrinolytic activities with molecular masses of approximately 70, 35, 30, and 28 kDa. The fibrinolytic activity of NnV was completely obliterated by phenylmethylsulfonyl fluoride, a prototype serine protease inhibitor. Based on amidolytic assays using chromogenic substrates specific for various kinds of serine proteases, NnV predominantly manifested a chymotrypsin-like feature. Its activity was completely eliminated at low pH (< 6) and high temperatures (> 37 °C). Some metal ions (Co2+, Cu2+, Zn2+ and Ni2+) strongly suppressed its fibrinolytic activity, while others (Ca2+ and Mg2+) failed to do so. Isolation of a serine protease with fibrionolytic activity from NnV revealed that only p3 showed the fibrinolytic activity, which was completely inhibited by PMSF. The present study showed that N. nomurai jellyfish venom has a chymotrypsin-like serine protease with fibrinolytic activity. Such information might be useful for developing clinical management of jellyfish envenomation and pharmacological agents with therapeutic potential for thrombotic diseases in the future.
Seong Kyeong Bae; Hyunkyoung Lee; Yunwi Heo; Min Jung Pyo; Indu Choudhary; Chang Hoon Han; Won Duk Yoon; Changkeun Kang; Euikyung Kim. In vitro characterization of jellyfish venom fibrin(ogen)olytic enzymes from Nemopilema nomurai. Journal of Venomous Animals and Toxins including Tropical Diseases 2017, 23, 1 -9.
AMA StyleSeong Kyeong Bae, Hyunkyoung Lee, Yunwi Heo, Min Jung Pyo, Indu Choudhary, Chang Hoon Han, Won Duk Yoon, Changkeun Kang, Euikyung Kim. In vitro characterization of jellyfish venom fibrin(ogen)olytic enzymes from Nemopilema nomurai. Journal of Venomous Animals and Toxins including Tropical Diseases. 2017; 23 (1):1-9.
Chicago/Turabian StyleSeong Kyeong Bae; Hyunkyoung Lee; Yunwi Heo; Min Jung Pyo; Indu Choudhary; Chang Hoon Han; Won Duk Yoon; Changkeun Kang; Euikyung Kim. 2017. "In vitro characterization of jellyfish venom fibrin(ogen)olytic enzymes from Nemopilema nomurai." Journal of Venomous Animals and Toxins including Tropical Diseases 23, no. 1: 1-9.
Various kinds of animal venoms and their components have been widely studied for potential therapeutic applications. This study evaluated whether Nemopilema nomurai jellyfish venom (NnV) has anticancer activity. NnV strongly induced cytotoxicity of HepG2 cells through apoptotic cell death, as demonstrated by alterations of chromatic morphology, activation of procaspase-3, and an increase in the Bax/Bcl-2 ratio. Furthermore, NnV inhibited the phosphorylation of PI3K, PDK1, Akt, mTOR, p70S6K, and 4EBP1, whereas it enhanced the expression of p-PTEN. Interestingly, NnV also inactivated the negative feedback loops associated with Akt activation, as demonstrated by downregulation of Akt at Ser473 and mTOR at Ser2481. The anticancer effect of NnV was significant in a HepG2 xenograft mouse model, with no obvious toxicity. HepG2 cell death by NnV was inhibited by tetracycline, metalloprotease inhibitor, suggesting that metalloprotease component in NnV is closely related to the anticancer effects. This study demonstrates, for the first time, that NnV exerts highly selective cytotoxicity in HepG2 cells via dual inhibition of the Akt and mTOR signaling pathways, but not in normal cells.
Hyunkyoung Lee; Seong Kyeong Bae; Munki Kim; Min Jung Pyo; MinKyung Kim; Sujeoung Yang; Chung-Kil Won; Won Duk Yoon; Chang Hoon Han; Changkeun Kang; Euikyung Kim. Anticancer Effect of Nemopilema nomurai Jellyfish Venom on HepG2 Cells and a Tumor Xenograft Animal Model. Evidence-Based Complementary and Alternative Medicine 2017, 2017, 1 -12.
AMA StyleHyunkyoung Lee, Seong Kyeong Bae, Munki Kim, Min Jung Pyo, MinKyung Kim, Sujeoung Yang, Chung-Kil Won, Won Duk Yoon, Chang Hoon Han, Changkeun Kang, Euikyung Kim. Anticancer Effect of Nemopilema nomurai Jellyfish Venom on HepG2 Cells and a Tumor Xenograft Animal Model. Evidence-Based Complementary and Alternative Medicine. 2017; 2017 ():1-12.
Chicago/Turabian StyleHyunkyoung Lee; Seong Kyeong Bae; Munki Kim; Min Jung Pyo; MinKyung Kim; Sujeoung Yang; Chung-Kil Won; Won Duk Yoon; Chang Hoon Han; Changkeun Kang; Euikyung Kim. 2017. "Anticancer Effect of Nemopilema nomurai Jellyfish Venom on HepG2 Cells and a Tumor Xenograft Animal Model." Evidence-Based Complementary and Alternative Medicine 2017, no. : 1-12.
Rumex japonicusHoutt. is traditionally used as a medicinal plant to treat patients suffering from skin disease in Korea. However, the beneficial effect ofRumex japonicusHoutt. on hair growth has not been thoroughly examined. Therefore, the present study aims to investigate the hair growth-promoting effect ofRumex japonicus(RJ) Houtt. root extract using human dermal papilla cells (DPCs), HaCaT cells, and C57BL/6 mice model. RJ induced antiapoptotic and proliferative effects on DPCs and HaCaT cells by increasing Bcl-2/Bax ratio and activating cellular proliferation-related proteins, ERK and Akt. RJ also increasedβ-catenin via the inhibition of GSK-3β. In C57BL/6 mice model, RJ promoted the anagen induction and maintained its period. Immunohistochemistry analysis demonstrated that RJ upregulated Ki-67 andβ-catenin expressions, suggesting that the hair growth effect of RJ may be mediated through the reinforcement of hair cell proliferation. These results provided important insights for the possible mechanism of action of RJ and its potential as therapeutic agent to promote hair growth.
Hyunkyoung Lee; Na-Hyun Kim; Hyeryeon Yang; Seong Kyeong Bae; Yunwi Heo; Indu Choudhary; Young Chul Kwon; Jae Kuk Byun; Hyeong Jun Yim; Byung Seung Noh; Jeong-Doo Heo; Euikyung Kim; Changkeun Kang. The Hair Growth-Promoting Effect ofRumex japonicusHoutt. Extract. Evidence-Based Complementary and Alternative Medicine 2016, 2016, 1 -10.
AMA StyleHyunkyoung Lee, Na-Hyun Kim, Hyeryeon Yang, Seong Kyeong Bae, Yunwi Heo, Indu Choudhary, Young Chul Kwon, Jae Kuk Byun, Hyeong Jun Yim, Byung Seung Noh, Jeong-Doo Heo, Euikyung Kim, Changkeun Kang. The Hair Growth-Promoting Effect ofRumex japonicusHoutt. Extract. Evidence-Based Complementary and Alternative Medicine. 2016; 2016 ():1-10.
Chicago/Turabian StyleHyunkyoung Lee; Na-Hyun Kim; Hyeryeon Yang; Seong Kyeong Bae; Yunwi Heo; Indu Choudhary; Young Chul Kwon; Jae Kuk Byun; Hyeong Jun Yim; Byung Seung Noh; Jeong-Doo Heo; Euikyung Kim; Changkeun Kang. 2016. "The Hair Growth-Promoting Effect ofRumex japonicusHoutt. Extract." Evidence-Based Complementary and Alternative Medicine 2016, no. : 1-10.
An enzyme in a nematocyst extract of the Nemopilema nomurai jellyfish, caught off the coast of the Republic of Korea, catalyzed the cleavage of chymotrypsin substrate in an amidolytic kinetic assay, and this activity was inhibited by the serine protease inhibitor, phenylmethanesulfonyl fluoride. We isolated the full-length cDNA sequence of this enzyme, which contains 850 nucleotides, with an open reading frame of 801 encoding 266 amino acids. A blast analysis of the deduced amino acid sequence showed 41% identity with human chymotrypsin-like (CTRL) and the CTRL-1 precursor. Therefore, we designated this enzyme N. nomurai CTRL-1. The primary structure of N. nomurai CTRL-1 includes a leader peptide and a highly conserved catalytic triad of His69, Asp117, and Ser216. The disulfide bonds of chymotrypsin and the substrate-binding sites are highly conserved compared with the CTRLs of other species, including mammalian species. Nemopilema nomurai CTRL-1 is evolutionarily more closely related to Actinopterygii than to Scyphozoan (Aurelia aurita) or Hydrozoan (Hydra vulgaris). The N. nomurai CTRL1 was amplified from the genomic DNA with PCR using specific primers designed based on the full-length cDNA, and then sequenced. The N. nomurai CTRL1 gene contains 2434 nucleotides and four distinct exons. The 5′ donor splice (GT) and 3′ acceptor splice sequences (AG) are wholly conserved. This is the first report of the CTRL1 gene and cDNA structures in the jellyfish N. nomurai.
Yunwi Heo; Young Chul Kwon; Seong Kyeong Bae; Duhyeon Hwang; Hye Ryeon Yang; Indu Choudhary; Hyunkyoung Lee; Seungshic Yum; Kyoungsoon Shin; Won Duk Yoon; Changkeun Kang; Euikyung Kim. Cloning a Chymotrypsin-Like 1 (CTRL-1) Protease cDNA from the Jellyfish Nemopilema nomurai. Toxins 2016, 8, 205 .
AMA StyleYunwi Heo, Young Chul Kwon, Seong Kyeong Bae, Duhyeon Hwang, Hye Ryeon Yang, Indu Choudhary, Hyunkyoung Lee, Seungshic Yum, Kyoungsoon Shin, Won Duk Yoon, Changkeun Kang, Euikyung Kim. Cloning a Chymotrypsin-Like 1 (CTRL-1) Protease cDNA from the Jellyfish Nemopilema nomurai. Toxins. 2016; 8 (7):205.
Chicago/Turabian StyleYunwi Heo; Young Chul Kwon; Seong Kyeong Bae; Duhyeon Hwang; Hye Ryeon Yang; Indu Choudhary; Hyunkyoung Lee; Seungshic Yum; Kyoungsoon Shin; Won Duk Yoon; Changkeun Kang; Euikyung Kim. 2016. "Cloning a Chymotrypsin-Like 1 (CTRL-1) Protease cDNA from the Jellyfish Nemopilema nomurai." Toxins 8, no. 7: 205.