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Despite the beneficial actions of antibiotics against bacterial infections, the use of antibiotics is a crucial etiological factor influencing microbial dysbiosis-associated adverse outcomes in human health. Based on the assumption that gut microbial dysbiosis can provoke behavioral or psychological disorders, the present study evaluated anxiety-linked behavioral changes in a mouse model of streptomycin-induced dysbiosis. Measuring anxiety-like behavior using the light–dark box and elevated plus maze tests indicated that streptomycin treatment caused acute anxiety in mice. As an intervention for dysbiosis-associated distress, the probiotic strain Escherichia coli Nissle 1917 (EcN) was evaluated for its effects on streptomycin-induced behavioral changes in mice. EcN supplementation persistently ameliorated anxiety responses in mice with streptomycin-induced dysbiosis. As an outcome of anxiety, body weight changes were marginally affected by antibiotic treatment. However, mice supplemented with EcN displayed acute retardation of body weight gain, since EcN is known to reduce food intake and increase energy expenditure. Taken together, EcN treatment prominently counteracted streptomycin-induced anxiety in mice, with the metabolically beneficial retardation of body weight gain. The present model simulates psychological disorders in antibiotic users. As a promising intervention, EcN treatment can facilitate psychological relief under conditions of dysbiotic stress by blocking the pathologic gut–brain circuit.
Kiwoong Park; Suhyeon Park; Arulkumar Nagappan; Navin Ray; Juil Kim; Sik Yoon; Yuseok Moon. Probiotic Escherichia coli Ameliorates Antibiotic-Associated Anxiety Responses in Mice. Nutrients 2021, 13, 811 .
AMA StyleKiwoong Park, Suhyeon Park, Arulkumar Nagappan, Navin Ray, Juil Kim, Sik Yoon, Yuseok Moon. Probiotic Escherichia coli Ameliorates Antibiotic-Associated Anxiety Responses in Mice. Nutrients. 2021; 13 (3):811.
Chicago/Turabian StyleKiwoong Park; Suhyeon Park; Arulkumar Nagappan; Navin Ray; Juil Kim; Sik Yoon; Yuseok Moon. 2021. "Probiotic Escherichia coli Ameliorates Antibiotic-Associated Anxiety Responses in Mice." Nutrients 13, no. 3: 811.
Particulate matter (PM) is a major and the most harmful component of urban air pollution, which may adversely affect human health. PM exposure has been associated with several human diseases, notably respiratory and cardiovascular diseases. In particular, recent evidence suggests that exposure to biomass-derived PM associates with airway inflammation and can aggravate asthma and other allergic diseases. Defective or excess responsiveness in the immune system regulates distinct pathologies, such as infections, hypersensitivity, and malignancies. Therefore, PM-induced modulation of the immune system is crucial for understanding how it causes these diseases and highlighting key molecular mechanisms that can mitigate the underlying pathologies. Emerging evidence has revealed that immune responses to biomass-derived PM exposure are closely associated with the risk of diverse hypersensitivity disorders, including asthma, allergic rhinitis, atopic dermatitis, and allergen sensitization. Moreover, immunological alteration by PM accounts for increased susceptibility to infectious diseases, such as tuberculosis and coronavirus disease-2019 (COVID-19). Evidence-based understanding of the immunological effects of PM and the molecular machinery would provide novel insights into clinical interventions or prevention against acute and chronic environmental disorders induced by biomass-derived PM.
Arulkumar Nagappan; Su Park; Su-Jun Lee; Yuseok Moon. Mechanistic Implications of Biomass-Derived Particulate Matter for Immunity and Immune Disorders. Toxics 2021, 9, 18 .
AMA StyleArulkumar Nagappan, Su Park, Su-Jun Lee, Yuseok Moon. Mechanistic Implications of Biomass-Derived Particulate Matter for Immunity and Immune Disorders. Toxics. 2021; 9 (2):18.
Chicago/Turabian StyleArulkumar Nagappan; Su Park; Su-Jun Lee; Yuseok Moon. 2021. "Mechanistic Implications of Biomass-Derived Particulate Matter for Immunity and Immune Disorders." Toxics 9, no. 2: 18.
Vitis coignetiae Pulliat (Meoru in Korea) has been used in Korean folk medicine for the treatment of inflammatory diseases and cancers. Evidence suggests that NF-κB activation is mainly involved in cancer cell proliferation, invasion, angiogenesis, and metastasis. TNF-α also enhances the inflammatory process in tumor development. Recently, flavonoids from plants have been reported to have inhibitory effects on NF-κB activities. We investigated the effects of anthocyanins extracted from the fruits of Vitis coignetiae Pulliat (AIM, anthocyanins isolated from Meoru (AIM)) on TNF-α-induced NF-κB activities in MCF-7 human breast cancer cells and the molecules involved in AIM-induced anti-cancer effects, especially on cancer metastasis. We performed cell viability assay, gelatin zymography, invasion assay, and western blot analysis to unravel the anti-NF-κB activity of AIMs on MCF-7 cells. AIM suppressed the TNF-α effects on the NF-κB-regulated proteins involved in cancer cell proliferation (COX-2, C-myc), invasion, and angiogenesis (MMP-2, MMP9, ICAM-1, and VEGF). AIM also increased the expression of E-cadherin, which is one of the hallmarks of the epithelial-mesenchymal transition (EMT) process. In conclusion, this study demonstrates that the anthocyanins isolated from the fruits of Vitis coignetiae Pulliat acts as an inhibitor of TNF-α induced NF-κB activation, and subsequent downstream molecules involved in cancer proliferation, invasion, adhesion, angiogenesis, and thus have anti-metastatic activities in MCF-7 breast cancer cells.
Anjugam Paramanantham; Min Jeong Kim; Eun Joo Jung; Arulkumar Nagappan; Jeong Won Yun; Hye Jung Kim; Sung Chul Shin; Gon Sup Kim; Won Sup Lee. Pretreatment of Anthocyanin from the Fruit of Vitis coignetiae Pulliat Acts as a Potent Inhibitor of TNF-α Effect by Inhibiting NF-κB-Regulated Genes in Human Breast Cancer Cells. Molecules 2020, 25, 2396 .
AMA StyleAnjugam Paramanantham, Min Jeong Kim, Eun Joo Jung, Arulkumar Nagappan, Jeong Won Yun, Hye Jung Kim, Sung Chul Shin, Gon Sup Kim, Won Sup Lee. Pretreatment of Anthocyanin from the Fruit of Vitis coignetiae Pulliat Acts as a Potent Inhibitor of TNF-α Effect by Inhibiting NF-κB-Regulated Genes in Human Breast Cancer Cells. Molecules. 2020; 25 (10):2396.
Chicago/Turabian StyleAnjugam Paramanantham; Min Jeong Kim; Eun Joo Jung; Arulkumar Nagappan; Jeong Won Yun; Hye Jung Kim; Sung Chul Shin; Gon Sup Kim; Won Sup Lee. 2020. "Pretreatment of Anthocyanin from the Fruit of Vitis coignetiae Pulliat Acts as a Potent Inhibitor of TNF-α Effect by Inhibiting NF-κB-Regulated Genes in Human Breast Cancer Cells." Molecules 25, no. 10: 2396.
Cryptotanshinone (CT), a diterpene that is isolated from Salvia miltiorrhiza Bunge, exhibits anti-cancer, anti-oxidative, anti-fibrosis, and anti-inflammatory properties. Here, we examined whether CT administration possess a hepatoprotective effect on chronic ethanol-induced liver injury. We established a chronic alcohol feeding mouse model while using C57BL/6 mice, and examined the liver sections with hematoxylin-eosin (H&E) and Oil Red O (ORO) staining. Further, we analyzed the lipogenesis, fatty acid oxidation, oxidative stress, and inflammation genes by using quantitative polymerase chain reaction (qPCR) and immunoblotting in in vivo, and in vitro while using HepG2 and AML-12 cells. CT treatment significantly ameliorated ethanol-promoted hepatic steatosis, which was consistent with the decreased hepatic triglyceride levels. Interestingly, CT activated the phosphorylation of AMP-activated protein kinase (AMPK), sirtuin 1 (SIRT1), and nuclear factor E2-related factor 2 (Nrf2) proteins. Importantly, compound C (AMPK inhibitor) significantly blocked the CT-mediated reduction in TG accumulation, but not Ex52735 (SIRT1 inhibitor), which suggested that CT countering ethanol-promoted hepatic steatosis is mediated by AMPK activation. Furthermore, CT significantly inhibited cytochrome P450 2E1 (CYP2E1) and enhanced both the expression of antioxidant genes and hepatic glutathione levels. Finally, CT inhibited the ethanol-induced inflammation in ethanol-fed mice and HepG2 cells. Overall, CT exhibits a hepatoprotective effect against ethanol-induced liver injury by the inhibition of lipogenesis, oxidative stress, and inflammation through the activation of AMPK/SIRT1 and Nrf2 and the inhibition of CYP2E1. Therefore, CT could be an effective therapeutic agent for treating ethanol-induced liver injury.
Arulkumar Nagappan; Ji-Hyun Kim; Dae Young Jung; Myeong Ho Jung. Cryptotanshinone from the Salvia miltiorrhiza Bunge Attenuates Ethanol-Induced Liver Injury by Activation of AMPK/SIRT1 and Nrf2 Signaling Pathways. International Journal of Molecular Sciences 2019, 21, 265 .
AMA StyleArulkumar Nagappan, Ji-Hyun Kim, Dae Young Jung, Myeong Ho Jung. Cryptotanshinone from the Salvia miltiorrhiza Bunge Attenuates Ethanol-Induced Liver Injury by Activation of AMPK/SIRT1 and Nrf2 Signaling Pathways. International Journal of Molecular Sciences. 2019; 21 (1):265.
Chicago/Turabian StyleArulkumar Nagappan; Ji-Hyun Kim; Dae Young Jung; Myeong Ho Jung. 2019. "Cryptotanshinone from the Salvia miltiorrhiza Bunge Attenuates Ethanol-Induced Liver Injury by Activation of AMPK/SIRT1 and Nrf2 Signaling Pathways." International Journal of Molecular Sciences 21, no. 1: 265.
Endogenous cannabinoids (ECs) are lipid-signaling molecules that specifically bind to cannabinoid receptor types 1 and 2 (CB1R and CB2R) and are highly expressed in central and many peripheral tissues under pathological conditions. Activation of hepatic CB1R is associated with obesity, insulin resistance, and impaired metabolic function, owing to increased energy intake and storage, impaired glucose and lipid metabolism, and enhanced oxidative stress and inflammatory responses. Additionally, blocking peripheral CB1R improves insulin sensitivity and glucose metabolism and also reduces hepatic steatosis and body weight in obese mice. Thus, targeting EC receptors, especially CB1R, may provide a potential therapeutic strategy against obesity and insulin resistance. There are many CB1R antagonists, including inverse agonists and natural compounds that target CB1R and can reduce body weight, adiposity, and hepatic steatosis, and those that improve insulin sensitivity and reverse leptin resistance. Recently, the use of CB1R antagonists was suspended due to adverse central effects, and this caused a major setback in the development of CB1R antagonists. Recent studies, however, have focused on development of antagonists lacking adverse effects. In this review, we detail the important role of CB1R in hepatic insulin resistance and the possible underlying mechanisms, and the therapeutic potential of CB1R targeting is also discussed.
Arulkumar Nagappan; Jooyeon Shin; Myeong Ho Jung. Role of Cannabinoid Receptor Type 1 in Insulin Resistance and Its Biological Implications. International Journal of Molecular Sciences 2019, 20, 2109 .
AMA StyleArulkumar Nagappan, Jooyeon Shin, Myeong Ho Jung. Role of Cannabinoid Receptor Type 1 in Insulin Resistance and Its Biological Implications. International Journal of Molecular Sciences. 2019; 20 (9):2109.
Chicago/Turabian StyleArulkumar Nagappan; Jooyeon Shin; Myeong Ho Jung. 2019. "Role of Cannabinoid Receptor Type 1 in Insulin Resistance and Its Biological Implications." International Journal of Molecular Sciences 20, no. 9: 2109.
Gomisin N (GN), a lignan derived from Schisandra chinensis, has been shown to possess antioxidant, anti-inflammatory, and anticancer properties. In the present study, we investigated the protective effect of GN against ethanol-induced liver injury using in vivo and in vitro experiments. Histopathological examination revealed that GN administration to chronic-binge ethanol exposure mice significantly reduced ethanol-induced hepatic steatosis through reducing lipogenesis gene expression and increasing fatty acid oxidation gene expression, and prevented liver injury by lowering the serum levels of aspartate transaminase and alanine transaminase. Further, it significantly inhibited cytochrome P450 2E1 (CYP2E1) gene expression and enzyme activity, and enhanced antioxidant genes and glutathione level in hepatic tissues, which led to decreased hepatic malondialdehyde levels. It also lowered inflammation gene expression. Finally, GN administration promoted hepatic sirtuin1 (SIRT1)-AMP-activated protein kinase (AMPK) signaling in ethanol-fed mice. Consistent with in vivo data, treatment with GN decreased lipogenesis gene expression and increased fatty acid oxidation gene expression in ethanol-treated HepG2 cells, thereby preventing ethanol-induced triglyceride accumulation. Furthermore, it inhibited reactive oxygen species generation by downregulating CYP2E1 and upregulating antioxidant gene expression, and suppressed inflammatory gene expression. Moreover, GN prevented ethanol-mediated reduction in SIRT1 and phosphorylated AMPK. These findings indicate that GN has therapeutic potential against alcoholic liver disease through inhibiting hepatic steatosis, oxidative stress and inflammation.
Arulkumar Nagappan; Dae Young Jung; Ji-Hyun Kim; Hoyoung Lee; Myeong Ho Jung. Gomisin N Alleviates Ethanol-Induced Liver Injury through Ameliorating Lipid Metabolism and Oxidative Stress. International Journal of Molecular Sciences 2018, 19, 2601 .
AMA StyleArulkumar Nagappan, Dae Young Jung, Ji-Hyun Kim, Hoyoung Lee, Myeong Ho Jung. Gomisin N Alleviates Ethanol-Induced Liver Injury through Ameliorating Lipid Metabolism and Oxidative Stress. International Journal of Molecular Sciences. 2018; 19 (9):2601.
Chicago/Turabian StyleArulkumar Nagappan; Dae Young Jung; Ji-Hyun Kim; Hoyoung Lee; Myeong Ho Jung. 2018. "Gomisin N Alleviates Ethanol-Induced Liver Injury through Ameliorating Lipid Metabolism and Oxidative Stress." International Journal of Molecular Sciences 19, no. 9: 2601.
Activation of the hepatic cannabinoid type 1 receptor (CB1R) induces insulin resistance and gluconeogenesis via endoplasmic reticulum (ER) stress, thereby contributing to hyperglycemia. Gomisin N (GN) is a phytochemical derived from Schisandra chinensis. In the current study, we investigated the inhibitory effects of GN on hepatic CB1R-mediated insulin resistance and gluconeogenesis in 2-arachidonoylglycerol (AG; an agonist of CB1R)-treated HepG2 cells and in high-fat diet (HFD)-induced obese mice. Treatment with 2-AG induced the expression of ER stress markers, serine/threonine phosphatase PHLPP1, Lipin1, and ceramide synthesis genes, but reduced the expression of ceramide degradation genes in HepG2 cells. However, GN reversed 2-AG-mediated effects and improved the 2-AG-mediated impairment of insulin signaling. Furthermore, GN inhibited 2-AG-induced intracellular triglyceride accumulation and glucose production in HepG2 cells by downregulation of lipogenesis and gluconeogenesis genes, respectively. In vivo, GN administration to HFD obese mice reduced the HFD-induced increase in fasting blood glucose and insulin levels, which was accompanied with downregulation of HFD-induced expression of CB1R, ER stress markers, ceramide synthesis gene, and gluconeogenesis genes in the livers of HFD obese mice. These findings demonstrate that GN protects against hepatic CB1-mediated impairment of insulin signaling and gluconeogenesis, thereby contributing to the amelioration of hyperglycemia.
Arulkumar Nagappan; Dae Young Jung; Ji-Hyun Kim; Myeong Ho Jung. Protective Effects of Gomisin N against Hepatic Cannabinoid Type 1 Receptor-Induced Insulin Resistance and Gluconeogenesis. International Journal of Molecular Sciences 2018, 19, 968 .
AMA StyleArulkumar Nagappan, Dae Young Jung, Ji-Hyun Kim, Myeong Ho Jung. Protective Effects of Gomisin N against Hepatic Cannabinoid Type 1 Receptor-Induced Insulin Resistance and Gluconeogenesis. International Journal of Molecular Sciences. 2018; 19 (4):968.
Chicago/Turabian StyleArulkumar Nagappan; Dae Young Jung; Ji-Hyun Kim; Myeong Ho Jung. 2018. "Protective Effects of Gomisin N against Hepatic Cannabinoid Type 1 Receptor-Induced Insulin Resistance and Gluconeogenesis." International Journal of Molecular Sciences 19, no. 4: 968.
Tetraarsenic hexoxide (As4O6) has been used in Korean folk remedy for the treatment of cancer since the late 1980’s. Evidence suggests that As4O6 show anti-cancer effects, whose mechanisms are different from those for As2O3. However, the detailed anticancer mechanism is still unclear. Here, we investigated the anticancer effects of As4O6 on SW620 human colon cancer cells. As4O6 induced cell death in a dose-dependent manner. Flow cytometry analysis revealed that As4O6 increased the sub-G1 (apoptotic cell population) and G2/M phase population in a dose-dependent manner. Further, nuclear condensation and cleaved nuclei were also observed upon staining with Hoechst 33342 in As4O6-treated SW620 cells. Western blot revealed that As4O6 significantly down-regulated the cyclin B1, cdc 2, pro-caspases -3, -8 and -9, and up-regulated p21 and cleavage of PARP in SW620 cells. In addition, As4O6 increased the expression of death receptor 5 (DR5), suppressed Bcl-2 and XIAP family proteins, and promoted the conversion of LC3-I to LC3-II in a Beclin-1 independent manner. Interestingly, As4O6 dephosphorylated Akt and JNK and phosphorylated p38 MAPK, and the cell death was inhibited by p38 MAPK inhibitor; whereas Akt inhibitor augmented the As4O6 induced cell death, suggesting p38 MAPK and AKT were associated with As4O6-induced cell death. Taken together, these findings suggest that As4O6 induced G2/M arrest, apoptosis and autophagic cell death at least in part through p38 MAPK and AKT pathways in SW620 human colon cancer cells. This study may explain the anecdotal anticancer effects showing central necrosis with dormant status of cancers when treated by As4O6 as folk remedy. Citation Format: Won Sup Lee, Jeong Won Yun, Min Jeong Kim, Arulkumar Nagappan, Jing Nan Lu, Seong-Hwan Chang, Jae-Hoon Jeong, GonSup Kim, Jin-Myung Jung, Soon Chan Hong. Tetra-arsenic hexoxide induces G2/M cell cycle arrest, apoptosis, and autophagy via p38 MAPK- and AKT-mediated pathways in SW620 human colon cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2107. doi:10.1158/1538-7445.AM2017-2107
Won Sup Lee; Jeong Won Yun; Min Jeong Kim; Arulkumar Nagappan; Jing Nan Lu; Seong-Hwan Chang; Jae-Hoon Jeong; GonSup Kim; Jin-Myung Jung; Soon Chan Hong. Abstract 2107: Tetra-arsenic hexoxide induces G2/M cell cycle arrest, apoptosis, and autophagy via p38 MAPK- and AKT-mediated pathways in SW620 human colon cancer cells. Experimental and Molecular Therapeutics 2017, 77, 2107 -2107.
AMA StyleWon Sup Lee, Jeong Won Yun, Min Jeong Kim, Arulkumar Nagappan, Jing Nan Lu, Seong-Hwan Chang, Jae-Hoon Jeong, GonSup Kim, Jin-Myung Jung, Soon Chan Hong. Abstract 2107: Tetra-arsenic hexoxide induces G2/M cell cycle arrest, apoptosis, and autophagy via p38 MAPK- and AKT-mediated pathways in SW620 human colon cancer cells. Experimental and Molecular Therapeutics. 2017; 77 ():2107-2107.
Chicago/Turabian StyleWon Sup Lee; Jeong Won Yun; Min Jeong Kim; Arulkumar Nagappan; Jing Nan Lu; Seong-Hwan Chang; Jae-Hoon Jeong; GonSup Kim; Jin-Myung Jung; Soon Chan Hong. 2017. "Abstract 2107: Tetra-arsenic hexoxide induces G2/M cell cycle arrest, apoptosis, and autophagy via p38 MAPK- and AKT-mediated pathways in SW620 human colon cancer cells." Experimental and Molecular Therapeutics 77, no. : 2107-2107.
Citrus platymamma Hort. ex Tanaka (Byungkyul in Korean) has been used in Korean folk medicine for the treatment of inflammatory disorders and cancer. However, the molecular mechanism underlying the anticancer properties of flavonoids isolated from C. platymamma (FCP) remains to be elucidated. Therefore, the present study attempted to identify the key proteins, which may be important in the anticancer effects of FCP on A549 cells using a proteomic approach. FCP showed a potent cytotoxic effect on the A549 human lung cancer cells, however, it had no effect on WI‑38 human fetal lung fibroblasts at the same concentrations. Furthermore, 15 differentially expressed protein spots (spot intensities ≥2‑fold change; P<0.05) were obtained from comparative proteome analysis of two‑dimensional gel electrophoresis maps of the control (untreated) and FCP‑treated A549 cells. Finally, eight differentially expressed proteins, one of which was upregulated and seven of which were downregulated, were successfully identified using matrix‑assisted laser desorption/ionization time‑of‑flight/time‑of‑flight tandem mass spectrometry and peptide mass fingerprinting analysis. Specifically, proteins involved in signal transduction were significantly downregulated, including annexin A1 (ANXA1) and ANXA4, whereas 14‑3‑3ε was upregulated. Cytoskeletal proteins, including cofilin‑1 (CFL1), cytokeratin 8 (KRT8) and KRT79, and molecular chaperones/heat shock proteins, including endoplasmin, were downregulated. Proteins involved in protein metabolism, namely elongation factor Ts were also downregulated. Consistent with results of the proteome analysis, the immunoblotting results showed that 14‑3‑3ε was upregulated, whereas CFL1, ANXA4 and KRT8 were downregulated in the FCP‑treated A549 cells. The majority of the proteins were involved in tumor growth, cell cycle, apoptosis, migration and signal transduction. These findings provide novel insights into the molecular mechanisms underlying FCP-induced anticancer effects on A549 cells.
Arulkumar Nagappan; Venu Venkatarame Gowda Saralamma; Gyeong Eun Hong; Ho Jeong Lee; Sung Chul Shin; Eun Hee Kim; Won Sup Lee; Gon Sup Kim. Proteomic analysis of selective cytotoxic anticancer properties of flavonoids isolated from Citrus platymamma on A549 human lung cancer cells. Molecular Medicine Reports 2016, 14, 3814 -3822.
AMA StyleArulkumar Nagappan, Venu Venkatarame Gowda Saralamma, Gyeong Eun Hong, Ho Jeong Lee, Sung Chul Shin, Eun Hee Kim, Won Sup Lee, Gon Sup Kim. Proteomic analysis of selective cytotoxic anticancer properties of flavonoids isolated from Citrus platymamma on A549 human lung cancer cells. Molecular Medicine Reports. 2016; 14 (4):3814-3822.
Chicago/Turabian StyleArulkumar Nagappan; Venu Venkatarame Gowda Saralamma; Gyeong Eun Hong; Ho Jeong Lee; Sung Chul Shin; Eun Hee Kim; Won Sup Lee; Gon Sup Kim. 2016. "Proteomic analysis of selective cytotoxic anticancer properties of flavonoids isolated from Citrus platymamma on A549 human lung cancer cells." Molecular Medicine Reports 14, no. 4: 3814-3822.
Decoctions of the dried flowers of Lonicera japonica Thunb. (Indongcho) have been utilized in folk remedies against various inflammatory diseases, and it is reported neuroprotective effects. The cytokines release from microglia is closely linked to various chronic neurodegenerative diseases like Alzheimer's disease and Parkinson's disease. It is still unknown whether the neuroprotective effects are associated with the antiinflammatory effects. Here, we determined whether polyphenols extracted from lyophilized Lonicera japonica Thunb. (PELJ) would inhibit inflammatory cytokines and mediators. We stimulated microglia with lipopolysaccharide (LPS) to produce inflammatory cytokines, and then assessed the effects of PELJ on these cytokines. PELJ significantly inhibited LPS-induced interleukin-1β and tumor necrosis factor-α expressions and LPS-induced nitric oxide (NO) and prostaglandin E2 expressions by down-regulating inducible enzyme NO synthase and cyclooxygenase-2 at the protein and mRNA levels. All the suppression of these mediators did not cause any significant cytotoxicity. PELJ also inhibited the nuclear translocation of nuclear factor-kappa B and phosphorylated Akt. These findings suggest that PELJ may offer substantial therapeutic potential for treating inflammatory and neurodegenerative diseases by inhibiting pro-inflammatory cytokines through inhibiting phosphoinositol 3-kinase /Akt/nuclear factor-kappa B signaling pathway. Copyright © 2016 John Wiley & Sons, Ltd.
Min Ho Han; Won Sup Lee; Arulkumar Nagappan; Su Hyun Hong; Ji Hyun Jung; Cheol Park; Hye Jung Kim; Gi-Young Kim; GonSup Kim; Jin-Myung Jung; Chung Ho Ryu; Sung Chul Shin; Soon-Chan Hong; Yung Hyun Choi. Flavonoids Isolated from Flowers ofLonicera japonicaThunb. Inhibit Inflammatory Responses in BV2 Microglial Cells by Suppressing TNF-α and IL-β Through PI3K/Akt/NF-kb Signaling Pathways. Phytotherapy Research 2016, 30, 1824 -1832.
AMA StyleMin Ho Han, Won Sup Lee, Arulkumar Nagappan, Su Hyun Hong, Ji Hyun Jung, Cheol Park, Hye Jung Kim, Gi-Young Kim, GonSup Kim, Jin-Myung Jung, Chung Ho Ryu, Sung Chul Shin, Soon-Chan Hong, Yung Hyun Choi. Flavonoids Isolated from Flowers ofLonicera japonicaThunb. Inhibit Inflammatory Responses in BV2 Microglial Cells by Suppressing TNF-α and IL-β Through PI3K/Akt/NF-kb Signaling Pathways. Phytotherapy Research. 2016; 30 (11):1824-1832.
Chicago/Turabian StyleMin Ho Han; Won Sup Lee; Arulkumar Nagappan; Su Hyun Hong; Ji Hyun Jung; Cheol Park; Hye Jung Kim; Gi-Young Kim; GonSup Kim; Jin-Myung Jung; Chung Ho Ryu; Sung Chul Shin; Soon-Chan Hong; Yung Hyun Choi. 2016. "Flavonoids Isolated from Flowers ofLonicera japonicaThunb. Inhibit Inflammatory Responses in BV2 Microglial Cells by Suppressing TNF-α and IL-β Through PI3K/Akt/NF-kb Signaling Pathways." Phytotherapy Research 30, no. 11: 1824-1832.
Jeonghee Lee; Hana Jin; Won Sup Lee; Arulkumar Nagappan; Yung Hyun Choi; Gon Sup Kim; Jinmyung Jung; Chung Ho Ryu; Sung Chul Shin; Soon-Chan Hong; Hye Jung Kim. Morin, a Flavonoid from Moraceae, Inhibits Cancer Cell Adhesion to Endothelial Cells and EMT by Downregulating VCAM1 and Ncadherin. Asian Pacific Journal of Cancer Prevention 2016, 17, 1 .
AMA StyleJeonghee Lee, Hana Jin, Won Sup Lee, Arulkumar Nagappan, Yung Hyun Choi, Gon Sup Kim, Jinmyung Jung, Chung Ho Ryu, Sung Chul Shin, Soon-Chan Hong, Hye Jung Kim. Morin, a Flavonoid from Moraceae, Inhibits Cancer Cell Adhesion to Endothelial Cells and EMT by Downregulating VCAM1 and Ncadherin. Asian Pacific Journal of Cancer Prevention. 2016; 17 (7):1.
Chicago/Turabian StyleJeonghee Lee; Hana Jin; Won Sup Lee; Arulkumar Nagappan; Yung Hyun Choi; Gon Sup Kim; Jinmyung Jung; Chung Ho Ryu; Sung Chul Shin; Soon-Chan Hong; Hye Jung Kim. 2016. "Morin, a Flavonoid from Moraceae, Inhibits Cancer Cell Adhesion to Endothelial Cells and EMT by Downregulating VCAM1 and Ncadherin." Asian Pacific Journal of Cancer Prevention 17, no. 7: 1.
Poncirin, a natural bitter flavanone glycoside abundantly present in many species of citrus fruits, has various biological benefits such as anti-oxidant, anti-microbial, anti-inflammatory and anti-cancer activities. The anti-cancer mechanism of Poncirin remains elusive to date. In this study, we investigated the anti-cancer effects of Poncirin in AGS human gastric cancer cells (gastric adenocarcinoma). The results revealed that Poncirin could inhibit the proliferation of AGS cells in a dose-dependent manner. It was observed Poncirin induced accumulation of sub-G1 DNA content, apoptotic cell population, apoptotic bodies, chromatin condensation, and DNA fragmentation in a dose-dependent manner in AGS cells. The expression of Fas Ligand (FasL) protein was up-regulated dose dependently in Poncirin-treated AGS cells Moreover, Poncirin in AGS cells induced activation of Caspase-8 and -3, and subsequent cleavage of poly(ADP-ribose) polymerase (PARP). Inhibitor studies’ results confirm that the induction of caspase-dependent apoptotic cell death in Poncirin-treated AGS cells was led by the Fas death receptor. Interestingly, Poncirin did not show any effect on mitochondrial membrane potential (ΔΨm), pro-apoptotic proteins (Bax and Bak) and anti-apoptotic protein (Bcl-xL) in AGS-treated cells followed by no activation in the mitochondrial apoptotic protein caspase-9. This result suggests that the mitochondrial-mediated pathway is not involved in Poncirin-induced cell death in gastric cancer. These findings suggest that Poncirin has a potential anti-cancer effect via extrinsic pathway-mediated apoptosis, possibly making it a strong therapeutic agent for human gastric cancer.
Venu Venkatarame Gowda Saralamma; Arulkumar Nagappan; Gyeong Eun Hong; Ho Jeong Lee; Silvia Yumnam; Suchismita Raha; Jeong Doo Heo; Sang Joon Lee; Won Sup Lee; Eun Hee Kim; Gon Sup Kim. Poncirin Induces Apoptosis in AGS Human Gastric Cancer Cells through Extrinsic Apoptotic Pathway by up-Regulation of Fas Ligand. International Journal of Molecular Sciences 2015, 16, 22676 -22691.
AMA StyleVenu Venkatarame Gowda Saralamma, Arulkumar Nagappan, Gyeong Eun Hong, Ho Jeong Lee, Silvia Yumnam, Suchismita Raha, Jeong Doo Heo, Sang Joon Lee, Won Sup Lee, Eun Hee Kim, Gon Sup Kim. Poncirin Induces Apoptosis in AGS Human Gastric Cancer Cells through Extrinsic Apoptotic Pathway by up-Regulation of Fas Ligand. International Journal of Molecular Sciences. 2015; 16 (9):22676-22691.
Chicago/Turabian StyleVenu Venkatarame Gowda Saralamma; Arulkumar Nagappan; Gyeong Eun Hong; Ho Jeong Lee; Silvia Yumnam; Suchismita Raha; Jeong Doo Heo; Sang Joon Lee; Won Sup Lee; Eun Hee Kim; Gon Sup Kim. 2015. "Poncirin Induces Apoptosis in AGS Human Gastric Cancer Cells through Extrinsic Apoptotic Pathway by up-Regulation of Fas Ligand." International Journal of Molecular Sciences 16, no. 9: 22676-22691.
Human telomerase reverse transcriptase (hTERT) RNA and p53 tumour suppressor were previously suggested as useful targets for cancer gene therapy. In this study, we investigated the effects of systemically delivered adenoviruses harboring trans-splicing ribozyme that could target hTERT and induce p53 transcript in targeted cancer cells in vivo using mice with Hep3B human hepatocellular carcinoma cells that metastasized to the liver. We observed that intravenous injection of this virus (0.5 X1011 Virus) produced efficient regression of Hep 3B tumor metastasized nodules. Next we performed in vitro study to know whether it has a synergistic effects with CDDP, we observed that CDDP (2.5 ug/ml) increased cytotoxic effects in vitro given with the virus (10 MOI), but in vivo study revealed that addition of CDDP or arsenic hexoxide (As4O6) did not improve the therapeutic efficacy of the virus treatment. Next we performed toxicity test with 4 doses (0.5 X1011, 1 X1011, 2 X1011, and 5 X1011, Virus), which revealed that there were no toxic death, but 2-4 fold increased in AST and ALT with no changes in bilirubin, BUN, Creatinine levels. In conclusion, this study demonstrates that the adenoviruses harboring trans-splicing ribozyme targeting hTERT and inducing p53 transcript represents a safe and promising cancer treatment for hepatocellular carcinoma. [This study was supported by a grant from the National R&D Program for Cancer Control, Ministry for Health, Welfare & Family Affairs, Republic of Korea. (0820050), and National Research Foundation of Korea (NRF) grant funded by the Korea government(MEST) (20120002631).]
Won Sup Lee; Hye Lim Kang; Arulkumar Nagappan; Jeong Won Yun; GonSup Kim; Soon Chan Hong; Sang-Jin Lee; In-Hoo Kim. Abstract 3547: Systemically delivered human telomerase reverse transcriptase (hTERT)-targeting p53-laden adenovirus shows strong antitumor effects in intrahepatic Hep3B xenograft mouse model. Experimental and Molecular Therapeutics 2015, 75, 3547 -3547.
AMA StyleWon Sup Lee, Hye Lim Kang, Arulkumar Nagappan, Jeong Won Yun, GonSup Kim, Soon Chan Hong, Sang-Jin Lee, In-Hoo Kim. Abstract 3547: Systemically delivered human telomerase reverse transcriptase (hTERT)-targeting p53-laden adenovirus shows strong antitumor effects in intrahepatic Hep3B xenograft mouse model. Experimental and Molecular Therapeutics. 2015; 75 ():3547-3547.
Chicago/Turabian StyleWon Sup Lee; Hye Lim Kang; Arulkumar Nagappan; Jeong Won Yun; GonSup Kim; Soon Chan Hong; Sang-Jin Lee; In-Hoo Kim. 2015. "Abstract 3547: Systemically delivered human telomerase reverse transcriptase (hTERT)-targeting p53-laden adenovirus shows strong antitumor effects in intrahepatic Hep3B xenograft mouse model." Experimental and Molecular Therapeutics 75, no. : 3547-3547.
Citrus platymamma hort. ex Tanaka (Rutaceae family) has been widely used in Korean folk medicine for its wide range of medicinal benefits including an anticancer effect. In the present study, we aimed to investigate the molecular mechanism of the anticancer effects of flavonoids isolated from Citrus platymamma (FCP) on AGS cells. FCP treatment significantly inhibited AGS cell growth in a dose‑dependent manner. Furthermore, FCP significantly increased the percentage of cells in the sub-G1 phase (apoptotic cell population), and apoptosis was confirmed by Annexin V double staining. Chromatin condensation and apoptotic bodies were also noted in the FCP-treated AGS cells. Moreover, immunoblotting results showed that FCP treatment significantly decreased the expression of procaspase-3, -6, -8 and -9, and PARP and increased cleaved caspase-3, cleaved PARP and the Bax/Bcl-xL ratio in a dose-dependent manner. In addition, the phosphorylation of AKT was significantly decreased, whereas extracellular signal-related kinase 1/2 (ERK1/2), c-Jun N-terminal kinase (JNK), and p38 mitogen-activated protein kinases (MAPKs) were significantly increased in the FCP-treated AGS cells. Taken together, the cell death of AGS cells in response to FCP was mitochondrial-dependent via modulation of the PI3K/AKT and MAPK pathways. These findings provide new insight for understanding the mechanism of the anticancer effects of FCP. Thus, FCP may be a potential chemotherapeutic agent for the treatment of gastric cancer.
Ho Jeong Lee; Arulkumar Nagappan; Hyeon Soo Park; Gyeong Eun Hong; Silvia Yumnam; Suchismita Raha; Venu Venkatarame Gowda Saralamma; Won Sup Lee; Eun Hee Kim; Gon Sup Kim. Flavonoids isolated from Citrus platymamma induce mitochondrial-dependent apoptosis in AGS cells by modulation of the PI3K/AKT and MAPK pathways. Oncology Reports 2015, 34, 1517 -1525.
AMA StyleHo Jeong Lee, Arulkumar Nagappan, Hyeon Soo Park, Gyeong Eun Hong, Silvia Yumnam, Suchismita Raha, Venu Venkatarame Gowda Saralamma, Won Sup Lee, Eun Hee Kim, Gon Sup Kim. Flavonoids isolated from Citrus platymamma induce mitochondrial-dependent apoptosis in AGS cells by modulation of the PI3K/AKT and MAPK pathways. Oncology Reports. 2015; 34 (3):1517-1525.
Chicago/Turabian StyleHo Jeong Lee; Arulkumar Nagappan; Hyeon Soo Park; Gyeong Eun Hong; Silvia Yumnam; Suchismita Raha; Venu Venkatarame Gowda Saralamma; Won Sup Lee; Eun Hee Kim; Gon Sup Kim. 2015. "Flavonoids isolated from Citrus platymamma induce mitochondrial-dependent apoptosis in AGS cells by modulation of the PI3K/AKT and MAPK pathways." Oncology Reports 34, no. 3: 1517-1525.
Pachymic acid (PA) is a lanostane‐type triterpenoid derived from Poria cocos mushroom that possess various biological effects such as anti‐cancer, antiinflammatory and anti‐metastasis effects. In this study, we investigated the anti‐cancer effects of PA in EJ bladder cancer cells. The results showed that PA significantly inhibited proliferation of EJ cells in a dose‐dependent manner. PA induced accumulation of sub‐G1 DNA content (apoptotic cell population), apoptotic bodies and chromatin condensation and DNA fragmentation in EJ cells in a dose‐dependent manner. PA also induces activation of caspase‐3, ‐8 and ‐9, and subsequent cleavage of poly (ADP‐ribose) polymerase, and significantly suppressed the inhibitor of apoptosis protein family proteins in a dose‐dependent manner. Furthermore, PA activates Bid and induced the loss of mitochondrial membrane potential (ΔΨm) with up‐regulated pro‐apoptotic proteins (Bax and Bad), down‐regulated anti‐apoptotic proteins (Bcl‐2 and Bcl‐xL) and cytochrome c release. In turn, PA increased the generation of reactive oxygen species (ROS); also, the ROS production was blocked by N‐acetyl‐L‐cysteine. The expressions of TNF‐related apoptosis inducing ligand and death receptor 5 were up‐regulated by PA in a dose‐dependent manner, suggesting extrinsic pathway also involved in PA‐induced apoptosis. This study provides evidence that PA might be useful in the treatment of human bladder cancer. Copyright © 2015 John Wiley & Sons, Ltd.
Jin-Woo Jeong; Won Sup Lee; Se-Il Go; Arulkumar Nagappan; Jun Young Baek; Jae-Dong Lee; Su-Jae Lee; Cheol Park; Gi Young Kim; Hye Jung Kim; Gon-Sup Kim; Taeg Kyu Kwon; Chung Ho Ryu; Sung Chul Shin; Yung Hyun Choi. Pachymic Acid Induces Apoptosis of EJ Bladder Cancer Cells by DR5 Up-Regulation, ROS Generation, Modulation of Bcl-2 and IAP Family Members. Phytotherapy Research 2015, 29, 1516 -1524.
AMA StyleJin-Woo Jeong, Won Sup Lee, Se-Il Go, Arulkumar Nagappan, Jun Young Baek, Jae-Dong Lee, Su-Jae Lee, Cheol Park, Gi Young Kim, Hye Jung Kim, Gon-Sup Kim, Taeg Kyu Kwon, Chung Ho Ryu, Sung Chul Shin, Yung Hyun Choi. Pachymic Acid Induces Apoptosis of EJ Bladder Cancer Cells by DR5 Up-Regulation, ROS Generation, Modulation of Bcl-2 and IAP Family Members. Phytotherapy Research. 2015; 29 (10):1516-1524.
Chicago/Turabian StyleJin-Woo Jeong; Won Sup Lee; Se-Il Go; Arulkumar Nagappan; Jun Young Baek; Jae-Dong Lee; Su-Jae Lee; Cheol Park; Gi Young Kim; Hye Jung Kim; Gon-Sup Kim; Taeg Kyu Kwon; Chung Ho Ryu; Sung Chul Shin; Yung Hyun Choi. 2015. "Pachymic Acid Induces Apoptosis of EJ Bladder Cancer Cells by DR5 Up-Regulation, ROS Generation, Modulation of Bcl-2 and IAP Family Members." Phytotherapy Research 29, no. 10: 1516-1524.
Spandidos Publications is a scientific publisher with a long-standing international reputation for excellent standards and high quality science publications
Hwang-Bo Hyun; Won Sup Lee; Se-Il Go; Arulkumar Nagappan; Cheol Park; Min Ho Han; Su Hyun Hong; GonSup Kim; Gi Young Kim; Jaehun Cheong; Chung Ho Ryu; Sung Chul Shin; Yung Hyun Choi. The flavonoid morin from Moraceae induces apoptosis by modulation of Bcl-2 family members and Fas receptor in HCT 116 cells. International Journal of Oncology 2015, 46, 2670 -2678.
AMA StyleHwang-Bo Hyun, Won Sup Lee, Se-Il Go, Arulkumar Nagappan, Cheol Park, Min Ho Han, Su Hyun Hong, GonSup Kim, Gi Young Kim, Jaehun Cheong, Chung Ho Ryu, Sung Chul Shin, Yung Hyun Choi. The flavonoid morin from Moraceae induces apoptosis by modulation of Bcl-2 family members and Fas receptor in HCT 116 cells. International Journal of Oncology. 2015; 46 (6):2670-2678.
Chicago/Turabian StyleHwang-Bo Hyun; Won Sup Lee; Se-Il Go; Arulkumar Nagappan; Cheol Park; Min Ho Han; Su Hyun Hong; GonSup Kim; Gi Young Kim; Jaehun Cheong; Chung Ho Ryu; Sung Chul Shin; Yung Hyun Choi. 2015. "The flavonoid morin from Moraceae induces apoptosis by modulation of Bcl-2 family members and Fas receptor in HCT 116 cells." International Journal of Oncology 46, no. 6: 2670-2678.
Spandidos Publications is a scientific publisher with a long-standing international reputation for excellent standards and high quality science publications
Won Sup Lee; Jeong Won Yun; Arulkumar Nagappan; Hyeon Soo Park; Jing Nan Lu; Hye Jung Kim; Seong-Hwan Chang; Dong Chul Kim; Jeong-Hee Lee; Jin-Myung Jung; Soon Chan Hong; Woo Song Ha; GonSup Kim. Tetraarsenic hexoxide demonstrates anticancer activity at least in part through suppression of NF-κB activity in SW620 human colon cancer cells. Oncology Reports 2015, 33, 2940 -2946.
AMA StyleWon Sup Lee, Jeong Won Yun, Arulkumar Nagappan, Hyeon Soo Park, Jing Nan Lu, Hye Jung Kim, Seong-Hwan Chang, Dong Chul Kim, Jeong-Hee Lee, Jin-Myung Jung, Soon Chan Hong, Woo Song Ha, GonSup Kim. Tetraarsenic hexoxide demonstrates anticancer activity at least in part through suppression of NF-κB activity in SW620 human colon cancer cells. Oncology Reports. 2015; 33 (6):2940-2946.
Chicago/Turabian StyleWon Sup Lee; Jeong Won Yun; Arulkumar Nagappan; Hyeon Soo Park; Jing Nan Lu; Hye Jung Kim; Seong-Hwan Chang; Dong Chul Kim; Jeong-Hee Lee; Jin-Myung Jung; Soon Chan Hong; Woo Song Ha; GonSup Kim. 2015. "Tetraarsenic hexoxide demonstrates anticancer activity at least in part through suppression of NF-κB activity in SW620 human colon cancer cells." Oncology Reports 33, no. 6: 2940-2946.
Flavonoids from Orostachys Japonicus A. Berger Induces Caspase-dependent Apoptosis at Least Partly through Activation of p38 MAPK Pathway in U937 Human Leukemic Cells Orostachys japonicus A. Berger;flavonoids;U937;apoptosis;p38 MAPK;leukemia cells; Background: Orostachys japonicus A. Berger (A. Berger) is commonly used as a folk remedy for cancer therapy. However, the mechanisms of its anti-cancer activity are poorly investigated in human cancer cells. In this study, we investigated whether flavonoids extracted from Orostachys japonicus A. Berger (FEOJ) might have anticancer effects in human leukemia cells, focusing on cell death mechanisms. Materials and Methods: U937 human leukemic cancer cells were used. Results: FEOJ induced apoptosis in a dose-dependent manner in human U937 cancer cells. Flow cytometry revealed significant accumulation of cells with sub-G1 DNA content at the concentrations of $200{\mu}g/mL$ and $400{\mu}g/mL$. FEOJ-induced apoptosis was caspase-dependent through loss of mitochondrial membrane potential (MMP, ${\Delta}{\Psi}m$) in human U937 cancer cells, which might be associated with suppression of Bcl-2 and XIAP proteins. FEOJ induced the p38 MAPK signaling pathway, playing at least in part an important role in FEOJ-induced apoptosis. Conclusions: This study suggested that FEOJ may induce caspase-dependent apoptosis in human leukemic cells by regulating MMP (${\Delta}{\Psi}m$) through suppressing Bcl-2 and X-IAP. In addition, the results indicated that upstream p38 MAPK signaling regulates the apoptotic effect of FEOJ. This study provides evidence that FEOJ might have anti-cancer potential for human leukemic cells.
Won Sup Lee; Jeong Won Yun; Arulkumar Nagappan; Ji Hyun Jung; Sang Mi Yi; Dong Hoon Kim; Hye Jung Kim; GonSup Kim; Chung Ho Ryu; Sung Chul Shin; Soon Chan Hong; Yung Hyun Choi; Jin-Myung Jung. Flavonoids from Orostachys Japonicus A. Berger Induces Caspase-dependent Apoptosis at Least Partly through Activation of p38 MAPK Pathway in U937 Human Leukemic Cells. Asian Pacific Journal of Cancer Prevention 2015, 16, 465 -469.
AMA StyleWon Sup Lee, Jeong Won Yun, Arulkumar Nagappan, Ji Hyun Jung, Sang Mi Yi, Dong Hoon Kim, Hye Jung Kim, GonSup Kim, Chung Ho Ryu, Sung Chul Shin, Soon Chan Hong, Yung Hyun Choi, Jin-Myung Jung. Flavonoids from Orostachys Japonicus A. Berger Induces Caspase-dependent Apoptosis at Least Partly through Activation of p38 MAPK Pathway in U937 Human Leukemic Cells. Asian Pacific Journal of Cancer Prevention. 2015; 16 (2):465-469.
Chicago/Turabian StyleWon Sup Lee; Jeong Won Yun; Arulkumar Nagappan; Ji Hyun Jung; Sang Mi Yi; Dong Hoon Kim; Hye Jung Kim; GonSup Kim; Chung Ho Ryu; Sung Chul Shin; Soon Chan Hong; Yung Hyun Choi; Jin-Myung Jung. 2015. "Flavonoids from Orostachys Japonicus A. Berger Induces Caspase-dependent Apoptosis at Least Partly through Activation of p38 MAPK Pathway in U937 Human Leukemic Cells." Asian Pacific Journal of Cancer Prevention 16, no. 2: 465-469.
Grifola frondosa (GF), distributed widely in far east Asia including Korea, is popularly used as traditional medicines and health supplementary foods, especially for enhancing the immune functions of the body. To extend the application of GF polysaccharides (GFP) for atopic dermatitis (AD), we investigated the effects of GFP on the 2,4-dinitrochlorobenzene-induced AD-like skin lesion in NC/Nga mice. GFP treatment significantly reduced the dorsa skin dermatitis score and combination treatment with GFP, and dexamethasone has a synergistic effect in AD-like skin lesion by reduced Serum IgE, mast cells infiltration, and cytokines expression. These results indicate that GFP suppressed the AD-like skin lesions by controlling the Th-1/Th-2-type cytokines in NC/Nga mice. These findings strongly suggest that GFP can be useful for AD patients as a novel therapeutic agent and might be used for corticosteroids replacement or supplement agent.
Hyeon Soo Park; Yong Hyeon Hwang; Mun Ki Kim; Gyeong Eun Hong; Ho Jeong Lee; Arulkumar Nagappan; Silvia Yumnam; Eun Hee Kim; Jeong Doo Heo; Sang Joon Lee; Chung Kil Won; Gon Sup Kim. Functional polysaccharides from Grifola frondosa aqueous extract inhibit atopic dermatitis-like skin lesions in NC/Nga mice. Bioscience, Biotechnology, and Biochemistry 2015, 79, 147 -154.
AMA StyleHyeon Soo Park, Yong Hyeon Hwang, Mun Ki Kim, Gyeong Eun Hong, Ho Jeong Lee, Arulkumar Nagappan, Silvia Yumnam, Eun Hee Kim, Jeong Doo Heo, Sang Joon Lee, Chung Kil Won, Gon Sup Kim. Functional polysaccharides from Grifola frondosa aqueous extract inhibit atopic dermatitis-like skin lesions in NC/Nga mice. Bioscience, Biotechnology, and Biochemistry. 2015; 79 (1):147-154.
Chicago/Turabian StyleHyeon Soo Park; Yong Hyeon Hwang; Mun Ki Kim; Gyeong Eun Hong; Ho Jeong Lee; Arulkumar Nagappan; Silvia Yumnam; Eun Hee Kim; Jeong Doo Heo; Sang Joon Lee; Chung Kil Won; Gon Sup Kim. 2015. "Functional polysaccharides from Grifola frondosa aqueous extract inhibit atopic dermatitis-like skin lesions in NC/Nga mice." Bioscience, Biotechnology, and Biochemistry 79, no. 1: 147-154.
The production of metabolites via in vitro culture is promoted by the availability of fully defined metabolic pathways. Withanolides, the major bioactive phytochemicals of Withania somnifera, have been well studied for their pharmacological activities. However, only a few attempts have been made to identify key candidate genes involved in withanolide biosynthesis. Understanding the steps involved in withanolide biosynthesis is essential for metabolic engineering of this plant to increase withanolide production. Transcriptome sequencing was performed on in vitro adventitious root and leaf tissues using the Illumina platform. We obtained a total of 177,156 assembled transcripts with an average unigene length of 1,033 bp. About 13% of the transcripts were unique to in vitro adventitious roots but no unique transcripts were observed in in vitro-grown leaves. A putative withanolide biosynthetic pathway was deduced by mapping the assembled transcripts to the KEGG database, and the expression of candidate withanolide biosynthesis genes -were validated by qRT PCR. The accumulation pattern of withaferin A and withanolide A varied according to the type of tissue and the culture period. Further, we demonstrated that in vitro leaf extracts exhibit anticancer activity against human gastric adenocarcinoma cell lines at sub G1 phase. We report here a validated large-scale transcriptome data set and the potential biological activity of in vitro cultures of W. somnifera. This study provides important information to enhance tissue-specific expression and accumulation of secondary metabolites, paving the way for industrialization of in vitro cultures of W. somnifera. The online version of this article (doi:10.1186/s12864-015-1214-0) contains supplementary material, which is available to authorized users.
Kalaiselvi Senthil; Murukarthick Jayakodi; Pankajavalli Thirugnanasambantham; Sang Choon Lee; Pradeepa Duraisamy; Preethi M Purushotham; Kalaiselvi Rajasekaran; Shobana Nancy Charles; Irene Mariam Roy; Arul Kumar Nagappan; Gon Sup Kim; Yun Sun Lee; Senthil Natesan; Tae-Sun Min; Tae Jin Yang. Transcriptome analysis reveals in vitro cultured Withania somnifera leaf and root tissues as a promising source for targeted withanolide biosynthesis. BMC Genomics 2015, 16, 14 .
AMA StyleKalaiselvi Senthil, Murukarthick Jayakodi, Pankajavalli Thirugnanasambantham, Sang Choon Lee, Pradeepa Duraisamy, Preethi M Purushotham, Kalaiselvi Rajasekaran, Shobana Nancy Charles, Irene Mariam Roy, Arul Kumar Nagappan, Gon Sup Kim, Yun Sun Lee, Senthil Natesan, Tae-Sun Min, Tae Jin Yang. Transcriptome analysis reveals in vitro cultured Withania somnifera leaf and root tissues as a promising source for targeted withanolide biosynthesis. BMC Genomics. 2015; 16 (1):14.
Chicago/Turabian StyleKalaiselvi Senthil; Murukarthick Jayakodi; Pankajavalli Thirugnanasambantham; Sang Choon Lee; Pradeepa Duraisamy; Preethi M Purushotham; Kalaiselvi Rajasekaran; Shobana Nancy Charles; Irene Mariam Roy; Arul Kumar Nagappan; Gon Sup Kim; Yun Sun Lee; Senthil Natesan; Tae-Sun Min; Tae Jin Yang. 2015. "Transcriptome analysis reveals in vitro cultured Withania somnifera leaf and root tissues as a promising source for targeted withanolide biosynthesis." BMC Genomics 16, no. 1: 14.