INDUCTION OF DNA DAMAGE AND APOPTOSIS BY ISODIHYDROAUROGLAUCIN ISOLATED FROM THE MARINE-DERIVED FUNGUS MICROSPORUM SP

Saeromi Kang,Jing Zhao,Xin Zhang,Ji Young Hwang,Byeng Wha Son,Dong-Kyoo Kim 한국환경독성학회 2009 한국독성학회 심포지움 및 학술발표회 Vol.2009 No.11

Ginsenoside Rg₃ promotes inflammation resolution through M2 macrophage polarization

Kang, Saeromi,Park, Soo-Jin,Lee, Ae-Yeon,Huang, Jin,Chung, Hae-Young,Im, Dong-Soon The Korean Society of Ginseng 2018 Journal of Ginseng Research Vol.42 No.1

Background: Ginsenosides have been reported to have many health benefits, including anti-inflammatory effects, and the resolution of inflammation is now considered to be an active process driven by M2-type macrophages. In order to determine whether ginsenosides modulate macrophage phenotypes to reduce inflammation, 11 ginsenosides were studied with respect to macrophage polarization and the resolution of inflammation. Methods: Mouse peritoneal macrophages were polarized into M1 or M2 phenotypes. Reverse transcription-polymerase chain reaction, Western blotting, and measurement of nitric oxide (NO) and prostaglandin $E_2$ levels were performed in vitro and in a zymosan-induced peritonitis C57BL/6 mouse model. Results: Ginsenoside $Rg_3$ was identified as a proresolving ginseng compound based on the induction of M2 macrophage polarization. Ginsenoside $Rg_3$ not only induced the expression of arginase-1 (a representative M2 marker gene), but also suppressed M1 marker genes, such as inducible NO synthase, and NO levels. The proresolving activity of ginsenoside $Rg_3$ was also observed in vivo in a zymosan-induced peritonitis model. Ginsenoside $Rg_3$ accelerated the resolution process when administered at peak inflammatory response into the peritoneal cavity. Conclusion: These results suggest that ginsenoside $Rg_3$ induces the M2 polarization of macrophages and accelerates the resolution of inflammation. This finding opens a new avenue in ginseng pharmacology.

Identification of a novel anti-inflammatory compound, α-cubebenoate from Schisandra chinensis

Kang, Saeromi,Lee, Kyoung-Pil,Park, Soo-Jin,Noh, Dae-Young,Kim, Jung-Min,Moon, Hyung Ryong,Lee, Young-Geun,Choi, Young-Whan,Im, Dong-Soon Elsevier 2014 Journal of Ethnopharmacology Vol.153 No.1

<P>Extracts of Schisandra chinensis have been used as an anti-fatigue and tonic agent. Because chronic fatigue syndrome is related to inflammatory and oxidative stress, we assessed whether Schisandra chinensis has anti-inflammatory constituents and studied the effect of a novel α-cubebenoate isolated from Schisandra chinensis.</P>

Omega-3 polyunsaturated fatty acids protect human hepatoma cells from developing steatosis through FFA4 (GPR120)

Kang, Saeromi,Huang, Jin,Lee, Bo-Kyung,Jung, Young-Suk,Im, Eunok,Koh, Jung-Min,Im, Dong-Soon Elsevier 2018 Biochimica et biophysica acta, Molecular and cell Vol.1863 No.2

<P>Protective effect of omega-3 polyunsaturated fatty acids (n-3 PUFA) on non-alcoholic fatty liver disease has been demonstrated. FFA4 (also known as GPR120; a G protein-coupled receptor) has been suggested to be a target of n-3 PUFA. FFA4 expression in hepatocytes has also been reported from liver biopsies in child fatty liver patients. In order to assess the functional role of FFA4 in hepatic steatosis, we used an in vitro model of liver X receptor (LXR)-mediated hepatocellular steatosis. FFA4 expression was confirmed in Hep3B and HepG2 human hepatoma cells. T0901317 (a specific LXR activator) induced lipid accumulation and docosahexaenoic acid (DHA; a representative n-3 PUFA) inhibited lipid accumulation. This DHA-induced inhibition was blunted by treatment of AH7614 (a FFA4 antagonist) and by transfection of FFA4 siRNA. SREBP-lc (a key transcription factor of lipogenesis) was induced by treatment with T0901317, and SREBP-lc induction was also inhibited by DHA at mRNA and protein levels. DHA-induced suppression of SREBP-lc expression was also blunted by FFA4-knockdown. Furthermore, DHA inhibited T0901317-induced lipid accumulation in primary hepatocytes from wild type mice, but not in those from FFA4 deficient mice. In addition, DHA-induced activations of G(q/11) proteins, CaMKK, and AMPK were found to be signaling components of the steatosis protective pathway. The results of this study suggest that n-3 PUFA protect hepatic steatosis by activating FFA4 in hepatocytes, and its signaling cascade sequentially involves FFA4, G(q/11) proteins, CaMKK, AMPK, and SREBP-lc suppression.</P>

Apelin protects against liver X receptor-mediated steatosis through AMPK and PPARα in human and mouse hepatocytes

Huang, Jin,Kang, Saeromi,Park, Soo-Jin,Im, Dong-Soon Elsevier 2017 Cellular signalling Vol.39 No.-

<P><B>Abstract</B></P> <P>Non-alcoholic fatty liver disease is the most commonly occurring chronic liver disease, and hepatic steatosis, a condition defined as extensive lipid accumulation in hepatocytes, is associated with liver dysfunction and metabolic diseases, such as, obesity and type II diabetes. Apelin is an adipokine that acts on a G protein-coupled receptor named APJ, and has been established to play pivotal roles in various physiological conditions. However, the function of apelin in hepatocytes has not been fully investigated. In order to assess the functional roles of apelin and APJ in hepatocytes, we used an in vitro model of liver X receptor (LXR)-mediated hepatocellular steatosis. In Hep3B human hepatoma cells, T0901317 (a specific LXR activator) induced lipid accumulation and this was inhibited by apelin. T0901317 also induced the expression of SREBP-1c, a key transcription factor for lipogenesis. Apelin not only inhibited SREBP-1c induction at the mRNA and protein levels but also induced lipolytic PPARα expression. Furthermore, these protective effects of apelin were inhibited by apelin F13A (a specific APJ antagonist). Furthermore, silencing of APJ by siRNA transfection also inhibited the actions of apelin. Specific inhibitors of cellular signaling components showed inhibition of lipid accumulation by apelin was mediated through G<SUB>i/o</SUB> proteins, AMPK, and SREBP-1c suppression during the early stage and through AMPK, ERKs, and PPARα induction during the late stage. In addition, the protective effect of apelin was confirmed in mouse primary hepatocytes. Our observations suggest apelin-APJ signaling in hepatocytes functions to protect against lipid accumulation in liver through two signaling pathways, that is, via AMPK activation and PPARα induction.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Apelin protected liver X receptor-mediated steatosis through APJ in human and mouse hepatocytes </LI> <LI> Early signaling by apelin was APJ➔Gi/o➔p38 MAPK and PI3K➔AMPK➔suppression of SREBP-1c➔lipogenesis suppression. </LI> <LI> Later signaling by apelin was APJ➔Gi/o➔PI3K and ERK➔PPARα induction➔enhanced lipolysis. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

Apoptotic activity of a new jasmonate analogue is associated with its induction of DNA damage

Zhao, Jing,Kang, Saeromi,Zhang, Xin,You, Song,Park, Jang-Su,Jung, Jee H,Kim, Dong-Kyoo Spandidos Publications 2010 ONCOLOGY REPORTS Vol.24 No.3

<P>The current study was undertaken to investigate the effects of methyl 5-chloro-4,5-didehydrojasmonate (J7), an analogue of methyl jasmonate, on the in vitro growth of human cervical carcinoma HeLa cells. Significantly decreased rates of viability (IC50 approximately 15 microM) as well as evidence of apoptosis were observed with J7. Cell morphological changes observed under light microscopy confirmed apoptosis occurrence. Furthermore, the results from Annexin V-FITC/PI double staining and the cell cycle arrest assay indicated that J7 induced earlier apoptosis of HeLa cells. J7 also reduced the expression of Bcl-2 and subsequent activation of a protease cascade involving caspase-9 and -3 by Western blot assay was observed. We also found that J7 was able to induce DNA damage. These findings suggest that J7 induces HeLa cell apoptosis by activation of caspase pathway and the apoptotic effect is associated with DNA damage. Therefore, J7 may be a candidate compound to be developed into an anticancer agent.</P>

INDUCTION OF APOPTOSIS AND CELL CYCLE ARREST IN HUMAN CERVICAL CARCINOMA HELA CELLS BY A JASMONATE DERIVATIVE

Jing Zhao,Saeromi Kang,Xin Zhang,Ji Young Hwang,Jee H. Jung,Dong-Kyoo Kim 한국환경독성학회 2009 한국독성학회 심포지움 및 학술발표회 Vol.2009 No.11

Anti-Allergic Effect of Oroxylin A from Oroxylum indicum Using in vivo and in vitro Experiments

( Ae Yeon Lee ),( Saeromi Kang ),( Soo Jin Park ),( Jin Huang ),( Dong Soon Im ) 한국응용약물학회 2016 Biomolecules & Therapeutics(구 응용약물학회지) Vol.24 No.3

Oroxylum indicum has long been used in Asian traditional medicine to prevent and treat respiratory diseases, diabetes, diarrhea and other conditions. Oroxylin A is a flavone that is present in Oroxylum indicum and in Scutellaria baicalensis. Because the root extracts of both plants have been shown to have anti-allergic effects, the authors investigated whether oroxylin A is likely to have beneficial effects on allergic asthma using female Balb/c mice and rat RBL-2H3 mast cells. Antigen-induced degranulation was measured in vitro by measuring b-hexosaminidase activity. A murine ovalbumin-induced allergic asthma model was used to test the in vivo efficacy of oroxylin A. Sensitization and challenge of ovalbumin induced allergic asthma responses, the accumulations of eosinophils and Th2 cytokine levels in bronchoalveolar lavage fluid and lung tissues. Oroxylin A administration decreased numbers of inflammatory cells, especially eosinophils, and reduced the expression and secretion of Th2 cytokines, including IL-4 and IL-13, in lung tissues and bronchoalveolar lavage fluid. Histologic studies showed oroxylin A reduced inflammatory signs and mucin production in lungs. These findings provide evidence that oroxylin A has potential use as an anti-allergic therapeutic.

Anti-Allergic Effect of Oroxylin A from Oroxylum indicum Using in vivo and in vitro Experiments

Lee, Ae-Yeon,Kang, Saeromi,Park, Soo-Jin,Huang, Jin,Im, Dong-Soon The Korean Society of Applied Pharmacology 2016 Biomolecules & Therapeutics(구 응용약물학회지) Vol.24 No.3

Oroxylum indicum has long been used in Asian traditional medicine to prevent and treat respiratory diseases, diabetes, diarrhea and other conditions. Oroxylin A is a flavone that is present in Oroxylum indicum and in Scutellaria baicalensis. Because the root extracts of both plants have been shown to have anti-allergic effects, the authors investigated whether oroxylin A is likely to have beneficial effects on allergic asthma using female Balb/c mice and rat RBL-2H3 mast cells. Antigen-induced degranulation was measured in vitro by measuring b-hexosaminidase activity. A murine ovalbumin-induced allergic asthma model was used to test the in vivo efficacy of oroxylin A. Sensitization and challenge of ovalbumin induced allergic asthma responses, the accumulations of eosinophils and Th2 cytokine levels in bronchoalveolar lavage fluid and lung tissues. Oroxylin A administration decreased numbers of inflammatory cells, especially eosinophils, and reduced the expression and secretion of Th2 cytokines, including IL-4 and IL-13, in lung tissues and bronchoalveolar lavage fluid. Histologic studies showed oroxylin A reduced inflammatory signs and mucin production in lungs. These findings provide evidence that oroxylin A has potential use as an anti-allergic therapeutic.

Therapeutic Effects of S-Petasin on Disease Models of Asthma and Peritonitis

( Kyoung Pil Lee ),( Saeromi Kang ),( Min Soo Noh ),( Soo Jin Park ),( Jung Min Kim ),( Hae Young Chung ) 한국응용약물학회 2015 Biomolecules & Therapeutics(구 응용약물학회지) Vol.23 No.1

To explore the anti-allergic and anti-inflammatory effects of extracts of Petasites genus, we studied the effects of s-petasin, a major sesquiterpene from Petasites formosanus (a butterbur species) on asthma and peritonitis models. In an ovalbumin-induced mouse asthma model, s-petasin significantly inhibited the accumulations of eosinophils, macrophages, and lymphocytes in bronchoalveolar fluids. S-petasin inhibited the antigen-induced degranulation of b-hexosamidase but did not inhibit intracellular Ca2+ increase in RBL-2H3 mast cells. S-petasin inhibited the LPS induction of iNOS at the RNA and protein levels in mouse peritoneal macrophages. Furthermore, s-petasin inhibited the production of NO (the product of iNOS) in a concentration-dependent manner in the macrophages. Furthermore, in an LPS-induced mouse model of peritonitis, s-petasin significantly inhibited the accumulation of polymorpho nuclear and mononuclear leukocytes in peritoneal cavity. This study shows that s-petasin in Petasites genus has therapeutic effects on allergic and inflammatory diseases, such as, asthma and peritonitis through degranulation inhibition in mast cells, suppression of iNOS induction and production of NO in macrophages, and suppression of inflammatory cell accumulation.