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( Xian Li ),( Ju Hye Yang ),( Ye Jin ),( Fansi Jin ),( Dong Young Kim ),( Jae Hoon Chang ),( Jung Ae Kim ),( Jong Keun Son ),( Tae Chul Moon ),( Kun Ho Son ),( Hyeun Wook Chang ) 영남대학교 약품개발연구소 2015 영남대학교 약품개발연구소 연구업적집 Vol.25 No.-
Ethnopharmacological relevance: 15,16-Dihydrotanshinone I (DHT-I), isolated from the dried root of Salvia miltiorrhiza Bung, which is traditionally used to treat cardiovascular and inflammatory diseases agent in Chinese medicine. DHT-I has been reported to have a broad range of biological activities, including antibacterial activity, and has been used to treat circulatory disorders, hepatitis, inflammation, cancer, and neurodegenerative diseases. Aim of the study: The aim of this study was to evaluate the anti-allergic inflammatory effects of DHT-I on degranulation and on the generation of eicosanoids, such as, prostaglandin D2 (PGD2) and leukotriene C4 (LTC4), in IgE/Ag-stimulated bone marrow-derived mast cells (BMMCs). Materials and methods: The anti-allergic inflammatory activity of DHT-I was evaluated using BMMCs. The effects of DHT-I on mast cell activation were investigated by following degranulation and eicosanoid generation using ELISA and immunoblotting and immunoprecipitation techniques. Results: DHT-I at a concentration of 20 μM markedly inhibited degranulation and the generation of PGD2 and LTC4 in IgE/Ag-stimulated BMMCs (about 90% inhibitions, respectively). Analyses of FcεRI-mediated signaling pathways demonstrated that DHT-I inhibited the phosphorylations of spleen tyrosine kinase (Syk) and linker for activation of T cells (LAT), and inhibited downstream signaling process, including [Ca2þ]i mobilization induced by the phosphorylation of phospholipase Cγ1 (PLCγ1), and the activations of mitogen-activated protein kinases (MAPKs) and the Akt-nuclear factor-κB (NF-κB) pathway. Conclusions: DHT-1 inhibits the release of allergic inflammatory mediators from IgE/Ag-stimulated mast cells by suppressing a FcεRI-mediated Syk-dependent signal pathway. This result suggests DHT-I offers a novel developmental basis for drugs targeting allergic inflammatory diseases. & 2015 Elsevier Ireland Ltd. All rights reserved.
Li, Xian,Park, Soon Jin,Jin, Fansi,Deng, Yifeng,Yang, Ju Hye,Chang, Jae-Hoon,Kim, Dong-Young,Kim, Jung-Ae,Lee, Youn Ju,Murakami, Makoto,Son, Kun Ho,Chang, Hyeun Wook Pergamon Press 2018 Biochemical pharmacology Vol.152 No.-
<P><B>Abstract</B></P> <P>AMP-activated protein kinase (AMPK) and its upstream mediators liver kinase B1 (LKB1) and sirtuin 1 (Sirt1) are generally known as key regulators of metabolism. We have recently reported that the AMPK pathway negatively regulates mast cell activation and anaphylaxis. Tanshinone IIA (Tan IIA), an active component of <I>Salvia miltiorrhiza</I> extract that is currently used for the treatment of cardiovascular and cerebrovascular diseases, shows anti-diabetic activity and improves insulin resistance in <I>db/db</I> mice through activation of AMPK. The aim of this study was to evaluate the anti-allergic activity of Tan IIA <I>in vivo</I> and to investigate the underlying mechanism <I>in vitro</I> in the context of AMPK signaling. The anti-allergic effect of Tan IIA was evaluated using mouse bone marrow-derived mast cells (BMMCs) from <I>AMPKα2</I> <SUP>−/−</SUP> or <I>Sirt1</I> <SUP>−/−</SUP> mice, or BMMCs transfected with siRNAs specific for AMPKα2, LKB1, or Sirt1. <I>AMPKα2</I> <SUP>−/−</SUP> and <I>Sirt1</I> <SUP>−/−</SUP> mice were used to confirm the anti-allergic effect of Tan IIA in anaphylaxis <I>in vivo</I>. Tan IIA dose-dependently inhibited FcεRI-mediated degranulation and production of eicosanoids and cytokines in BMMCs. These inhibitory effects were diminished by siRNA-mediated knockdown or genetic deletion of AMPKα2 or Sirt1. Moreover, Tan IIA inhibited a mast cell-mediated local passive anaphylactic reaction in wild-type mice, but not in <I>AMPKα2</I> <SUP>−/−</SUP> or <I>Sirt1</I> <SUP>−/−</SUP> mice. In conclusion, Tan IIA suppresses FcεRI-mediated mast cell activation and anaphylaxis through activation of the inhibitory Sirt1-LKB1-AMPK pathway. Thus, Tan IIA may be useful as a new therapeutic agent for mast cell-mediated allergic diseases.</P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>
( Seung Lark Hwang ),( Ju Hye Yang ),( Yong Tae Jeong ),( Yong Deuk Kim ),( Xian Li ),( Yue Lu ),( Young Chae Chang ),( Kun Ho Chang ),( Kun Ho Son ),( Hyeun Wook Chang ) 영남대학교 약품개발연구소 2013 영남대학교 약품개발연구소 연구업적집 Vol.23 No.0
The aim of the present study was to determine the effect of Tanshinone IIA (Tan IIA) on endoplasmic reticulum (ER) stress-induced insulinresistance in L6 myotubes and db/db mice. ER stress markers, RNA-activated protein kinase-like ER resident kinase (PERK), JNK, and AMPK activity were determined in tunicamycin-treated L6 myotubes. Insulin resistance was monitored using glucose uptake assays in vitro and blood glucose levels in vivo. Tan IIA clearly suppressed the phosphorylations of PERK and JNK and potentiated insulin-mediated Akt phosphorylation as well as glucose uptake via AMPK activation under ER stress. Furthermore, these effects are completely abrogated by siRNA-mediated knockdown of AMPK or LKB1. In addition, Tan IIA reduced blood glucose levels and body weights in db/db mice without altering food intake. These findings suggest that Tan IIA enhances insulin sensitivity and improves glucose metabolic disorders by increasing AMPK activity and attenuating ERstress-induced insulin resistance. ⓒ2012 Elsevier lnc. All rights reserved.
Role of miR-511 in the Regulation of OATP1B1 Expression by Free Fatty Acid
( Jin Fu Peng ),( Li Liu ),( Cheng Xian Guo ),( Shi Kun Liu ),( Xiao Ping Chen ),( Li Hua Huang ),( Hong Xiang ),( Zhi Jun Huang ),( Hong Yuan ),( Guo Ping Yang ) 한국응용약물학회 2015 Biomolecules & Therapeutics(구 응용약물학회지) Vol.23 No.5
MicroRNAs (miRNAs) are a family of non-coding RNA that are able to adjust the expression of many proteins, including ATPbinding cassette transporter and organic cation transporter. We sought to evaluate the effect of miR-511 on the regulation of OATP1B1 expression by free fatty acids. When using free fatty acids to stimulate Chang liver cells, we found that the expression of miR-511 increased significantly while the expression of OATP1B1 decreased. We also proved that SLCO1B1 is the target gene of miR-511 with a bioinformatics analysis and using the dual luciferase reporter assay. Furthermore, the expressions of SLCO1B1 and OATP1B1 decreased if transfecting Chang liver cells with miR-511, but did not increase when transfecting the inhibitors of miR-511 into steatosis cells. Our study indicates that miR-511 may play an important role in the regulation of OATP1B1 expression by free fatty acids.
Role of miR-511 in the Regulation of OATP1B1 Expression by Free Fatty Acid
Peng, Jin Fu,Liu, Li,Guo, Cheng Xian,Liu, Shi Kun,Chen, Xiao Ping,Huang, Li Hua,Xiang, Hong,Huang, Zhi Jun,Yuan, Hong,Yang, Guo Ping The Korean Society of Applied Pharmacology 2015 Biomolecules & Therapeutics(구 응용약물학회지) Vol.23 No.5
MicroRNAs (miRNAs) are a family of non-coding RNA that are able to adjust the expression of many proteins, including ATP-binding cassette transporter and organic cation transporter. We sought to evaluate the effect of miR-511 on the regulation of OATP1B1 expression by free fatty acids. When using free fatty acids to stimulate Chang liver cells, we found that the expression of miR-511 increased significantly while the expression of OATP1B1 decreased. We also proved that SLCO1B1 is the target gene of miR-511 with a bioinformatics analysis and using the dual luciferase reporter assay. Furthermore, the expressions of SLCO1B1 and OATP1B1 decreased if transfecting Chang liver cells with miR-511, but did not increase when transfecting the inhibitors of miR-511 into steatosis cells. Our study indicates that miR-511 may play an important role in the regulation of OATP1B1 expression by free fatty acids.
The comparison of microbial communities in thyroid tissues from thyroid carcinoma patients
Liu Chen-Jian,Chen Si-Qian,Zhang Si-Yao,Wang Jia-Lun,Tang Xiao-Dan,Yang Kun-Xian,Li Xiao-Ran 한국미생물학회 2021 The journal of microbiology Vol.59 No.11
Thyroid carcinoma is a common endocrine organ cancer associated with abnormal hormone secretion, leading to the disorder of metabolism. The intestinal microbiota is vital to maintain digestive and immunologic homeostasis. The relevant information of the microbial community in the gut and thyroid, including composition, structure, and relationship, is unclear in thyroid carcinoma patients. A total of 93 samples from 25 patients were included in this study. The results showed that microbial communities existed in thyroid tissue; gut and thyroid had high abundance of facultative anaerobes from the Proteobacteria phyla. The microbial metabolism from the thyroid and gut may be affected by the thyroid carcinoma cells. The cooccurrence network showed that the margins of different thyroid tissues were unique areas with more competition; the stabilization of microcommunities from tissue and stool may be maintained by several clusters of species that may execute different vital metabolism processes dominantly that are attributed to the microenvironment of cancer.