title: Dihydroaustrasulfone Alcohol (WA-25) Impedes Macrophage Foam Cell Formation by Regulating the Transforming Growth Factor-β1 Pathway.
abstract: Atherosclerosis is considered an inflammatory disease. However, clinically used anti-atherosclerotic drugs, such as simvastatin, have many side effects. Recently, several unique marine compounds have been isolated that possess a variety of bioactivities. In a previous study, we found a synthetic precursor of the marine compound (austrasulfone), which is dihydroaustrasulfone alcohol (WA-25), has anti-atherosclerotic effects in vivo. However, the detailed mechanisms remain unclear. Therefore, to clarify the mechanisms through which WA-25 exerts anti-atherosclerotic activity, we used RAW 264.7 macrophages as an in vitro model to evaluate the effects of WA-25. In lipopolysaccharide (LPS)-stimulated RAW 264.7 cells, WA-25 significantly inhibited expression of the pro-inflammatory proteins, inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). In contrast, simvastatin increased the COX-2 expression compared to WA-25. In addition, WA-25 impedes foam cell formation and up-regulated the lysosomal and cyclic adenosine monophosphate (cAMP) signaling pathway. We also observed that transforming growth factor β1 (TGF-β1) was up-regulated by WA-25 and simvastatin in LPS-induced RAW 264.7 cells, and the promising anti-atherosclerosis effects of WA-25 were disrupted by blockade of TGF-β1 signaling. Besides, WA-25 might act through increasing lipolysis than through alteration of lipid export. Taken together, these data demonstrate that WA-25 may have potential as an anti-atherosclerotic drug with anti-inflammatory effects.
authors.affiliation: Department of Marine Biotechnology and Resources, National Sun Yat-sen University, Kaohsiung 80424, Taiwan. cvyc.wang@gmail.com.|Division of Cardiology, Department of Internal Medicine, Kaohsiung Armed Forces General Hospital, Kaohsiung 80284, Taiwan. cvyc.wang@gmail.com.
authors.forename: Yi-Chen
authors.initials: YC
authors.lastname: Wang
authors.affiliation: Doctoral Degree Program in Marine Biotechnology, National Sun Yat-sen University and Academia Sinica, Kaohsiung 80424, Taiwan. hanchun25@gmail.com.
authors.forename: Han-Chun
authors.initials: HC
authors.lastname: Hung
authors.affiliation: Doctoral Degree Program in Marine Biotechnology, National Sun Yat-sen University and Academia Sinica, Kaohsiung 80424, Taiwan. qscjuejuejue@gmail.com.
authors.forename: Chien-Wei
authors.initials: CW
authors.lastname: Feng
authors.affiliation: Center for Neuroscience, National Sun Yat-sen University, Kaohsiung 80424, Taiwan. johnjohnkings@gmail.com.
authors.forename: Shi-Ying
authors.initials: SY
authors.lastname: Huang
authors.affiliation: Doctoral Degree Program in Marine Biotechnology, National Sun Yat-sen University and Academia Sinica, Kaohsiung 80424, Taiwan. anubis0620@gmail.com.
authors.forename: Chun-Hong
authors.initials: CH
authors.lastname: Chen
authors.affiliation: Department of Marine Biotechnology and Resources, National Sun Yat-sen University, Kaohsiung 80424, Taiwan. chas6119@gmail.com.
authors.forename: Yen-You
authors.initials: YY
authors.lastname: Lin
authors.affiliation: Department of Biomedical Engineering, National Defense Medical Center, Taipei 11490, Taiwan. bme02@mail.ndmctsgh.edu.tw.
authors.forename: Yao-Chang
authors.initials: YC
authors.lastname: Chen
authors.affiliation: School of Medicine, College of Medicine and Department of Pediatrics, E-DA Hospital, I-Shou University, Kaohsiung 84001, Taiwan. y520729@gmail.com.
authors.forename: San-Nan
authors.initials: SN
authors.lastname: Yang
authors.affiliation: National Museum of Marine Biology and Aquarium, Pingtung 94450, Taiwan. x2219@nmmba.gov.tw.
authors.forename: Jui-Hsin
authors.initials: JH
authors.lastname: Su
authors.affiliation: Department of Marine Biotechnology and Resources, National Sun Yat-sen University, Kaohsiung 80424, Taiwan. sheu@mail.nsysu.edu.tw.|Graduate Institute of Natural Products, Kaohsiung Medical University, Kaohsiung 80708, Taiwan. sheu@mail.nsysu.edu.tw.|Department of Medical Research, China Medical University Hospital, China Medical University, Taichung 40402, Taiwan. sheu@mail.nsysu.edu.tw.
authors.forename: Jyh-Horng
authors.initials: JH
authors.lastname: Sheu
authors.affiliation: Doctoral Degree Program in Marine Biotechnology, National Sun Yat-sen University and Academia Sinica, Kaohsiung 80424, Taiwan. wzh@mail.nsysu.edu.tw.|Marine Biomedical Laboratory & Center for Translational Biopharmaceuticals, Department of Marine Biotechnology and Resources, National Sun Yat-sen University, Kaohsiung 80424, Taiwan. wzh@mail.nsysu.edu.tw.
authors.forename: Zhi-Hong
authors.initials: ZH
authors.lastname: Wen
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002074:Butanones / Q000494:pharmacology*; D002460:Cell Line; D000242:Cyclic AMP / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D005487:Foam Cells / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D013450:Sulfones / Q000494:pharmacology*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*
chemical_list: D000893:Anti-Inflammatory Agents; D002074:Butanones; D013450:Sulfones; D053773:Transforming Growth Factor beta1; C000590752:dihydroaustrasulfone alcohol; D000242:Cyclic AMP; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2