title: Zerumbone, a Bioactive Sesquiterpene, Ameliorates Diabetes-Induced Retinal Microvascular Damage through Inhibition of Phospho-p38 Mitogen-Activated Protein Kinase and Nuclear Factor-κB Pathways.
abstract: Zerumbone ameliorates retinal damage by blocking advanced glycation end products and their receptor system in streptozotocin-diabetic rats. Because of the multiple factors involved in diabetic retinopathy (DR) etiology, the mechanisms of zerumbone that are mainly responsible for its ameliorative effect on DR need to be further clarified. In the present study, zerumbone (20 mg or 40 mg/kg) or fenofibric acid (100 mg/kg) was orally administered to diabetic rats by intragastric gavage once daily for three consecutive months. Zerumbone displayed similar characteristics to fenofibric acid in reducing retinal vascular permeability and leukostasis in diabetic rats. Fundus photographs showed that large retinal vessel diameters were decreased in zerumbone-treated diabetic rats. Zerumbone not only down-regulated the gene expression of retinal angiogenic parameters, but also reduced the expression of inflammatory cytokines and chemokines in the retina of diabetic rats. Moreover, zerumbone reduced the p38 MAPK phosphorylation and abrogated the nuclear translocation of NF-κB p65 in the retina of diabetic rats. In conclusion, treatment of diabetic rats with zerumbone attenuates the severity of retinal inflammation and angiogenesis, via inhibition of p38 MAPK and NF-κB signaling pathways. These benefits of zerumbone for DR appear to be linked to its antihyperglycemic and antihyperlipidemic effects.
authors.affiliation: Center for Basic Medical Science, Collage of Health Science, Central Taiwan University of Science and Technology, Taichung 40601, Taiwan. waynedoctor@gmail.com.|Department of Urology, Jen-Ai Hospital, Taichung 41625, Taiwan. waynedoctor@gmail.com.
authors.forename: Wayne Young
authors.initials: WY
authors.lastname: Liu
authors.affiliation: Department of Pharmacy and Master Program, Collage of Pharmacy and Health Care, Tajen University, Pingtung 90741, Taiwan. d850084@yahoo.com.tw.
authors.forename: Thing-Fong
authors.initials: TF
authors.lastname: Tzeng
authors.affiliation: Department of Pharmacy and Master Program, Collage of Pharmacy and Health Care, Tajen University, Pingtung 90741, Taiwan. iml@tajen.edu.tw.
authors.forename: I-Min
authors.initials: IM
authors.lastname: Liu
mesh_terms: D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000473:pathology*; D003930:Diabetic Retinopathy / Q000188:drug therapy* / Q000517:prevention & control*; D011345:Fenofibrate / Q000031:analogs & derivatives / Q000627:therapeutic use; D017127:Glycation End Products, Advanced / Q000037:antagonists & inhibitors; D008297:Male; D055806:Microvessels / Q000187:drug effects* / Q000293:injuries; D051381:Rats; D017208:Rats, Wistar; D012160:Retina / Q000187:drug effects; D012171:Retinal Vessels / Q000187:drug effects* / Q000293:injuries; D012717:Sesquiterpenes / Q000627:therapeutic use*; D015398:Signal Transduction / Q000187:drug effects; D013311:Streptozocin; D051996:Transcription Factor RelA / Q000037:antagonists & inhibitors* / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D017127:Glycation End Products, Advanced; C498145:Rela protein, rat; D012717:Sesquiterpenes; D051996:Transcription Factor RelA; C403304:zerumbone; D013311:Streptozocin; C006012:fenofibric acid; D048051:p38 Mitogen-Activated Protein Kinases; D011345:Fenofibrate
keywords: NF-κB; diabetic retinopathy; p38 MAPK; zerumbone