title: Betanin reduces the accumulation and cross-links of collagen in high-fructose-fed rat heart through inhibiting non-enzymatic glycation.
abstract: We attempted to determine whether betanin (from natural pigments) that has antioxidant properties would be protective against fructose-induced diabetic cardiac fibrosis in Sprague-Dawley rats. Fructose water solution (30%) was accessed freely, and betanin (25 and 100 mg/kg/d) was administered by intra-gastric gavage continuously for 60 d. Rats were sacrificed after overnight fast. The rat blood and left ventricle were collected. In vitro antiglycation assay in bovine serum albumin/fructose system was also performed. In rats treated only with fructose, levels of plasma markers: glucose, insulin, HOMA and glycated hemoglobin rised, left ventricle collagen accumulated and cross-linked, profibrotic factor-transforming growth factor (TGF)-β1 and connective tissue growth factor (CTGF) protein expression increased, and soluble collagen decreased, compared with those in normal rats, showing fructose induces diabetic cardiac fibrosis. Treatment with betanin antagonized the changes of these parameters, demonstrating the antifibrotic role of betanin in the selected diabetic models. In further mechanistic study, betanin decreased protein glycation indicated by the decreased levels of protein glycation reactive intermediate (methylglyoxal), advanced glycation end product (N(ε)-(carboxymethyl) lysine) and receptors for advanced glycation end products (AGEs), antagonized oxidative stress and nuclear factor-κB activation elicited by fructose feeding, suggesting inhibition of glycation, oxidative stress and nuclear factor-κB activation may be involved in the antifibrotic mechanisms. Betanin also showed anitglycative effect in BSA/fructose system, which supported that anitglycation was involved in betanin's protective roles in vivo. Taken together, the potential for using betanin as an auxillary therapy for diabetic cardiomyopathy deserves to be explored further.
authors.affiliation: College of Life Science and Engineering, Shenyang University, Shenyang 110044, China. Electronic address: hanjunyan@aliyun.com.
authors.forename: Junyan
authors.initials: J
authors.lastname: Han
authors.affiliation: College of Basic Medical Science, China Medical University, Shenyang 110001, China.
authors.forename: Chang
authors.initials: C
authors.lastname: Tan
authors.affiliation: College of Life Science and Engineering, Shenyang University, Shenyang 110044, China.
authors.forename: Yiheng
authors.initials: Y
authors.lastname: Wang
authors.affiliation: College of Life Science and Engineering, Shenyang University, Shenyang 110044, China.
authors.forename: Shaobin
authors.initials: S
authors.lastname: Yang
authors.affiliation: College of Food, Shenyang Agricultural University, Shenyang 110866, China. Electronic address: tandehongsy@126.com.
authors.forename: Dehong
authors.initials: D
authors.lastname: Tan
mesh_terms: D000818:Animals; D050859:Betacyanins / Q000494:pharmacology*; D001786:Blood Glucose / Q000032:analysis; D003094:Collagen / Q000378:metabolism*; D055513:Connective Tissue Growth Factor / Q000378:metabolism; D005355:Fibrosis / Q000378:metabolism / Q000473:pathology; D005632:Fructose / Q000494:pharmacology; D006442:Glycated Hemoglobin / Q000032:analysis; D017127:Glycation End Products, Advanced / Q000097:blood; D006031:Glycosylation / Q000187:drug effects; D006321:Heart / Q000187:drug effects*; D007328:Insulin / Q000097:blood; D008239:Lysine / Q000031:analogs & derivatives / Q000032:analysis; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
chemical_list: D050859:Betacyanins; D001786:Blood Glucose; D003094:Collagen; D055513:Connective Tissue Growth Factor; D005632:Fructose; D006442:Glycated Hemoglobin; D017127:Glycation End Products, Advanced; D007328:Insulin; D008239:Lysine; D016328:NF-kappa B; D053773:Transforming Growth Factor beta1; C020228:betanin; C048496:N(6)-carboxymethyllysine
keywords: AGEs; Diabetic cardiomyopathy; Insulin; Methylglyoxal; NF-κB