Silymarin: a novel antioxidant with antiglycation and antiinflammatory properties in vitro and in vivo.
The current study was designed to evaluate the effects of silymarin (SM) on advanced glycation endproduct (AGE) formation and monocyte activation induced by S100b, a specific ligand of receptor for AGEs. The in vivo verification of antiglycation, antioxidant, and antiinflammatory capacities was examined by 12 weeks of SM administration in streptozotocin-diabetic rats. In vitro glycation assays demonstrated that SM exerted marked inhibition during the late stages of glycation and subsequent crosslinking. Dual action mechanisms, namely, antioxidant and reactive carbonyl trapping activities, may contribute to its antiglycation effect. SM produced a significant decrease in monocytic interleukin-1β and COX-2 levels and prevented oxidant formation caused by S100b, which appeared to be mediated by inhibition of p47phox membrane translocation. Chromatin immunoprecipitation demonstrated that S100b increased the recruitment of nuclear factor-kappaB transcription factor as well as cAMP response element-binding-binding protein and coactivator-associated arginine methyltransferase-1 cofactors to the interleukin-1β promoter, whereas these changes were inhibited with SM treatment. In vivo, SM reduced tissue AGE accumulation, tail collagen crosslinking, and concentrations of plasma glycated albumin. Levels of oxidative and inflammatory biomarkers were also significantly decreased in SM-treated groups compared with the diabetic group. These data suggest that SM supplementation may reduce the burden of AGEs in diabetics and may prevent resulting complications.
Wu
Chi-Hao
CH
Department of Food Science and Biotechnology, National Chung Hsing University, Taichung, Taiwan.
Huang
Shang-Ming
SM
Yen
Gow-Chin
GC
D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D001011:Aorta / Q000166:cytology / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D002460:Cell Line; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000378:metabolism; D019587:Dietary Supplements; D017127:Glycation End Products, Advanced / Q000378:metabolism*; D006031:Glycosylation; D006801:Humans; D007249:Inflammation / Q000378:metabolism*; D008297:Male; D009000:Monocytes / Q000166:cytology / Q000502:physiology; D019255:NADPH Oxidases / Q000378:metabolism; D009414:Nerve Growth Factors / Q000378:metabolism; D010084:Oxidation-Reduction; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins / Q000378:metabolism; D012838:Silymarin / Q000627:therapeutic use*; D051996:Transcription Factor RelA / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000975:Antioxidants; D015415:Biomarkers; D017127:Glycation End Products, Advanced; D009414:Nerve Growth Factors; D017382:Reactive Oxygen Species; C498145:Rela protein, rat; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins; C579160:S100B protein, human; C579158:S100b protein, rat; D012838:Silymarin; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha; D019255:NADPH Oxidases; C060505:neutrophil cytosolic factor 1