Mangiferin attenuates renal fibrosis through down-regulation of osteopontin in diabetic rats.
This study was designed to investigate the effects of mangiferin on renal fibrosis, osteopontin production, and inflammation in the kidney of diabetic rats. Diabetes was induced through the single administration of streptozotocin (55 mg/kg, i.p.). Diabetic rats were treated with mangiferin (15, 30, and 60 mg/kg/day, i.g.) for 9 weeks. The kidney was fixed in 10% formalin for glomerulus fibrosis examination using Masson trichrome staining. Kidney and blood were obtained for assays of the associated biochemical parameters. Chronic mangiferin treatment prevented renal glomerulus fibrosis evidenced by decreases in Mason-stained positive area of glomeruli, protein expression of type IV collagen, and α-smooth muscle actin in the kidney of diabetic rats, in comparison with decreases in mRNA and protein expression of osteopontin as well as protein expression of cyclooxygenase 2 and NF-кB p65 subunit in the renal cortex of diabetic rats. Moreover, mangiferin reduced the levels of interleukin 1β in both the serum and the kidney of diabetic rats. Our findings demonstrate that mangiferin prevents the renal glomerulus fibrosis of diabetic rats, which is realized through the suppression of osteopontin overproduction and inflammation likely via inactivation of NF-кB.
Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical College, Xuzhou, 221004, Jiangsu, China.
Xia
X
Zhu
Ya-Qin
YQ
Cheng
Lei
L
Du
Yu
Y
Li
Fan
F
Zhang
Hao
H
Guo
Yao-Wu
YW
Liu
Xiao-Xing
XX
Yin
D000199:Actins / Q000378:metabolism; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D001835:Body Weight / Q000187:drug effects; D024141:Collagen Type IV / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D015536:Down-Regulation; D005355:Fibrosis; D007249:Inflammation / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D007674:Kidney Diseases / Q000473:pathology; D007678:Kidney Glomerulus / Q000187:drug effects* / Q000473:pathology; D008297:Male; D053495:Osteopontin / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013311:Streptozocin; D051996:Transcription Factor RelA / Q000378:metabolism; D044004:Xanthones / Q000494:pharmacology*
D000199:Actins; D001786:Blood Glucose; D024141:Collagen Type IV; D051546:Cyclooxygenase 2; D053583:Interleukin-1beta; D053495:Osteopontin; D012333:RNA, Messenger; D013311:Streptozocin; D051996:Transcription Factor RelA; D044004:Xanthones; C498145:Rela protein, rat; C506897:Spp1 protein, rat; C498862:Acta2 protein, rat; C013592:mangiferin; C489691:Ptgs2 protein, rat
diabetic nephropathy; glomerulus fibrosis; inflammation; mangiferin; osteopontin