Ameliorative effects of arctiin from Arctium lappa on experimental glomerulonephritis in rats.
Membranous glomerulonephritis (MGN) remains the most common cause of adult-onset nephrotic syndrome in the world and up to 40% of untreated patients will progress to end-stage renal disease. Although the treatment of MGN with immunosuppressants or steroid hormones can attenuate the deterioration of renal function, numerous treatment-related complications have also been established. In this study, the ameliorative effects of arctiin, a natural compound isolated from the fruits of Arctium lappa, on rat glomerulonephritis induced by cationic bovine serum albumin (cBSA) were determined. After oral administration of arctiin (30, 60, 120 mg/kgd) for three weeks, the levels of serum creatinine (Scr) and blood urea nitrogen (BUN) and 24-h urine protein content markedly decreased, while endogenous creatinine clearance rate (ECcr) significantly increased. The parameters of renal lesion, hypercellularity, infiltration of polymorphonuclear leukocyte (PMN), fibrinoid necrosis, focal and segmental proliferation and interstitial infiltration, were reversed. In addition, we observed that arctiin evidently reduced the levels of malondialdehyde (MDA) and pro-inflammatory cytokines including interleukin-6 (IL-6) and tumor necrosis factor (TNF-alpha), suppressed nuclear factor-kappaB p65 (NF-kappaB) DNA binding activity, and enhanced superoxide dismutase (SOD) activity. These findings suggest that the ameliorative effects of arctiin on glomerulonephritis is carried out mainly by suppression of NF-kappaB activation and nuclear translocation and the decreases in the levels of these pro-inflammatory cytokines, while SOD is involved in the inhibitory pathway of NF-kappaB activation. Arctiin has favorable potency for the development of an inhibitory agent of NF-kappaB and further application to clinical treatment of glomerulonephritis, though clinical studies are required.
Wu
Jian-Guo
JG
Department of Pharmacognosy, School of Pharmacy, Second Military Medical University, Shanghai 200433, PR China.
Wu
Jin-Zhong
JZ
Sun
Lian-Na
LN
Han
Ting
T
Du
Jian
J
Ye
Qi
Q
Zhang
Hong
H
Zhang
Yu-Guang
YG
D000818:Animals; D031170:Arctium / Q000737:chemistry*; D004247:DNA / Q000378:metabolism; D004365:Drugs, Chinese Herbal / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use*; D005663:Furans / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use*; D005921:Glomerulonephritis / Q000188:drug therapy* / Q000473:pathology / Q000652:urine; D005960:Glucosides / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use*; D015850:Interleukin-6 / Q000097:blood; D007668:Kidney / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D007677:Kidney Function Tests; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D008517:Phytotherapy; D011507:Proteinuria / Q000188:drug therapy; D051381:Rats; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
D004365:Drugs, Chinese Herbal; D005663:Furans; D005960:Glucosides; D015850:Interleukin-6; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D008315:Malondialdehyde; D004247:DNA; D013482:Superoxide Dismutase; C077992:arctiin