Treatment of db/db diabetic mice with triptolide: a novel therapy for diabetic nephropathy.
BACKGROUND
Current research on the progression of diabetic nephropathy (DN) suggests many important factors; metabolic disturbance, haemodynamic abnormity, chronic inflammation, oxidative stress, innate immune system activation and podocyte lesion. Triptolide, which is active diterpene purified from the traditional Chinese medicine Tripterygium wilfordii Hook F (TwHF), has anti-inflammatory, anti-oxidative, immunosuppressive and podocyte-protective effects. Herein, we investigated the therapeutic effects of triptolide on DN in db/db diabetic mice and studied the potential mechanisms.


METHODS
db/db mice with DN were administrated with triptolide or valsartan. After 4, 8 and 12 weeks of treatment, 24-h urine albumin level, blood biochemical parameters and body weight were measured. Glomerulus area, glomerulus volume to Bowman's capsule volume ratio, podocyte changes and inflammatory and oxidative stress markers were quantitatively determined to evaluate renal lesions.


RESULTS
The albuminuria in db/db diabetic mice was markedly attenuated after triptolide treatment, accompanied with alleviated glomerular hypertrophy and podocyte injury. In addition, the inflammation and oxidative stress in the kidneys were also attenuated, accompanied with improved hyperlipidaemia and obesity. The efficacy increased with the prolonging of triptolide treatment, and the efficacy in high-dose triptolide group was superior to that in the low-dose group. The effect of triptolide on glomerular hypertrophy was similar to valsartan, but the effects of triptolide on renal inflammation and oxidative stress were more profound than those of valsartan.


CONCLUSIONS
Triptolide can dramatically attenuate albuminuria and renal lesion accompanied with dyslipidaemia and obesity in db/db diabetic mice. It is a new drug that exerts comprehensive protective effects on preventing DN progression.
Gao
Qing
Q
Research Institute of Nephrology, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China.
Shen
Wenwen
W
Qin
Weisong
W
Zheng
Chunxia
C
Zhang
Mingchao
M
Zeng
Caihong
C
Wang
Shengyu
S
Wang
Jianping
J
Zhu
Xiaodong
X
Liu
Zhihong
Z
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D001786:Blood Glucose / Q000032:analysis; D001835:Body Weight / Q000187:drug effects; D018932:Chemokine CCL2 / Q000032:analysis; D003893:Desmin / Q000032:analysis; D003928:Diabetic Nephropathies / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D004224:Diterpenes / Q000627:therapeutic use*; D004852:Epoxy Compounds / Q000627:therapeutic use; D005919:Glomerular Filtration Rate; D007150:Immunohistochemistry; D007668:Kidney / Q000473:pathology / Q000503:physiopathology / Q000648:ultrastructure; D008055:Lipids / Q000097:blood; D008099:Liver / Q000503:physiopathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008854:Microscopy, Electron; D010616:Phenanthrenes / Q000627:therapeutic use*; D050199:Podocytes / Q000473:pathology; D017382:Reactive Oxygen Species / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology; D013777:Tetrazoles / Q000627:therapeutic use; D014633:Valine / Q000031:analogs & derivatives / Q000627:therapeutic use; D000068756:Valsartan
D000894:Anti-Inflammatory Agents, Non-Steroidal; D001786:Blood Glucose; C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D003893:Desmin; D004224:Diterpenes; D004852:Epoxy Compounds; D008055:Lipids; D010616:Phenanthrenes; D017382:Reactive Oxygen Species; D013777:Tetrazoles; C001899:triptolide; D000068756:Valsartan; D014633:Valine