Metabonomic analysis of the therapeutic effect of Zhibai Dihuang Pill in treatment of streptozotocin-induced diabetic nephropathy.
BACKGROUND
Zhibai Dihuang Pill (ZDP) is one of ancient traditional Chinese medicines (TCMs), which is usually used for the treatment of kidney deficiency for thousands of years in China.


OBJECTIVE
Traditional Chinese medicines (TCMs) usually operate in vivo through multi-components, multi-ways and multi-targets. However, the molecular mechanisms of TCMs remain unclear. In the present work, nuclear magnetic resonance (NMR)-based metabonomic analysis was used to evaluate the therapeutic effect of Zhibai Dihuang Pill (ZDP) on diabetic nephropathy (DN) rats induced by streptozotocin and to address the underlying molecular mechanism.


METHODS
Male rats were divided into three groups: control, DN and ZDP-treated DN (ZDP-DN), respectively. Based on (1)H NMR spectra of sera, urine and kidney extracts from the rats, principle component analysis (PCA) was performed to identify different metabolic profiles. Kidney portions and serum and urine samples were also subjected to histopathological or biochemical examination.


RESULTS
PCA scores plots demonstrate that the cluster of DN rats is separated from that of control rats, while some of ZDP-DN rats are located close to control rats, indicating that metabolic profiles of these ZDP-DN rats are restored toward those of control rats. Our results illustrate that ZDP treatment could lower the levels of lipids and 3-hydrobutyrate, and raise the level of lactate in sera of DN rats. Moreover, ZDP treatment could also reduce the levels of glucose, 3-hydrobutyrate and lactate, enhance the level of betaine in kidney tissues.


CONCLUSIONS
Our study indicates that ZDP treatment can ameliorate DN symptoms by intervening in some dominating metabolic pathways, such as inhibiting glucose and lipid metabolism, enhancing methylamine metabolism. Our work may be of benefit to both evaluation of the therapeutic effect of TCM and elucidation of the underlying molecular mechanism.
Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
Liangcai
L
Zhao
Hongchang
H
Gao
Yongxiang
Y
Zhao
Donghai
D
Lin
D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D004365:Drugs, Chinese Herbal / Q000494:pharmacology / Q000627:therapeutic use*; D005947:Glucose / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D007668:Kidney / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D050356:Lipid Metabolism / Q000187:drug effects; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D055432:Metabolomics; D008744:Methylamines / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D004365:Drugs, Chinese Herbal; D007004:Hypoglycemic Agents; D008744:Methylamines; C540472:zhibai dihuang; C027451:methylamine; D005947:Glucose