title: Metabolomic and lipidomic study of the protective effect of Chaihuang-Yishen formula on rats with diabetic nephropathy.
abstract: BACKGROUND
  Chaihuang-Yishen formula (CHYS) is a Chinese herbal formula that has been shown clinically to effectively treat chronic kidney disease including diabetic nephropathy (DN), also known as diabetic kidney disease. Our previous animal studies showed that numerous intrarenal metabolites were associated with the development of DN. In the present work, an integrated metabolomic and lipidomic analysis was used to further examine whether CHYS could attenuate the development of DN by regulating the disordered metabolic pathways.
  
  
  METHODS
  Progressive diabetic kidney disease was induced in Wistar rats by uninephrectomy and a single intraperitoneal injection of streptozocin. Over 20 weeks, one group of animals was treated with CHYS and another group went untreated. Effects of CHYS on metabolomic and lipidomic changes in the renal cortex of diabetic rats were studied using gas chromatography/time-of-flight mass spectrometry, ultra-performance liquid chromatography/time-of-flight mass spectrometry, and tandem MS-based metabolomic and lipidomic. The well-established drug fosinopril was used as positive control throughout the experiment.
  
  
  RESULTS
  Like fosinopril, treatment with CHYS produced a renoprotective effect against DN. Metabolomic and lipidomic analyses showed that the therapeutic effect of CHYS on DN was significantly associated with inhibition of the elevated organic toxins including several uremic toxins and glucuronides, and normalization of diminished phospholipids, especially sphingomyelins.
  
  
  CONCLUSIONS
  Improved abnormal metabolic and lipidomic disorders, such as accumulation of uremic toxins and glucuronides and phospholipids, may be mechanisms by which treatment of CHYS inhibits DN. Results from this study provide new evidence for the pharmacologic characteristics of CHYS on DN.
authors.affiliation: Department of Pharmacy, China-Japan Friendship Hospital, Beijing, China.
authors.forename: Tie
authors.initials: T
authors.lastname: Zhao
authors.affiliation: Department of Pharmacology, Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, Yinghua Donglu, Hepingli, Chaoyang District, Beijing 100029, China.
authors.forename: Haojun
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Pharmacy, China-Japan Friendship Hospital, Beijing, China.
authors.forename: Xianglin
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Pharmacology, Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, Yinghua Donglu, Hepingli, Chaoyang District, Beijing 100029, China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Zhao
authors.affiliation: Department of Medicine and Therapeutics, and Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong SAR, China.
authors.forename: Hui-Yao
authors.initials: HY
authors.lastname: Lan
authors.affiliation: Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology (Ministry of Education), Department of Chemistry, Tsinghua University, Beijing, China.
authors.forename: Qionglin
authors.initials: Q
authors.lastname: Liang
authors.affiliation: Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology (Ministry of Education), Department of Chemistry, Tsinghua University, Beijing, China.
authors.forename: Guoan
authors.initials: G
authors.lastname: Luo
authors.affiliation: Department of Pharmacology, Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, Yinghua Donglu, Hepingli, Chaoyang District, Beijing 100029, China. Electronic address: lp8675@163.com.
authors.forename: Ping
authors.initials: P
authors.lastname: Li
mesh_terms: D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism; D003928:Diabetic Nephropathies / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism*; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D007672:Kidney Cortex / Q000187:drug effects / Q000378:metabolism; D008297:Male; D055442:Metabolome / Q000187:drug effects*; D055432:Metabolomics / Q000379:methods; D051381:Rats; D017208:Rats, Wistar; D013311:Streptozocin / Q000494:pharmacology
chemical_list: D004365:Drugs, Chinese Herbal; D013311:Streptozocin
keywords: Chaihuang-Yishen formula; Diabetic nephropathy; Lipidomics; Metabolomics; UPLC–TOF MS