title: Untargeted serum metabolomics reveals Fu-Zhu-Jiang-Tang tablet and its optimal combination improve an impaired glucose and lipid metabolism in type II diabetic rats.
abstract: Fu-Zhu-Jiang-Tang tablet, a six-herb preparation, was proved to show beneficial effects on type II diabetes patients in clinical. This study aims to optimize the component proportion of the six-herb preparation and explore the serum metabolic signatures of type II diabetes rats after treatment with Fu-Zhu-Jiang-Tang tablet and its optimal combination. The component proportion of the preparation was optimized using uniform experimental design and machine learning techniques. Untargeted GC-MS metabolomic experiments were carried out with serum samples from model group and treatment groups. Data were normalized, multivariate and univariate statistical analysis performed and metabolites of interest putatively identified. 23 metabolites were significantly changed by Fu-Zhu-Jiang-Tang tablet treatment and the majority of these were decreased, including various carbohydrates (glucose, mannose, fructose, allose and gluconic acid), unsaturated fatty acids (palmitic acid, 9-octadecenoic acid, oleic acid, arachidonic acid), alanine, valine, propanoic acid, 3-hydroxybutyrate, along with pyrimidine and cholesterol. Increased concentrations of oxalic acid, leucine, glycine, serine, threonine, proline, lysine and citrate were observed. In the optimal combination-fed group, 21 metabolites were significantly affected and strikingly, the magnitudes of changes here were generally much greater than that of Fu-Zhu-Jiang-Tang tablet treated rats. 18 metabolites affected in both groups included various carbohydrates (mannose, glucose, allose, fructose and gluconic acid), unsaturated fatty acids (palmitic acid, 9-octadecenoic acid, oleic acid and arachidonic acid), short-chain fatty acids (oxalic acid, 3-hydroxybutyrate), and amino acids (alanine, valine, leucine, glycine, proline and lysine), as well as pyrimidine. Metabolites exclusively affected in optimal combination treated rat included succinic acid, cysteine and phenylalanine, whilst four metabolites (propanoic acid, citrate, serine and threonine) were only altered in Fu-Zhu-Jiang-Tang tablet treated rat. Our investigation demonstrated Fu-Zhu-Jiang-Tang tablet and its optimal combination treatments were able to ameliorate impaired glucose and lipid metabolism, down- regulate the high level of glucose to a lower level and reverse abnormal levels of metabolites in serum of type II diabetes rats. However, the optimal combination treatment was able to maximize the magnitudes of changes in some metabolites. These findings may be helpful in clarifying the anti-diabetic mechanism of FZJT tablet and its optimal combination.
authors.affiliation: School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, PR China; Jiangsu Key Laboratory of Chinese Medicine Processing, Nanjing University of Chinese Medicine, Nanjing, 210023, PR China. Electronic address: taoyi1985812@126.com.
authors.forename: Yi
authors.initials: Y
authors.lastname: Tao
authors.affiliation: School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, PR China; Jiangsu Key Laboratory of Chinese Medicine Processing, Nanjing University of Chinese Medicine, Nanjing, 210023, PR China.
authors.forename: Xi
authors.initials: X
authors.lastname: Chen
authors.affiliation: School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, PR China; Jiangsu Key Laboratory of Chinese Medicine Processing, Nanjing University of Chinese Medicine, Nanjing, 210023, PR China.
authors.forename: Hao
authors.initials: H
authors.lastname: Cai
authors.affiliation: School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, PR China; Jiangsu Key Laboratory of Chinese Medicine Processing, Nanjing University of Chinese Medicine, Nanjing, 210023, PR China; Department of Microbiology and Immunology, Nanjing University of Chinese Medicine, Nanjing, 210023, PR China.
authors.forename: Weidong
authors.initials: W
authors.lastname: Li
authors.affiliation: School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, PR China; Jiangsu Key Laboratory of Chinese Medicine Processing, Nanjing University of Chinese Medicine, Nanjing, 210023, PR China.
authors.forename: Baochang
authors.initials: B
authors.lastname: Cai
authors.affiliation: School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, PR China; Jiangsu Key Laboratory of Chinese Medicine Processing, Nanjing University of Chinese Medicine, Nanjing, 210023, PR China.
authors.forename: Chuan
authors.initials: C
authors.lastname: Chai
authors.affiliation: School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, PR China.
authors.forename: Liuqing
authors.initials: L
authors.lastname: Di
authors.affiliation: Department of Microbiology and Immunology, Nanjing University of Chinese Medicine, Nanjing, 210023, PR China.
authors.forename: Liyun
authors.initials: L
authors.lastname: Shi
authors.affiliation: School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, PR China.
authors.forename: Lihong
authors.initials: L
authors.lastname: Hu
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D004365:Drugs, Chinese Herbal / Q000627:therapeutic use*; D005947:Glucose / Q000378:metabolism*; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D050356:Lipid Metabolism / Q000187:drug effects*; D008297:Male; D055442:Metabolome / Q000187:drug effects*; D055432:Metabolomics; D010179:Pancreas / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D001786:Blood Glucose; D004365:Drugs, Chinese Herbal; D007004:Hypoglycemic Agents; D005947:Glucose
keywords: GC–MS; Metabolomic; Type II diabetes; Uniform experimental design