title: A metabolic profiling analysis of the acute toxicological effects of the realgar (As₂S₂) combined with other herbs in Niuhuang Jiedu Tablet using ¹H NMR spectroscopy.
abstract: BACKGROUND
  Niuhuang Jiedu Tablet (NJT), composed of Realgar (As₂S₂), Bovis Calculus Artificialis, Borneolum Synthcticum, Gypsum Fibrosum, Rhei Radix et Rhizoma (RR), Scutellariae Radix (SR), Platycodonis Radix (PR) and Glycyrrhizae Radix et Rhizoma (GR), is an effective formula of traditional Chinese medicine (TCM) used in treating acute tonsillitis, pharyngitis, periodontitis and mouth ulcer. In the formula, significant level of realgar (As₂S₂) as a potentially toxic element is contained. In our pervious experiments, NJT was significantly less toxic than realgar (As₂S₂), and the material bases of toxicity alleviation effect to realgar (As₂S₂) were RR, SR, PR and GR. However, the toxicity alleviation effect of each above mentioned four herbs to realgar (As₂S₂) and their synergistic detoxification effects to realgar (As₂S₂) were still obscure.
  
  
  METHODS
  Male Wistar rats were divided into 11 groups: control, group R (treated with Realgar), group RRSPG (treated with Realgar, RR, SR, PR and GR), group RRSP (treated with Realgar, RR, SR and PR), group RRSG (treated with Realgar, RR, SR and GR), group RRPG (treated with Realgar, RR, PR and GR), group RSPG (treated with Realgar, SR, PR and GR), group RR (treated with Realgar and RR), group RS (treated with Realgar and SR), group RP (treated with Realgar and PR) and group RG (treated with Realgar and GR). Based on (1)H NMR spectra of urine and serum from rats, PCA and PLS-DA were performed to identify different metabolic profiles. Liver and kidney histopathology examinations and serum clinical chemistry analysis were also performed.
  
  
  RESULTS
  The metabolic profiles of groups RR, RS, RP and RG were similar to those of group R, while the metabolic profiles of groups RRSPG, RRSP, RRSG, RRPG and RSPG were almost in line with those of control group. Statistics results were confirmed by the histopathological examination and biochemical assay.
  
  
  CONCLUSIONS
  The present work suggested that the toxicity alleviation effects of RR, SR, PR and GR to realgar (As₂S₂) were not obvious when combined with realgar (As₂S₂) respectively, but they had synergistic detoxification effects on realgar (As₂S₂) mutually.
authors.affiliation: School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, PR China; Key Laboratory of Structure-Based Drug Design and Discovery (Shenyang Pharmaceutical University), Ministry of Education, Shenyang 110016, PR China.
authors.forename: Wenfeng
authors.initials: W
authors.lastname: Xu
authors.affiliation: School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, PR China; Key Laboratory of Structure-Based Drug Design and Discovery (Shenyang Pharmaceutical University), Ministry of Education, Shenyang 110016, PR China.
authors.forename: Haifeng
authors.initials: H
authors.lastname: Wang
authors.affiliation: School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, PR China; Key Laboratory of Structure-Based Drug Design and Discovery (Shenyang Pharmaceutical University), Ministry of Education, Shenyang 110016, PR China.
authors.forename: Gang
authors.initials: G
authors.lastname: Chen
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, PR China.
authors.forename: Wen
authors.initials: W
authors.lastname: Li
authors.affiliation: Mathematics Teaching & Research Section, Shenyang Pharmaceutical University, Shenyang 110016, PR China.
authors.forename: Rongwu
authors.initials: R
authors.lastname: Xiang
authors.affiliation: School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, PR China; Key Laboratory of Structure-Based Drug Design and Discovery (Shenyang Pharmaceutical University), Ministry of Education, Shenyang 110016, PR China.
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Zhang
authors.affiliation: School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, PR China; Key Laboratory of Structure-Based Drug Design and Discovery (Shenyang Pharmaceutical University), Ministry of Education, Shenyang 110016, PR China. Electronic address: peiyueh@vip.163.com.
authors.forename: Yuehu
authors.initials: Y
authors.lastname: Pei
mesh_terms: D000818:Animals; D001152:Arsenicals; D001688:Biological Products; D004365:Drugs, Chinese Herbal / Q000633:toxicity*; D007668:Kidney / Q000187:drug effects / Q000473:pathology; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008297:Male; D055442:Metabolome / Q000187:drug effects*; D066244:Proton Magnetic Resonance Spectroscopy; D017208:Rats, Wistar; D013440:Sulfides / Q000633:toxicity*; D013607:Tablets
chemical_list: D001152:Arsenicals; D001688:Biological Products; D004365:Drugs, Chinese Herbal; D013440:Sulfides; D013607:Tablets; C570000:niuhuang; C058317:arsenic disulfide
keywords: Metabonomics; NMR spectroscopy; Niuhuang Jiedu Tablet; Reaglar (As(2)S(2)); Toxicity