title: One-month toxicokinetic study of SHENMAI injection in rats.
abstract: BACKGROUND
  'SHENMAI' injection (SMI) has been widely used in cardioprotection and modulation of the immune system because of its great efficacy. SMI primarily comprises the saponins from Panax ginseng and Ophiopogon japonicas. The profiles of saponins in SMI during long-term toxicokinetics remain unclear. MiR-146a possesses excellent sensitivity as a bio-marker in the innate immunity modification effect of SMI.
  
  
  OBJECTIVE
  Is to monitor the exposure level of SMI during a one-month toxicokinetic experiment, an analytical method involving ESI-LC-MS/MS technology was developed to determine 20 (S)-protopanaxadiol-type ginsenoside (Rb1, Rb2, Rc, Rd), 20 (S)-protopanaxatriol-type ginsenoside (Rg1, Re, Rf), oleanolic acid-type ginsenoside (Ro), and ophiopogonin D in rats. The levels of AST, CK, ALT, SOD, GSH-pX, MDA, miR-146a, and ECG were measured to explore the effects of SMI in cardiologic function and immune activity.
  
  
  RESULTS
  Results show that the levels of AST, CK, and MDA decreased upon the administration of SMI. The level of miR-146a increased upon the administration of SMI dosage. During the administration of SMI, increasing exposure levels of 20 (S)-protopanaxadiol-type ginsenosides were also observed.
  
  
  CONCLUSIONS
  The 20 (S)-protopanaxadiol-type ginsenosides were considered potential PK/TK markers because of their high exposure levels that continuously increased. Oxidative stress was slightly alleviated during the toxicokinetic study. Based on the level of miR-146a, negatively regulated innate immunity was observed. The regulation became more serious with increasing exposure levels of 20 (S)-protopanaxadiol-type ginsenosides. Negatively regulated innate immunity could be induced by long-term administration of SMI (>0.4g/kg).
authors.affiliation: Center for Safety Evaluation, Zhejiang Academy of Medical Sciences, No. 182 Tianmushan Road, Hangzhou 310013, Zhejiang, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Yu
authors.affiliation: Center for Safety Evaluation, Zhejiang Academy of Medical Sciences, No. 182 Tianmushan Road, Hangzhou 310013, Zhejiang, China. Electronic address: xinyanfei@gmail.com.
authors.forename: Yan-Fei
authors.initials: YF
authors.lastname: Xin
authors.affiliation: Center for Safety Evaluation, Zhejiang Academy of Medical Sciences, No. 182 Tianmushan Road, Hangzhou 310013, Zhejiang, China.
authors.forename: Li-Qiang
authors.initials: LQ
authors.lastname: Gu
authors.affiliation: Center for Safety Evaluation, Zhejiang Academy of Medical Sciences, No. 182 Tianmushan Road, Hangzhou 310013, Zhejiang, China.
authors.forename: Hai-Yan
authors.initials: HY
authors.lastname: Gao
authors.affiliation: Center for Safety Evaluation, Zhejiang Academy of Medical Sciences, No. 182 Tianmushan Road, Hangzhou 310013, Zhejiang, China.
authors.forename: Li-Juan
authors.initials: LJ
authors.lastname: Xia
authors.affiliation: Center for Safety Evaluation, Zhejiang Academy of Medical Sciences, No. 182 Tianmushan Road, Hangzhou 310013, Zhejiang, China.
authors.forename: Zhen-Qiang
authors.initials: ZQ
authors.lastname: You
authors.affiliation: Center for Safety Evaluation, Zhejiang Academy of Medical Sciences, No. 182 Tianmushan Road, Hangzhou 310013, Zhejiang, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Xie
authors.affiliation: Chiatai QingChunbao Pharmaceutical Co., Ltd., Hangzhou, Zhejiang, China.
authors.forename: Zhu-Feng
authors.initials: ZF
authors.lastname: Ma
authors.affiliation: Chiatai QingChunbao Pharmaceutical Co., Ltd., Hangzhou, Zhejiang, China.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Center for Safety Evaluation, Zhejiang Academy of Medical Sciences, No. 182 Tianmushan Road, Hangzhou 310013, Zhejiang, China. Electronic address: nndsvc@mail.hz.zj.cn.
authors.forename: Yao-Xian
authors.initials: YX
authors.lastname: Xuan
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D015415:Biomarkers / Q000097:blood; D003402:Creatine Kinase / Q000097:blood; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000633:toxicity*; D020834:Ethnopharmacology; D005260:Female; D036145:Ginsenosides / Q000008:administration & dosage / Q000097:blood / Q000633:toxicity*; D007113:Immunity, Innate / Q000187:drug effects* / Q000276:immunology; D008297:Male; D008516:Medicine, Chinese Traditional; D035683:MicroRNAs / Q000097:blood; D017207:Rats, Sprague-Dawley; D012503:Saponins / Q000008:administration & dosage / Q000097:blood / Q000633:toxicity*; D013150:Spirostans / Q000008:administration & dosage / Q000097:blood / Q000633:toxicity*; D013997:Time Factors; D066007:Toxicokinetics
chemical_list: D015415:Biomarkers; D004338:Drug Combinations; D004365:Drugs, Chinese Herbal; D036145:Ginsenosides; C554180:MIRN146 microRNA, rat; D035683:MicroRNAs; D012503:Saponins; D013150:Spirostans; C009252:fructus schizandrae, radix ginseng, radix ophiopogonis drug combination; C046996:ophiopogonin D; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D003402:Creatine Kinase
keywords: Ginseoside Rb1 (PubChem CID: 9898279); Ginseoside Rb2 (PubChem CID: 5458674); Ginseoside Rc (PubChem CID: 100018); Ginseoside Rd (PubChem CID: 12855925); Ginseoside Re (PubChem CID: 73149); Ginseoside Rf (PubChem CID: 441922); Ginseoside Rg1 (PubChem CID: 441923); Malondialdehyde (PubChem CID: 10964).; Mir-146a; SHENMAI injection; Toxicokinetic; ophiopogonin D (PubChem CID: 3080802)