title: Subchronic safety evaluation of CMS-1 (a botanical antihypertensive product derived from Semen Cnidium monnieri) in Sprague-Dawley rats and beagle dogs.
abstract: CMS-1, mainly composed of imperatorin as its active compound, is a partially purified fraction of a Chinese herbal medicine, Semen Cnidium monnieri. CMS-1 has the potential to be further developed as a new treatment for hypertension. Thus, we studied its toxicity in both Sprague-Dawley rats and beagle dogs. Rats (0-900mg/kg/day) and dogs (0-450mg/kg/day) received CMS-1 orally for 30 consecutive days, followed by a 15-day recovery period. The major target organs of CMS-1 toxicity are the GI (inappetence), liver (hepatocellular necrosis, enzyme elevation), thymus (atrophy), cardiovascular (hypotension), changes in ECG T and P waveforms, elevation of nitrous oxide levels and hematological (RBC parameters disturbances) systems. Most treatment-induced adverse effects were reversible or showed a progressive recovery upon discontinuation of the treatment. The No Observed Adverse Effect Level (NOAEL) was 100mg/kg/day for rats and 50mg/kg/day for dogs. This non-clinical study suggests that clinical monitoring of CMS-1 in patients should focus on the gastrointestinal system, blood tests for liver functions, electrolytes, and blood homeostasis, cardiovascular functions, and immune functions.
authors.affiliation: Department of Hygiene and Health Toxicology, Second Military Medical University, Shanghai 200433, China.
authors.forename: Xue-Lian
authors.initials: XL
authors.lastname: Gong
authors.affiliation: Department of Hygiene and Health Toxicology, Second Military Medical University, Shanghai 200433, China.
authors.forename: Ting-Ting
authors.initials: TT
authors.lastname: Gao
authors.affiliation: Department of Respiratory Medicine, Changhai Hospital, Second Military Medical University, Shanghai 200433, China.
authors.forename: Li-Jun
authors.initials: LJ
authors.lastname: Zhao
authors.affiliation: Department of Hygiene and Health Toxicology, Second Military Medical University, Shanghai 200433, China.
authors.forename: Hai
authors.initials: H
authors.lastname: Zhu
authors.affiliation: Department of Hygiene and Health Toxicology, Second Military Medical University, Shanghai 200433, China.
authors.forename: Zhen-Na
authors.initials: ZN
authors.lastname: Xia
authors.affiliation: Research & Engineering Center for Natural Medicine, Xi'an Jiaotong University, Xi'an 710061, China. Electronic address: lvlu2004@mail.xjtu.edu.cn.
authors.forename: Wen
authors.initials: W
authors.lastname: Lu
authors.affiliation: Department of Hygiene and Health Toxicology, Second Military Medical University, Shanghai 200433, China. Electronic address: newdrug@smmu.edu.cn.
authors.forename: Guo-Cai
authors.initials: GC
authors.lastname: Lu
mesh_terms: D000818:Animals; D000959:Antihypertensive Agents / Q000009:adverse effects*; D031048:Cnidium / Q000009:adverse effects*; D004285:Dogs; D005260:Female; D006403:Hematologic Tests / Q000379:methods; D008297:Male; D009609:Nitrous Oxide / Q000378:metabolism; D019055:No-Observed-Adverse-Effect Level; D058958:Organs at Risk; D010946:Plants, Medicinal / Q000009:adverse effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012449:Safety
chemical_list: D000959:Antihypertensive Agents; D009609:Nitrous Oxide
keywords: Beagle dogs; CMS-1; Imperatorin; Rats; Subchronic toxicity