title: Subchronic exposure to mitragynine, the principal alkaloid of Mitragyna speciosa, in rats.
abstract: BACKGROUND
  Mitragyna speciosa is a popular medicinal plant in Southeast Asia which is commonly used for its morphine-like effects. Although the analgesic properties of Mitragyna speciosa and its ability to ameliorate withdrawal signs after abrupt cessation of opioid abuse are well known, information about the long-term safety of the plant's active compounds is lacking. In this work, we evaluated the effects of sub-chronic exposure to mitragynine, the principal alkaloid of Mitragyna speciosa leaves in rats.
  
  
  METHODS
  Male and female Sprague-Dawley rats received three doses of mitragynine (1, 10, 100mg/kg, p.o) for 28 days respectively. Food intake and relative body weight were measured during the experiment. After completion of drug treatment biochemical, hematological, and histological analyses were performed.
  
  
  RESULTS
  No mortality was observed in any of the treatment groups. The groups of rats treated with the lower and intermediate doses showed no toxic effects during the study. However, the relative body weight of the group of female rats treated with the 100mg/kg dose was decreased significantly. Food intake also tended to decrease in the same group. Only relative liver weight increased after treatment with the high dose of mitragynine (100mg/ kg) in both the male and female treatment groups of rats. Biochemical and hematological parameters were also altered especially in high dose treatment group which corresponds to the histopathological changes.
  
  
  CONCLUSIONS
  The study demonstrated that mitragynine is relatively safe at lower sub-chronic doses (1-10mg/kg) but exhibited toxicity at a highest dose (sub-chronic 28 days: 100mg/kg). This was confirmed by liver, kidney, and brain histopathological changes, as well as hematological and biochemical changes.
authors: Centre for Drug Research, Universiti Sains Malaysia, 11800 Minden, Penang, Malaysia.
authors: Azadeh
authors: A
authors: Sabetghadam
authors: Surash
authors: S
authors: Ramanathan
authors: Sreenivasan
authors: S
authors: Sasidharan
authors: Sharif Mahsufi
authors: SM
authors: Mansor
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D004435:Eating / Q000187:drug effects; D005260:Female; D007668:Kidney / Q000187:drug effects / Q000473:pathology; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008297:Male; D032065:Mitragyna / Q000737:chemistry*; D009928:Organ Specificity; D018515:Plant Leaves / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D046948:Secologanin Tryptamine Alkaloids / Q000008:administration & dosage / Q000302:isolation & purification / Q000633:toxicity*; D059550:Toxicity Tests, Subchronic
chemical_list: D046948:Secologanin Tryptamine Alkaloids; C001801:mitragynine