title: Genotoxicity, acute and subchronic toxicity studies of nano liposomes of Orthosiphon stamineus ethanolic extract in Sprague Dawley rats.
abstract: BACKGROUND
  Orthosiphon stamineus (OS) Benth is a medicinal plant and native in Southeast Asia. Pharmacological effects of OS are attributed to the presence of lipophilic flavones. However; lipophilic compounds suffer from poor aqueous solubility which limits the OS oral bioavailability and therapeutic applications. Therefore, OS was prepared in nano formulation form using liposomes from soybean phospholipids. The aim of the present study is to evaluate the in vitro genotoxicity and in vivo oral toxicity of nano liposomes of OS ethanolic extract (OS-EL).
  
  
  METHODS
  In the acute toxicity study Sprague Dawley female rats were given a single dose of the OS-EL at 5000 mg/kg/day orally and screened for two weeks after administration. In the subchronic study, three different doses of OS-EL were administered for 28 days. Mortality, clinical signs, body weight changes, hematological and biochemical parameters, gross findings, organ weights, and histological parameters were monitored during the study. Genotoxicity was assessed using the Ames test with the TA98 and TA100 Salmonella typhimurium strains. High-performance liquid chromatography was performed for identification and quantification of the major marker compounds in OS-EL. Heavy metal detection was performed using an atomic absorption spectrometer.
  
  
  RESULTS
  The acute toxicity study showed that the LD50 of the extract was greater than 5000 mg/kg. In the repeated dose 28-day oral toxicity study, the administration of 250 mg/kg, 500 mg/kg, and 1000 mg/kg/day of OS-EL per body weight revealed no significant difference in food and water consumptions, bodyweight change, haematological and biochemical parameters, relative organ weights, gross findings or histopathology compared to the control group. The Ames test revealed that the OS-EL did not have any potential to induce gene mutations in S. Typhimurium.
  
  
  CONCLUSIONS
  Analyses of these results with the information of signs, behaviour, and health monitoring could lead to the conclusion that the long-term oral administration of OS-EL for 28 days does not cause sub-chronic toxicity.
authors.affiliation: Department of Pharmaceutical Chemistry, School of Pharmaceutical Sciences, Universiti Sains Malaysia, Minden, Penang, 11800, Malaysia.
authors.forename: Armaghan
authors.initials: A
authors.lastname: Shafaei
authors.affiliation: Department of Pharmaceutical Chemistry, School of Pharmaceutical Sciences, Universiti Sains Malaysia, Minden, Penang, 11800, Malaysia.
authors.forename: Kameh
authors.initials: K
authors.lastname: Esmailli
authors.affiliation: Department of Pharmacology, School of Pharmaceutical Sciences, EMAN Testing & Research Laboratory, Universiti Sains Malaysia, Minden, Penang, 11800, Malaysia.
authors.forename: Elham
authors.initials: E
authors.lastname: Farsi
authors.affiliation: Department of Pharmaceutical Chemistry, School of Pharmaceutical Sciences, Universiti Sains Malaysia, Minden, Penang, 11800, Malaysia.
authors.forename: Abdalrahim F A
authors.initials: AF
authors.lastname: Aisha
authors.affiliation: Department of Pharmacology, School of Pharmaceutical Sciences, EMAN Testing & Research Laboratory, Universiti Sains Malaysia, Minden, Penang, 11800, Malaysia.
authors.forename: Amin Malik Shah
authors.initials: AM
authors.lastname: Abul Majid
authors.affiliation: Department of Pharmaceutical Chemistry, School of Pharmaceutical Sciences, Universiti Sains Malaysia, Minden, Penang, 11800, Malaysia. ismailzhari@gmail.com.
authors.forename: Zhari
authors.initials: Z
authors.lastname: Ismail
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D001835:Body Weight / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000737:chemistry; D005260:Female; D007928:Lethal Dose 50; D008081:Liposomes / Q000008:administration & dosage / Q000493:pharmacokinetics; D009152:Mutagenicity Tests; D009929:Organ Size / Q000187:drug effects; D031342:Orthosiphon / Q000737:chemistry*; D010936:Plant Extracts / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012486:Salmonella typhimurium / Q000187:drug effects / Q000235:genetics; D012995:Solubility; D018675:Toxicity Tests
chemical_list: D008081:Liposomes; D010936:Plant Extracts; D000431:Ethanol