title: Effect of a botanical composition, UP446, on respiratory, cardiovascular and central nervous systems in beagle dogs and rats.
abstract: Extensive safety evaluation of UP446, a botanical composition comprised of standardized extracts from roots of Scutellaria baicalensis and heartwoods of Acacia catechu, has been reported previously. Here we carried out additional studies to assess the effect of UP446 on respiratory, cardiovascular and central nervous (CNS) systems. A Functional observational battery (FOB) and whole body plethysmography system in rats and implanted telemetry in dogs were utilized to evaluate the potential CNS, respiratory and cardiovascular toxicity, respectively. UP446 was administered orally at dose levels of 800, 2000 and 5000 mg/kg to SpragueDawley rats and at 4 ascending dose levels (0, 250, 500 and 1000 mg/kg) to beagle dogs. No abnormal effects were observed on the cage side, open field, hand held, and sensori-motor observations suggestive of toxicity in respiratory, cardiovascular and central nervous (CNS) systems. Rectal temperatures were comparable for each treatment groups. Similarly, respiratory rate, tidal volume and minute volume were unaffected by any of the treatment groups. No UP446 related changes were observed on blood pressure, heart rate and electrocardiogram in beagle dogs at dose levels of 250, 500 and 1000 mg/kg. Some minor incidental, non-dose correlated changes were observed in the FOB assessment. These data suggest that UP446 has minimal or no pharmaco-toxicological effect on the respiratory, cardiovascular and central nervous systems.
authors.affiliation: Unigen Inc., 3005 1st Ave., Seattle, WA 98121, USA. Electronic address: myimam@unigen.net.
authors.forename: Mesfin
authors.initials: M
authors.lastname: Yimam
authors.affiliation: Unigen Inc., #450-86, Maebong-Ro, Dongnam-Gu, Cheonan-Si, Chungnam 330-863, Republic of Korea.
authors.forename: Young Chul
authors.initials: YC
authors.lastname: Lee
authors.affiliation: Unigen Inc., 3005 1st Ave., Seattle, WA 98121, USA.
authors.forename: Qi
authors.initials: Q
authors.lastname: Jia
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002319:Cardiovascular System / Q000187:drug effects*; D002490:Central Nervous System / Q000187:drug effects*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004562:Electrocardiography; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D010936:Plant Extracts / Q000008:administration & dosage / Q000633:toxicity*; D028321:Plant Preparations / Q000008:administration & dosage / Q000633:toxicity*; D010993:Plethysmography, Whole Body; D017207:Rats, Sprague-Dawley; D012119:Respiration / Q000187:drug effects; D012137:Respiratory System / Q000187:drug effects*; D018570:Risk Assessment; D013686:Telemetry; D013997:Time Factors; D018675:Toxicity Tests / Q000379:methods
chemical_list: D010936:Plant Extracts; D028321:Plant Preparations; C574443:UP446
keywords: Acacia catechu; Cardiovascular system; Central nervous system; Respiratory system; Scutellaria baicalensis