title: Dietary safety of cycloastragenol from Astragalus spp.: subchronic toxicity and genotoxicity studies.
abstract: Extracts, teas, and other preparations of Astragalus roots (e.g., Radix Astragali) are historically recognized traditional medicines and foods. Cycloastragenol (CAG), a bioactive triterpene aglycone from Astragalus root extracts, is being developed as a modern dietary ingredient. To this end, studies assessing subchronic toxicity and genotoxic potential were conducted. In the subchronic study with recovery component, rats ingested 0, 40, 80, or 150 mg/kg/d CAG by oral gavage for ⩾91 consecutive days. No treatment-related mortalities occurred and no cardiac effects were identified. Although several endpoints among those monitored (i.e., clinical observations, body weight, food consumption, ophthalmology, urinalysis, hematology, clinical chemistry, gross pathology, organ weights, or histopathology) exhibited statistically significant effects, none was adverse. The oral no-observed-adverse-effect level (NOAEL) for CAG was >150 mg/kg/d in male and female rats. CAG (⩽5000 μg/plate) did not induce mutagenicity in Salmonella typhimurium or Escherichia coli tester strains. Although the in vitro chromosome aberration assay gave a moderately positive response (likely due to poor solubility) for one intermediate concentration (1.50mM) with metabolic activation, responses were negative in all other test groups. Finally, in the in vivo micronucleus assay no clastogenicity was observed in peripheral erythrocytes from mice administered 2000 mg/kg CAG by intraperitoneal injection.
authors: Burdock Group, 859 Outer Road, Orlando, FL 32814, United States. Electronic address: nszabo@burdockgroup.com.
authors: Nancy J
authors: NJ
authors: Szabo
mesh_terms: D000818:Animals; D027883:Astragalus Plant / Q000737:chemistry*; D002869:Chromosome Aberrations; D004305:Dose-Response Relationship, Drug; D005247:Feeding Behavior / Q000187:drug effects; D005260:Female; D008297:Male; D015162:Micronucleus Tests; D019055:No-Observed-Adverse-Effect Level; D009929:Organ Size / Q000187:drug effects; D010936:Plant Extracts / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012502:Sapogenins / Q000302:isolation & purification / Q000633:toxicity*; D059550:Toxicity Tests, Subchronic
chemical_list: D010936:Plant Extracts; D012502:Sapogenins; C061014:cycloastragenol
keywords: 2-AA; 2-NF; 2-aminoanthracene; 2-nitrofluorene; 9-AA; 9-aminoacridine; AAALAC; ANOVA; AST; ATCC; American Type Culture Collection; Analysis of Variance; Association for Assessment and Accreditation of Laboratory Animal Care International; Astragalus; CAG; CK; CPA; Clastogenic; Cycloastragenol; DMSO; EMS; FOB; GLP; GRAS; Genotoxic; IACUC; ICH; Institutional Animal Care and Use Committee; International Conference on Harmonisation; LDH; MCH; MEM; MMS; MTD; Mutagenic; NOAEL; NaN(3); OECD; Organisation for Economic Co-operation and Development; PCE; Subchronic; TCM; WHO; World Health Organization; aspartate aminotransferase; astragaloside; creatine phosphokinase; cycloastragenol; cyclophosphamide; dimethyl sulfoxide; ethylmethanesulfonate; functional observational battery; generally recognized as safe; good laboratory practice; i.p.; intraperitoneal; lactate dehydrogenase; maximum tolerated dose; mean corpuscular hemoglobin; methylmethanesulfonate; minimal essential medium; no-observed-adverse-effect level; polychromatic erythrocytes; rel. PCE; relative PCE; sodium azide; traditional Chinese medicine