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Furthermore, beagle dogs were administered IAAS (10, 30, 60\u00a0mg\/kg\u00a0bw) once via the duodenum to evaluate its effects on the cardiovascular and respiratory systems. IAAS with or without S9-induced metabolic activation showed no genotoxicity in the Ames test up to 500\u00a0\u03bcg\/plate, in the mammalian chromosomal aberration test up to 710\u00a0\u03bcg\/mL, or in the MN test up to 800\u00a0mg\/kg\u00a0bw. No abnormal neurobehavioral effects were observed in mice following treatment with up to 960\u00a0mg\/kg\u00a0bw of IAAS. Moreover, blood pressure, heart rate, electrocardiogram parameters, and depth and rate of breathing in anesthetized beagle dogs did not differ among the IAAS doses or from the vehicle group. These data indicated that IAAS did not induce mutagenicity, clastogenicity, or genotoxicity, and no pharmaco-toxicological effects were observed in the respiratory, cardiovascular, or central nervous systems. Our results increased understanding of safety considerations associated with IAAS, and may indicate that IAAS is a possible drug candidate.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Graphic Abstract<\/jats:title>\n                \n              <\/jats:sec>","DOI":"10.1007\/s13659-020-00242-4","type":"journal-article","created":{"date-parts":[[2020,4,30]],"date-time":"2020-04-30T06:03:42Z","timestamp":1588226622000},"page":"119-129","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Genotoxicity and Safety Pharmacology Studies of Indole Alkaloids Extract from Leaves of Alstonia scholaris (L.) R. 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