Safety and efficacy assessment of standardized herbal formula PM012

Spatial learning and memory capacities of hPS2m transgenic mice were evaluated using the Morris Water Maze. Simultaneously, PM012 was repeatedly administered orally to male and female SD rats (15/sex/group) at doses of 0 (vehicle control), 500, 1,000 and 2,000 mg/kg/day for 4 or 26 weeks. To evaluate the recovery potential, 5 animals of each sex were assigned to vehicle control and 2,000 mg/kg/day groups during the 4-week recovery period.The results showed that PM012-treated hPS2m transgenic mice showed significantly reduced escape latency when compared with the hPS2m transgenic mice. The repeated oral administration of PM012 over 26 weeks in male and female rats induced an increase and increasing trend in thymus weight in the female treatment groups (main and recovery groups), but the change was judged to be toxicologically insignificant. In addition, the oral administration of the herbal medicine PM012 did not cause adverse effects as assessed by clinical signs, mortality, body weight, food and water consumption, ophthalmology, urinalysis, hematology, serum biochemistry, blood clotting time, organ weights and histopathology. The No Observed Adverse Effects Levels of PM012 was determined to be 2,000 mg/kg/day for both sexes, and the target organ was not identified.These results suggest that PM012 has potential for use in the treatment of the Alzheimer's disease without serious adverse effects.Alzheimer's disease (AD) is the major cause of dementia and underlies more than 60% of dementia cases [1]. AD occurs more frequently in older age groups [2]. AD is characterized by the impairment of cognitive performance such as attention, memory and learning, in addition to changes in cholinergic markers, including levels of acetylcholine (ACh) and choline acetyltransferase (ChAT) [3-5]. In addition, β-amyloid precursor protein (β-APP), Presenilin 1 (PS1), Presenilin 2 (PS2), and apolipoprotein E type 4 (APOE-E4) mutations are linked to the early onset of AD [6-10]. Of these,